Darryl Holman's Research: Fecundability and Pregnancy Loss
Demographers have long noted that fecundability (the monthly
probability that a sexually active couple becomes pregnant) appears to
decline with a woman's age, beginning in the early twenties. This
decline has traditionally been interpreted as a true decline in
fecundability caused by declining coital frequency with age or marital
duration, a deteriorating uterine environment, declining ovarian
function, or an increased incidence of sterility. But, because very
early pregnancies are not detectable in a non-invasive way, it has been
impossible to distinguish between ovarian cycles in which no pregnancy
has occurred and cycles in which a pregnancy terminated at a very early
gestational age. In other words, fecundability is confounded by early
pregnancy loss. To demographers, the difference between a failure to
conceive and the loss of a conceptus is fundamental: one is a pure
fertility process and the other is mortality. This distinction has
obvious implications for clinical research and practice as well.
For my dissertation research, I attempted to solve this long-standing
problem in demography. I developed a stochastic model of the process
of conception, the gestational-age specific risk of pregnancy loss, and
the incomplete sensitivity and specificity of the assays used to detect
early pregnancies. I collected new endocrine and questionnaire
observations in a one-year study of rural Bangladeshi women. The
results provided a rather unexpected picture of fecundability and
pregnancy loss. Most of the age-related decline in apparent
fecundability was caused by an age-related increase in pregnancy loss,
not by a decline in total fecundability. Total fecundability remained
high and nearly constant across the reproductive span until falling
sharply around age 40 (Holman 1996; Holman et al. 2000;
Holman and Wood 2001).
The work showed that pregnancies in older women
tend to be lost at earlier gestational ages, most likely because
conceptuses in older women have a higher probability of chromosomal
abnormalities. Portions of this work have been published (O'Connor et
al. 1998; Holman et al. in press; Holman et al. 2000; Holman and
Wood 2001), but because of the complexity of this project--it required
rethinking the field, laboratory, and statistical methods--the full
scope of this work will appear as a monograph from Cambridge University
Press (Holman, forthcoming).
Holman DJ. (forthcoming)
Fecundability, Pregnancy Loss, and Reproductive Aging in Women,
Cambridge University Press, Cambridge Studies in Biological
Holman DJ (1996) Total Fecundability and
Fetal Loss in Rural Bangladesh. Doctoral Dissertation, The Pennsylvania
State University, University Park.
Holman DJ, O'Connor KA, Wood JW
(in press) Age and female reproductive function: Identifying the most
important biological determinants. In Hill A, Mascie-Taylor N, Leridon
H, Sauvain-Dugerdil C (eds.) Age: Human Clock and Scale of Social
Organization. Oxford: Oxford University Press.
Holman DJ, Wood JW, and Campbell KL
(2000) Age-dependent decline of female fecundity is caused by early
fetal loss. Chapter 9 in te Velde ER, Broekmans F, and Pearson P (eds.)
Female Reproductive Ageing. Studies in Profertility series, Vol 9,
Carnforth, UK: Parthenon Publishing Group. pp. 123-136.
Holman DJ, Wood JW (2001) Pregnancy
loss and fecundability in women. In Ellison PT (ed.) Reproductive
Ecology and Human Evolution. Hawthorne, NY: Aldine de Gruyter. pp.
O'Connor KA, Holman DJ and Wood JW
(1998) Declining fecundity and ovarian aging in natural fertility
populations. Maturitas. 30:127-136.
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