Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women

Kissell KA; Danaher MR; Schisterman EF; Wactawski-Wende J; Ahrens KA; Schliep K; Perkins NJ; Sjaarda L; Weck J; Mumford SL

doi:10.1093/humrep/deu142

Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women

Kissell KA, Danaher MR, Schisterman EF, Wactawski-Wende J, Ahrens KA, Schliep K, Perkins NJ, Sjaarda L, Weck J, Mumford SL

Published August 2014 Human reproduction (Oxford, England), 29(8), 1764-1772

DOI 10.1093/humrep/deu142 PMID 24925522 PMC PMC4093994

RRM Academy Synopsis

AMH Levels Vary Across the Menstrual Cycle in Healthy Women

AMH rose and fell in a consistent pattern across the menstrual cycle, peaking in the mid-follicular phase, dipping near ovulation, and partly recovering afterward. A prospective study followed 259 healthy women through up to two menstrual cycles, drawing blood up to eight times per cycle.

Key Findings

AMH varied significantly across the cycle (P < 0.01), highest in the mid-follicular phase, lowest around ovulation, then higher again by late luteal (P < 0.01 and P = 0.01).
Of 509 total cycles from 259 women, 42 (8.3%) were cycles without ovulation, from 35 women: 28 with one such cycle and 7 with two.
After age adjustment, AMH was higher in cycles without ovulation than in ovulatory cycles overall, and lowest of all in women whose cycles were entirely ovulatory (P = 0.02).
25 of 259 women (9.65%) had at least one AMH reading low enough to flag low ovarian reserve: 18 (6.95%) stayed low throughout, 7 (2.7%) crossed that line only sometimes.
The average within-cycle swing in AMH differed by age group: women 20 or younger showed a larger average swing than women over 35 did (P < 0.01).

Interpretation

This cohort study, the BioCycle Study, followed 259 healthy, regularly cycling women ages 18 to 44, each tracked for one or two menstrual cycles with blood drawn up to eight times per cycle and visits timed using fertility monitors to match cycle phases. The pattern held across age groups and in cycles with and without ovulation. The authors note the shift, while statistically real, is not large enough on its own to change when AMH should be measured in clinical practice. The findings support further research into how cycle timing affects AMH-based fertility assessment.

RRM Context

Restorative reproductive medicine depends on knowing where a woman is in her cycle when a hormone test is done. Charting the cycle is how that point gets found in practice. This study found that AMH shifts across the menstrual cycle, even in healthy women.

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

Abstract

Study Question

Does serum anti-Müllerian hormone (AMH) vary significantly throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy premenopausal women?

Summary Answer

Serum AMH levels vary statistically significantly across the menstrual cycle in both ovulatory and sporadic anovulatory cycles of healthy eumenorrheic women.

What Is Known Already

Studies to date evaluating serum AMH levels throughout the menstrual cycle have conflicting results regarding intra-woman cyclicity. No previous studies have evaluated an association between AMH and sporadic anovulation.

Study Design, Size, Duration

We conducted a prospective cohort study of 259 regularly menstruating women recruited between 2005 and 2007.

Participants/Materials, Setting, Methods

Women aged 18-44 years were followed for one (n = 9) or two (n = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak progesterone concentration ≤5 ng/ml and no serum LH peak on the mid or late luteal visits. Serum AMH was measured at up to eight-time points throughout each cycle.

Main Results and the Role of Chance

Geometric mean AMH levels were observed to vary across the menstrual cycle (P < 0.01) with the highest levels observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid-follicular versus late luteal, P = 0.05). Patterns were similar across all age groups and during ovulatory and anovulatory cycles, with higher levels of AMH observed among women with one or more anovulatory cycles (P = 0.03).

Limitations, Reasons for Caution

Ovulatory status was not verified by direct visualization. AMH was analyzed using the original Generation II enzymatically amplified two-site immunoassay, which has been shown to be susceptible to assay interference. Thus, absolute levels should be interpreted with caution, however, patterns and associations remain consistent and any potential bias would be non-differential.

Wider Implications of the Findings

This study demonstrates a significant variation in serum AMH levels across the menstrual cycle regardless of ovulatory status. This variability, although statistically significant, is not large enough to warrant a change in current clinical practice to time AMH measurements to cycle day/phase.

Study Funding/Competing Interests

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001). The authors have no conflicts of interest to declare.

Topics

Menstrual Cycle › Cycle Biomarkers › Hormonal Markers · Reproductive Endocrinology › Ovarian Hormones › Progesterone · Diagnostics › Hormone Testing › Timing of Testing

Enrique F Schisterman, Neil J Perkins, Sunni L Mumford, Karen C Schliep, Lindsey A Sjaarda, Jean Wactawski-Wende

E Schisterman, N Perkins, S Mumford, K Schliep, L Sjaarda, J Wactawski-Wende

PMID 24925522 24925522 DOI 10.1093/humrep/deu142 10.1093/humrep/deu142 Kissell et al. 2014, Kissell 2014

Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women

AMH Levels Vary Across the Menstrual Cycle in Healthy Women

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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