MCHFirst Trimester of Pregnancy

1.         Explain the purpose of antepartum care.

Anonymous Beckman 68-69

It is to help achieve as good a maternal and infant outcome as possible. Starts with the correct Dx. Of pregnancy, through the periodic exams and screening test, patient education, delivery, and the final visit, usually about 6 wks after delivery.

Anonymous Beckman 68-69.

It is to help achieve as good a maternal and infant outcome as possible. Starts with the correct dx. of pregnancy, through the periodic exams and screening tests, patient education, delivery, and the final visit, usually about 6 weeks after delivery.

Anonymous OB/GYN Pg 69

The purpose of antepartum care is to help achieve as good a maternal and infant outcome as possible.

Suzy

Counseling and education of the pregnant woman constitutes a major part of prenatal care, monitor the pregnancy, detect complications and abnormalities.  Ballweg 586

Screen for impaired fetal growth, malpresentation, anemia, preclampsia, and physical exam. Swartz 666

Early and consistent prenatal care improves the outcome of pregnancy.  Only 1% of pregnant women in the US receive no prenatal care.  Each prenatal revisit is a time to renew the bond established with the client at the initial visit, evaluate the data that has been gathered, and determine whether the pregnancy is progressing normally.  Vigilance for complications are discussion about healthy lifestyle habits and options for labor and birth.  NMH 45, 183

Anonymous OB & GYN, p.79

Antepartum care or pregnancy care between conception and the onset of labor is to help achieve as good a maternal and infant outcome as possible.

Anonymous

Beckmann p. 69 – The purpose of antepartum care is to help achieve as good a maternal and infant outcome as possible.  Antepartum care ends with a final visit, generally 6 weeks following delivery.

Wheeler p. 337 – A growing body of literature notes that postpartum health concerns are commonly unrecognized by health care professionals.  Painful perineum, and hemorrhoids, urinary incontinence, backache and depression are underreported.  Consequently, an early postpartum visit to identify and discuss these problems should occur sometime in the first 2 weeks.

2.         First Prenatal Visit - List the items included in a comprehensive history (including gravida and para), complete physical exam, routine obstetrical laboratory tests (include reasons why each is done), and counseling and education issues that should be addressed at this visit (including nutrition and supplements).

Anonymous
Hx- demographics, menstrual hx, LMP, #of pregnancies and outcomes, abortions, complications, multiple gestations, onset labor, length of labor, complications of labor, types of deliveries,
analgesia/anesthesia, condition of perineum, infant outcome, signs and symptoms of pregnancy to date, pregnancy tests/outcomes, contraceptive history, sexual hx, family/genetic hx, nutrition hx, substance use, social situation, psychological, environment-housing finance, etc.
Physical to include-skin pigment changes, mouth/gum changes, thyroid may increase in size, breast changes size/pigment, cardiac systolic flow murmur, pelvic exam.
Lab tests- blood type and Rh/antibody, Hgb/Hct,pap, GC, chlamydia, rubella titer, UA and cx, glucose if suspect set up for gestational diabetes, Hep B antigen, Herpes is lesion present, renal fcn tests for hypertensive patients, HIV, TB.
Educational issues-  orient to provider, setting, discuss schedule of visits and lab tests, review nutritional goals, expected development and bodily changes of fetus and mom, possible danger signs, sexuality, substance abuse, exercise.  Also identify any psych/social or environmental obstacles and refer appropriately.

Anonymous Beckman ch. 5, Balweg p 588-589.

History: Focuses on previous pregnancy outcomes and medical or surgical conditions that may affect preg. Includes: Hx of past pregnancies (including gravida/para/abortion), PMH with focus upon conditions affecting preg, info pertinent to genetic screening, and info about the course of the current pregnancy (especially important to get menstrual hx. and sexual hx to determine the gestational age). Special attention to diet; alcohol, tobacco, substance abuse, and medications.

PE:  Both texts stated that a thorough PE was to be performed, and in Beckman that a pelvic with pap smear and cultures for GC and Chlamydia were to be done.

Routine Ob labs:

CBC: determines hematologic status, r/o anemia.

UA with C&S: r/o UTI and check renal function.

Blood group, Rh: Blood type, Rh status, and risk of isoimmunization.

Antibody screen: To detect maternal antibodies that may harm fetus.

Serologic test for syphilis (RPR,VDRL): To detect previous/current infection, if (+) then further testing is required.

Hep B surface antigen: Tells carrier status or if active disease, (+) = Further testing.

Rubella titer: Most have evidence of prior infection. If (-), then special precautions to prevent acquiring during pregnancy (harmful to fetus), and mom will be vaccinated after it’s birth.

Pap: Cervical dysplasia, CA.

Cervical culture for GC/chlamydia: Both cause forms of conjunctivitis in newborn, associated with premature labor and post partum endometritis.

Hemoglobin electrophoresis: To detect sickle cell trait and sickle cell disease.

HIV titer: Should be offered to all patients at risk and some doc’s just do it routinely.

Anonymous OB/GYN Pg 71-74

History:

• Previous pregnancy outcome and any medical or surgical conditions that may affect pregnancy

• Information pertinent to genetic screening

• Information about the course of the current pregnancy  

• Special attention is given to diet

• The use of tobacco, alcohol, medications, and substance abuse

Labs:

Counseling and education:

• Patient is given information about routine prenatal care

• Warning signs of complications

• Whom to contact with questions or problems   

• A nutritional and social service information

• A PE including a pap smear and cultures for GC/chlamydia

Suzy NMH

Comprehensive history 49-99

• Cultural values

• Maternal Age – risk factors

  • Young – low birth weight, anemia, stillbirth, preeclampsia, preterm birth but those under 18 were at relatively low risk for obstetric complications.

  • Older – chromosomal and genetic risks >34 years of age.

•     Menstrual history – establish due date

•     Contraceptive History – Women who become pregnant without a spontaneous menstrual period after stopping “the pill” should have a sonogram to accurately determine the estimated date of birth (EDB) IUD in place will need to be removed >13 weeks, <13 weeks refer.  Midtrimester chance of septic abortion.

•     Obstetric History – information about previous pregnancies includes the month and year that the pregnancy ended, the gestational age at the end of the pregnancy, the type of delivery (spontaneous, forceps, vacuum extraction, or cesarean), the length of labor (preferably from the first contraction), analgesia or anesthesia used, episiotomy or lacerations, birth weight, sex of the child, place of birth, type of health care provider, complications, and the current health of each child.

• Gravida: who is or has been pregnant

• Nulligravida: who has never been or is not currently pregnant

• Para:  a number that refers to the number of babies delivered that were of sufficient size (500g) or gestational age (20weeks) to be considered viable.

• Nullipara: a woman in her fist pregnancy or has not carried a pregnancy beyond an elective or spontaneous abortion

• Primipara: who had had only one pregnancy in which the fetus reached the age of viability.

• Multipara: who has carried 2 or more pregnancies (as opposed to fetuses) to viability

•     Medical/Surgical History – Organic disease or other conditions that may or may not have received a medical diagnosis.  Mental illness, GYN, STD, surgeries, accidents, traumas, and breast surgery.

•     Pharmacologic Treatment – medications, complementary and alternative medicine that she uses.

•     Family history – identify for risk for genetic disease.  Should include drug and alcohol use by close family members.

•     Baby’s father – race, ethnic background and family medical history to identify potential genetic problems.  Father’s drug and alcohol use.  Heavy marijuana users who consider this drug harmless are not likely to admit to a problem.

•     Foreign Travel or residence – parasites, malaria, hepatitis or tuberculosis.

•     Sexual history – screen for sexual dysfunction.  Relieve anxiety, dispel myths, and offer suggestions to improve.  

•     Screen for abuse - Identify a client with a history of physical, emotional and sexual abuse.

•     Environmental Exposures – toxins or pesticides on farmland, school, home, garden, occupation, hobbies, buildings, and ingestion of food and water.  X-rays during the current pregnancy caries a risk of genetic effects and birth defects.  >5 rads are not associated with congenital malformations.  Plain films-low exposure, CT-give the most radiation.  Most sensitive period of exposure for developing leukemia is about the 7^th month of preg. All other cancers is the first 6 months.

•     Habits undermining health – smoking, substance abuse (alcohol, drugs 80-87)

•     Social History – socioeconomic status could affect birth weight.  Family constellation (support), living situation, sources of support, sources of stress, occupation, education, interests, hobbies, goals, religious preference.

•     Pets – congenital toxoplasmosis can occur.  Cats-many women, particularly those who have had or have a cat as a pet, have protective antibodies and are not at risk for the disease.  Dangerous pets, such as ferrets and some breeds of dogs.  Living with a large number of pets, likely to unsanitary conditions.

•     Weapons

•     Good health habits – encourage, reinforce, educate.  Breast and skin examinations, immunizations, nutrition, exercise (pg 93-99)

Physical exam 100-122

Introduction, height, weight, blood pressure, skin, thyroid, lungs, heart, breasts, mammary agenesis (absence or marked reduction of breast tissue), nipples, abdomen, fetal heart tones, fundal height, extremities, pelvic exam, external genitalia, vagina and cervix, labs, bimanual exam, clinical pelvimetry, and dating pregnancy.

Routine obstetrical laboratory tests 117-

Vaginal Tests

•                    Pap smear – detect cervical cancer or HPV

•                    Chlamydia – protect mother during pregnancy and baby during delivery.

•                    Gonorrhea– infection during pregnancy are associated with septic, spontaneous abortion, premature rupture of membranes, prematurity, intrauterine growth restriction, chorioamnionitis, disseminated gonococcal infection, postpartum endometritis.  Transfer to baby during delivery.

•                    Wet Smear – if discharge present, check for

o     Trichomonal - Premature onset of contractions, low birth weight, preterm delivery

o     Bacterial Vaginosis – Preterm birth

o     Candidiasis -

•                    Urine – protein, glucose, UTI, preeclampsia and diabetes.

Blood tests

•                    Rh factor:  Rh D antigen is said to be Rh-positive, those with out are Rh-negative

Fetal cells as early as 6 weeks have Rh D antigen.  Identify babies who could be sick or die from Rh disease (hemolytic disease of newborn) and women who should receive anti-D immunoglobulin (Ig) to prevent this disease. Incompatible mother – baby

•                    Antibody screen: Blood type, identifies women with antibodies (rare blood types) that can cause hemolytic disease.

•                    CBC: anemia and thrombocytopenia

•                    Syphilis:  untreated during pregnancy cause infant death in up to 40%

•                    Rubella: devastating effects of congenital rubella, eye lesions, heart disease, deafness, CNS defects, anemia, hepatitis, pneumonitis, bone defects, and chromosome abnormalities most likely to occur in the first trimester.  

• Hepatitis B: rarely alters the course of hepatitis B infection, infants born to HbsAg-positive women are at risk for developing chronic active hepatitis and have an increased chance of dying from liver cirrhosis, hepatoma, hepatocellular carcinoma, or fulminate liver failure.

• HIV: Early identification of HIV-positive status gives women the opportunity to take advantage of treatment, make informed decisions about their high-risk behaviors, and continue the pregnancy.

• Triple Screen – at risk for delivering babies with Down Syndrome, trisomy 18, and neural tube defects.  

Alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3).

• Quadruple (Quad) Screen: - another useful marker for Down syndrome

• Gestational Diabetes Mellitus – when any degree of glucose/carbohydrate intolerance begins.

• Special Tests – Sickle Cell, hemoglobin Electrophoresis, Varicella, Type – Herpes Simplex Virus, Thyroid-stimulating hormone, tuberculosis, Group B Strep, and Genetic testing.

• Chorionic Villus Sampling(CVS) – early prenatal diagnostic tool taking aspirated cells from the placental bed to determine fetal karyotype.

• Amniocentesis – Fetal cells fro karyotyping from the amniotic fluid for chromosomal abnormalities.

• Fetal Fibronectin – detect preterm labor. Vaginal specimen for the fFN. Recent intercourse false-positive.

• Ultrasound examinations – estimate date of birth, multiple gestation present, structural abnormalities, locate placentas, measure amniotic fluid volume, assess fetal growth, measure the length of the cervix, reassure families about fetal well-being, and facilitate bonding.  Possible sex of baby.

• Antepartal fetal surveillance

  • Nonstress test evaluates the fetal heart rate without “stressing” the baby with uterine contractions.  

  • Contraction stress test fetal heart rate is evaluated under conditions of stress(contraction)

Counseling and education issues pgs 174-180

•     Danger Signs – report vaginal bleeding, cramping, contractions, fever above 38C, persistent vomiting, rupture of membranes, UTI symptoms.

•     What to Avoid Handout listing recommendations Appendix 6-1

•     Tips for a Healthier Pregnancy

o     Nutrition (pg39-41 Appendix E) based on diet assessment, discuss good diet, pyramid, reading labels, and serving size.

o     Supplements – If you took it before, continue.  Otherwise Institute of Medicine does not recommend for healthy, nonsmoking women whose prepregnancy weight is appropriate for height.  Iron is recommending beginning the 13^th week at 30mg.

•                    Exercise: did before, continue at moderate-intensity for 60 minutes 5 times a week. Clients should be told about the benefits of weight-bearing exercise-improving cardiovascular functions, keeping sown weight, decreasing backache, improving sleep, increasing energy, and for some increasing emotional well-being.

•                    Frequency of Prenatal visits

Nulliparas                                        Multiparas

First visit: 6-8 weeks                        First visit: 6-8 weeks

Second visit: within 4 wks of first      Second visit: 14-16 weeks

Third visit: 14-16 weeks                   Third visit: 24-28 wks

Fourth visit: 24-28 wks                     Fourth visit: 32 wks

Fifth visit: 32 wks                             Fifth visit: 35 wks

Sixth visit: 36 wks                             Sixth visit: 39 wks

Seventh visit: 38 wks                        Seventh visit: 41 wks

Eight  visit: 40 wks

Ninth visit: 41 wks

Anonymous OB & GYN, 81-83

                    After the diagnosis of pregnancy is confirmed, an appointment is scheduled for the first prenatal visit, at which time a comprehensive history is taken-which should include number of  pregnancies and outcomes: G , P, Abs including details, surgical and medical conditions that

may affect the pregnancy, pertinent genetic screening, and information about the current

pregnancy.

Complete Physical Exam-a complete physical exam is performed including PAP test

and cervical cultures for Neisseria gonorrhea and Chlamydia trachomatis.

Routine Lab Tests-1.CBC  2. UA, Culture & Sensitivity  3. Blood Group Rh, 4. Antibody

Screen, 5. Serology for syphilis (RPR,VDRL), 6. Hep B Surface Antigens, 7. Rubella titer

8. PAP, 9. Cervical culture for N.gonorrhea, 10. Hemoglobin electrophoresis, 11. HIVtiter

by ELISA, If positive-Western Blot, 12. Glucose screening-1 hour.

        Table 5.6 in Ob & Gyn, page 91 for patient education form/checklist.

Anonymous Beckmann p. 71

After the diagnosis of pregnancy has been established, a prenatal appointment is made, at which time a comprehensive history is taken, focusing on previous pregnancy outcome and any medical or surgical conditions that may affect pregnancy.  The details of a recommended history include a history of past pregnancies, past medical history with specific attention to issues that may affect pregnancy, information pertinent to genetic screening, and information about the course of the current pregnancy.  Special attention is also given to the diet; the use of tobacco, alcohol, and medications; and substance abuse.  Routine laboratory studies are ordered, and the patient is given instructions concerning routine prenatal care, warning signs of complications, whom to contact with questions or problems, and nutritional and social service information.  A complete physical exam is performed, including a Pap test and a cervical culture for Neisseria gonorrhea and Chlamydia trachomatis.

If medical or obstetric problems are identified during the initial assessment or at any subsequent visit, the pregnancy is designated “at risk,” and appropriate specific management is initiated.

Table 5.1 Routine Obstetric Laboratory Tests –

1. CBC – to determine hematologic status; to rule out anemia.

2. UA and urine culture & sensitivity – to evaluate for UTI and renal function.

3. Blood group, Rh – to determine blood type, Rh status, and risk of isoimmunization.

4. Antibody screen – to detect maternal antibodies, which may damage fetus or make procurement of compatible blood for transfusion more difficult.

5. Serologic test for syphilis (RPR, VDRL) – to detect previous/current infection; if positive, specific treponemal test required.

6. Hepatitis B surface antigen – to detect carrier status or active disease; if positive, further testing indicated.

7. Rubella titer – if patient is seronegative, special precautions are needed to avoid infection, which can severely affect the fetus; vaccination is then required post partum.

8. Cervical cytology (Pap smear) – to screen for cervical dysplasia/cancer.

9. Cervical culture for Neisseria gonorrhea – to screen for infection; causes neonatal conjunctivitis; association with premature labor and postpartum endometriosis.

10. Hemoglobin electrophoresis – to detect sickle-cell trait (HbSA), associated with a higher risk for UTI, and sickle-cell disease (HbSS), at risk for multiple fetal and maternal complications.

11. HIV titer by ELISA; Western blot if HIV+ by ELISA – should be offered to all patients at risk; may be offered to all patients at provider’s discretion.

12. Glucose screening – to screen for glucose intolerance in high-risk patients; usually at 28 weeks in low risk patients.

SUBSEQUENT ASSESSMENTS:

13. MSAFP at 15 to 18 weeks – elevated levels seen with neural tube defects, gastroschisis, and omphalocele; low levels associated with Down syndrome.

14. Hematocrit at 25 to 28 weeks – to rule out anemia.

15. Glucose screening at 24 to 28 weeks – to screen for glucose intolerance.

(Wheeler p. 177 – Tips for a Healthier Pregnancy – The role of prenatal vitamins in prenatal care is unclear.  They are not necessarily necessary according to Wheeler.  Official recommendations vary on the use of oral iron in pregnancy; some sources recommend it, some do not.  All clear?)

3.         Gestational Age and EDC - List the methods for assessment of gestational age and EDC (estimated date of confinement or due date).  For each, describe the method, be able to apply the method to a hypothetical case problem, and discuss its accuracy.

Anonymous

By LMP- add 7 days to the first day of the last normal menstrual flow and then subtract 3 months.

By Pelvic Exam- accurate within 1-2 weeks until second trimester.

By Fundus Height- from 16-35 weeks gestation, fundal height in cm is roughly equal to gest. age in weeks.

By Ultrasound- most accurate. In 1^st trimester, accurate within 1-2 weeks by using measurements of the gestational sac and embryo/fetus. In 2^nd trimester, accuracy is +/- 2 weeks. In late 3^rd, only +/- 2-3 weeks.

(Beckmann, p.74)

Anonymous Beckmann

Gestational Age- date of onset of last period and a pelvic examination are ok but obstetric ultrasound exam is the most accurate measurement available in the determination of gestational age. pg 74

EDC- is calculated by adding 7 days to the first day of the last normal menstrual flow and counting back 3 months.  pg 74

Anonymous OB/GYN Pg 74

• Menstrual history: Normal pregnancy lasts 40+/- 2 weeks, calculated from the first day of the last period. Calculation of the EDC is accomplished by adding 7 days to the first day of the last period and counting back three months. In a patient with an idealized 28 day cycle, ovulation occurs on day 14, so that the fertilization age or conception age of the normal pregnancy is usually 38 weeks.

• Pelvic examination: By an experienced examiner is accurate within 1-2 weeks until the second trimester, at which time the lower uterine segment forms, thereby making clinical estimation of gestational age less accurate. From 36 weeks of gestation, the fundal height in centimeters is roughly equal to the number of weeks of gestational age in normal singleton pregnancies.

