Darryl Holman's Research
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. 2005; 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.
- 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 (2005) 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.