Effect of inter-cycle interval on oocyte production in humans in the presence of the weak androgen DHEA and follicle stimulating hormone: a case-control study.

David H Barad,Norbert Gleicher,Emanuela Lazzaroni,Vitaly A Kushnir,Ho-Joon Lee

doi:10.1186/1477-7827-12-68

Abstract

BackgroundIn various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages. To assess whether similar synergism may also exist in humans we investigated women on androgen (dehydroepiandrosterone, DHEA) supplementation with varying concomitant FSH exposure.MethodsIn a case controlled cohort study we determine if time interval between IVF cycles of IVF treatment with FSH had an effect on ovarian response to ovulation induction in women supplemented with DHEA. Among 85 women with known low functional ovarian reserve (LFOR), supplemented with DHEA, and undergoing at least 3 consecutive IVF cycles, 68 demonstrated short (<120 days) intervals between repeated cycles (Group 1) and were, therefore, considered to have consistent FSH exposure. In contrast 17 women (Group 2) demonstrated long (> = 120 days) intervals between repeated cycles and, therefore, were considered to demonstrate inconsistent FSH exposure. Trends in oocyte yields were compared between these groups, utilizing mixed model repeated measures ANOVA, adjusted for initial age and FSH dose.ResultsOnly women in Group I demonstrated a linear increase in oocyte yields across their three cycles of treatments (F = 7.92; df 1, 68.6; p = 0.017). Moreover, the analysis revealed a significant interaction between the two patient groups and cycle number for retrieved oocytes (F = 6.32, df = 2, 85.9, p = 0.003).ConclusionsThis study offers preliminary confirmatory evidence that repeated short interval exposure to androgens in combination with FSH improves human FOR. A higher level of evidence will require prospectively randomized studies.

Highlights

In various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages
Women selected for Group 2, were further matched for age and level of ovarian reserve, based on FSH and anti-Müllerian hormone (AMH) levels, and women with an intervening pregnancy between In vitro fertilization (IVF) cycles were excluded from analysis
FSH dose increased across the three cycles, in Group 1, there was no significant interaction between FSH dosage and cycles of treatment with respect to

Summary

Introduction

In various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages. Increasing androgen receptors appear on granulosa cells of human follicles from transitional to primary and secondary follicle stages [2]. Granulosa cell specific androgen receptor knockout (ARKO) mice have provided evidence of reduced follicle progression and increased follicle atresia compared to wild type mice at these early stages of follicle maturation [3]. It has been reported that in rodents at least one function of androgens at these early follicle stages is increasing the sensitivity of granulosa cells to follicle stimulating hormone (FSH) [4,5]. It appears that androgens and FSH at these early follicle stages act synergistically. Whether this applies to the human experience is, unknown

Objectives

Methods

Results

Discussion

Conclusion