• Obstetric ultrasound: Is the most accurate measurement available in the determination of gestational age.

Suzy Swartz 661, NMH 53

Estimated date of birth (EDB) or the estimated date of delivery (EDD) or the estimated date of confinement (EDC).

Naegele's rule:  

First day of the last normal menstrual period (LNMP) + 9 months + 7 days=EDB

example (LNMP Jan 10 + 9 months + 7 days = October 17th due date)

                        -or-

LNMP -- 3 months + 7 days + 1 year = EDB

example (Sept 26 -- 3 months + 7 days + year = July 3rd due date)

Gestation calculator or "wheel" will vary as much as 4 days.

Note: Women who have a history of long or short menstrual cycles (longer than 35 days or less than 21 days) required an adjustment in EDB.  

            35 day cycle.....should have 14 days rather than 7 days added

            21 day cycle.....would have 7 days subtracted

Anonymous  OB & GYN, 83-84

For each, describe the method, be able to apply it, and discuss accuracy.

1.     Gestational age is calculated from the first day of the last menstrual period with a normal Pregnancy lasting 40 ± 2 weeks. “Calculation of the EDC is accomplished by adding 7 days to the first day of the last normal menstrual flow and counting back 3 months.” A history of irregular periods or medications that alter the menstrual cycle and some psychoactives make this method less accurate. However, many women who are trying to achieve conception by taking their basal body temperatures may more accurately pin-point conception.

2.     Pelvic Exam: An experienced examiner is accurate in determining gestational age within one or two weeks until the 2^nd trimester, when the lower uterine segment starts to form, making the EDC less accurate.

3.     OB Ultrasound: This is the most accurate determination of gestational age available until late in the third trimester when accuracy drops to ± 2 or 3 weeks.

Anonymous Beckmann p. 72

Every effort is made to assess accurately gestational age from which the EDC (due date or EDD) is calculated.  This information is crucial to obstetric management, because it is needed to manage situations such as possible preterm labor or postdates pregnancy.

•        Initial assessment of gestational age is made by obtaining a thorough menstrual history.  “Normal” pregnancy lasts 38-42 weeks, calculated from the first day of the last normal menses (menstrual or gestational age).  Calculation of the EDC is accomplished by adding 7 days to the 1^st day of the last normal menstrual flow and counting back 3 months.  In a patient with a 28 day menstrual cycle, ovulation occurs on day 14, so that the fertilization age or conception age of the normal pregnancy is actually 38 weeks.

•        To establish an accurate gestational age, the date of the onset of the last normal menses is crucial.  A light bleeding episode should not be mistaken for a normal menstrual period.  To summarize the rest of the paragraph, an unreliable history is unreliable while a reliable history is reliable.  (That sounds obvious but I wrote it with possible test question scenarios in mind.)

•        Pelvic examination by an experienced examiner is accurate in determining gestational age within 1 to 2 weeks until the 2^nd trimester.  From 16 to 18 weeks of gestation until 36 weeks of gestation, the fundal height in centimeters is roughly equal to the number of weeks of gestational age in normal singleton pregnancies.

•        Obstetric ultrasound examination is the most accurate measurement available in the determination of gestational age.  In the 1^st trimester, determination within plus or minus 1-2 weeks accuracy is possible.  In the 2^nd trimester accuracy is within plus or minus 2 weeks.  In the latter part of the 3^rd trimester accuracy is within plus or minus 2-3 weeks.

4.         Describe the following prenatal screening tests and discuss why/when you would have them done:    Added 2004
Maternal serum alpha-fetoprotein (MSAFP)
Amniocentesis
Chorionic villas sampling(CVS)
Fetal Ultrasonography

Zen Seeker Current OB/GYN 9th

Maternal Serum Analyte Testing
Frequently known as the "triple screen," this test includes maternal serum alpha-fetoprotein (msAFP), β-hCG, and estriol. In some institutions, only the msAFP is used, while in other institutions a fourth test, inhibin, is included, making it a "quad test." The usefulness of this screen is its ability to identify pregnancies at an increased risk for open neural tube defects, as well as for certain chromosomal abnormalities, especially trisomy 21 (75% sensitivity for Down syndrome detection). This test is effective at 15-19 weeks' gestation and can therefore identify an at-risk pregnancy in time to pursue more definitive diagnosis, if desired. It is important to note, however, that the triple screen is not a definitive test and that many positive screens have yielded normal fetuses and many abnormal fetuses have had normal screens.

Amniocentesis-Amniocentesis is frequently performed under the guidance of ultrasonography. A needle is inserted transcutaneously through the abdominal wall into the amniotic cavity, and fluid is removed. There are many uses for this amniotic fluid, including cytology for detection of infection, alpha-fetoprotein evaluation for neural tube defect assessment, assessment of fetal lung maturity (which will be discussed later in the chapter), and the most common indication of cytogenetic analysis. In this case, amniocentesis is often performed between 15 and 20 weeks' gestation and fetal cells from the amniotic fluid are obtained. Risks associated with the procedure are considered to be very low, with the risk of abortion as a result of amniocentesis considered to be between 1 in 200 to 1 in 450 amniocenteses.
 

Chorionic villus sampling-Chorionic villus sampling (CVS) is an alternative to amniocentesis. It is performed between 10 and 12 weeks' gestation, and can be performed either transcervically or transabdominally. CVS is also performed under sonographic guidance, with the passing of a sterile catheter or needle into the placental site. Chorionic villi are aspirated and undergo cytogenetic analysis. The benefit of CVS over amniocentesis is its availability earlier in pregnancy; however, the rate of abortion is higher-as high as 1%. One disadvantage of CVS is that unlike amniocentesis, it does not allow diagnosis of neural tube defects.
 

Ultrasound-Ultrasound has had a continuous evolution over the last 20 years, with better equipment being produced each year. Real-time sonography allows a 2-D image to demonstrate fetal anatomy, as well as characteristics such as fetal weight, movement, volume of amniotic fluid, and structural anomalies such as myomas or placenta previa which may affect the pregnancy. 3-D sonography allows volume to be ascertained, creating a three-dimensional appearing image on the 2-D screen, which assists in identifying certain anatomical anomalies. Most recently, 4-D machines have been developed, which produce a 3-D image in real time. As the machines become more technically advanced and the computers that run them become faster, the images obtained will continue to improve and push the boundaries of sonographic prenatal diagnosis.

Diagnostic ultrasonography is widely used in the assessment of the pregnancy and the fetus. It is not, however, the standard of care, nor is it recommended by ACOG for every pregnancy. The indications for ultrasonography are multiple and diverse, and the type and timing of the examination varies depending on the information being sought.

A basic ultrasound examination should provide such information as fetal number, presentation, documentation of fetal viability, placental location, and assessment of gestational age. A limited ultrasound examination is a goal-directed search for a suspected problem or finding. A limited ultrasound may be used for guidance during procedures such as amniocentesis or external cephalic version, assessment of fetal well being, or documentation of presentation or placental location intrapartum. A comprehensive ultrasound examination provides information on fetal anatomy, growth, anomalies, and physiologic complications.

Ultrasound evaluation of fetal anatomy may detect some major structural anomalies. Gross malformations such as anencephaly and hydrocephaly are more commonly diagnosed and rarely missed; however, more subtle anomalies such as facial clefts, diaphragmatic hernias, and neural tube defects are more commonly reported to have been missed by ultrasound. The basic fetal anatomy survey should include visualization of the cerebral ventricles, four-chamber view of the heart, and examination of the spine, stomach, urinary bladder, umbilical cord insertion site, and renal region. Any indication of an anomaly should be followed by a more comprehensive sonogram. Typically, the fetal anatomic survey is performed at 17-20 weeks; however, there is controversy surrounding the potential benefits of an earlier sonogram at 14-16 weeks using the transvaginal probe. The earlier scan allows earlier detection of anomalies that are almost always present by the second trimester, as well as allowing greater detailed viewing of the fetal anatomy by using the higher-resolution vaginal transducers.

Entire Section -

Screening Tests

Screening tests are performed at the appropriate time during the pregnancy.

A. FASTER (First and Second Trimester Evaluation of Risk for Aneuploidy) Trial

Transvaginal sonography between 103/7 weeks and 136/7 weeks to visualize and measure nuchal translucency, along with serum measurements of PAPP-A and free β-hCG is currently being studied in several institutions throughout the United States as a screen for Down syndrome, as well as other aneuploidies and malformations.

B. Maternal Serum Analyte Testing

Frequently known as the "triple screen," this test includes maternal serum alpha-fetoprotein (msAFP), β-hCG, and estriol. In some institutions, only the msAFP is used, while in other institutions a fourth test, inhibin, is included, making it a "quad test." The usefulness of this screen is its ability to identify pregnancies at an increased risk for open neural tube defects, as well as for certain chromosomal abnormalities, especially trisomy 21 (75% sensitivity for Down syndrome detection). This test is effective at 15-19 weeks' gestation and can therefore identify an at-risk pregnancy in time to pursue more definitive diagnosis, if desired. It is important to note, however, that the triple screen is not a definitive test and that many positive screens have yielded normal fetuses and many abnormal fetuses have had normal screens.

C. Diabetes Screen

Routine screening consists of performing a glucose challenge test between 24 and 28 weeks. The test consists of a 50-g oral glucose load with a plasma glucose level drawn exactly 1 hour after. If the value is over 140 mg/dL, a more specific glucose tolerance test (GTT) should be performed. The GTT involves obtaining a fasting plasma glucose level, giving a 100-g oral glucose load, then drawing plasma levels at 1 hour, 2 hours, and 3 hours after the glucose load. A test is considered positive for gestational diabetes if two out of the four values are elevated.

D. Isoimmunization

A patient who is Rh-negative with a pregnancy fathered by an Rh-positive man should be screened for antibodies at the first prenatal visit and again at 24-28 weeks. If there continues to be no antibodies, Rhogam should be administered at 28 weeks to prevent sensitization of the mother during the last trimester and delivery. In the event of a previously isoimmunized patient, the typing and screening performed at the initial visit would detect antibodies, which are reported as a numerical titer. These titers should be followed every 4 weeks to assess for worsening isoimmunization. In the presence of worsening titers, follow-up with amniocentesis may be appropriate. Peak systolic velocity of the fetal middle cerebral artery as determined by sonographic Doppler evaluation has been demonstrated to correlate with degree of fetal anemia, allowing for noninterventional diagnosis and management of fetal isoimmunization; however, the definitive treatment is intrauterine fetal transfusion.

E. Beta Hemolytic Streptococcus

This is also known as the group B Streptococcus (GBS) test, and between 10% and 30% of pregnant women are colonized with GBS in the vaginal or rectal areas. Whereas they are usually asymptomatic colonizations, perinatal transmission can result in a severe and potentially fatal neonatal infection. Any documented GBS bacteriuria needs to be treated at the time of diagnosis, as well as intrapartum. Intrapartum antibiotic prophylaxis has been shown to decrease the risk of perinatal GBS transmission. There are two approaches to screening: Screen patients at 35-37 weeks' gestation and treat positive cultures with intrapartum antibiotics, or treat patients based on risk factors with intrapartum antibiotic prophylaxis.

Fetal Assessment

Comprehensive fetal assessment begins in the first trimester with nuchal translucency and continues throughout the pregnancy into labor and delivery. Conceptually, antepartum testing in pregnancies at risk falls into one of two categories: assessment of prenatal diagnosis and assessment of fetal well-being.

A. Assessment of Prenatal Diagnosis

Performed during all trimesters, the techniques used are diverse, and the information obtained varies according to the quality of imaging, depth of investigation, and gestational age of pregnancy.

1. Ultrasound-Ultrasound has had a continuous evolution over the last 20 years, with better equipment being produced each year. Real-time sonography allows a 2-D image to demonstrate fetal anatomy, as well as characteristics such as fetal weight, movement, volume of amniotic fluid, and structural anomalies such as myomas or placenta previa which may affect the pregnancy. 3-D sonography allows volume to be ascertained, creating a three-dimensional appearing image on the 2-D screen, which assists in identifying certain anatomical anomalies. Most recently, 4-D machines have been developed, which produce a 3-D image in real time. As the machines become more technically advanced and the computers that run them become faster, the images obtained will continue to improve and push the boundaries of sonographic prenatal diagnosis.

Diagnostic ultrasonography is widely used in the assessment of the pregnancy and the fetus. It is not, however, the standard of care, nor is it recommended by ACOG for every pregnancy. The indications for ultrasonography are multiple and diverse, and the type and timing of the examination varies depending on the information being sought.

A basic ultrasound examination should provide such information as fetal number, presentation, documentation of fetal viability, placental location, and assessment of gestational age. A limited ultrasound examination is a goal-directed search for a suspected problem or finding. A limited ultrasound may be used for guidance during procedures such as amniocentesis or external cephalic version, assessment of fetal well being, or documentation of presentation or placental location intrapartum. A comprehensive ultrasound examination provides information on fetal anatomy, growth, anomalies, and physiologic complications.

Ultrasound evaluation of fetal anatomy may detect some major structural anomalies. Gross malformations such as anencephaly and hydrocephaly are more commonly diagnosed and rarely missed; however, more subtle anomalies such as facial clefts, diaphragmatic hernias, and neural tube defects are more commonly reported to have been missed by ultrasound. The basic fetal anatomy survey should include visualization of the cerebral ventricles, four-chamber view of the heart, and examination of the spine, stomach, urinary bladder, umbilical cord insertion site, and renal region. Any indication of an anomaly should be followed by a more comprehensive sonogram. Typically, the fetal anatomic survey is performed at 17-20 weeks; however, there is controversy surrounding the potential benefits of an earlier sonogram at 14-16 weeks using the transvaginal probe. The earlier scan allows earlier detection of anomalies that are almost always present by the second trimester, as well as allowing greater detailed viewing of the fetal anatomy by using the higher-resolution vaginal transducers.

2. Aneuploidy screening-Multiple sonographic markers for aneuploidy have been identified. The presence of single or multiple markers adjusts the patient's age-related risk of aneuploidy based on the particular markers present. Such sonographic findings include, but are not limited to:

• Echogenic intracardiac focus

• Choroid plexus cysts

• Pyelectasis

• Echogenic bowel

• Short femur

• Hypomineralization of the fifth digit of the fetal hand

3. Amniocentesis-Amniocentesis is frequently performed under the guidance of ultrasonography. A needle is inserted transcutaneously through the abdominal wall into the amniotic cavity, and fluid is removed. There are many uses for this amniotic fluid, including cytology for detection of infection, alpha-fetoprotein evaluation for neural tube defect assessment, assessment of fetal lung maturity (which will be discussed later in the chapter), and the most common indication of cytogenetic analysis. In this case, amniocentesis is often performed between 15 and 20 weeks' gestation and fetal cells from the amniotic fluid are obtained. Risks associated with the procedure are considered to be very low, with the risk of abortion as a result of amniocentesis considered to be between 1 in 200 to 1 in 450 amniocenteses.

4. Chorionic villus sampling-Chorionic villus sampling (CVS) is an alternative to amniocentesis. It is performed between 10 and 12 weeks' gestation, and can be performed either transcervically or transabdominally. CVS is also performed under sonographic guidance, with the passing of a sterile catheter or needle into the placental site. Chorionic villi are aspirated and undergo cytogenetic analysis. The benefit of CVS over amniocentesis is its availability earlier in pregnancy; however, the rate of abortion is higher-as high as 1%. One disadvantage of CVS is that unlike amniocentesis, it does not allow diagnosis of neural tube defects.

5. Fetal blood sampling-Also referred to as cordocentesis or percutaneous umbilical blood sampling (PUBS), this is an option for chromosomal or metabolic analysis of the fetus. Benefits of the procedure include a rapid result turnaround rate and the ability to perform the procedure in the second and third trimester. Intravascular access to the fetus is useful for the assessment and treatment of certain fetal conditions such as Rh sensitization and alloimmune thrombocytopenia. There is a higher risk of fetal death, however, when compared to the other methods. Fetal loss rates are approximately 2%, but can vary depending on the fetal condition involved.

B. Assessment of Fetal Well-Being

1. Fetal monitoring techniques-Assessment of fetal status can be performed using a wide variety of techniques.

a. External fetal monitoring-The external measurement of the fetal heart rate is done by using a continuous beam of ultrasound waves focused on the fetal heart. This ultrasound monitor utilizes Doppler effects to sample the frequency of moving fetal heart valves and the atrial and the ventricular systole. The complex received signal wave is then peak detected and entered into the heart rate monitor. The computer averages several consecutive frequencies, which helps minimize artifact, before the signal is displayed and printed. This process of averaging is called autocorrelation, and produces a fetal heart rate pattern which closely resembles that derived from a fetal ECG, although there is more baseline variability inherent in this method.

b. Internal fetal monitoring-The internal measurement of the fetal heart rate is an invasive procedure, utilizing an electrode attached to the fetal scalp. A bipolar spiral electrode is placed transcervically and penetrates the fetal scalp. A reference electrode is placed on the maternal thigh to eliminate electrical interference. The fetal ECG is detected, and the R wave is the signal used for peak detection and for counting. This signal is very clear, and allows accurate beat-to-beat and baseline variability to be measured. Artifact is kept to a minimum, and there is little need for autocorrelation.

c. Sonographic fetal monitoring-There have been reports of a number of sonographically related surveillance techniques for fetal status published in the literature. Such testing techniques as biophysical profile and Doppler velocimetry have been extensively studied and widely used for antepartum evaluation. Doppler velocimetry is a noninvasive technique based on vascular impedance. Most often, the umbilical artery is utilized for this purpose. Both the peak values as well as the actual waveform can be utilized to identify abnormally growing fetuses, or fetuses at risk of cardiac failure or other adverse outcome. Most of the benefit is seen in growth-restricted pregnancies, and use for generalized surveillance is not recommended. Biophysical profile consists of fetal heart rate evaluation combined with sonographically assessed parameters of fetal well being, including fetal breathing movements, fine motor movement, gross fetal tone, and amniotic fluid volume.

2. Fetal heart rate interpretation-

a. Antepartum fetal surveillance-In determining which patients should have antepartum fetal surveillance, a major factor to consider is the lack of evidence that any routine surveillance method results in a decreased risk of fetal death. Therefore, we generally begin monitoring in pregnancies in which the risks of fetal demise are known to be increased. These can include maternal conditions such as antiphospholipid syndrome, lupus, diabetes, or other maternal medical problems. They can also include pregnancy-related conditions such as preeclampsia, IUGR, multiple gestation, poor obstetrical history, or postterm pregnancy.

Antepartum surveillance should include a nonstress test (NST) as a minimum. The addition of sonographic monitoring is common, most often as some variant of the biophysical profile. The criteria for the NST are: baseline between 120 and 160 bpm, the presence of periodic accelerations (ie, two accelerations in 20 minutes) of fetal heart rate of 15 bpm over baseline for 15 seconds, the absence of decelerations of the fetal heart rate, and the subjective assessment of variability of the fetal heart rate. In the case of a nonreassuring NST, further evaluation or delivery depend on the clinical context. In a patient at term, delivery is warranted. Near term, determination of fetal lung maturity can be considered. Remote from term poses a more challenging dilemma to the clinician. If resuscitative efforts are not successful in restoring reactivity to the NST, ancillary tests or testing techniques may prove useful in avoiding a premature iatrogenic delivery for nonreassuring fetal heart rate patterns, since the false-positive rate may be as high as 50-60%.

