RESUMO
OBJECTIVE: To study the association between AMH and time to pregnancy. While it has been hypothesized that serum anti-Müllerian hormone (AMH) levels may indicate the chance of conception, findings have been mixed. Given that any association is expected to be modest, and it is possible that previous studies have been underpowered, we investigated this relationship in the largest prospective cohort to date. DESIGN: Prospective time-to-pregnancy cohort study. SUBJECTS: 3,150 US women who had been trying to conceive for less than 3 months and had purchased a Modern Fertility Hormone Test. EXPOSURE: We developed a discrete time-to-event model utilizing a binomial complementary log-log error structure within a generalized additive modeling framework, adjusting for confounding factors such as age, BMI, parity, smoking status, PCOS, and others. Sensitivity analyses were performed in women with regular menstrual cycles (21-35 days), who did not report using fertility treatments, using alternate AMH categories (<0.7, 0.7-8.5, >8.5 ng/mL), and AMH as a continuous measure. MAIN OUTCOME MEASURES: Primary outcomes included cumulative conception probability within 12 cycles and relative fecundability per menstrual cycle. Conception was defined by a self-reported positive pregnancy test. RESULTS: Participants contributed 7.21 ± 5.32 cycles, with 1,325 (42.1%) achieving a pregnancy. Women with low AMH (<1ng/mL, n=427) had a lower chance of natural conception (Adjusted Hazard Ratio (adjHR 0.77, 95%CI 0.64, 0.94, p=0.009) compared to women with a normal AMH (1 - 5.5ng/mL). There was no difference between high (5.5+ ng/ml) and normal AMH categories (adjHR 1.11, 95% CI 0.94, 1.31, p=0.2). The inclusion of AMH improved the model (net reclassification index 0.10 [ 0.06 - 0.14); P<0.001). The instantaneous probability of conception was highest in cycle 4 across all AMH categories: the probability of natural conception was 11.2% (95% CI 9.0, 14.0) for low AMH, 14.3% (95% CI 12.3, 16.5) for normal AMH, and 15.7% (95%CI 12.9, 19.0) for high AMH. In the regular cycles sensitivity analysis (n=1,791), the low AMH group had a lower chance of conception (adjHR 0.77 95% CI 0.61, 0.97, p = 0.028) in the low AMH group compared to normal AMH, and similarly in the continuous model (adjHR 0.90; 95% CI 0.85-0.95, p<0.0001). CONCLUSION: Low AMH levels (<1 ng/ml) are independently associated with a modest but significant reduction in the chance of conception.
RESUMO
OBJECTIVE: To determine how the contraceptive-specific serum antimüllerian hormone (AMH) levels compare across ages and percentiles in a reproductive-age cohort. DESIGN: Cross-sectional analysis of a prospectively recruited cohort. SETTING: Community. PATIENT(S): This study included US-based women of reproductive age who purchased a fertility hormone test and consented to participate in research between May 2018 and November 2021. At the time of hormone testing, participants were users of various contraceptives (combined oral contraceptive [n = 6,850], progestin-only pill [n = 465], hormonal [n = 4,867] or copper [n = 1,268] intrauterine device, implant [n = 834], vaginal ring [n = 886]) or women with regular menstrual cycles (n = 27,514). INTERVENTION(S): Contraceptive use. MAIN OUTCOME MEASURE(S): Age and contraceptive-specific estimates of AMH. RESULT(S): There were contraceptive-specific effects on AMH with effect estimates ranging from 0.83 (95% confidence interval [CI], 0.82-0.85) (17% lower) for the combined oral contraceptive pill to no effect (1.00; 95% CI, 0.98-1.03) for the hormonal intrauterine device. We did not observe age-specific differences in suppression. However, there were differential suppressive effects of the contraceptive method across AMH percentiles, with the greatest effect at lower percentiles and least effect at higher percentiles. For example, for women taking the combined oral contraceptive pill, the AMH level was 32% lower at the 10th percentile (coefficient, 0.68; 95% CI, 0.65-0.71), 19% lower at the 50th percentile (coefficient, 0.81; 95% CI, 0.79-0.84), and 5% lower at the 90th percentile (coefficient, 0.95; 95% CI, 0.92-0.98), with other forms of contraception showing similar discordances. CONCLUSION(S): These findings reinforce the body of literature that shows that hormonal contraceptives have different impacts on the AMH levels at a population level. These results add to this literature that these effects are not consistent; instead, the greatest impact occurs at the lower AMH percentiles. However, these contraceptive-dependent differences are small compared with the known biological variability in ovarian reserve at any given age. These reference values enable robust assessment of an individual's ovarian reserve relative to their peers without requiring cessation or potentially invasive removal of contraception.
