Sequence variants in FSHR and CYP19A1 genes and the ovarian response to controlled ovarian stimulation.

OBJECTIVE:To examine whether sequence variants within the FSHR and CYP19A1 genes are related to the ovarian response to controlled ovarian stimulation (COS). DESIGN:Genetic association study using both single-gene and combined analyses of women with sequence variants undergoing in vitro fertilization treatment. SETTING:Academic research institute hospital. PATIENT(S):Seven hundred and five women undergoing ovarian stimulation with recombinant follicle-stimulating hormone (FSH). INTERVENTION(S):Peripheral blood extraction, DNA purification, and FSHR c.919G>A (rs6165, p.Thr307Ala) and CYP19A1 c.*19C>T (rs10046) sequence variants analyses. MAIN OUTCOME MEASURE(S):Single-gene statistical analysis and combined statistical analysis with the SPSS17.0 software; FSHR c.919G>A and CYP19A1 c.*19C>T sequence variant genotypes and clinical parameters related to the COS response as oocyte retrieval and hormone levels, doses of exogenous FSH. RESULT(S):Women with genotype Ala/Ala at FSHR position 307 had higher basal levels of FSH and were more likely to have a low ovarian response compared with other genotypes. Women with genotype TT at CYP19A1 yielded fewer oocytes after ovarian stimulation. The combined analysis of these two sequence variants revealed that these two single-nucleotide variants have a synergistic effect in conferring the risk of a low ovarian response. CONCLUSION(S):Our results support an association of sequence variants in the genes that participate in estrogen synthesis, notably the FSHR and CYP19A1 genes, with the outcome of COS.

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