Darryl Holman's Research

Darryl Holman's Research: Fecundability and Fetal 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. 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.

References cited

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.