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

Anne Z Steiner; David Pritchard; Frank Z Stanczyk; James S Kesner; Juliana W Meadows; Amy H Herring; Donna D Baird

doi:10.1001/jama.2017.14588

Diagnostics Hormone Testing

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

Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, Baird DD

Published October 10, 2017 JAMA, 318(14), 1367-1376

DOI 10.1001/jama.2017.14588 PMID 29049585 PMC PMC5744252

RRM Academy Synopsis

Low AMH and high FSH were not linked to lower fertility in women 30-44

A prospective cohort of 750 women aged 30-44 with no history of infertility found that low antimüllerian hormone (AMH) was not associated with a lower chance of conceiving. High follicle-stimulating hormone (FSH) gave the same result. By 6 cycles, a predicted 65 out of 100 women with low AMH had conceived, versus 62 out of 100 with normal AMH.

Key Findings

After adjustment, predicted conception by 6 cycles was 65% (95% CI, 50%-75%) among 84 women with low AMH and 62% (95% CI, 57%-66%) among 579 women with normal AMH.
By 12 cycles, predicted conception was 84% (95% CI, 70%-91%) with low AMH and 75% (95% CI, 70%-79%) with normal AMH, a difference without statistical significance.
High serum FSH (83 women) versus normal (654): 63% (95% CI, 50%-73%) versus 62% (95% CI, 57%-66%) by 6 cycles, and 82% (95% CI, 70%-89%) versus 75% (95% CI, 70%-78%) by 12.
High urinary FSH (69 women) versus normal (660): 61% (95% CI, 46%-74%) versus 62% (95% CI, 58%-66%) by 6 cycles, and 70% (95% CI, 54%-80%) versus 76% (95% CI, 72%-80%) by 12.
Inhibin B levels, measured in 737 women, showed no association with the chance of conceiving in any one cycle (hazard ratio 0.999; 95% CI, 0.997-1.001, per 1-unit increase).

Interpretation

The study is a prospective time-to-pregnancy cohort of women recruited from the community in North Carolina. Participants had no history of infertility, lived with a male partner and had tried to conceive for 3 months or less. Of the women, 77% were white and 62% held a graduate degree. Conception meant a positive pregnancy test, and the models adjusted for age, body mass index, race, smoking and recent hormonal contraceptive use. The authors list the lack of ovulation assessment and of partner semen samples among the limitations.

RRM Context

Restorative Reproductive Medicine is cycle-charting-informed and looks for the causes of reduced fertility in both partners. AMH reflects how many follicles remain. Among women aged 30 to 44 with no history of infertility who had tried to conceive for 3 months or less, this cohort found no link between low values and the chance of conceiving. A cause-based evaluation draws on each woman's own ovulation pattern and her partner's health.

Our editorial summary of this paper, not the article's abstract.

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.

Topics

Diagnostics › Hormone Testing › Serum Panels · Reproductive Endocrinology › Ovarian Hormones › Estrogen · Fertility Awareness › Biomarkers › Urinary Hormone Monitoring

Anne Z Steiner, David Pritchard, Frank Z Stanczyk, James S Kesner, Juliana W Meadows, Amy H Herring, Donna D Baird

A Steiner, Dave Pritchard, D Pritchard, F Stanczyk, Jim Kesner, Jimmy Kesner, J Kesner, J Meadows, A Herring, D Baird

PMID 29049585 29049585 DOI 10.1001/jama.2017.14588 10.1001/jama.2017.14588 Steiner et al. 2017, Steiner 2017

Keywords

Biomarkers, Inhibin B, Inhibins, Anti-Mullerian Hormone, Follicle Stimulating Hormone