Endocrinologia e Síndrome Metabólica
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ESR1 and FSHR Gene Polymorphisms Influence Ovarian Response to FSH in Poor Responder Women with Normal FSH Levels

Rod A, Jarzabek K, Wolczynski S, Benhaim A, Reznik Y, Denoual-Ziad C, Herlicoviez M and Mittre H

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;<17] for PRs, FSHR307[Thr;Thr]/ ESR1 (TA)[>16;<17] and FSHR307[Thr;Ala]/ ESR1 (TA)[>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.