Abstract
In COS (Controlled Ovarian Stimulation), individual response are highly variable. A number of studies have evaluated the ovarian response to FSH in women most often aged over 35 years and with high FSH level. But we see also a poor response to ovarian stimulation in young women (<32 years) with normal FSH levels.The aim of this study was to evaluate the relationship between FSHR and ESR1 gene polymorphism in this young women population. For 70 patients, the FSHR p.Ala307Thr (rs6165) and p.Ser680Asn (rs6166) single-nucleotide polymorphisms (SNPs), the ESR1 PvuII T/C (rs2234693) SNP, and the (TA)n microsatellite polymorphism were studied alone or in combination. We found that the frequency of the p.307[Ala;Ala] FHSR genotype was 3-fold higher in poor responders (PRs) to COS (Controlled Ovarian Stimulation) than in good responders (GRs).The frequency of ESR1 polymorphism was not correlated with the FSH response. In the combined analysis of FSHR and ESR, ESR1 polymorphism seems to improve the efficiency of prediction of the FSHR polymorphism. The more specifics genotypes were FSHR307[Ala;Ala]/ ESR1 (TA)[>16; 16; 16;>16] for GRs. Our study show the involvement of ESR1 and FSHR polymorphisms and the multi-genic spectrum of ovarian response to gonadotropin in women with normal gonadotropin levels. Moreover, the poor response to FSH linked to the 307GG genotype was not associated with an increase in plasma FSH.
Highlights
Stimulation of ovarian follicular development is crucial for successful in vitro fertilization (IVF)-embryo transfer therapy
The results of the present study show that the FSHR307 or FSHR680 polymorphisms were efficient markers in predicting poor ovarian response to follicle-stimulating hormone (FSH) stimulation in IVF in young population with normal FSH level
A meta-analysis [7] found that the FSHR p.680Ser allele was associated with higher circulating FSH, it does not seem to have any real impact on the number of oocytes produced
Summary
Stimulation of ovarian follicular development is crucial for successful in vitro fertilization (IVF)-embryo transfer therapy. Several ovarian stimulation protocols have been developed. The mainly responsible actor of follicular maturation is the follicle-stimulating hormone (FSH) [1]. Individual response to FSH stimulation are highly variable among women and is difficult to predict. The term POR refers to the ovarian response and, one FSH stimulated cycle is considered essential for the diagnosis of POR [2]. FSH exerts its stimulatory effect by binding to its receptor (FSHR). Several single-nucleotide polymorphisms (SNPs) in the FSHR and estrogen receptor alpha (ESR1) genes have been identified, but only a few of them are associated with ovarian response to FSH [6,7,8]
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