C. Ancillary Tests

1. Vibroacoustic stimulation-An auditory source, often an artificial larynx, is placed on the maternal abdomen. A short burst of sound is delivered to the fetus. This has proven successful in shortening the duration needed for the test to show reactivity, without compromising the predictive value of the absence of acidosis with a reactive NST.

2. Fetal scalp stimulation-The presence of an acceleration after a vaginal exam where the examiner stimulates the fetal vertex with the examining finger confirms the absence of acidosis (pH > 7.2).

3. Oxytocin challenge test-This may be used to elicit a confirmatory abnormal fetal heart rate response, with one report showing a better correlation with adverse outcome than the NST alone. Other studies, however, have demonstrated no improvement in predicting morbidity over an NST. This is performed by intravenous infusion of dilute oxytocin until three contractions occur in 10 minutes. A positive test indicates decreased fetal reserve, with a 20-40% incidence of abnormal fetal heart rate (FHR) patterns in labor. A positive test is the presence of a late deceleration after each of the three contractions, a negative test shows no decelerations, and anything else is equivocal. Repetitive variable decelerations are termed "suspicious" and are associated with abnormal FHR patterns in labor, particularly in postterm gestations.
 

4.         Common Concerns/Problems - For each of the following be able to discuss etiology, treatment, and patient education: headaches, blurry vision, nausea and vomiting, tiredness, vaginal discharge, and faintness.

Anonymous

Headache- Beckmann, p. 82

            Etiology: Unknown

            Treatment: Tylenol (usual dose)

            Pt. Education: Common in early pregnancy. Often resolves by 2^nd trimester.

Nausea/Vomiting- Beckmann, p. 82, Verrilli, pp. 29-31

            Etiology: Body reacting to hormones, decreased B6 and glycogen, emotions.

            Treatment: Small frequent meals, avoid empty stomach w/ crackers, cereal.

            Pt. Education: Normal, usually resolves in 2^nd trimester, avoid strong odors.

Fatigue- Beckmann, p. 82

            Etiology: anemia or reaction to hormones of pregnancy

            Treatment: Adjust schedule to accommodate lack of energy.

            Pt. Education: reassure that symptoms will disappear in 2^nd trimester.

Vaginal Discharge- Beckmann, p. 83, Verrilli, pp 36-37

            Etiology: Hormones of pregnancy can increase normal vaginal secretions.

            Treatment: none

            Pt. Education: try the following: wearing skirts (air flow helps), wear cotton briefs, frequent warm (not hot) baths help pt. feel clean, don’t douche.

            Important to distinguish from vaginitis (itchiness, malodour) and spontaneous rupture of membranes (clear, thin fluid)

Faintness- Verrilli, pp 25-26

            Etiology: Standing for long periods of time may cause hypotension. Anemia

            Treatment: Avoid standing for long periods of time. Eat small, frequent meals to maintain even blood sugar level, treat any anemia.

            Pt. Education: After 4^th month of pregnancy, don’t lie flat on back. Move around frequently when standing.

Anonymous Obstetrics and Gyn p. 82-83, also Bates p. 434

Headaches – Headaches are common in early and  may be severe.  The etiology of such headaches in not known.  Treatment with acetaminophen in usual doses is recommended.  Pt education for these may be to warn patients of them and to encourage relaxing and comforting exercises or therapies.

Nausea and Vomiting – The majority of women experience some degree of upper GI symptoms during their first trimester.  These are classically worse in the morning.  Possible causes include hormonal changes of pregnancy leading to slowed peristalsis throughout the GI tract, changes in taste and smell, the growing uterus, or emotional factors.  Treatment consists of frequent small meals, avoidance of an “empty stomach” by ingesting crackers or other bland carbohydrates, and patience.  Antinausea medications are sometimes used.  Giving expectant mothers this information will be helpful for them in their preparation and transition to pregnancy.

Tiredness – In early pregnancy, patients often complain of extreme fatigue that is unrelieved by rest.  Rapid change in energy requirement; hormonal changes (progesterone has a sedative effect) are causes.  There is no specific treatment, other than adjustment of the patient’s schedule to the extent possible to accommodate this temporary lack of energy.  Patients can be reassured that the symptoms disappear in the  second trimester.

Vaginal Discharge – The hormonal milieu of pregnancy often causes an increase in the normal vaginal secretions.  These normal secretions must be distinguished from vaginitis, which has symptoms of itching and malodor, and spontaneous rupture of membranes, for which thin, clear fluid appears.  Pt education of these symptoms is important.

Faintness – Somewhat associated with fatigue, can be another symptom caused by the rapid change in hormones and nutrient requirements associated with pregnancy.  Patients should be counseled and educated on the importance of adequate rest, fluid and nutritional value during pregnancy.

Anonymous

HA  - etiology unknown

•        Tx- acetaminophen in usual doses is recommended

•        Pt. ed – Common in early pregnancy, often resolves by 2^nd trimester

N/V – etiology- body reacting to hormones, decreased B^ and glycongen, emotions?

•        Tx – small frequent meals, avoid empty stomach with crackers, cereal

•        Pt ed – normal, usually resolves in 2^nd trimester, avoid strong odors

Tiredness – etilogy – anemia or reaction to hormones of pregnancy

•        Tx – Adjust schedule to accommodate lack of energy

•        Pt. ed. – reassure symptoms will diappear in 2^nd trimester

Vaginal discharge – etiology- hormones of pregnancy can increase normal vaginal secretions.

•        Tx- none

•        Pt. ed – wear skirts for more air flow, wear cotton briefs, frequent warm baths help pt. feel clean, don’t douche.  Important to distinguish from vaginitis (itchiness, malodor) and spontaneous rupture of membranes (clear, thin fluid)

Faintness – etiology – standing for long periods of time may cause hypotension, anemia

•        Tx – Avoid standing for long periods of time.  Eat small, frequent meals to maintain even blood sugar level, treat any anemia

•        Pt. ed.- After 4^th month of pregnancy, don’t lie flat on back. Move around frequently when standing

Suzy NMH 200-202

Headaches

Etiology:  Benign vascular headache of pregnancy, tension, migraine, cluster, sinus, hypertension, brain hemorrhage, tumor, or preeclampsia.  Questions need to be asked and evaluate.

Treatment:  Rest or acetaminophen only!  

Patient education: If the headache is severe, constant, unusual, or associated with neurologic sings (stiff neck or neuro deficits) need to be seen.

Blurry Vision

Etiology:  Can be a sign of preeclampsia or brain tumor.

Treatment: Need to be seen.

Patient education:  If you have visual changes like “sparkly” spots or flashing lights in front of the eyes or blurred vision you need to be seen.  “Floaters” are often confused with “sparkly”

Nausea and Vomiting

Etiology:  50-80% experience morning sickness in early pregnancy.  But hyperemesis gravidarum, multiple gestation, molar pregnancy, hepatitis, gallbladder disease, gastroenteritis, phyelonephritis, migraine, flu syndrome, food poisoning, malaria, migraines, medications, drug or alcohol effect, pancreatitis, and intestinal parasites.

Treatment:  supporative measures like lying down, changing diet, drinking teas, acupressure, acupuncture, or hypnosis.  Antiemetics can be useful.

Patient education: Make aware of morning sickness symptoms and to be aware of any other conditions.

Tiredness Swartz 659, NMH 226

Etiology: Easy fatigability is common during early pregnancy. Some physicians believe that estrogen has a soporific effect and is the cause of the fatigue.  

Treatment: Rest

Patient education: Common discomforts of pregnancy, ask about remedies the client is using and provide safe relief measures.

Vaginal discharge pg 213

Etiology: An increase in vaginal discharge is common in pregnancy, especially in the last few weeks when the cervical glands are particularly active.  Could also be a sign of STD, cervicitis, vaginitis, or preterm labor that may be confused with ruptured membranes.

Treatment: Vaginal exam.

Patient education:  Discuss symptoms of vaginal infections, unusual discharge, odor, itching, burning, or dysuria.  Report any increase or change in vaginal discharge.

Faintness Tintinelli 1628, NMH 226

Etiology: Cardio output is increased by 1.0 to 1.5 L/min a week 10 of pregnancy and remains elevated until the end of pregnancy.  Heart rate increases by 10 to 20 beats per minute in the second trimester, accompanied by decreases in systolic and diastolic blood pressures of 10 to 15 mmHg causing hypotension.

Treatment:  When rising from supine or sitting position, start slowly.

Patient education:  Common discomforts of pregnancy, ask about remedies the client is using and provide safe relief measures.

Anonymous OB & GYN, 94

                    Headaches-are common in early pregnancy and etiology is unknown. Acetominophen in Usual doses is recommended and generally adequate.

                    Blurry Vision-increased corneal thickness due to water retention and decreased intraocular Pressure may manifest in the first trimester and will resolve within 6-8wks. of delivery.(70)

                    Nausea & Vomiting-The majority of pregnant women experience upper GI problems, including the classic “morning sickness” usually beginning of the first trimester. Treatment consists of frequent small meals, avoidance of an empty stomach by eating crackers or other bland carbohydrates, and patience. (I’m not making this up-check page 94) Although they go on to say that hospitalization with fluid and electrolyte therapy may be required in some

extreme cases. Maybe Debbie or Ann have some suggestions here. HELP!

Anonymous Beckmann p. 82

•        Travel – Travel is not prohibited during pregnancy, although it is customary for patients to avoid distant travel in the last months of pregnancy (b/c labor may begin away from home).

•        Headaches – Headaches are common in early pregnancy and may be severe.  The etiology of such headaches is unknown.  Treatment is with acetaminophen. (Wheeler p. 200 – Most headaches during pregnancy are benign and respond to rest or acetominophen.  Neither aspirin nor ibuprophen are recommended during pregnancy due to bleeding problems with ASA and premature closure of the ductus arteriosus and newborn pulmonary hypertension with ibuprophen.  Distinguish a more common benign headache from a headache requiring immediate evaluation.  A very small number of pregnant women will have intracranial pathology.)

•        Nausea and Vomiting – The majority of pregnant women experience some degree of upper GI symptoms in the 1^st trimester of pregnancy.  Classically, these symptoms are worse in the morning (morning sickness).  However, patients may experience symptoms at other times or even throughout the day.  Treatment includes frequent small meals, avoidance of an “empty stomach” and patience.  (Wheeler p. 201 – 50-80% of pregnant women experience nausea and vomiting in early pregnancy.  Etiology is unknown.  Box 7-4 on p. 202 includes a list of differential diagnoses for vomiting in pregnancy.  Treatment includes antiemetics, vitamin B6, antihistamines, acupressure, hypnosis, ginger root.)

•        Fatigue – In early pregnancy, patients often complain of an extreme fatigue that is unrelieved by rest.  There is no specific treatment, other than adjustment of the patient’s schedule to accommodate this.  These symptoms typically disappear in the 2^nd trimester.

•        Leg Cramps – Leg cramps, usually affecting the calves, are common during pregnancy.  Massage and rest are often advised.  Calcium is frequently employed but efficacy is unknown.

•        Back Pain – Low back pain is common, especially in late pregnancy.  The altered center of gravity caused by the growing fetus places unusual stress on the lower spine and associated muscles and ligaments.  Treatment includes heat, massage, analgesia and possible girdle use.

•        Varicose Veins and Hemorrhoids – Varicose veins are not caused by pregnancy but often first appear during the course of gestation.  For many, they are considered unsightly and they cause aching.  Support hose can diminish the discomfort.  Hemorrhoids are varicosities of the hemorrhoidal veins.  Treatment includes sitz baths and local preparations.  Varicose veins and hemorrhoids regress postpartum, although neither condition may abate completely.

•        Vaginal Discharge – Hormones associated with pregnancy often cause an increase in normal vaginal secretions.  These normal secretions must be distinguished from vaginitis, which has symptoms of itching and malodor, and spontaneous rupture of membranes, for which thin, clear fluid appears. (Wheeler p. 213 – An increase in vaginal discharge is common in pregnancy, especially in the last few weeks when the cervical glands are particularly active.  However, increased vaginal discharge may also be a symptom of an STD, cervicitis, vaginitis, or PTL and may be confused with ruptured membranes.  A discussion about symptoms of vaginal infection should be a part of prenatal health education.  Instruct women to report increase or change in vaginal discharge.)

•        Blurred Vision – The most common visual complaint of pregnant women is blurred vision.  This is caused by swelling of the lens and resolves after pregnancy.  Changes in lens prescriptions should not be encouraged during pregnancy (b/c transient problem).  (Wheeler p. 201 – Visual changes, particularly scotoma, blurred vision or flashing lights in front of the eyes, can be signs of preeclampsia or even a brain tumor.  “Sparkly” spots must always be taken seriously.  They should not be confused with “floaters.”)

•        Faintness - not found in Beckmann or Wheeler.

5.         Describe the differences between "morning sickness" and hyperemesis gravidarum including presentation, diagnosis, and treatment.

Anonymous Beckmann, pp 224-225

Morning Sickness typically presents as nausea in the morning (although can happen throughout day) with occasional emesis. Hyperemesis Gravidarum is a more severe nausea and vomiting accompanied by weight loss, dehydration, ketosis and electrolyte disturbances. Tx for morning sickness is listed above. Tx for Hyperemesis Gravidarum includes hospitalization, NPO, rehydration with balanced crystalloid solutions, gradual return to oral diet.

Anonymous OB/GYN p56

 Morning sickness normally starts at 4 to 8 wks of gestational age and abates by 14 – 16 wks.  The symptoms vary but as the name suggests the pregnant pt may have periods of nausea and vomiting at a regular point and for a regular duration during the day.  This normally does not have significant nutritional effects such as weight loss associated with it.  If these types of symptoms continue to occur beyond the middle of the 2^nd trimester or if there is an associated weight loss, ketonemia, and electrolyte imbalance at any time, the diagnosis of hyperemesis gravidarum should be considered.  The treatment of this is hospitalization to receive parenteral fluid and electrolyte replacement.  Gradual and progressive reinstatement of normal diet should follow.  Treatment of morning sickness is reassurance, suggested frequent small meals and avoidance of those foods found to exacerbate the nausea and vomiting.

Anonymous Beckman 224 

Morning sickness

•        The majority of women experience some degree of nausea and vomiting during pregnancy.  

•        Symptoms typically present in the morning, although it can happen throughout the day, with occasional emesis.

•        At least 66% of women experience experience nausea and 50% emesis in the 1^st trimester, with the frequency of these symptoms lessening in 2^nd and 3^rd trimesters

Hyperemesis gravidarum

• Intractable emesis during pregnancy

• Is a more severe N and V accompanied by weight loss, dehydration, ketosis and electrolyte disturbances.

• Tx – hospitalization and treatment with balanced crystalloid solutions and necessary electrolytes and “NPO status” generally eliminate symptoms and correct metabolic disturbances in a short time.  

Anonymous Ob Gyn p. 224

Morning sickness is explained in G6. Hyperemesis gravidarum is different than morning sickness because it is a more severe form of N/V. It occurs in only 4 out 1000 pregnancies; it is associated with severe symptoms as well as weight loss, dehydration, ketosis, and electrolyte imbalances. Hospitalization and treatment with balanced crystalloid solutions and necessary electrolytes and “NPO status” generally eliminates symptoms and correct metabolic disturbances in a short time. Diet then can be reinstituted slowly and progressively. Recurrences sometimes necessitate repeat hospitalizations.

Suzy NMH 213, 231

Morning Sickness: 50% to 80% experience nausea or vomiting.  

Hyperemesis gravidarum: Intractable vomiting in pregnancy associated with significant weight loss (>5% of body weight), dehydration, acidosis, alkalosis, and hypokalemia.

Diagnosis: based on a rapid maternal pulse >100 beats per minute, poor skin turgor, moderate to heavy ketonuria, and weight loss.  

Treatment: Iv fluids with appropriate electrolytes.  Antiemetics prochlorperazine (compazine) and promethazine (Phenergan), oral diphenhydramine (Benadryl) and oral or intramuscular hydroxyzine (Vistaril).  Reglan before eating.

Anonymous  Ob & GYN, 64

                    Morning sickness typically begins between 4 and 8 weeks of gestation and abates by the 14^th or 16^th week. If symptoms persist beyond the middle of the second trimester and there is an associated weight loss, ketonemia, or electrolyte imbalance at any time, hyperemesis gravid-

arium should be considered. Women with this severe form of nausea and vomiting should be

hospitalized and given parenteral fluids and electrolyte replacement. Stressors should also be

reduced, if possible.

Anonymous

Beckmann p. 224 – The majority of women experience some degree of nausea and vomiting during pregnancy.  At least 66% of women experience nausea and 50% emesis in the 1^st trimester, with the frequency of these symptoms lessening as the 2^nd and 3^rd trimesters ensue.  Prenatal vitamin supplements may aggravate these GI symptoms and can be withheld during this time.  See prior question for treatment of morning sickness.  Also, Beckmann and Wheeler made much mention of a compound medication of historical interest called Bendectin (combo of doxylamine and B6).  It was an effective antiemetic but was pulled from the market due to litigious concerns and unfounded teratogenic claims.)

Symptoms of nausea and vomiting in early pregnancy should not be presumed to be morning sickness.  It is necessary to rule out other more serious causes.

Hyperemesis gravidarum (intractable emesis during pregnancy) is a more severe form of nausea and vomiting. Occurring in 4 of 1000 pregnancies.  It is associated with weight loss, dehydration, ketosis and electrolyte disturbances.  Hospitalization and treatment with balanced crystalloid solutions and necessary electrolytes and NPO status generally eliminate symptoms and correct metabolic disturbances in a short time.  Diet can then be reinstituted slowly and progressively.  Recurrences sometimes necessitate repeat hospitalizations.  

(Wheeler p. 231 – Intractable vomiting in pregnancy is known as hyperemesis gravidarum and is associated with significant weight loss (more than 5% body weight), dehydration, acidosis, alkalosis, and hypokalemia.  IV fluids and antiemetics are usually required for both outpatient and inpatient treatment.  A diagnosis is based on a rapid maternal pulse (+100 bpm), poor skin turgor, moderate to heavy ketonuria, and weight loss.  UA and blood chemistry labs can help ID electrolyte imbalance.)

6.         Substance Abuse - Outline the risks to the fetus due to maternal use of tobacco, alcohol, cocaine, marijuana, opiates, and hallucinogens.    Discuss the role of the primary care provider when a pregnant patient is using one of the above substances.

Ky CMDT p21-24 Dershwitz p34-38

PCP role:  report to department of social services.

Tobacco:  ↓ growth rate of fetus.  The more mom smokes the slower the rate.  Associated with mild neurodevelopmental handicaps.

Alcohol:  FAS thought to be one of the most common causes of mental retardation.  FAS characterized by intrauterine growth retardation, microcephaly, microphthalmia, short palpebral fissures, ptosis, cardiac defects, developmental delay and intellectual impairment.  Dose-response relationship (more etoh = greater likelihood).  Associated with poor maternal nutrition.

Cocaine:  vasocontrictive & hypertensive properties cause adverse outcomes. ↑ risk of spontaneous abortion, placental abruptions and fetal death, ↓birth weight, length & head circumference.  ↑ risk for neurologic & behavioral abnormalities like infactions, tremors, irritability & muscular rigidity.  ↓ mother-infant bonding.

Marijuana:  crosses placenta.  associated with shorter gestation, ↓ fetal weight gain and length.  Not shown to have long term effects.  Does not cause malformations.  Infants of moms who smoke 2 or more per/day are not at risk for developmental delays.  Infants of moms who smoke 6+ joints/day may have tremors, startling, altered visual response to stimuli in the first 4 days of life.

