Hum. Reprod. Advance Access published online on October 19, 2009
Human Reproduction, doi:10.1093/humrep/dep366
Comparison of inter- and intra-cycle variability of anti-Müllerian hormone and antral follicle counts
1 Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, PO Box 85500, Room F.05.126, 3508 GA Utrecht, The Netherlands 2 Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, VU University Medical Center (VUmc), PO Box 7057, 1007 MB Amsterdam, The Netherlands 3 Department of Obstetrics and Gynaecology, Sint Lucas Andreas Ziekenhuis, PO Box 9243, 1006 AE Amsterdam, The Netherlands 4 Department of Public Health, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands 5 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
6 Correspondence address. Tel: +31-88-755-3629; Fax: +31-88-755-5433; E-mail: j.vandisseldorp-2{at}umcutrecht.nl
BACKGROUND: The antral follicle count (AFC) and anti-Müllerian hormone (AMH) both represent age-related follicular decline quite accurately, although long-term follow-up studies are still lacking. The best ovarian reserve test would need only a single, cycle-independent measurement to be representative.
METHODS: To compare the inter- and intra-cycle stability of AFC and AMH, we used age-adjusted intra-class correlation coefficients (ICCs). To measure inter-cycle stability across a number of up to four menstrual cycles, we used data, prospectively collected for the purpose of an other study, from 77 regularly cycling, infertile women aged 24–40 years. AMH and AFC values were measured on cycle day 3. To study intra-cycle variability, we used data from a prospective cohort study of 44 regularly cycling volunteers, aged 25–46 years and measured AMH and assessed the AFC (2–10 mm) every 1–3 cycle days.
RESULTS: Between menstrual cycles, AFC and AMH varied between 0 and 25 follicles (median 10), and 0.3 and 27.1 ng/ml (median 4.64). The difference in age-adjusted ICC between AMH [ICC, 0.89 (95% CI, 0.84–0.94)] and AFC [ICC, 0.71 (95% CI, 0.63–0.77)] was 0.18 (95% CI, 0.12–0.27). For the intra-cycle variation, 0–43 antral follicles (median 7) were counted per volunteer. The difference in age-adjusted ICC between AMH [ICC, 0.87 (95% CI, 0.82–0.91)] and AFC [ICC, 0.69 (95% CI, 0.46–0.82)] was 0.18 (95% CI, 0.034–0.42).
CONCLUSIONS: Serum AMH demonstrated less individual intra- and inter-cycle variation than AFCs and may therefore be considered a more reliable and robust means of assessing ovarian reserve in subfertile women.
Key words: antral follicle count/anti-Müllerian hormone/Müllerian inhibiting substance/menstrual cycle variability/measurement reliability
Submitted on June 9, 2009; resubmitted on September 1, 2009; accepted on September 17, 2009.