Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation

Purpose This retrospective study was designed to analyze the FSHR gene variants in subjects with primary and secondary amenorrhea with hypergonadotropic hypogonadism. Materials and methods Eighty six women with primary or secondary amenorrhea and 100 normally cycling proven fertile women of Indian origin were retrospectively studied. These subjects were systematically screened for entire FSHR gene. Results The frequency distribution of polymorphism at −29 position of FSHR gene is altered in women with primary and secondary amenorrhea as compared to controls. AA genotype at −29 position of FSHR gene seems to be associated with increased serum FSH levels in the study subjects. We have identified a novel homozygous mutation C 1723 T (Ala 575 Val) in one woman with primary amenorrhea. Conclusions Our findings suggest that increased serum FSH levels in subjects with primary amenorrhea correlated to FSHR genotype at position −29. We identified a novel homozygous mutation C 1723 T (Ala 575 Val) in a woman with primary amenorrhea.

Section: Introductionmentioning

confidence: 94%

Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea

Achrekar

Modi

Meherji

et al. 2010

“…As the polymorphisms Thr307Ala and Asn680Ser are in linkage disequilibrium [3,18,19] the genotype of the FSHR 307 assays should in theory match the genotype of the FSHR 680 assays. Thus, the samples with limited samples material were analysed for minimum one of the two polymorphisms for each genotyping method, except for sample 22 in which all sample material was used for CADMA-based-and sequencing analysis.…”

Section: Analytical Sensitivity Of the Cadma-based Genotyping Assaysmentioning

confidence: 99%

“…Recently, a number of studies have shown that genetic polymorphisms of the gonadotropins and their receptors may affect the outcome of COS [2][3][4][5][6]. Especially the common polymorphisms of the FSH receptor (FSHR), rs6165 (c.919A > G, p. Thr307Ala, FSHR 307) and rs6166 (c.2039A>G, p. Asn680Ser, FSHR 680), has been shown to influence the sensitivity to exogenous FSH administration and the number of follicles recruited [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Especially the common polymorphisms of the FSH receptor (FSHR), rs6165 (c.919A > G, p. Thr307Ala, FSHR 307) and rs6166 (c.2039A>G, p. Asn680Ser, FSHR 680), has been shown to influence the sensitivity to exogenous FSH administration and the number of follicles recruited [2][3][4][5][6]. Despite some discordance in the literature [4,7,8], heterozygous and homozygous carriers of the Ser680 allele appear to require significantly higher amounts of FSH during COS in order to achieve successful stimulation, compared to the homozygous wildtype (Asn680) [4,6,[9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genotyping common FSHR polymorphisms based on competitive amplification of differentially melting amplicons (CADMA).

Borgbo

Kristensen

Lindgren

et al. 2014

Purpose To provide an improved platform for simple, reliable, and cost-effective genotyping. Background Modern fertility treatments are becoming increasingly individualized in an attempt to optimise the follicular response and reproductive outcome, following controlled ovarian stimulation. As the field of pharmacogenetics evolve, genetic biomarkers such as polymorphisms of the follicle stimulating hormone receptor (FSHR) may be included as a predictive tool for individualized fertility treatment. However, the currently available genotyping methods are expensive, time-consuming or have a limited analytical sensitivity. Here, we present a novel version of "competitive amplification of differentially melting amplicons" (CADMA), providing an improved platform for simple, reliable, and cost-effective genotyping. Methods Two CADMA based assays were designed for the two common polymorphisms of the FSHR gene: rs6165 (c.919A > G, p. Thr307Ala, FSHR 307) and rs6166 (c.2039A>G, p. Asn680Ser, FSHR 680). To evaluate the reliability of the new CADMA-based assays, the genotyping results were compared with two conventional PCR based genotyping methods; allele-specific PCR (AS-PCR) and Sanger sequencing. Results The genotype frequencies for both polymorphisms were 35 % (TT), 42 % (CT), and 23 % (CC), respectively. A 100 % accordance was observed between the CADMA-based genotyping results and sequencing results, whereas 5 discrepancies were observed between the AS-PCR results and the CADMA-based genotyping results. Comparing the CADMAbased assays to (AS-PCR) and Sanger sequencing, the CADMA based assays showed an improved analytical sensitivity and a wider applicability. Conclusions The new assays provide a reliable, fast and userfriendly genotyping method facilitating a wider implication in clinical practise.

“…In the majority of the studies, the presence of G/G was linked to a reduced sensitivity to exogenous FSH. This was demonstrated by a higher total dose of gonadotropins used during ovarian stimulation for IVF [5,6,9,11], a lower peak of estradiol levels on the day of hCG administration [6,19], a lower number of retrieved oocytes [11,15], and a higher incidence of the G/G variant in hypo-responder patients [20]. Furthermore, in a small study conducted with 37 patients, the A/A (Asn/Asn) variant was correlated to the severity of ovarian hyperstimulation syndrome (OHSS) [21].…”

Section: Introductionmentioning

confidence: 99%

The carriers of the A/G-G/G allelic combination of the c.2039 A>G and c.-29 G>A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles

Allegra

Marino

Raimondo

et al. 2016

Purpose The objective of this study was the elucidation of the possible role of the single-nucleotide polymorphisms (SNP) at position -29 and 2039 of the FSH receptor gene (FSHR) as independent predictive markers of ovarian response. Indeed, the tailoring of reproductive treatments is crucial for both maximizing the success of IVF patients and obtaining a reduction in hypo-or hyper-response rates. Methods This prospective, observational study analyzed the association of -29 and 2039 FSHR polymorphisms with the number of retrieved oocytes in 140 patients attending an IVF/ ICSI cycle for severe male factors (≤5,000,000 spermatozoa/ mL) or tubal factors at the ANDROS Day