Opiates:  Heroin: crosses placenta w/in one hour and penetrates all tissues.  Simultaneous withdraw sx with mom. No structural defects associated with prenatal exposure.  Low birth weight, ↑ frequency of chorioamnionitis due to maternal infxn.  Behavior problems and learning disabilities.  Some postnatal growth deficiencies and microcephaly.  Methadone tx can retard the problems heroin causes and the earlier methadone is started the more the fetal growth catches back up.  Kids with methadone exposure still have same behavioral/sleep disturbances including depressed interactive behavior, poor self-calming, tremors, increased tone, ↓physical/emotional intimacy.

Hallucinogens:  PCP: crosses placenta.  Newborn is normal in most pregnancies.  Mood lability and difficulties being consoled abate by 3 months.

Anonymous

Tobacco:  increased risk of spontaneous abortion, ectopic pregnancy, preterm delivery, abruptio placentae, placenta previa and decreased birth weight.

Alcohol:  prenatal and postnatal growth deficiency, mental retardation, behavioral disturbances, and congenital defects such as craniofacial anomalies.

Cocaine:  increased incidence of spontaneous abortion, preterm labor and delivery, intrauterine growth restriction, meconium-stained amniotic fluid, and placental abrution.  In utero cerebral infarction has been reported.  Additionally, there are many congenital anomalies:  intestinal atresia, limb-reduction defects, disruptive brain anomalies, congenital heart defects, prune-belly syndrome, and urinary track anomalies.

Marijuana:  THC is a highly active psychotropic compound that is teratogenic in animal models but equivocally so in human studies.  Its use should be avoided in pregnancy.

Opiates:  heroin abuse is associated with a threefold to sevenfold increase in the rates of still-birth, fetal growth restriction, premature labor and delivery, and neonatal mortality.  Newborn narcotic withdrawal is seen in 66% of infants (of mothers on opiates) and is potentially fatal.

Hallucinogens:  there is no good evidence of direct chromosomal damage or untoward pregnancy outcome from the use of lysergic acid diethylamide (LSD) or other hallucinogenic substances.  However, there are very few studies of this type of drug abuse in pregnancy.  

Anonymous Dershewitz pg 35-38

Alcohol=intrauterine growth retardation,microcephaly,short palpebral fissures, ptosis flattened nasal bridge, long smooth philtrum, and thin vermilion of the upper lip. Maybe hypoplastic fingers and toe nails, contractures of various joints,cardiac defects v/s defects.Developmental delay and later intellectual impairment is seen.. There is no known “safe” alcohol drinking amount known. Babies w/d 6-12 hrs after birth, tremulous,hypertonia and irritability.Alcohol passes through breast milk but effects on baby insignificant because the toxic metabolite “acetaldehyde” does not pass through.

Marijuana=most frequently abused drug in U.S. crosses placenta,result in shorter gestations and decreased fetal weight gain and length, but not decreased head circumference. Not shown to have any definite long-term effects on growth. Babies born to mom’s who smoke 2 joints(cigarettes)weekly have no developmental, growth or malformations. Babies born to moms who smoke >6 joints weekly have tremors,startling and altered visual response to stimuli in the first 4 days of life.

Cocaine=passes placenta,powerful vasoconstrictor and hypertensive agent.Greater chance spontaneous abortion.placental abruptions and fetal death. Reduced birth weight,length and head circumference. Risk for neurological and behavioral abnormalities leke cerebral infarctions, tremors, irritability, and muscular rigidity.Crosses breast milk.

Heroin=usually used with other drugs,fetus and mom go through w/d symptoms,baby will have withdrawl within first 24-48 hrs after birth.tremors, irritability, high-pitched crying,rubbing of the face and knees against the sheets, sweating vomiting diarrhea hypertonia and rarely seizures.High incidence of low birth weight.3-6 yrs old kids born in heroin addiction have shown low weight, length and head circumference.Increase in behavioral problems and learning disabilities.Overall intellectual ability not impaired.Crosses breast milk.

Methadone=prevent intrauterine growth defiiency in babies of moms using heroin. No known association to birth defects. Withdrawl occur 75%-90% kids severity is correlated to use by mom.

High incidence  of seizure than kids exposed to heroin. Behavioral and sleep disturbance,poor self-calming,depressed behavior,tremors increased tone and decreased physical and emotional intimacy.Increase incidence in hyperactivity,learning disorders,poor social adjustment and behavior disorders in kids that were born with methadone addiction. Crosses breast milk.

Lysergic Acid(LSD)=chromosomal breakage in leukocytes, concern that it could be teratogenic.reports based on presumed LSD and identityof what taken unknown.Lack of reported experience, unknown if in breast milk.

Role of provider=discourage breast feeding in pts. using drugs, be supportive with tight swaddling of the infant in a blanket.Baby kept in as quiet area as possible to decrease sensory input. High caloric formula required due to inceased activity due to increased crying, irritability poor feeding vomiting , diarrhea etc...detoxification decision should be based on several widely standard abstinence scoring sheets help clinical judgement of  those who see the infant on different shifts document  the w/d signs, chart response to medication.

Anonymous

• Tobacco- increased risk of spontaneous abortion, increased risk of ectopic pregnancy, decreased birth weight (avg 1 lb), increased risk of preterm delivery, increased risk of abruptio placentae and placenta previa, increased risk of sudden infant death syndrome, increased risk of developmental problems

• Alcohol- minor anomalies, moderate growth deficiencies, “mild” mental retardation, congenital anomalies, craniofacial anomalies

• Cocaine  - Increased incidence of spontaneous abortion, preterm labor and delivery, intrauterine growth restriction, meconium-stained amniotic fluid, placental abruption and in utero cerebral infarction has been reported. Association with congenital anomalies such as; segmental intestinal atresia, limb-reduction defects, disruptive brain anomalies, congenital heart defects, prune-belly syndrome and urinary tract anomalies.

• Marijuana – THC is a highly active psychotropic compound that is teratogenic in animal models but equivocally so in human studies and should be avoided.

• Opiates -  heroin abuse is associated with a 3-7 x increase in rates of still-birth, fetal growth restriction, premature labor and delivery, and neonatal mortality.  Methadone treatment in pregnancy is assoc. with improved outcomes.  Infants can also experience withdrawal syndrome.

• Hallucinogens -  No good evidence of direct chromosomal or untoward pregnancy outcome from the use of LSD or others.  Few studies and should be avoided.

Anonymous Beckman pg230 to 232

•        Tobacco causes vasoconstriction with altered placental perfusion and an increase in carbon monoxide. These result in an in creased risk of: T 16.3. PG 204

o       Spontaneous abortions

o       Ectopic pregnancies

o       Average one lb decrease in birth weight

o       Increased preterm delivery

o       Preterm rupture of membranes

o       Abruptio placentae

o       Placenta previa

o       Sudden infant death syndrome

o       Developmental problems

•        Alcohol 3oz /day of ETOH can result in fetal Alcohol syndrome T16.17 Pg 231

o       Mental retardation

o       Craniofacial anomalies

o       Performance defects

o       flattened nasal bridge

o       Lowered IQ

o       absent to hypoplastic philtrum (depression on upper lip)

o       Growth

o       broad upper lip

o       Prenatal & postnatal growth

o       micrognathia (small mandible)

o       Congenital anomalies

o       microphtalmia (small eye)

o       Brain defects

o       short nose

o       Cardiac defects (V/septal)

o       short palperbral fissure (lid slit)

o       Spinal defects

•        Cocaine Maternal death from MI, arrhythmias, aortic rupture, stroke, seizures, bowel ischemia, hyperthermia, and sudden death syndrome.  Other risks to the neonate result from poor diet, hygiene, lake of health /prenatal care, physical and emotional violence increased sexually transmitted diseases. Risks include:

o       Spontaneous abortions

o       Preterm labor

o       Premature ruptured membranes

o       Intrauterine growth restriction

o       Meconium stained amniotic fluid

o       Placenta abruption

o       In utero cerebral infarction

o       Congenital anomalies

•         Segmental intestinal atresia

•         Limb-reduction deficits

•         Disruptive brain anomalies

•         Congenital heart defects

•         Prune-belly syndrome

•         Urinary tract anomalies

o       Surviving infants

•         SIDs

•         Poor learning performance

•         Behavioral problems

•        Marijuana equivocally teratogenic

•        Opiates 3 to 7 X still births

o       Fetal growth restriction

o       Premature labor and delivery

o       Neonatal mortality

o       66% of infants have newborn narcotic withdrawal syndrome

•         s/sx – high pitched cry, poor feeding, hypertonicity, tremor hyperirritability, sneezing, diarrhea, and seizures. Symptoms occur in 1 to 10 days post delivery.

•        Hallucinogens.   No studies to show effects. Recommend not using during pregnancy  

Anonymous  Ob & GYN, 252-53

                    The vasoconstrictive properties of nicotine restrict placental perfusion exposing the fetus to less oxygen and nutritional support. Alcohol is well-know to be a central nervous system depressant. As little a 3 ounces a day has been associated with fetal alcohol syndrome negatively affecting intrauterine growth  with resulting mental retardation, behavioral disturbances, and craniofacial abnormalities. Cocaine is associated with increased incidence of spontaneous abortion and fetal demise. And if that’s not enough, intestinal atresia, limb reduction deficits, heart and urinary tract  abnormalities, prune-belly syndrome, and brain anomalies. Marijuana has been shown to be tertogenic in animal model studies but equivocally so in humans. Its use should be avoided during pregnancy. Opiates such as heroin are associated with a 3-7 fold increase in stillbirths, premature labor and delivery, fetal growth restriction, and neonatal mortality due to newborn narcotic with-drawal syndrome. Methadone treatment in pregnancy is associated with improved outcomes.Hallucinogens have not been studied and the use in pregnancy, or out of pregnancy, should be actively discouraged. Because of the concequences to mother and fetus, help and encour- agement should be offered and given at every opportunity.

Anonymous Beckmann p. 230

Role of primary care provider when a patient is using one of the above substances – Management of patients involved in the use and abuse of these materials is compounded by a variety of social problems, frequently inadequate prenatal care and poor nutrition.  Despite frustrations, help and encouragement to these patients must be given at every opportunity, because the consequences are so significant to the mother and her offspring.

Smoking – Complications result from the effects of carbon monoxide and altered placental perfusion caused by vasoconstriction induced by nicotine.  Smoking endangers the pregnant woman and the fetus.  Specific effects:  decreased fertility, increased risk of spontaneous abortion, increased risk of ectopic pregnancy, decreased birth weight (average = 1 pound), increased risk of preterm delivery (preterm labor, premature rupture of membranes), increased risk of abruptio placentae and placenta previa, increased risk of SIDS, increased risk of developmental problems.  It is estimated that 33% of pregnant women smoke.

Alcohol – Ethyl alcohol is a potent CNS depressant.  With the ingestion of approximately 3 ounces of alcohol daily during pregnancy, fetal alcohol syndrome is observed.  Effects consist of prenatal and postnatal growth deficiency, mental retardation, behavioral disturbances, and congenital defects such as craniofacial anomalies.  In theory, lesser consumption is associated with lesser effects (fetal alcohol effects).  Fetal alcohol effects include minor anomalies, moderate growth deficiency, “mild” mental retardation, and subtle behavioral changes.  The best recommendation during pregnancy is abstinence from alcohol consumption.  The performance defects associated with fetal alcohol syndrome include an average IQ of 60 to 70 for severely affected infants, fine motor dysfunction, infant irritability, and hyperactivity in later childhood.  The risk of spontaneous abortion is also increased in patients consuming alcohol.  Ethanol freely crosses the BBB, presumably causing its deleterious effects by direct toxicity of ethanol and its metabolites such as acetaldehyde.  Toxicity appears to be dose related and is greatest in first trimester exposure.  FAS effects in summary:  mental retardation (performance defects + lowered IQ), growth (pre and postnatal growth restriction), congenital abnormalities (brain defects, spinal defects, cardiac defects – esp. ventricular septal defects), craniofacial anomalies (flattened nasal bridge, absent to hypoplastic philtrum, broad upper lip, micrognathia, microphthalmia, short nose, short palpebral fissure).

Cocaine – Cocaine is a very potent CNS stimulant.  Cocaine use is associated with an increased incidence of spontaneous abortion, in utero fetal demise, premature rupture of membranes (20%), preterm labor and delivery (25%), intrauterine growth restriction (25-30%), meconium stained amniotic fluid (30%), and placental abruption (6-10%).  In utero cerebral infarction is possible.  Cocaine use is associated with congenital anomalies such as segmental intestinal atresia, limb-reduction defects, disruptive brain anomalies, congenital heart defects, prune-belly syndrome, and urinary tract anomalies.  Surviving infants are at higher risk for SIDS, poor learning performance, and behavioral problems.

Marijuana – Between 5-15% of pregnant women are thought to use marijuana during pregnancy.  The active component (THC) is a highly active psychotropic compound that is teratogenic in animal models but equivocally so in human studies.  (I think the author may have meant unequivocally).  MJ use should be avoided in pregnancy.

Opiates – Heroin use is associated with a 3-7fold increase in the rates of stillbirth, fetal growth restriction, premature labor and delivery, and neonatal mortality, probably as a result of drug effects and user lifestyle.  Methadone treatment in pregnancy is associated with improved outcomes.  Newborn narcotic syndrome is seen in up to 66% of infants and is potentially fatal.  The syndrome is less frequently seen in the offspring of methadone treated women.  Neonatal withdrawal syndrome is characterized by high-pitched cry, poor feeding, hypertonicity, tremor, hyperirritability, sneezing, diarrhea, and seizures.  Neonatal symptoms usually appear in 1-2 days but can appear up to 10 days after birth.

Hallucinogens – No studies show effects – but there are few studies.  Use should be actively discouraged.

7.         Identify the patient who should receive an injection of RhoGAM (Rh immunoglobulin) and when it should be administered.

Ky Beckmann OB/GYN p169-70

This is passive immunization for mom after exposure to incompatible fetal blood.  Rh- mom’s who deliver Rh+ babies get RhoGAM intramuscular w/in 72 hours of delivery.

Anonymous  

Rh- pregnant pts. who have no Ab on initial screening should be retested at 28 weeks. If no sensitization has occurred, they are given RhoGAM to protect them form AB formation further in pregnancy – unless the father is known to be Rh- as well. After delivery, the childs blood type and Rh status are determined and if the child is Rh+, then a second dose of RhoGAM should be given.

Other situations where this should be given:

-At approx. 28 weeks of pregnancy

-Within 3 days of delivery of an Rh+ infant

-At the time of amniocentesis

-After + Kleihauer-Betke test

-After ectopic pregnancy

-After spontaneous or induced abortion

Anonymous Beckman Pg 178, 140, 190, 229,230

• Rh-negative mothers who give birth to Rh-positive (give before discharge)

• Ectopic pregnancies (give to prevent Rh sensitization)

• Spontaneous AB’s (give to mothers who are Rh-negative to avoid hemolytic interaction)

• Fetal / maternal hemorrhage (as a result of abdominal trauma)

Anonymous Table 11.2 Ob & Gyn, p.170     

An Rh negative mother who could give birth to an Rh positive baby (that is unless the father of the baby is known to be Rh neg.) should be given the RhoGAM injection:

            @ approx. 28 weeks pregnancy

            @ within 3 day of delivery of an Rh positive infant

            @ the time of amniocentesis

            @ positive Kleihauer-Berke test results

            @ ectopic pregnancy diagnosis

            @ time of abortion-spontaneous or induced

Anonymous Beckmann p. 151

Indications for Rh Immune Globulin Administration in an Unsensitized Rh-negative patient (unless the father of the infant is known to be Rh-):  at 28 weeks gestation, within 3 days of delivering an Rh-positive infant, at the time of amniocentesis, after positive Kleihauer-Betke test, after ectopic pregnancy, after a spontaneous or induced abortion.  Also, any circumstance in pregnancy in which fetomaternal hemorrhage can occur warrants Rh immune globulin administration.

8.         Describe the prevalence of domestic violence including risk of abuse in pregnancy.  

Ky Dershwitz p149-51.  UpToDate: search DV.  Beckmann OB/GYN p621

A United States Department of Justice survey of 50,000 households in 1992 and 1993 estimated that over 1 million women and 150,000 men are victims each year of physical abuse or sexual assault by their partner

DV experienced by 25-50% of women during their life.

Pregnancy: Domestic violence often begins or, if already present, increases during pregnancy and the postpartum period [18-20]. The relationship between domestic violence and pregnancy is illustrated by the following findings:

• A review of the obstetrical literature found that physical abuse occurred during 7 to 20 percent of pregnancies. This is higher than the prevalence of gestational diabetes and preeclampsia, conditions for which pregnant women are routinely screened.

• Women with an unintended pregnancy had a three-fold higher risk of physical abuse compared to those whose pregnancy was planned.

Anonymous OB/GYN-3^rd ed.  Beckman  pg.580

 Domestic violence is experienced by an estimated 25-50% of women during their life and is suggested as a significant source of illness and injury to women. One in five women who present to the ER has been injured by her partner. In approx. 90% of domestic homicides there is a history of a police call for domestic violence within the year. An estimated ¾ of women indicate that they have been victims of domestic violence and would have discussed the situation with their physician if they had been asked.  

      Domestic violence may involve physical, sexual and/or emotional or psychological abuse. Unfortunately, pregnancy appears to be a period of greater risk for such episodes.

Anonymous [OB/GYN text – pp 579-580]

25-50% of women experience domestic violence at some time during their life. One in five women who present to an emergency room has been injured by her partner. In approximately 90% of domestic homicides there is a history of a police call for domestic violence within one year. These include physical abuse, sexual abuse and/or emotional abuse and are usually cyclic and repetitive. Unfortunately, pregnancy appears to be a period of greater risk for episodes of domestic violence.

Anonymous Beckman  pg.580

 Domestic violence is experienced by an estimated 25-50% of women during their life and is suggested as a significant source of illness and injury to women. One in five women who present to the ER has been injured by her partner. In approx. 90% of domestic homicides there is a history of a police call for domestic violence within the year. An estimated ¾ of women indicate that they have been victims of domestic violence and would have discussed the situation with their physician if they had been asked.  

      Domestic violence may involve physical, sexual and/or emotional or psychological abuse. Unfortunately, pregnancy appears to be a period of greater risk for such episodes.

Anonymous  

Domestic violence is experienced by an estimated 25-50% of women during their life, and an estimated  ¾  of the women victimized state that they would have discussed the situation with their physician if they had been asked. Because pregnancy is associated with greater risk for physical violence, all patients should be asked about the presence of violence in their lives as part of the initial history. (Ob & Gyn, 621-22) The SAFE acronym may be used.

S- Does the patient feel safe at home? If not, who or what does she fear and why?

A- Has the patient felt abused in a relationship? How? In the current relationship?

F- Are there friends or family who can help? Who can the patient turn to for support?

E- Does she have a plan in an emergency? Where she could go-childcare-for help?

