Serum anti-Mullerian hormone levels are negatively related to Follicular Output RaTe (FORT) in normo-cycling women undergoing controlled ovarian hyperstimulation

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V.K. Genro1,2,3,4, M. Grynberg1,2,3, J.B. Scheffer1,2,3, I. Roux1,2,3, R. Frydman1,2,3 and R. Fanchin1,2,3,*

1Service de Gynécologie-Obstétrique et Médecine de la Reproduction, AP-HP, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France

2Univ Paris-Sud, Clamart F-92140, France

3INSERM, U782, Clamart F-92140, France

4Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Porto Alegre, Brazil *Correspondence address. Tel: +33-1-45-37-40-53; Fax: +33-1-45-37-49-80; E-mail: renato.fanchin{at}abc.ap-hop-paris.frReceived August 25, 2010. Revision received November 9, 2010. Accepted November 24, 2010. BACKGROUND Since in rodents anti-Müllerian hormone (AMH) has been shown to inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a relationship exists between serum AMH levels and antral follicle responsiveness to exogenous FSH in normo-cycling women.

METHODS Serum AMH, estradiol (E2) and FSH levels were prospectively measured on cycle day 3 in patients undergoing controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and standardized FSH doses. In 162 patients, follicles were counted after pituitary suppression and before FSH administration (baseline; small antral follicles; 3–8 mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16–22 mm). Antral follicle responsiveness to FSH was estimated by the Follicular Output RaTe (FORT), determined by the ratio pre-ovulatory follicle count on dhCG × 100/small antral follicle count at baseline.

RESULTS Serum AMH levels were positively correlated with the number of small antral follicles at baseline (r = 0.59; P < 0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT was 47.5 ± 1.4% and failed to be influenced by the woman's age, BMI or basal E2 and FSH level. Conversely, multiple regression analysis showed that FORT was negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of duration of COH and total FSH dose.

CONCLUSIONS The percentage of follicles that effectively respond to FSH by reaching pre-ovulatory maturation is negatively and independently related to serum AMH levels. Although the mechanisms underlying this finding remain unclear, it is in keeping with the hypothesis that AMH inhibits follicle sensitivity to FSH.

© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (3): 671-677. doi: 10.1093/humrep/deq361 First published online: December 21, 2010

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PC6 levels in uterine lavage are closely associated with uterine receptivity and significantly lower in a subgroup of women with unexplained infertility

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Sophea Heng1, Natalie J. Hannan1, Luk J.F. Rombauts2, Lois A. Salamonsen1 and Guiying Nie1,*

1Prince Henry's Institute of Medical Research, PO Box 5152, 246 Clayton Rd, Clayton, VIC 3168, Australia

2Department of Obstetrics and Gynecology, Monash University, Clayton, VIC 3168, Australia *Correspondence address. Tel: +61-3-9594-4380; Fax: +61-3-9594-6125; E-mail: guiying.nie{at}princehenrys.orgReceived November 15, 2010. Revision received December 19, 2010. Accepted December 29, 2010. BACKGROUND Embryo implantation requires a healthy embryo and a receptive uterus. Uterine incompetence contributes significantly to implantation failure and infertility. To date, there are no reliable biochemical methods that can determine whether the uterus is receptive. Proprotein convertase 5/6 (PC6) is tightly regulated in the uterus and critical for receptivity and implantation; its secretory nature predicts PC6 to be secreted into the uterine cavity. The present study examines whether PC6 is detectable in uterine lavage and whether there is any correlation between secreted PC6 levels and uterine receptivity.

METHODS Western blotting determined the presence of PC6 protein in uterine lavage. A sensitive and high-throughput activity assay was established and validated. This assay was applied to 103 lavages collected from different phases of the menstrual cycle from women with proven fertility or unexplained infertility.

RESULTS Uterine lavage contained PC6 protein with levels paralleling enzymatic activity. PC6 levels were significantly higher in the receptive than in the non-receptive phase in fertile women, and the putative receptive phase levels in a subgroup of women with unexplained infertility were significantly lower than in the fertile counterparts.

CONCLUSIONS PC6 levels in uterine lavage are significantly elevated in the luteal phase of fertile women and markedly reduced in a subgroup of women with unexplained infertility. Uterine fluid is a valuable source of material to evaluate uterine function. Detection of PC6 in uterine fluid may lead to the development of a rapid and relatively non-surgical assessment of uterine receptivity.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 840-846. doi: 10.1093/humrep/der002 First published online: January 27, 2011

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