Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age

Abstract

Importance: Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential.

Objective: To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age.

Design, setting, and participants: Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area.

Exposures: Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH.

Main outcomes and measures: The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result.

Results: A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001).

Conclusions and relevance: Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.

Figures

Figure 1

Study flow chart of participants in the cohort *Number screened and reasons and numbers for exclusions are not available

Figure 2

Adjusted Kaplan Meier Curves for time to pregnancy with 95% confidence intervals by AMH. Model adjusted for age, body mass index, race, current smoking status, history of prior pregnancy, and hormonal contraceptive use in the preceding year. The number of women at risk during each cycle of attempt are provided in supplemental table 1. The median (interquartile range) number of cycles each woman contributed was 4 cycles (2–6).

Figure 3

Adjusted Kaplan Meier Curves for time to pregnancy with 95% confidence intervals by early follicular phase serum FSH. Model adjusted for age, body mass index, race, current smoking status, history of prior pregnancy, and hormonal contraceptive use in the preceding year. The number of women at risk during each cycle of attempt are provided in supplemental table 1. The median (interquartile range) number of cycles each woman contributed was 4 cycles (2–6).

Figure 4

Adjusted Kaplan Meier Curves for time to pregnancy with 95% confidence intervals by early follicular phase, creatinine-corrected, urinary FSH. Model adjusted for age, body mass index, race, current smoking status, history of prior pregnancy, and hormonal contraceptive use in the preceding year. The number of women at risk during each cycle of attempt are provided in supplemental table 1. The median (interquartile range) number of cycles each woman contributed was 4 cycles (2–6).