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Objective To investigate if polymorphisms of some genes involved in folliculogenesis predict ovarian response. Methods This prospective randomized study includes 124 egg donors genotyped for six SNPs ESR1 (rs2234693), AMHR2 (rs2002555), GDF-9 (rs10491279 and rs254286), AMH (rs10407022) and LHCBR (rs229327) genes and four STRs in ESR1 rs3138774), SHBG (rs6761), CYP19A1 (rs60271534) and AR genes (CAG repeats in exon 1). All donors followed standard ovarian stimulation protocol using a daily dose of 225 UI. The genotypes obtained were compared with the ovarian stimulation outcome. Results Regarding the number of retrieved oocytes, we found statistical differences for the ESR1 SNP and STR (19.3 ± 8.9 for TT vs 15.3 ± 6.2 for CC/CT, P = 0.027; 19.1 ± 8.3 for 17repeats, P = 0.020). Moreover, women carrying TT in the ESR1 at position c.-397T>C with ESR1 (TA)n=17 retrieved the highest number of oocytes (20.4 ± 9.3) (P = 0.001). Concerning AMHR2, we observed an association with the length of stimulation (9.1 ± 1.4 d for AA vs 9.7 ± 1.3 d for AG/GG, P = 0.021) and gonadotropin received (2050 ± 319 for AA vs 2188 ± 299 for AG/GG, P = 0.017). No significant differences were observed for the other polymorphisms (P > 0.05). Conclusion The polymorphisms in ESR1 and AMHR2 genes showed a clear association with the number of retrieved oocytes and the stimulation data, respectively. Our results suggest that polymorphisms in the genes for key reproductive hormones receptors could be used to predict the ovarian response and to personalize the stimulation prior the treatment.

Conflicting data have been reported on the comparative doses of recombinant follicle-stimulating hormone (rFSH) and urinary highly purified follicle-stimulating hormone (HP-FSH) required for ovarian stimulation. Nothing is known about the clinical efficacy of rFSH or HP-FSH depending on the N680S follicle-stimulating hormone receptor (FSHR) polymorphism. Our aim was to investigate whether the N680S polymorphism of the FSHR gene affects ovarian response with different forms of FSH.This retrospective cohort study includes 382 cycles performed at Instituto Bernabeu from 191 oocyte donors. All donors carried out two cycles: one with rFSH and the other one with HP-FSH (group 1, n=63), both with HP-FSH (group 2, n=100) or both with rFSH (group 3, n=28). The results were compared by pairs from each patient. The main outcomes were oocyte yield, metaphase II matured oocytes (MII), days of stimulation, and gonadotropin dosage.No significant differences were found when we compared the cycles for donors in group 1. However, according to the FSHR polymorphism, statistical differences were shown. For the SS genotype, more oocytes (16.9 vs. 18.4) and MII (12.8 vs. 15.5) were yielded in the HP-FSH cycle. For the NS genotype, more oocyte (20.1 vs. 16.9) and MII (17.4 vs. 14.2) were yielded in the rFSH cycle. For the NN genotype, no differences were found. No differences were found when we compared the cycles in groups 2 and 3 irrespective of the FSHR polymorphism.For the first time, we have shown in a population of egg donors that the N680S FSHR gene polymorphism affects the efficacy of HP-FSH or rFSH. The FSHR genotype is an important factor to determine the dosage and the nature of the gonadotropin selected for ovarian stimulation.