Anonymous Beckmann p. 580

Domestic violence is experienced by an estimated 25-50% of women during their life.  One in five women who present to an ER have been injured by a partner.  In approximately 90% of domestic homicides there is a history of a police call for domestic violence within the year.  About 10% of adolescents are battered by a parent.  An estimated 75% of women indicate that they have been victims of domestic violence and would have discussed the situation with their physician if they had been asked.  Domestic violence may involve one or more of three presentations:  physical abuse, sexual abuse or psychological abuse.  Recognition is the first, most important, and most often missed issue.  All patients should be asked about the presence of violence in their lives as part of the routine health history.  When addressing this issue with a patient, the acronym SAFE is used.  S – does the patient feel safe?  A – has the patient been abused?  F – are their friends or family that can help?  E – does the patient have an emergency plan?  Unfortunately, pregnancy appears to be a period of greater risk for episodes of physical abuse.  If there is evidence of immediate risk to the patient or her children or someone else, law enforcement contact is required.

9.         List the warning signs during pregnancy for which a woman should seek medical care.

Ky Eisenberg p117

• Severe lower abdominal pain on one or both sides, that doesn’t subside.  Especially if accompanied by bleeding, nausea and vomiting

• Severe upper mid-abdominal pain w/ or w/out nausea & swelling hands & face

• Slight vaginal spotting

• Heavy vaginal bleeding

• Bleeding from nipples, rectum bladder

• Coughing up blood

• Gush or steady leaking of fluid from vagina

• Sudden increase in thirst accompanied by a paucity of urination or no urination at all for an entire day

• Swelling or puffiness of hands, face, eyes.  If very sudden and severe ow w/ headache or vision difficulties

• Painful or burning urination esp if chills and fever

• Vision disturbances that persist > 2 hours

• Fainting or dizziness

• Severe nausea & vomiting, vomiting more often than 2-3 times/day in 1^st trimester, vomiting later in pregnancy when no previous vomiting occurred

• Absence of noticeable fetal movement for greater than 24 hours after 20^th week.

• All-over itching, with or without dark urine pale stools, jaundice

Anonymous Beckman pg. 202-4

     I’m not sure what the specific answer they are looking for. I will give you what I know-

- bleeding of any during the second half of pregnancy

- abdominal pain, amenorrhea and vaginal bleeding (ectopic- but all of these symptoms may not always be present)

- vomiting later in pregnancy (after 32 wks gestation) assoc. also with RUQ abd. pain (HELLP syndrome)

- Pica

- Cramping

- Nausea, vomiting, anorexia with periumbilical or RLQ abd. pain (appendicitis)

- Cholestasis- pts present with generalized, intense pruritis assoc. with fatigue, jaundice and often dark urine.

- Cholelithiasis- food assoc. colic.  Lab results show elevated LFT’s and bilirubin.

- Acute fatty liver- Occurs late in pregnancy with vague GI symptoms increasing in severity over days. Headache, mental confusion and epigastric pain may insue. Must be treated immediately.

- No fetal movement in 24 hrs (I’m not positive on this number)

- Uterine tenderness and or vaginal bleeding after abdominal trauma (ie: MVC)

- Dysuria

- Vaginal discharge

Anonymous  While Waiting, p. 5.

•        Severe or persistent headache

•        Blurred vision or spots before your eyes

•        Severe abdominal pain or cramps, perhaps with nausea or diarrhea

•        Severe or persistent vomiting

•        Severe, unexplained pain in the shoulder

•        High fever (above 101°F)

•        Marked swelling in your upper body (face or hands)

•        A sudden weight gain in just a few days

•        Vaginal bleeding

•        Gush or flow of watery fluid from your vagina

•        Marked decreased in output of urine

•        Regular contractions, getting stronger as time progresses

•        Marked decrease or stopping of fetal movement you feel (from the fifth month on)

 Anonymous Beckman

• bleeding during any part of pregnancy

• abdominal pain, amenorrhea and vaginal bleeding (ectopic- but all of these symptoms may not always be present)

• vomiting later in pregnancy (after 32 wks gestation) assoc. also with RUQ abd. pain (HELLP syndrome)

• Pica

• Cramping

• Nausea, vomiting, anorexia with periumbilical or RLQ abd. pain (appendicitis)

• Cholestasis- pts present with generalized, intense pruritis assoc. with fatigue, jaundice and often dark urine.

• Cholelithiasis- food assoc. colic.  Lab results show elevated LFT’s and bilirubin.

• Acute fatty liver- Occurs late in pregnancy with vague GI symptoms increasing in severity over days. Headache, mental confusion and epigastric pain may insue. Must be treated immediately.

• No fetal movement in 24 hrs (I’m not positive on this number)

• Uterine tenderness and or vaginal bleeding after abdominal trauma (ie: MVC)

• Dysuria

• Vaginal discharge

Anonymous  Tintinelli Chapt.99-101 Ob & Gyn, Chapt 5-6

       Nausea, Vomiting associated with hyperemesis and weight loss. Abdominal pain, vaginal bleeding, edema, dysuria-UTI leading to pyelonephritis Hypertension, decrease in fetal movement, abdominal trauma, and signs of early labor Including: contractions every 5 minutes for over an hourSudden gush of fluid or constant leakage of fluid Any significant bleeding or decrease in fetal movement  

Anonymous Beckmann

•     Bleeding during any part of pregnancy

•     abdominal pain + amenorrhea + vaginal bleeding (think ectopic)

•     vomiting in later pregnancy (after 32 weeks)

•     vomiting in later pregnancy + RUQ pain (think HELLP syndrome)

•     pica

•     cramping

•       nausea + vomiting + periumbilical or RLQ pain (think appendicitis and know that appendicitis is the most common cause of surgical emergency in pregnancy)

•      cholestasis

•     cholelithiasis

•     acute fatty liver presents with vague GI symptoms increasing in severity over several days, headache, mental confusion, epigastric pain; occurs late in pregnancy and must be treated immediately

•     no fetal movement in ___ hours  (dealer’s choice) (gettin punchy)

•     uterine tenderness or vaginal bleeding after abdominal trauma

•     dysuria

•     vaginal discharge (change in, etc.)

11. Describe the pathophysiology, clinical presentation, important physical exam findings, differential diagnosis, work-up, and treatment of a women presenting with an ectopic pregnancy.   Added 2004

Zen Seeker Current OB/GYN 9th

ECTOPIC PREGNANCY

In ectopic pregnancy, a fertilized ovum implants in an area other than the endometrial lining of the uterus (Fig 14-7). More than 95% of extrauterine pregnancies occur in the fallopian tube.

Figure 14-7. Sites of ectopic pregnancies. (Adapted with permission from Benson RC: Handbook of Obstetrics & Gynecology, 8th ed. Lange, 1983.)The incidence of ectopic pregnancy has increased from 4.5/1000 in 1970 to 19.7/1000 in 1992. This may be due, at least in part, to a higher incidence of salpingitis, an increase in ovulation induction, and more tubal sterilizations.

Ectopic pregnancy is a significant cause of maternal morbidity and mortality as well as fetal loss. It is the leading cause of pregnancy-related death in the first trimester, and accounts for 9% of all pregnancy-related deaths. The development of sensitive β-hCG assays, along with the increasing use of ultrasound and laparoscopy, has allowed for earlier diagnosis of ectopic pregnancy. This has resulted in a decrease in both maternal morbidity and mortality.

Classification & Incidence

Ectopic pregnancy may be classified as follows (Fig 14-7).

1. Tubal (> 95%)—Includes: ampullary (55%), isthmic (25%), fimbrial (17%), and interstitial (2%).

2. Other (< 5%)—Includes: cervical, ovarian, and abdominal (primary abdominal pregnancies have been reported, but most abdominal pregnancies are secondary pregnancies, from tubal abortion or rupture and subsequent implantation in the bowel, omentum, or mesentery).

3. Intraligamentous

4. Heterotopic pregnancy—An ectopic pregnancy occurs in combination with an intrauterine pregnancy in 1 in 15,000-40,000 spontaneous pregnancies, and in up to 1% of patients undergoing in vitro fertilization.

5. Bilateral ectopic—These pregnancies have occasionally been reported.

Etiology

The etiology of ectopic pregnancy is not well understood. However, several risk factors have been found to be associated with ectopic pregnancy (Table 14-3).
 

Table 14-3. Risk factors for ectopic pregnancy.
Risk Factor	Odds Ratio1
High risk
Tubal surgery	21.0
Sterilization	9.3
Previous ectopic pregnancy	8.3
In-utero exposure to diethylstilbestrol	5.6
Use of IUD	4.2-45.0
Documented tubal pathology	3.8-21.0
Moderate risk
Infertility	2.5-21.0
Previous genital infections	2.5-3.7
Multiple sexual partners	2.1
Slight risk
Previous pelvic/abdominal surgery	0.9-3.8
Cigarette smoking	2.3-2.5
Vaginal douching	1.1-3.1
Early age at first intercourse (< 18 years)	1.6
1Single values indicate common odds ratio from homogeneous studies; point estimates indicate range of values from heterogeneous studies.
Reproduced, with permission, from Pisarska et al: Ectopic pregnancy. Lancet 1998;351:1115.

A. Tubal Factors

Ectopic pregnancy is 5-10 times more common in women who have had salpingitis. In women with ectopic pregnancies, up to 50% will have had salpingitis previously and in most of these patients, the uninvolved tube is also abnormal. Other tubal factors that interfere with the progress of the fertilized ovum include adherent folds of tubal lumen due to salpingitis isthmica nodosa, developmental abnormalities of the tube or abnormal tubal anatomy due to DES exposure in utero, previous tubal surgery including tubal ligation with a 16-50% ectopic pregnancy rate if pregnancy occurs after tubal ligation, conservative treatment of an unruptured ectopic with a recurrent ectopic rate of 4-16%, and tubal anastomosis with a 4% ectopic rate. Adhesions from infection or previous abdominal surgery, endometriosis, and even leiomyomas have been associated with ectopic pregnancy. Most of these abnormalities are bilateral and irreversible.

B. Zygote Abnormalities

A variety of zygote abnormalities have been reported in ectopic pregnancy, including chromosomal abnormalities, gross malformations, and neural tube defects. The theory is that these abnormal preembryos are more likely to result in abnormal or ectopic implantation.

C. Ovarian Factors

Ovarian factors that may result in the development of an ectopic pregnancy are fertilization of an unextruded ovum, transmigration of the ovum into the contralateral tube with subsequent delayed and faulty implantation, and postmidcycle ovulation and fertilization.

D. Exogenous Hormones

Abnormal hormonal stimulation and/or exogenous hormones may play a role in ectopic gestation. For example, of pregnancies occurring in women taking progestin-only oral contraceptives, 4-6% are ectopic pregnancies. This may be due to progesterone's smooth muscle relaxant effects and subsequent "ovum trapping." Patients with DES exposure are also at risk, as are patients undergoing ovulation induction.

E. Other Factors

Intrauterine device (IUD) users are also at risk for ectopic pregnancy if pregnancy occurs, although the risk of ectopic pregnancy is still lower than if no contraceptive method is used. Whether the IUD prevents intrauterine but not ectopic pregnancy or whether an associated salpingitis is responsible for this increased risk is unclear. Smoking and increasing age are also associated with ectopic pregnancy. Multiple previous elective abortions are also felt to be a risk factor for ectopic pregnancy, as postabortal infection may lead to salpingitis.

Time of Rupture

Rupture is usually spontaneous. Isthmic pregnancies tend to rupture earliest, at 6 to 8 weeks' gestation, due to the small diameter of this portion of the tube. Ampullary pregnancies rupture later, generally at 8-12 weeks. Interstitial pregnancies are the last to rupture, usually at 12-16 weeks, as the myometrium allows more room to grow than the tubal wall. Interstitial rupture is quite dangerous, as its proximity to uterine and ovarian vessels can result in massive hemorrhage.

After rupture, the conceptus may be resorbed or remain as a mass in the abdominal cavity or cul-de-sac. Rarely, if not damaged during rupture, it may implant elsewhere in the abdominal cavity and continue to grow.

Clinical Findings

No specific symptoms or signs are pathognomonic for ectopic pregnancy, and many disorders can present similarly. Normal pregnancy, threatened or incomplete abortion, rupture of an ovarian cyst, ovarian torsion, gastroenteritis, and appendicitis can all be confused with ectopic pregnancy. Since early diagnosis is crucial, a high index of suspicion should be maintained when any pregnant woman in the first trimester presents with bleeding and/or abdominal pain. Fifteen to twenty percent of ectopic gestations will present as surgical emergencies.

A. Symptoms

The following symptoms may assist in the diagnosis of ectopic pregnancy.

1. Pain—Pelvic or abdominal pain is present in close to 100% of cases. Pain can be unilateral or bilateral, localized or generalized. The presence of subdiaphragmatic or shoulder pain is more variable, depending on the amount of intraabdominal bleeding.

2. Bleeding—Abnormal uterine bleeding, usually spotting, occurs in roughly 75% of cases, and represents decidual sloughing.

3. Amenorrhea—Secondary amenorrhea is variable. Approximately half of women with ectopic pregnancies have some spotting at the time of their expected menses, and thus do not realize they are pregnant.

4. Syncope—Dizziness, lightheadedness, and/or syncope is present in one-third to one-half of cases.

5. Decidual cast—A decidual cast is passed in 5-10% of ectopic pregnancies, and may be mistaken for products of conception.

B. Signs

On examination, the following signs are important in the diagnosis of ectopic gestation.

1. Tenderness—Diffuse or localized abdominal tenderness is present in over 80% of ectopic pregnancies. Adnexal and/or cervical motion tenderness is present in over 75% of cases.

2. Adnexal mass—A unilateral adnexal mass is palpated in one-third to one-half of patients. Occasionally, a cul-de-sac mass is present. However, the patient's discomfort may preclude an adequate examination.

3. Uterine changes—The uterus may undergo typical changes of pregnancy, including softening and a slight increase in size.

Laboratory Findings

Hematocrit:The hematocrit will vary depending on the patient population and the degree, if any, of intraabdominal bleeding.

White blood count: The white blood count is variable, and it is not uncommon to see a leukocytosis.

Pregnancy tests: The β-hCG is positive in virtually 100% of ectopic pregnancies. However, a positive test only confirms pregnancy and does not indicate whether it is intrauterine or extrauterine. In normal pregnancy, β-hCG should double every 2 days. However, while two-thirds of ectopic pregnancies have abnormal serial titers, the remaining third show a normal progression. Ultrasound is often helpful in differentiating ectopic from intrauterine pregnancy.

Special Examinations

Several special procedures are helpful in diagnosing ectopic pregnancy.

1. Ultrasound—Ultrasound is useful in evaluating patients at risk for ectopic pregnancy, namely by documenting the presence or absence of an intrauterine pregnancy (IUP). β-hCG titers and ultrasound complement one another in detecting ectopic pregnancy, and have led to earlier detection with a subsequent decrease in adverse outcome. By correlating β-hCG titers with ultrasound findings, an ectopic pregnancy can often be differentiated from an IUP. Furthermore, ultrasound can help distinguish a normal intrauterine pregnancy from a blighted ovum, incomplete abortion, or complete abortion.

A normal intrauterine sac appears regular and well-defined on ultrasound. It has been described as a "double ring," which represents the decidual lining and the amniotic sac. In ectopic pregnancy, ultrasound may reveal only a thickened, decidualized endometrium. With more advanced ectopics, decidual sloughing with resultant intracavitary fluid or blood may create a so-called "pseudogestational sac." This sac is small and irregular as compared to a true gestational sac, but at times can be confused with a normal sac.

An intrauterine sac should be visible by transvaginal ultrasound when the β-hCG is approximately 1000 mIU/mL, and by transabdominal ultrasound approximately 1 week later, when the β-hCG is 1800-3600 mIU/mL. Thus, when an empty uterine cavity is seen with a β-hCG titer above this threshold, the patient is likely to have an ectopic pregnancy. An empty cavity is less of a concern when a β-hCG below the threshold is obtained, as this may be associated with an ectopic pregnancy, but may also be seen with an early IUP.

The presence of an adnexal mass with an empty uterus is also of concern. If the β-hCG is low, this may represent an early IUP with a corpus luteum cyst. However, if the β-hCG is above the discriminatory value, an ectopic is likely. A "tubal ring" seen on ultrasound may represent an unruptured ectopic, with a gestational sac and sometimes embryo surrounded by a distorted fallopian tube. This complex is seen adjacent to but separate from both the uterus and ovary. If rupture has occurred, ultrasound may reveal a dilated fallopian tube with fluid in the cul-de-sac.

2. Laparoscopy—The need for laparoscopy in the diagnosis of ectopic pregnancy has declined with the increasing use of ultrasound. It is still useful, however, in certain situations when a definitive diagnosis is difficult, especially in the case of a desired, potentially viable intrauterine pregnancy when a D&C is contraindicated. Laparoscopy may also be used as definitive management in early ectopic gestation.

3. D&C—D&C may confirm or exclude intrauterine pregnancy in the case of an undesired pregnancy. D&C may interrupt an intrauterine gestation and should not be performed if the pregnancy is desired, unless the β-hCG titers have plateaued or fallen and the pregnancy is definitely abnormal. When chorionic villi are recovered, the diagnosis of an intrauterine pregnancy is confirmed. On the other hand, if only decidua is obtained on D&C, ectopic pregnancy is highly likely.

4. Laparotomy—Laparotomy is indicated when the presumptive diagnosis of ectopic pregnancy in an unstable patient necessitates immediate surgery, or when definitive therapy is not possible by medical management or laparoscopy.

5. Culdocentesis—Culdocentesis is the transvaginal passage of a needle into the posterior cul-de-sac in order to determine whether free blood is present in the abdomen (Fig 14-8). The procedure is simple and safe and may be useful in the diagnosis of intraperitoneal bleeding. It is generally accomplished with the unanesthetized patient in the dorsal lithotomy position. A speculum is placed in the vagina and the posterior lip of the cervix grasped with a tenaculum. The vagina is cleansed. An 18-gauge spinal needle is attached to a 10-mL syringe, and with gentle traction on the cervix, the needle is passed into the cul-de-sac.

Figure 14-8. Culdocentesis.

This procedure will reveal nonclotting blood if intra-abdominal bleeding has occurred. If the blood clots, it is likely from a punctured vessel in the vaginal wall. Usually, the cul-de-sac will contain some straw-colored fluid, and this may be used to determine if the needle has been properly placed when there is no bleeding. If culdocentesis is positive, laparoscopy or laparotomy should be performed immediately. Indeed, some argue that the main purpose of culdocentesis is to better prioritize patients so that those with positive culdocenteses are taken immediately to the operating room.

Although nonclotting blood is assumed to be from a ruptured ectopic, similar results can also be obtained under other circumstances (eg, a hemorrhagic corpus luteum), and thus a positive result is not diagnostic of a ruptured ectopic pregnancy. Furthermore, a negative result may rule out a ruptured or leaking ectopic but not an intact one.

Pathology

In tubal ectopic pregnancy, implantation is typically in the wall of the tube, in the connective tissue beneath the serosa. There may be little or no decidual reaction and minimal defense against the permeating trophoblast. The trophoblast invades blood vessels to cause local hemorrhage. A hematoma in the subserosal space enlarges as pregnancy progresses. Distention of the tube then predisposes to rupture.

Bleeding is of uterine origin and is caused by endometrial involution and decidual sloughing. Atypical changes in the endometrium may be suggestive of ectopic pregnancy. The Arias-Stella reaction consists of hyperchromatic, hypertrophic, irregularly-shaped nuclei, and foamy, vacuolated cytoplasm. These changes can also be seen in normal pregnancy and in miscarriage, and are therefore not diagnostic of ectopic pregnancy.

Occasionally, endometrial tissue may be passed as a so-called decidual cast. Superficial secretory endometrium usually is present, but no trophoblastic cells are seen. Grossly, this can be confused with passage of products of conception and spontaneous abortion.

