Abstract
Background/aimsReported associations of controlled ovarian hyperstimulation response (COH) with genotypes of the Ser680Asn (N680S) polymorphism in the follicle stimulating hormone receptor (FSHR) gene have conflicting results.MethodsPubMed and Embase databases were searched for studies that investigated the N680S polymorphism in the FSHR gene in COH. Parameters used to examine ovarian response were poor and hyper-responses to COH. Using the meta-analytic approach, we estimated ovarian response risk (odds ratio [OR] with 95% confidence intervals) according to genotype.ResultsOur findings showed that SS genotype carriers were most likely to be poor responders (OR 1.61, p = 0.08) compared to the NN and NS genotypes which showed no associations (OR 0.93-0.95, p = 0.75-0.78). Heterogeneity of these pooled ORs warranted examining its sources. We detected outlying studies in each of the three N680S genotypes. Omitting these outliers erased the heterogeneity of the recalculated pooled outcomes. It also materially altered the SS effects where carriers became slightly unlikely to be poor responders (OR 0.90, p = 0.52). The S allele carrier effect was modulated for poor responders (OR 1.24, p = 0.39) in the Non-Hispanic Caucasian (NHC) subgroup. The likelihood of the S allele carriers (OR 1.47, p = 0.02) and the unlikelihood of the N allele carriers (OR 0.64, p = 0.007) were significant in our hyper-response findings. Confined to NHC retained significance of the S allele effects (OR 1.57, p = 0.01) but not among the N allele carriers (OR 0.68, p = 0.18).ConclusionsIn summary, this is a meta-analytical confirmation of the FSHR SS genotype role in COH response. Hyper-responder analysis strengths lie on the non-heterogeneity and robustness of its results. Non-robustness and heterogeneity of the poor-responder results compose its limitations. Thus, poor response findings probably require caution as to the interpretation as a susceptibility marker for ovarian response.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-014-0122-2) contains supplementary material, which is available to authorized users.
Highlights
In vitro fertilization (IVF) is a multi-step process involving collection of oocyte-containing follicles after controlled ovarian hyperstimulation (COH) with rFSH
follicle-stimulating hormone (FSH) effects are mediated by FSH receptor (FSHR), a G-protein-coupled receptor expressed in granulosa cells [15] which mediates FSH signal transduction through adenylate cyclase activation and elevation of intracellular cAMP [16]
Inclusion criteria included: (1) case? control study design evaluating the association between FSHR polymorphisms and ovarian response, (2) sufficient genotype frequency data presented to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). (3) Control frequencies must be in Hardy-Weinberg Equilibrium (HWE)
Summary
In vitro fertilization (IVF) is a multi-step process involving collection of oocyte-containing follicles after controlled ovarian hyperstimulation (COH) with rFSH (recombinant Follicle-stimulation hormone). These are: age [6], hormonal status [7], cigarette smoking [8] and ovarian reserve [6,9] Apart from these proposed predictors, polymorphisms in various genes, such as estrogen receptor alpha (ESR1), cytochrome P450 19A (CYP19A) and follicle-stimulating hormone (FSH) have been investigated as markers to predict ovarian response [1,10,11,12,13]. This leads to an amino acid change at position 680 from serine (AGT) to asparagine (AAT) [18] These two SNPs are related to ovarian response and affect gene function by changing the e gene product properties and modifying response to FSH [19]. Clinical studies have demonstrated that the N680S polymorphism determines ovarian response to FSH stimulation in patients undergoing IVF treatment [11,22,23]
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