☆ 4.4 Article

The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation

CLINICAL ENDOCRINOLOGY (2015)

Journal

CLINICAL ENDOCRINOLOGY

Volume 82, Issue 4, Pages 577-583

Publisher

WILEY

DOI: 10.1111/cen.12573

Keywords

Funding

National Natural Science Foundation of China [81170569, 81070490]
Shanghai Institute of Parenthood Planned Research [PD2012-3]

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Abstract

ObjectivePolymorphisms in the follicle-stimulating hormone receptor (FSHR) gene are reported to be associated with the ovarian response in controlled ovarian hyperstimulation (COH), although there remains some discordance between studies. Here, using the largest patient sample to date, we evaluated the association of the p.Ser680Asn ((SN)-N-680) polymorphism in the FSHR gene with the outcome of COH. DesignCohort study. SettingMedical academy and hospital. PatientsA total of 1250 infertile Chinese women undergoing IVF/ICIS-ET treatment were included. MeasuresThe association between an FSHR polymorphism ((SN)-N-680) and the ovarian response was analysed. Genotyping was performed by utilizing direct sequencing and the Sequenom MassARRAY iPLEX platform. Follicular fluid oestradiol (E-2) and follicle-stimulating hormone (FSH) concentrations were determined using electrochemiluminesence immunoassays. The ovarian response parameters were analysed based on the FSHR genotypes. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotypes and alleles. ResultsThere were linear correlations between the basal FSH level, exogenous gonadotropin consumption, and oocytes retrieved and the Ser680 alleles. Patients in the homozygous SS group demonstrated higher basal FSH levels, required more dosage of exogenous gonadotropin for ovarian stimulation, and had fewer numbers of oocytes retrieved compared with patients in the homozygous NN and heterozygous groups. Logistic regression analysis revealed that the OR of a poor ovarian response for the NS genotype was 179 (95% CI 128-261; P<0001), whereas that for the SS genotype was 225 (95% CI 140-358; P<0001) after adjusting for age, BMI and basal FSH level. The concentration of E-2 in the follicular fluid was significantly higher in subjects with the NN genotype than the SS genotype (772545ng/ml vs. 1299 +/- 504ng/ml). ConclusionsFollicle-stimulating hormone receptor gene polymorphism at position 680 is associated with different ovarian responses to controlled ovarian hyperstimulation.

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A Novel Mutation in the FSH Receptor (I423T) Affecting Receptor Activation and Leading to Primary Ovarian Failure

Teresa Zarinan, Julio Mayorga, Eduardo Jardon-Valadez, Ruben Gutierrez-Sagal, Jose Luis Maravillas-Montero, Nancy R. Mejia-Dominguez, Ivan Martinez-Luis, Omar G. Yacini-Torres, Ma del-Carmen Cravioto, Eric Reiter, Alfredo Ulloa-Aguirre

Summary: A novel missense mutation (I423T) in the FSHR second transmembrane domain was identified in a woman with primary ovarian failure, leading to impaired receptor expression and signaling. Meanwhile, the D408Y mutation severely affected membrane expression and signal transduction. Molecular dynamics simulations showed important disruptions in both mutant FSHRs, explaining the differences in expression levels, signaling, and phenotypic expression between I423T and D408Y mutant FSHRs.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)