Prevention

Prevention of sexually transmitted disease, with early and vigorous treatment of cases that do occur, may avoid tubal damage with subsequent ectopic pregnancy. Other risk factors for ectopic pregnancy are more difficult to control. Early diagnosis of unruptured tubal pregnancy by maintaining a high index of suspicion, and liberally using β-hCG titers, ultrasound, and laparoscopy will minimize potential problems from hemorrhage, infertility, and extensive surgery.

Treatment

A. Expectant Management

Because many ectopic pregnancies resolve spontaneously, it may be reasonable to manage an asymptomatic, compliant patient expectantly if β-hCG titers are low (< 200 mIU/mL) or decreasing, and the risk of rupture is low.

B. Surgical Treatment

The extent of surgery depends on the degree of damage to the uterus and adnexae. Preservation of the ovary should be attempted if feasible. Conservative surgery (ie, preservation of the fallopian tube) may be indicated in the hemodynamically stable patient with an ampullary pregnancy who wishes to preserve fertility.

A linear salpingostomy may be performed with a small (< 3 cm), intact ampullary pregnancy. The linear incision is allowed to heal by secondary intention. A linear salpingotomy involves closure of the incision and may be recommended in similar situations. Subsequent reproductive performance is comparable, with intrauterine pregnancy rates of 40-90%, but recurrent ectopic rates may be higher, up to 16%.

If the physician is competent in operative laparoscopy, both of these procedures can be performed through the laparoscope, assuming the pregnancy is < 3 cm, unruptured, and easily accessible. With both salpingostomy and salpingotomy, a β-hCG titer should be obtained weekly after surgery to ensure adequate removal of trophoblast and rule out a persistent ectopic. In stable patients, laparoscopy is preferred over laparotomy because of the associated reduction in morbidity and cost.

"Milking" the pregnancy out of the distal end of the tube is often tempting, but this has been associated with persistent trophoblast and need for reexploration, as well as increased risks of recurrent ectopic pregnancy.

With an isthmic ectopic pregnancy, segmental resection with subsequent anastomosis (usually at a later date) is typically recommended. As opposed to ampullary ectopics, the muscularis is well-developed, forcing the pregnancy to grow in the lumen. More conservative treatment such as salpingostomy or salpingotomy would likely cause scarring and compromise of the lumen. Furthermore, a tubal fistula may result if the tube were allowed to heal by secondary intention.

With fimbrial pregnancy, products of conception are often visible at the most distal end of the tube, which may be "plucked out." As with ampullary ectopics, "milking" should be avoided.

Interstitial pregnancies require at least a cornual wedge resection, with uterine reconstruction and sometimes salpingectomy on the affected side. If there has been extensive tissue damage or if the patient is unstable, a hysterectomy may be needed.

Cervical ectopics may be associated with massive hemorrhage and may mandate hysterectomy. Attempts at medical management with methotrexate should be considered. Ovarian pregnancy requires oophorectomy and sometimes salpingectomy on the affected side. Abdominal pregnancy involves delivery of the fetus (sometimes at term) with ligation of the umbilical cord close to the placenta. The placenta is usually left in place to avoid hemorrhage following removal.

C. Emergency Treatment

Immediate surgery is indicated when the diagnosis of ectopic pregnancy with hemorrhage is made. Blood products should be available as transfusion is often necessary. There is no place for conservative therapy in a hemodynamically unstable patient.

D. Medical Management

Methotrexate (MTX), a folinic acid antagonist, has been shown to destroy proliferating trophoblast and may be effective in the medical management of small, unruptured ectopic pregnancies in asymptomatic women. Exclusion criteria include a noncompliant patient, peptic ulcer disease, immunodeficiency, pulmonary disease, liver disease, renal disease, blood dyscrasias, hemodynamic instability, free fluid in the cul-de-sac plus pelvic pain, or known sensitivity to MTX. Relative contraindications include an adnexal mass ≥ 3.5 cm or an extrauterine gestation with fetal heart motion, because of the higher failure rate. In select cases, approximately 90% of ectopics resolve, taking on average just under 1 month. Protocols vary from single to multiple injections, typically given systemically. The dose of MTX depends on the patient's body surface area, and nomograms are available for determining the correct dose. Follow-up β-hCG levels, along with a complete blood count, serum creatinine, and serum aspartate transaminase are obtained, for comparison with baseline values. β-hCG levels should decrease by at least 15% 4-7 days after MTX administration. Failure of MTX therapy is suggested by a persistent rise or plateau in β-hCG titer, worsening pain in conjunction with a hemoperitoneum on ultrasound, and/or hemodynamic instability, and demands either another dose of MTX or surgery. Available studies comparing MTX to traditional surgical management report similar subsequent tubal patency and fertility rates. Arguments against its use include its toxicity, namely marrow suppression, dermatitis, and stomatitis, as well as potential for treatment failure and tubal rupture.

Chronic ectopics, with decreasing but persistent β-hCG titers, pose a management dilemma. Some will resolve on their own, while others will require surgery. Unfortunately, at present it is impossible to predict which patients will fail expectant management.

Rho (D) immune globulin should be given to any Rh-negative mother with the diagnosis of ectopic pregnancy, as sensitization can occur just as with intrauterine pregnancy.
 

12. For the laboratory assessment of ectopic pregnancy, discuss how serial beta-hCG can be used to detect early, asymptomatic ectopic pregnancies.

Zen Seeker Current OB/GYN 9th

Pregnancy tests: The β-hCG is positive in virtually 100% of ectopic pregnancies. However, a positive test only confirms pregnancy and does not indicate whether it is intrauterine or extrauterine. In normal pregnancy, β-hCG should double every 2 days. However, while two-thirds of ectopic pregnancies have abnormal serial titers, the remaining third show a normal progression. Ultrasound is often helpful in differentiating ectopic from intrauterine pregnancy.

13. Describe inevitable, incomplete, complete, and missed spontaneous abortions, (miscarriage).    Added 2004

Zen Seeker Current OB/GYN 9th

SPONTANEOUS ABORTION

ESSENTIALS OF DIAGNOSIS
• Suprapubic pain, uterine cramping, and/or back pain.
• Vaginal bleeding.
• Cervical dilatation.
• Extrusion of products of conception.
• Disappearance of symptoms and signs of pregnancy.
• Negative pregnancy test or quantitative β-hCG that is not properly increasing.
• Abnormal ultrasound findings (eg, empty gestational sac, fetal disorganization, lack of fetal growth).

General Considerations

Spontaneous abortion is the most common complication of pregnancy. It is defined as delivery occurring before the 20th completed week of gestation. It implies delivery of all or any part of the products of conception, with or without a fetus weighing less than 500 grams. Threatened abortion is bleeding of intrauterine origin occurring before the 20th completed week, with or without uterine contractions, without dilatation of the cervix, and without expulsion of the products of conception. Complete abortion is the expulsion of all of the products of conception before the 20th completed week of gestation, while incomplete abortion is the expulsion of some, but not all, of the products of conception. Inevitable abortion refers to bleeding of intrauterine origin before the 20th completed week, with dilatation of the cervix without expulsion of the products of conception. In missed abortion, the embryo or fetus dies in utero, but the products of conception are retained in utero. In septic abortion, infection of the uterus and sometimes surrounding structures occur.

Incidence

Although the true incidence of spontaneous abortion is unknown, approximately 15% of clinically evident pregnancies and 60% of chemically evident pregnancies end in spontaneous abortion. Eighty percent of spontaneous abortions occur prior to 12 weeks' gestation.

The incidence of abortion is influenced by the age of the mother and by a number of pregnancy-related factors, including whether a previous full-term normal pregnancy has occurred, the number of previous spontaneous abortions, whether there has been a previous stillbirth, and whether a previous infant was born with malformations or known genetic defects. Additionally, parental influences, including balanced translocation carriers and medical complications, may influence the rate of spontaneous abortion.

Etiology

In approximately 50% of spontaneous abortions occurring during the first trimester, there is an abnormal karyotype. This incidence decreases to 20-30% in second trimester losses, and 5-10% in third trimester losses. As will be discussed below, the first trimester losses are typically autosomal trisomies or monosomy X, while later losses reflect chromosomal abnormalities seen in neonates.

Other suspected causes of spontaneous abortion account for a smaller percentage of losses. In a significant percentage of spontaneous abortions, the etiology is unknown. Infection, anatomic defects, endocrine factors, immunologic factors, and maternal systemic disease are felt to play a role in spontaneous abortion.

A. Morphologic and Genetic Abnormalities

Aneuploidy (an abnormal chromosomal number) is responsible for a large percentage of early spontaneous abortions, accounting for at least 50% of these losses.

Autosomal trisomies have been noted for every chromosome except chromosome number 1. Together, the autosomal trisomies make up just over 50% of all aneuploid losses. Trisomy 16 is the most commonly encountered trisomy in spontaneous abortions.

Monosomy X or Turner syndrome is the single most common aneuploidy in spontaneous losses, comprising approximately 20% of these conceptuses.

Polyploidy, usually in the form of triploidy, is found in approximately 20% of all miscarriages. Polyploid conceptions typically result in empty sacs or blighted ovums but occasionally can lead to partial hydatidiform moles.

The remaining half of early abortuses appear to have normal chromosomal complements. Of these, 20% have other genetic abnormalities which may account for the loss. Mendelian or polygenic factors resulting in anatomic defects may play a role. These tend to be more common in later fetal losses.

B. Maternal Factors

1. Systemic disease

a. Maternal infections—Organisms such as Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, Streptococcus agalactiae, herpes simplex virus, cytomegalovirus, and Listeria monocytogenes have been implicated in spontaneous abortion. Although these agents have been identified in early losses, a causal relationship has not been established.

b. Other diseases—Endocrine disorders such as hyperthyroidism or poorly controlled diabetes mellitus; cardiovascular disorders, such as hypertensive or renal disease; and connective tissue disease, such as systemic lupus erythematosus may also be associated with spontaneous abortion.

2. Uterine defects—Congenital anomalies that distort or reduce the size of the uterine cavity, such as unicornuate, bicornuate, or septate uterus, carry a 25-50% risk of miscarriage. A diethylstilbestrol (DES)-related anomaly, such as a T-shaped or hypoplastic uterus, also carries an increased risk of miscarriage. Acquired anomalies, particularly submucous or intramural myomas, have been associated with spontaneous abortions as well.

Previous scarring of the uterine cavity following dilatation and curettage (Asherman's syndrome), myomectomy, or unification procedures has been implicated in spontaneous miscarriage, as have anatomic or functional incompetence of the uterine cervix.

3. Immunologic disorders—Blood group incompatibility due to ABO, Rh, Kell, or other less common antigens has been associated with spontaneous abortions. Furthermore, similar maternal and paternal HLA may enhance the possibility of abortion by causing insufficient maternal immunologic recognition of the fetus.

4. Malnutrition—Severe malnutrition has been implicated in spontaneous losses.

5. Emotional disturbances—Emotional causes of abortion are speculative. There is no valid evidence to support the concept that abortion may be induced by fright, grief, anger, or anxiety.

C. Toxic Factors

Agents such as radiation, antineoplastic drugs, anesthetic gases, alcohol, and nicotine have been shown to be embryotoxic. Other agents such as lead, ethylene oxide, and formaldehyde may also be toxic.

D. Trauma

Direct trauma, such as injury to the uterus from a gunshot wound, or indirect trauma, such as surgical removal of an ovary containing the corpus luteum of pregnancy, may result in spontaneous abortion.

Pathology

In spontaneous abortion, hemorrhage into the decidua basalis often occurs. Necrosis and inflammation appear in the area of implantation. The pregnancy becomes partially or entirely detached. Uterine contractions and dilatation of the cervix result in expulsion of most or all of the products of conception.

Clinical Findings

A. Threatened Abortion

At least 20% of pregnant women have some first trimester bleeding. In most cases, this is thought to represent an implantation bleed. The cervix remains closed and slight bleeding with or without cramping may be noted.

B. Inevitable Abortion

Abdominal or back pain and bleeding with an open cervix indicate impending abortion. Abortion is inevitable when cervical effacement, cervical dilatation, and/or rupture of the membranes is noted.

C. Incomplete Abortion

Figure 14-1. Incomplete abortion. At right: Product of incomplete abortion. (Reproduced, with permission, from Benson RC: Handbook of Obstetrics & Gynecology, 8th ed. Lange, 1983.)

In incomplete abortion the products of conception have partially passed from the uterine cavity. In gestations of less than 10 weeks' duration, the fetus and placenta are usually passed together. After 10 weeks, they may be passed separately with a portion of the products retained in the uterine cavity. Cramps are usually present. Bleeding generally is persistent and is often severe.

D. Complete Abortion

Figure 14-2. Complete abortion. At right: product of complete abortion. (Reproduced, with permission, from Benson RC: Handbook of Obstetrics & Gynecology, 8th ed. Lange, 1983.)

Complete abortion is identified by passage of the entire conceptus. Slight bleeding may continue for a short time, although pain usually ceases.

E. Missed Abortion

Missed abortion implies that the pregnancy has been retained following death of the fetus. It is not known why the pregnancy is not expelled. It is possible that normal progestogen production by the placenta continues while the estrogen levels fall, which may reduce uterine contractility.

F. Blighted Ovum

Blighted ovum or anembryonic pregnancy represents a failed development of the embryo, so that only a gestational sac, with or without a yolk sac, is present.

Laboratory Findings

A. Complete Blood Count

If significant bleeding has occurred, the patient will be anemic. Both the white blood cell count and the sedimentation rate may be elevated even without the presence of infection.

B. Pregnancy Tests

Falling or abnormally low plasma levels of β-hCG are predictive of an abnormal pregnancy, either a blighted ovum, spontaneous abortion, or ectopic pregnancy.

Ultrasonography

Transvaginal ultrasound is helpful in documenting intrauterine pregnancies as early as 4-5 weeks' gestation. Fetal heart motion should be seen in embryos > 5 mm from crown to rump, or in embryos at least 5-6 weeks' gestation. Ultrasound is useful in determining which pregnancies are viable and which are most likely to miscarry. Perhaps more than any other tool, ultrasound has proven most helpful in the differential diagnosis of early pregnancy complications.

In threatened abortion, ultrasound will reveal a normal gestational sac and viable embryo. However, a large or irregular sac, an eccentric fetal pole, the presence of a large (> 25% of sac size) retrochorionic bleed, and/or a slow fetal heart rate (< 85 bpm) carry a poor prognosis. Miscarriage becomes less and less likely the further the gestation progresses, but most pregnancies are lost weeks before mothers complain of signs or symptoms. If a viable fetus of 6 weeks or less is seen on ultrasound, the risk of miscarriage is approximately 15-30%. This decreases to 5-10% at 7-9 weeks' gestation and less than 5% after 9 weeks' gestation.

In incomplete abortion, the gestational sac is usually deflated, and irregular, echogenic material representing placental tissue is seen in the uterine cavity. In complete abortion, the endometrium appears closely apposed, with no visible products of conception.

An embryo or fetus without heart motion is consistent with a missed abortion, while an abnormal gestational sac, without a yolk sac or embryo, is consistent with a blighted ovum.

Figure 14-3. Intrauterine pregnancy at 8 weeks' gestation, demonstrating embryo (E) and yolk sac (YS).
 

Figure 14-4. Embyronic demise at 8 weeks' gestation, with irregular gestational sac and deflated yolk sac (YS).

Figure 14-5. Empty gestational sac, consistent with a blighted ovum.
 

Figure 14-6. Empty uterus (U) with an adnexal mass (A) suspicious for an ectopic pregnancy. β-hCG at the time of transabdominal ultrasound was just over 100 mIU.
 

Ectopic pregnancy may cause similar symptoms of miscarriage, namely menstrual abnormality and abdominal or pelvic pain. An adnexal mass may or may not be present. Ultrasound can virtually exclude an ectopic pregnancy by documenting an intrauterine pregnancy, as the chance of a simultaneous intra- and extrauterine pregnancy (heterotopic pregnancy) is exceedingly rare in spontaneous pregnancies, occurring in only one in 15,000-40,000 pregnancies.

Hydatidiform mole usually ends in abortion before the fifth month. Theca lutein cysts, when present, cause bilateral ovarian enlargement; the uterus may be unusually large. Bloody discharge may contain hydropic villi.

Other entities that may be confused with abortion include cervical infection, extruding pedunculated myoma, and cervical neoplasia. However, the pregnancy test will be negative, unless a pregnancy coexists.

Complications

Severe or persistent hemorrhage during or following abortion may be life threatening. The more advanced the gestation, the greater the likelihood of excessive blood loss. Sepsis develops most frequently after selfinduced abortion. Infection, intrauterine synechia, and infertility are other complications of abortion. Perforation of the uterine wall may occur during dilatation and curettage (D&C) because of the soft and vaguely outlined uterine wall and may be accompanied by injury to the bowel and bladder, hemorrhage, infection, and fistula formation.

Multiple pregnancy with the loss of one fetus and retention of another ("vanishing twin") is not only possible but has been well documented in 20% of early pregnancies closely monitored by ultrasound. Usually the fetus is simply resorbed, but the loss of one fetus in multiple gestation may be accompanied by cramping or vaginal bleeding.

Even with very early miscarriage, a loss can have a significant effect on the family. The fact that most of these losses are unexpected intensifies this grief. Each person responds differently to his or her tragedy. It is the health care worker's responsibility to help parents mourn by acknowledging their loss and identifying potential support systems.

Prevention

Some losses can be prevented by early obstetric care, with adequate treatment of maternal disorders such as diabetes and hypertension, by protection of pregnant women from environmental hazards, and from exposure to infectious diseases.

Treatment

Successful management of spontaneous abortion depends upon early diagnosis. Every patient should receive a general physical examination, and a complete history should be taken. Laboratory studies should include a complete blood count, blood typing, and cervical cultures to determine pathogens in case of infection.

If the diagnosis of threatened abortion is made, bed rest and pelvic rest is typically recommended, although neither has been shown to be helpful in preventing subsequent miscarriage. Prognosis is good when bleeding and/or cramping resolve. D&C may be necessary if significant bleeding persists or if products of conception are retained.

If the diagnosis of inevitable or incomplete abortion is made, evacuation of the uterus by suction D&C should be promptly performed. A type and cross-match for possible blood transfusion and determination of Rh status should be obtained. The prognosis for the mother is excellent if the retained tissue is promptly and completely evacuated.

If the diagnosis of complete abortion is made, the patient should be observed for further bleeding. The products of conception should be examined. As with inevitable and incomplete abortion, the prognosis for the mother is excellent.

If abortion has occurred after the first trimester, hospitalization should be considered. Oxytocics are helpful in contracting the uterus, limiting blood loss, and aiding in expulsion of clots and tissue. Ergot preparations, which contract the cervix as well as the uterus, may also be given if needed. A D&C may be necessary if significant bleeding persists or if products of conception are retained.

Treatment of Complications

Uterine perforation may be manifested by signs of intraperitoneal bleeding, rupture of the bowel or bladder, or peritonitis. Oftentimes, there are no clinical signs and no sequelae. When uterine perforation is suspected, however, laparoscopy and/or laparotomy is indicated to determine the extent of laceration or bowel injury.

14. Discuss how to manage a patient with heavy vaginal bleeding. Include the tests that should be done, how/why the material in the vaginal vault should be examined, and what can be done if bleeding is diffuse.   Added 2004

Linda Dale

It looks like I goofed and didn't include chapter 14 on the reading list for this section (it is on "Complications of Pregnancy") but it should be on this section as well. It will help you answer this objective. Yes, I'm looking specifically at first trimester of pregnancy on this objective although basically the same question will be asked later regarding 2nd and 3rd trimester bleeding as well.

Part of the question, "how/why the material in the vaginal vault should be examined" might be a little obscure. Basically, you will need to determine if the passed material is the entire product of conception, if it contains hydropic villi, (hydatidiform mole), or if it is merely bloody discharge and the fetus or placenta is retained, (perhaps requiring a D&C).

Zen Seeker

Incomplete info -

Between 20% and 30% of women experience some vaginal bleeding during their first 20 weeks of pregnancy. Up to 10% of women have it in their third trimester. While it is often a normal part of the process of gestation, it may indicate complications. You should report vaginal bleeding to your health-care provider right away.
 

First-trimester bleeding may be caused by:

• Implantation of the fertilized egg in the uterus.

• Hormonal changes.

• Undetermined factors that cause no harm to the mother or baby.
   

More serious causes of first-trimester bleeding may include:

• Miscarriage. Almost all women who miscarry will have vaginal bleeding prior to the loss of the pregnancy.

• Ectopic pregnancy. This is when the fertilized egg develops outside of the uterus.

• Molar pregnancy. Also known as a hydatidiform mole or trophoblastic disease, this is a condition in which the placenta does not form properly.

• Luteal phase deficiency. This is when the ovary does not produce enough progesterone.

• Bacterial vaginosis. Women with this reproductive tract infection are twice as likely to experience first-trimester bleeding than those without it.

Current OB/GYN 9th

Complications of spontaneous abortion
Severe or persistent hemorrhage during or following abortion may be life threatening. The more advanced the gestation, the greater the likelihood of excessive blood loss. Sepsis develops most frequently after selfinduced abortion. Infection, intrauterine synechia, and infertility are other complications of abortion. Perforation of the uterine wall may occur during dilatation and curettage (D&C) because of the soft and vaguely outlined uterine wall and may be accompanied by injury to the bowel and bladder, hemorrhage, infection, and fistula formation.

Multiple pregnancy with the loss of one fetus and retention of another ("vanishing twin") is not only possible but has been well documented in 20% of early pregnancies closely monitored by ultrasound. Usually the fetus is simply resorbed, but the loss of one fetus in multiple gestation may be accompanied by cramping or vaginal bleeding.

Even with very early miscarriage, a loss can have a significant effect on the family. The fact that most of these losses are unexpected intensifies this grief. Each person responds differently to his or her tragedy. It is the health care worker's responsibility to help parents mourn by acknowledging their loss and identifying potential support systems.

Treatment

Successful management of spontaneous abortion depends upon early diagnosis. Every patient should receive a general physical examination, and a complete history should be taken. Laboratory studies should include a complete blood count, blood typing, and cervical cultures to determine pathogens in case of infection.

If the diagnosis of threatened abortion is made, bed rest and pelvic rest is typically recommended, although neither has been shown to be helpful in preventing subsequent miscarriage. Prognosis is good when bleeding and/or cramping resolve. D&C may be necessary if significant bleeding persists or if products of conception are retained.

If the diagnosis of inevitable or incomplete abortion is made, evacuation of the uterus by suction D&C should be promptly performed. A type and cross-match for possible blood transfusion and determination of Rh status should be obtained. The prognosis for the mother is excellent if the retained tissue is promptly and completely evacuated.

If the diagnosis of complete abortion is made, the patient should be observed for further bleeding. The products of conception should be examined. As with inevitable and incomplete abortion, the prognosis for the mother is excellent.

If abortion has occurred after the first trimester, hospitalization should be considered. Oxytocics are helpful in contracting the uterus, limiting blood loss, and aiding in expulsion of clots and tissue. Ergot preparations, which contract the cervix as well as the uterus, may also be given if needed. A D&C may be necessary if significant bleeding persists or if products of conception are retained.

Treatment of Complications

Uterine perforation may be manifested by signs of intraperitoneal bleeding, rupture of the bowel or bladder, or peritonitis. Oftentimes, there are no clinical signs and no sequelae. When uterine perforation is suspected, however, laparoscopy and/or laparotomy is indicated to determine the extent of laceration or bowel injury.

14. Briefly discuss gestational trophoblastic disease in regards to the following:   Added 2004
Definition
Incidence
Hydatidiform mole (molar pregnancy)
Symptoms
Treatment

Zen Seeker Current OB/GYN 9th

50. Gestational Trophoblastic Diseases - Tricia E. Markusen, MD, & April Gale O'Quinn, MD

Introduction

ESSENTIALS OF DIAGNOSIS
• Uterine bleeding in first trimester.
• Absence of fetal heart tones and fetal structures.
• Rapid enlargement of the uterus; uterine size greater than anticipated by dates.
• β-hCG titers greater than expected for gestational age.
• Expulsion of vesicles.
• Hyperemesis.
• Theca lutein cysts.
• Onset of preeclampsia in the first trimester.

General Considerations

Gestational trophoblastic neoplasms include the tumor spectrum of hydatidiform mole (complete and partial), invasive mole (chorioadenoma destruens), placental-site trophoblastic tumor (PSTT), and choriocarcinoma. They arise from fetal tissue within the maternal host and are composed of both syncytiotrophoblastic and cytotrophoblastic cells, except PSTT, which is derived from intermediate trophoblastic cells. In addition to being the first and only disseminated solid tumors that have proved to be highly curable by chemotherapy, they elaborate a unique and characteristic tumor marker, human chorionic gonadotropin (hCG).

Hydatidiform mole is the most common gestational trophoblastic neoplasm. Its incidence varies worldwide from 1 in 125 deliveries in Mexico and Taiwan to 1 in 1500 deliveries in the U.S. The incidence is higher in women under 20 and over 40 years of age, in patients of low economic status, and in those whose diets are deficient in protein, folic acid, and carotene. Molar pregnancy occurs in fewer than 2% of subsequent gestations in women with a history of mole.

Hydatidiform mole should be suspected in any woman with bleeding in the first half of pregnancy, passage of vesicles, hyperemesis gravidarum, or preeclampsia-eclampsia with onset before 24 weeks. Absent fetal heart tones and a uterus too large for the estimated duration of gestation on physical examination support the diagnosis. Ultrasonography and serial β-hCG determinations are necessary to establish a firm diagnosis of hydatidiform mole.

Invasive mole is reported in 10-15% of patients who have had primary molar pregnancy. Although considered a benign neoplasm, invasive mole is locally invasive and may produce distant metastases.

PSTT is a rare variant of gestational trophoblastic tumor. It may arise from a hydatidiform mole or less commonly from a normal term pregnancy. The tumor is generally confined to the uterus and metastasizes late in its course. Syncytiotrophoblastic cells are generally absent from this tumor, resulting in minimal secretion of β-hCG in relation to tumor burden. However, human placental lactogen (hPL) is secreted and these levels can be monitored to follow response.

Choriocarcinoma is rare, reported in 2-5% of all cases of gestational trophoblastic neoplasia. The incidence in the U.S. is 1 in 40,000 pregnancies, but it is higher in Asia. In about half of all cases of choriocarcinoma, the antecedent gestational event is hydatidiform mole. One-fourth follow term pregnancy, and the remainder occur following abortion.

A generalization worth repeating is that any woman presenting with bleeding or a tumor in any organ who has a recent history of molar pregnancy, abortion, or term pregnancy should have at least one β-hCG assay to be sure that metastatic gestational trophoblastic neoplasia is not the cause. This is important, for the cure rate of properly treated metastatic gestational trophoblastic neoplasia is approximately 90%.

Etiology & Pathogenesis

Gestational trophoblastic tumors arise in fetal rather than maternal tissue. Cytogenetic studies have demonstrated that true moles are usually (perhaps always) euploid, paternal in origin, and sex chromatin-positive 46,XX or 46,XY; transitional moles are usually trisomic; and partial moles are triploid. The development of an ovum under the influence of a sperm nucleus requires the absence or inactivation of the ovum nucleus and the presence of a dispermic fertilization or the duplication of its chromosomes. This provides important insight into the pathogenesis of gestational trophoblastic neoplasms, because this process results in a homozygous conceptus with a propensity for altered growth.

To date, hydatidiform mole has been considered to be derived from extraembryonic trophoblasts. Histologic similarities between molar vesicles and chorionic villi support the view that one is derived from the other. However, detailed morphologic study of a hysterectomy specimen containing an intact molar pregnancy presents a new concept regarding genesis of hydatidiform mole as a transformation of the embryonic inner cell mass at a stage just prior to the laying down of endoderm. At this stage in embryogenesis, the inner cell mass has the capability of developing into trophoblasts, ectoderm, and endoderm. If normal development is interrupted, such that the inner cell mass loses its capacity to differentiate into embryonic ectoderm and endoderm, a divergent development pathway is created. This pathway may then result in formation of trophoblasts (from the inner cell mass) that develop into cytotrophoblasts and syncytiotrophoblasts with sufficient differentiation to produce extraembryonic mesoderm, giving rise to molar vesicles with loose primitive mesoderm in their villous core. In contrast, choriocarcinoma is less well differentiated and, lacking this capability, is composed of only cytotrophoblasts and syncytiotrophoblasts.

Thus, the ultimate cause of gestational trophoblastic disease may be genetic. Nonetheless, there are interesting clinical correlates, some of which were mentioned earlier. Additionally, evidence indicates that the distribution of ABO blood groups in women with gestational trophoblastic neoplasms and their sexual partners differs from that of the general population. The most remarkable findings are that group A women impregnated by group O men have an almost 10-fold greater risk of developing choriocarcinoma than group A women with group A partners and that women with group AB have a relatively poor prognosis. A study of the ABO blood groups of children resulting from pregnancies prior or subsequent to choriocarcinoma revealed fewer instances than expected in which the child was ABO-incompatible with its mother. The leukocytes of these children frequently showed antigenic differences from the mothers' cells. Although these antigens are regarded as strong transplantation antigens, they seem notably weaker than the ABO factors—evidence that choriocarcinoma is able to grow and to kill in spite of the immune response it evokes. Further, gestational trophoblastic tissue may suppress the maternal immune response via such factors as interleukins and tumor necrosis factor (TNF).

Pathology

Four distinct forms of gestational trophoblastic neoplasia are recognized: hydatidiform mole, invasive mole (chorioadenoma destruens), placental-site trophoblastic tumor (PSTT), and choriocarcinoma.

A. Hydatidiform Mole

Hydatidiform mole is an abnormal pregnancy characterized grossly by multiple grapelike vesicles filling and distending the uterus, usually in the absence of an intact fetus (Fig 50-1). Most hydatidiform moles are recognizable on gross examination, but some are small and may seem to be ordinary abortuses.

Figure 50-1. Hysterectomy specimen with anterior wall incised, displaying typical miliary, clear, "grapelike" vesicles filling the uterine cavity. Hysterectomy was performed for primary treatment for molar gestation.

Microscopically, moles may be identified by three classic findings: edema of the villous stroma, avascular villi, and nests of proliferating syncytiotrophoblastic or cytotrophoblastic elements surrounding villi (Fig 50-2). Today with earlier clinical diagnosis, the classic pathologic presentation of molar pregnancies is less common. Therefore, it can be more difficult to differentiate histologically between a molar pregnancy and a nonmolar hydropic abortion. The likelihood of malignant sequelae is increased in patients whose trophoblastic cells show increased proliferation and anaplasia. Although histologic study of the trophoblast provides some basis for predicting a benign or malignant course for the mole, the correlation is not absolute, and it is essential to obtain accurate, sensitive gonadotropin assays in all patients who have had hydatidiform moles.
 

Figure 50-2. Photomicrograph of hydatidiform mole characterized by well-developed but avascular villi with stromal edema and minimal trophoblastic proliferation.

Two forms of hydatidiform moles exist—complete (true) and partial moles. The clinical, pathologic, and genetic characteristics of both are outlined in Table 50-1.
 

B. Invasive Mole (Chorioadenoma Destruens)

Invasive mole is a hydatidiform mole that invades the myometrium or adjacent structures. It may totally penetrate the myometrium and be associated with uterine rupture and hemoperitoneum (Fig 50-3). The microscopic findings are the same as in hydatidiform mole (Fig 50-4). Since adequate myometrium is rarely obtained at curettage, the diagnosis is made by histologic study less frequently now than formerly, because fewer hysterectomies are performed in patients with trophoblastic disease. Metastatic lesions may contain invasive mole, but most will be choriocarcinoma regardless of the morphologic features of the uterine tumor.

Figure 50-3. Hysterectomy specimen showing invasive mole penetrating the myometrium and serosal surface of the uterus that resulted in life-threatening intraperitoneal hemorrhage.
 

Figure 50-4. Photomicrograph of invasive mole. The pattern of hydatidiform mole is maintained with avascular villi and stromal edema, but they are deep within the uterine wall, interspersed among smooth-muscle bundles.
 

C. Placental-Site Trophoblastic Tumor

PSTT is derived from the intermediate trophoblasts of the placental bed, with minimal or absent syncytiotrophoblastic tissue. Histologically, local invasion occurs into the myometrium and lymphatics. Vascular invasion is less common. It may occur with any type of pregnancy.

D. Choriocarcinoma

Choriocarcinoma is a pure epithelial tumor composed of syncytiotrophoblastic and cytotrophoblastic cells. It may accompany or follow any type of pregnancy. Histologic examination discloses no villi, but instead sheets or foci of trophoblasts on a background of hemorrhage and necrosis. A histopathologic diagnosis of choriocarcinoma in any site is an indication for prompt treatment after confirmation by gonadotropin excretion measurements. Assessment of trophoblastic tissue following or accompanying pregnancy may be difficult because of the histologic similarity of the trophoblastic pattern in very early human pregnancy and in choriocarcinoma. The entire specimen must be processed for histologic study when curettage is done, because specimens may reveal only small, isolated areas of choriocarcinoma. Careful search usually discloses the villous pattern in the tissue of early normal pregnancy.

Choriocarcinoma may also arise from ectopic pregnancy. In confusing situations, β-hCG testing may clarify the diagnosis and document the need for therapy.

Malignant gestational trophoblastic neoplasia is diagnosed in the setting of invasive mole, placental-site trophoblastic tumors, choriocarcinomas, and postmolar rising or plateauing (decline of < 10% for at least 3 values over more than 14 days) β-hCG values.

Clinical Findings

A. Symptoms and Signs

Abnormal uterine bleeding, usually during the first trimester, is the most common symptom, occurring in over 90% of patients with molar pregnancies. Three-fourths of patients with bleeding have this symptom before the end of the third month of pregnancy. Only one-third of patients have profuse vaginal bleeding.

Nausea and vomiting, frequently excessive but at times difficult to distinguish from similar complaints normally occurring in pregnancy, have been reported to occur in 14-32% of patients with hydatidiform mole. Ten percent of patients with molar pregnancies have nausea and vomiting severe enough to require hospitalization.

Disproportionate uterine size is the most common sign of molar gestation. About half of patients have excessive uterine size for gestational date, but in one-third the uterus is smaller than expected.

Multiple theca lutein cysts causing enlargement of one or both ovaries occur in 15-30% of women with molar pregnancies. In about half the cases, both ovaries are enlarged and may be a source of pain. Involution of the cysts proceeds over several weeks, usually paralleling the decline of hCG level. Operation is indicated only if rupture and hemorrhage occur or if the enlarged ovaries become infected. Patients with associated theca lutein cysts appear to have a greater likelihood of developing malignant sequelae of gestational trophoblastic neoplasia.

Preeclampsia in the first trimester or early second trimester—an unusual finding in normal pregnancy—has been said to be pathognomonic of hydatidiform mole, although it occurs in only 10-12% of those patients.

Hyperthyroidism from production of thyrotropin by molar tissue occurs in up to 10% of patients with hydatidiform mole. The manifestations disappear following evacuation of the mole. An occasional patient may require brief antithyroid therapy. These classic symptoms and signs are becoming less prevalent today due to the earlier diagnosis of molar pregnancies. For instance, at the New England Trophoblastic Disease Center, the incidence of excessive uterine enlargement, hyperemesis, and preeclampsia is 28%, 8%, and 1%, respectively. Hyperthyroidism and respiratory insufficiency have become negligible. Although these classic signs and symptoms have decreased, the incidence of persistent postmolar gestational trophoblastic disease has remained static, stressing the continued importance of postmolar β-hCG surveillance.

B. Laboratory Findings

The most important characteristic of gestational trophoblastic neoplasms is their capacity to produce hCG. This hormone may be detected in serum or urine in virtually all patients with hydatidiform mole or malignant trophoblastic disease. Careful monitoring of β-hCG levels is necessary for diagnosis, treatment, and follow-up in all cases of trophoblastic disease.

The amount of hCG found in the serum or excreted in the urine correlates closely with the number of viable tumor cells present. Studies indicate that one tumor cell produces from about 5 × 10^-5 to 5 × 10^-4 IU of hCG in 24 hours. Thus, a patient excreting 10⁶ IU of hCG in 24 hours has about 10¹¹ viable tumor cells.

The usefulness of a gonadotropin assay depends on the level of the patient's β-hCG titer and the sensitivity of the test. Today, sensitive and specific immunoassays are available to differentiate hCG from LH by measuring the beta chain of hCG. Serial β-hCG levels are best monitored in the same laboratory using the same immunoassay technique.

The rate and constancy of the decline in hCG titer are important. Using the serum β-hCG radioimmunoassay, a normal postmolar pregnancy hCG regression curve based on weekly determinations in patients undergoing spontaneous remission has been constructed (Fig 50-5). This provides a reference with which random or serial values can be compared. In most instances, the β-hCG values exhibit a progressive decline to normal within 14 weeks following evacuation of a molar pregnancy. If metastases are detected or if the hCG titer rises or plateaus, it must be concluded that viable tumor persists.

Figure 50-5. Normal postmolar pregnancy regression curve of serum β-hCG measured by radioimmunoassay. Vertical bars indicate 95% confidence limits. (Reproduced, with permission of the American College of Obstetricians and Gynecologists, from Schlaerth JB et al: Prognostic characteristics of serum human chorionic gonadotropin titer regression following molar pregnancy. Obstet Gynecol 1981;58:478.)
 

C. X-ray Findings

Transabdominal amniocentesis combined with amniography may be used to confirm the presence of hydatidiform mole, although this is rarely utilized today given the extensive use of transvaginal and transabdominal ultrasound and β-hCG levels.

D. Special Examinations

The simplicity, safety, and reliability of ultrasonography make it the diagnostic method of choice for patients with suspected molar pregnancy. In a molar pregnancy, the characteristic ultrasound pattern includes multiple echoes formed by the interface between the molar villi and the surrounding tissue without the presence of a normal gestational sac or fetus (Fig 50-6). This study should be done in any patient who experiences bleeding in the first half of pregnancy and has a uterus greater than 12 weeks' gestational size. Even when the uterus is smaller, ultrasonography may be very specific in differentiating between a normal pregnancy and hydatidiform mole.

Figure 50-6. A gray-scale ultrasonogram depicting the typical intrauterine multiple-echo pattern of hydatidiform mole.
 

Differential Diagnosis

Gestational trophoblastic disease must be distinguished from normal pregnancy. Ultrasonography is useful, and quantitative hCG levels afford another means of differentiation. In general, β-hCG assays with values greater than 100,000 mIU/mL are usual with molar pregnancies, in contrast to normal pregnancy values below 60,000 mIU/mL.

Complications

The maternal/fetal barrier contains leaks large enough to permit passage of cellular and tissue elements. Trophoblastic deportations to the lungs are frequent and have totally unpredictable manifestations, including spontaneous regression. A dramatic but now less common life-threatening complication of molar pregnancy in patients with uterine enlargement beyond 16 weeks' gestational size is a syndrome of acute pulmonary insufficiency characterized by sudden onset of dyspnea, often with cyanosis. Symptoms usually begin within 4-6 hours after evacuation. Historically, the syndrome has been attributed to massive deportation of trophoblasts to the pulmonary vasculature, but the most likely cause may be pulmonary edema secondary to cardiac dysfunction and excessive fluid administration. Nevertheless, massive fatal pulmonary embolization by gross deportation of villous tissue masses may occur, as documented by postmortem examination.

Treatment

A. Hydatidiform Mole

1. Evacuation—When the diagnosis has been confirmed, molar pregnancy should be terminated.

Suction curettage is the method of choice. It is safe, rapid, and effective in nearly all cases. Intravenous oxytocin should be started after a moderate amount of tissue has been removed and may be continued for 24 hours postevacuation if necessary. Suction curettage with the largest curette possible should be followed by gentle sharp curettage, and tissue from the decidua basalis should be submitted for pathologic study separately. Suction curettage can be safely accomplished even when the uterus is as large as in a 28-week pregnancy. Blood loss usually is moderate, but precautions should be taken for massive transfusion. When a large hydatidiform mole (> 12 weeks in size) is evacuated by suction curettage, a laparotomy setup should be readily available, since hysterotomy, hysterectomy, or bilateral hypogastric artery ligation may be necessary if perforation or hemorrhage occurs.

Before the use of suction curettage, hysterectomy was frequently used for patients with uteri beyond 12-14 weeks in size. Hysterectomy remains an option for good surgical candidates not desirous of future pregnancy and for older women (who are more likely to develop malignant sequelae). If theca lutein cysts are encountered at hysterectomy, the ovaries should remain intact, because regression to normal size will occur as the hCG titer diminishes. Hysterectomy does not eliminate the need for careful follow-up and β-hCG testing, although the likelihood of metastatic disease following hysterectomy for gestational trophoblastic disease is low (decreases from 20% to 3.5%).

Hysterotomy is no longer a method of choice in typical cases. The higher incidence of malignant disease following hysterotomy is probably attributable to greater uterine enlargement in patients selected for this therapy. Current recommendations restrict hysterotomy to cases complicated by hemorrhage.

Prostaglandin induction, oxytocin induction, and intra-amniotic instillation of prostaglandin or hypertonic solutions (saline, glucose, urea, etc) are no longer acceptable methods for evacuation of a molar pregnancy.

2. Prophylactic chemotherapy—It is controversial whether prophylactic chemotherapy (with methotrexate or dactinomycin) following a complete hydatidiform molar pregnancy should be offered to patients considered at high risk for persistent gestational trophoblastic disease (age > 35 years, history of prior molar pregnancy, trophoblastic hyperplasia) or in whom poor follow-up is anticipated. Several studies indicate that the incidence of postmolar gestational trophoblastic disease may be decreased with prophylactic chemotherapy. However, further studies are required to determine if the potential side effects warrant such treatment.

3. Surveillance following molar pregnancy—Regardless of method of termination, close follow-up with serial β-hCG titers is essential for every patient because of the incidence of malignant disease. The incidence is commonly thought to be 20-30%. Despite earlier diagnosis of molar pregnancies, the incidence of persistent gestational trophoblastic disease has not decreased. Three-fourths of patients with malignant nonmetastatic trophoblastic disease and half of patients with malignant metastatic disease develop these tumors as sequelae to hydatidiform mole. In the remainder, disease arises following term pregnancy, abortion, or ectopic pregnancy.

Several clinical features of hydatidiform mole are recognized as having a high association with malignant trophoblastic neoplasia. In general, at diagnosis, the larger the uterus and the higher the hCG titer, the greater the risk for malignant gestational trophoblastic disease. The combination of theca lutein cysts and uterine size excessive for gestational age is associated with an extremely high risk (57%) of malignant sequelae. Pathologic specimens with marked nuclear atypia, presence of necrosis or hemorrhage, and trophoblastic proliferation may also increase the risk of persistent disease.

Effective contraceptive measures should be implemented and maintained throughout the period of surveillance in these patients. Oral contraceptives are the most widely used method.

Following evacuation of hydatidiform mole, the patient should have serial β-hCG determinations at weekly intervals until serum hCG declines to nondetectable levels (β-hCG radioimmunoassay) on three successive assays. If titer remission occurs spontaneously within 14 weeks and without a titer plateau, the β-hCG titer than should be repeated monthly for at least 1 year before the patient is released from close medical supervision (in cases of partial moles, β-hCG may be followed for 6-12 months). Thereafter, the patient may enter into a regular gynecologic care program.

Gynecologic examination should be done 1 week after evacuation, at which time blood may be taken for the first postevacuation hCG titer. Estimates of uterine size and presence of adnexal masses (theca lutein cysts) and a careful search of the vulva, vagina, urethra, and cervix should be made for evidence of genital tract metastases. Unless symptoms develop, the examination should be repeated at 4-week intervals throughout the observation period.

Chest x-ray should be obtained prior to evacuation, and if pulmonary metastases are noted, at 4-week intervals thereafter until spontaneous remission is confirmed, then at 3-month intervals during the remainder of the surveillance period.

A patient who has entered into spontaneous remission with negative titers, examinations, and chest x-rays for 1 year and who is desirous of becoming pregnant may terminate contraceptive practices. Successful pregnancy is usual, and complications are similar to those of patients in the general population. The risk of repeat molar pregnancy is 1-2%, but increases to approximately 25% following the second molar pregnancy.

Therapy for progressive gestational trophoblastic neoplasia after delivery of a hydatidiform mole is usually instituted because of an abnormal hCG regression curve. While the hCG titer usually returns to normal within 1-2 weeks after evacuation of a hydatidiform mole, it should be normal by 8 weeks. The most critical period of observation is the first 4-6 weeks postevacuation. Few patients whose hCG titers are normal during this interval will require treatment. Approximately 70% of patients achieve a normal hCG level within 60 days postevacuation.

In the past, therapy was recommended if the hCG titer remained elevated at or beyond 60 days after termination of molar pregnancy. However, current data suggest that an additional 15% of patients demonstrate a continuous decline in titers and ultimately achieve normal titers without treatment. About 15% of patients who have elevated titers at 60 days postevacuation demonstrate a rising or plateauing titer. Nearly half of these patients have histologic evidence of choriocarcinoma, and the rest have invasive mole.

Delayed postevacuation bleeding is uncommon after molar pregnancy, but it signifies the presence of invasive mole or choriocarcinoma and is invariably attended by an enlarging uterus and abnormal hCG regression pattern. On pelvic examination, the enlarged uterus may have the characteristics of an intrauterine pregnancy. Curettage is effective in stopping the bleeding, although little intracavitary tissue will be present in most of these cases.

In summary, the indications for initiating chemotherapy during the postmolar surveillance period are (1) β-hCG levels rising for 2 successive weeks or constant for 3 successive weeks; (2) β-hCG levels elevated at 15 weeks' postevacuation; (3) rising β-hCG titer after reaching normal levels; and (4) postevacuation hemorrhage. Treatment should also be instituted whenever there is a tissue diagnosis of choriocarcinoma. However, histologic confirmation is unnecessary, because the development of metastasis is a sufficient justification for chemotherapy.

B. Malignant Gestational Trophoblastic Neoplasia

Once the diagnosis of malignant trophoblastic disease has been established, obtain an accurate history and perform a physical examination, including pelvic examination. Most patients have an enlarged uterus, and ovarian enlargement due to theca lutein cysts is common. Sites of metastasis must be sought, especially in the lower genital tract. Obtain a chest x-ray and scans of the liver and brain. CT scan is now the diagnostic procedure of choice for brain, lung (40% of patients with negative chest x-rays may show evidence of pulmonary micrometastases on chest CT), liver, and renal metastases. In brain metastasis, evaluation of the ratio of serum hCG to the concentration of hCG in cerebrospinal fluid (normal > 60:1) may be helpful. Carefully consider the baseline hematologic counts as well as hepatic and renal function, which may be critical in the risk and monitoring of drug toxicity.

After sites of metastases or of abnormal function have been identified, the patient's desires for preservation of reproductive function are known, and the disease has been categorized as nonmetastatic or metastatic, specific therapy should be started.

1. Nonmetastatic gestational trophoblastic disease—Trophoblastic disease confined to the uterus is the most common malignant lesion seen in gestational trophoblastic neoplasia. The diagnosis is usually made during follow-up after evacuation of molar pregnancy. If there is no evidence of spread outside the uterus, histologic examination may be important, for nonmetastatic choriocarcinoma is a more serious condition than nonmetastatic hydatidiform mole. Therapy for patients with nonmetastatic malignant trophoblastic disease includes (1) single-agent chemotherapy; and (2) combined chemotherapy and hysterectomy, with surgery done on the third day of drug therapy if the patient does not wish to preserve reproductive function and her disease is known to be confined to the uterus.

Table 50-2 summarizes the recommended chemotherapy regimens available for nonmetastatic gestational trophoblastic disease (and low-risk gestational trophoblastic disease). Single-agent chemotherapy using methotrexate or dactinomycin has demonstrated clear-cut superiority over other protocols. The therapeutic efficacy of the two drugs is apparently equivalent; however, no randomized controlled study has compared the response rate and side effect profile of single-agent chemotherapy with methotrexate to that of dactinomycin. The regimen of choice has therefore not been standardized. However, weekly intramuscular methotrexate injections provide a convenient and cost-effective alternative to the more intense 5-day regimens with methotrexate or dactinomycin, and with minimal side effects. Treatment failure (indicated by rising β-hCG or presence of new metastasis) or intolerable side effects with one regimen should result in administration of the other agent. Overall, the complete response rate ranges from 60-98% with salvage rates approaching 100%. Methotrexate is contraindicated in the presence of hepatocellular disease or when renal function is impaired. Each treatment cycle should be repeated as soon as normal tissues (bone marrow and gastrointestinal mucosa) have recovered, with a minimum 7-day window between the last day of one course and the first day of the next.
 

During treatment, weekly quantitative β-hCG titers and complete blood counts should be obtained. Before each course of therapy, liver and renal function assessments should be done. At least one course of drug therapy should be given after the first normal β-hCG determination. The number of treatment cycles necessary to induce remission is proportionate to the magnitude of the β-hCG concentration at the start of therapy. An average of 3 or 4 courses of single-agent therapy is required. After remission has been induced and treatment is completed, β-hCG assays should be obtained monthly for 12 months.

2. Metastatic gestational trophoblastic disease—Treatment in metastatic disease utilizes either single-agent chemotherapy (Table 50-2) or multiple-agent chemotherapy. Multiple-agent chemotherapy is used in cases where resistance to a single agent is anticipated. Several systems have been developed to help determine which patients will require at onset more aggressive therapy:
 

3. Clinical Classification of Malignant Gestational Trophoblastic Disease

National Cancer Institute—This system is utilized in the United States to determine if the patient has a good or poor prognosis to respond well to single-agent chemotherapy (Table 50-3).
 

World Health Organization—This scoring system is based on an individual's risk factors, including age, type of antecedent pregnancy, interval from antecedent pregnancy to initiation of chemotherapy, pretreatment β-hCG level, blood type (but this criterion not consistently used), size of largest tumor, site of metastases, number of metastases, and prior chemotherapy. Patients are categorized into low-, medium-, and high-risk based on their total score (Table 50-4).
 

Revised FIGO (International Federation on Gynecology and Obstetrics)—This staging system is based on site of disease extension with presence or absence of 2 risk factors: β-hCG level and interval since antecedent pregnancy (Table 50-5).
 

No single system is consistently being used internationally, thereby making comparisons in treatment success difficult.

a. Good-prognosis patients—Based on the clinical classification of malignant disease, patients can be expected to respond satisfactorily to single-agent chemotherapy if (1) metastases are confined to the lungs or pelvis; (2) serum β-hCG levels are below 40,000 mIU/mL at the onset of treatment; and (3) therapy is started within 4 months of apparent onset of disease.

The most common site of metastasis is the lung. When a patient develops pulmonary metastases and elevation of hCG titer, choriocarcinoma is a more likely cause than metastatic mole. Invasive mole may also metastasize to the lungs, and hydatidiform mole has occasionally been reported to metastasize to the chest. Probably any form of metastasis (even benign deportation) should suggest metastatic trophoblastic disease.

In these patients, single-agent chemotherapy (Table 50-2) is generally successful. Methotrexate is considered the drug of choice. Ideally, the 5-day treatment cycle is given every other week, because tumor regrowth becomes significant after treatment gaps of 2 weeks or longer. Once negative titers have been achieved, an additional course is administered. If resistance to methotrexate occurs, manifested either by rising or plateauing titers or by the development of new metastases, or if negative titers are not achieved by the fifth course of methotrexate, the patient should be given dactinomycin. Dactinomycin should be initiated as well for patients who experience severe side effects with methotrexate.

The advantage of single-agent chemotherapy is that it is less toxic and its toxicity is less apt to be irreversible than is the case with multiple-agent chemotherapy.

There is a tendency to approach the treatment of these patients too lightly, probably because of the "good-prognosis" (low-risk) designation. But failure of drug therapy does occur in about 10% of cases, and meticulous care by physicians familiar with these problems is necessary for good results.

b. Poor-prognosis patients—Poor-prognosis patients, based on the Clinical Classification of Malignant Disease, are those with any of these risk factors: (1) serum β-hCG titers greater than 40,000 mIU/mL; (2) disease diagnosed more than 4 months after molar pregnancy; (3) brain or liver metastases; (4) prior unsuccessful chemotherapy; or (5) onset following term gestation. These patients respond poorly (< 40% response rate) to single-agent therapy. A poor response is also seen in patients with revised FIGO stage IIIC and all stages of IV and with WHO scores > 7. These patients present a serious challenge. Many have been previously treated with chemotherapy and have become resistant to that treatment while accumulating considerable toxicity and depleting bone marrow reserves. Prior unsuccessful chemotherapy is one of the worst prognostic factors.

Generally, these patients require prolonged hospitalization and many courses of chemotherapy. They often need specialized care and other life-support measures, including hyperalimentation, antibiotics, and transfusions to correct the effects of marrow depression.

Central nervous system involvement, particularly brain metastasis with focal neurologic signs suggestive of intracranial hemorrhage, is common in choriocarcinoma. Since patients with brain or liver metastases are at great risk of sudden death from hemorrhage from these lesions, it has been standard practice when treating them to include immediate institution of whole-brain or whole-liver irradiation concomitantly with combination chemotherapy. It is uncertain whether radiation therapy exerts its beneficial effect by destroying tumor in combination with drug therapy or by preventing fatal hemorrhage and thus keeping the patient alive until remission with chemotherapy can be achieved. For acute bleeding episodes, surgical intervention or angiographic embolization can be considered.

Cerebral metastasis should be treated over a 2-week period with radiation given in a dosage of 300 rads daily, 5 days a week, to a total organ dose of 3000 rads. Whole-liver irradiation is usually accomplished over 10 days to attain a 2000-rad whole-organ dose given at a rate of 200 rads daily, 5 days a week. Other treatment options include selective hepatic artery chemotherapy infusion.

Prior treatments for poor prognosis/high-risk gestational trophoblastic disease have included MAC (methotrexate, dactinomycin, and chlorambucil or cyclophosphamide) and the modified Bagshawe protocol (CHAMOCA: cyclophosphamide, hydroxyurea, methotrexate, vincristine, cyclophosphamide, and dactinomycin). Currently, EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine) chemotherapy (Table 50-6) provides the best response rate (approximately 80%) with the lowest side effect profile. The cycle is repeated every 2 weeks. The same tests must be employed to detect toxicity as are used when single-agent chemotherapy is given, but monitoring must be even more vigilant because of the possibility of combined toxicity.
 

Treatment of malignant trophoblastic disease must be continued with repeated courses of combination chemotherapy until β-hCG titers return to nondetectable levels. Complete remission is documented only after three consecutive weekly normal β-hCG titers have been achieved. It is recommended that all high-risk patients receive at least three courses of triple-agent chemotherapy after β-hCG titers have returned to normal. After remission is achieved, follow-up is the same as for hydatidiform mole and nonmetastatic or good-prognosis disease.

Salvage therapy for disease not responsive to EMA/ CO substitutes cisplatin and etoposide (EP-EMA) for cyclophosphamide and vincristine (CO) (Table 50-6). Close monitoring of renal function is required because of nephrotoxicity secondary to cisplatin and as methotrexate is renally excreted. Other treatment options include such agents as paclitaxel, topotecan, and high-dose chemotherapy with autologous bone marrow transplantation.

In resistant cases, adjunctive measures along with chemotherapy may include hysterectomy, resection of metastatic tumors, or irradiation of unresectable lesions.

4. Placental-Site Trophoblastic Tumor (PSTT)— Treatment of PSTT generally is resistant to chemotherapy. Therefore hysterectomy is the recommended route of treatment. Partial uterine resection involving the tumor is possible if the patient desires to retain fertility. Chemotherapy is indicated in cases of metastatic disease. EP-EMA is the preferred regimen over EMA/CO, with paclitaxel and topotecan used when resistance develops. The greatest adverse outcomes are associated with an interval > 2 years from antecedent pregnancy to diagnosis.

Prognosis

The prognosis for hydatidiform mole following evacuation is uniformly excellent, though surveillance is needed as outlined in the text. The prognosis for malignant nonmetastatic disease with appropriate therapy is also quite good, since almost all patients are cured. Over 90% of patients have been able to preserve reproductive function, but first-line therapy failed in 6.5% of patients with nonmetastatic disease. In one large reported series, no death from toxicity occurred, and only one patient died of the disease.

In poor-prognosis metastatic disease, the best results are with EMA/CO chemotherapy and concurrent radiation as indicated. Seventy-five to 85% of patients achieve remission with a 69% salvage rate. This is a similar response to agents used previously (MAC) but with fewer side effects. Brain and liver metastases have the worst prognosis with reports of survival ranging from 0-60% for hepatic involvement and 50-80% for CNS involvement at diagnosis. Survival decreases to < 20% when prior chemotherapy agents have been utilized or if CNS metastases develop while undergoing treatment. Deaths from toxicity have decreased considerably. Recurrence, when it happens, is usually in the first several months after termination of therapy but may be as late as 3 years.

Secondary Tumors

Multiple-agent chemotherapy (specifically utilizing etoposide) but not single-agent chemotherapy has been associated with a 50% increased risk for secondary tumors. One retrospective study found that the relative risk for developing myeloid leukemia and colon cancer was 16.6 and 4.6, respectively. When survival exceeded 25 years, the relative risk for developing breast cancer was 5.8.

Subsequent Pregnancy Outcome

Subsequent pregnancies are not at increased risk for complications such as preterm labor, anomalies, or stillbirth. These pregnancies should, however, be monitored early with ultrasound and β-hCG levels because there is a small risk of recurrent gestational trophoblastic disease (1-2%). Following delivery, the placenta should be sent to pathology and a β-hCG level should be checked at the 6-week postpartum visit.

In cases where pregnancy occurs prior to the completion of standard postmolar surveillance (less than 1 year), the pregnancy may be continued with close observation, and the risks discussed with the patient. Most pregnancies end with a good outcome, but there is a small risk for delayed diagnosis of recurrence.