Effect of follicle-stimulating hormone receptor Asn680Ser polymorphism on the outcomes of controlled ovarian hyperstimulation: an updated meta-analysis of 16 cohort studies

Tang, Huilin; Yan, Yingying; Wang, Tiansheng; Zhang, Ting; Shi, Weili; Fan, Rong; Yao, Yao; Zhai, Suodi

doi:10.1007/s10815-015-0600-5

Cited by 38 publications

(27 citation statements)

References 37 publications

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“…We additionally assessed the ovarian response to COS as well as the time and amount of gonadotrophins required to reach a mean follicle diameter of 18 mm in normal oocyte donors and infertile patients from the IVF group bearing different N680S FSHR variants. Despite the low number of oocyte donors with the GG genotype, we consistently detected an association of this genotype with a lower number of oocytes retrieved after gonadotrophin administration, thus confirming previous studies on the effect of the S680S phenotype on the ovarian sensitivity and response to exogenous FSH administration [ 6 , 7 , 15 – 17 , 44 – 46 ]. The lower number of oocytes retrieved in donors with the GG genotype was not apparent in the infertile women, finding that may be due to the age-dependent vanishing effect of the N680S polymorphism on the ovarian response to COS, as previously suggested [ 6 ].…”

Section: Discussionsupporting

confidence: 88%

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry

García-Jiménez¹,

Zariñán

Rodríguez-Valentín

et al. 2018

Reprod Biol Endocrinol

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BackgroundFSHR SNPs may influence the ovarian sensitivity to endogenous and exogenous FSH stimulation. Given the paucity of data on the FSHR c.919A > G, c.2039A > G and − 29G > A SNPs in Hispanic population, we here analyzed their frequency distribution in Mexican mestizo women.MethodsSamples from 224 Mexican mestizo women enrolled in an IVF program as well as a genotype database from 8182 Mexican mestizo subjects, were analyzed for FSHR SNPs at positions c.919, c.2039 and − 29G > A. Association between the genetic variants and reproductive outcomes was assessed.ResultsThe c.919 and c.2039 SNPs were in strong linkage disequilibrium and their corresponding genotype frequencies in the IVF group were: AA 46.8%, AG 44.2%, and GG 8.9%, and AA 41.9%, AG 48.2% and GG 9.8%, respectively. For the -29G > A SNP, genotype frequencies were 27% (GG), 50% (GA) and 23% (AA). In normal oocyte donors with the c.2039 GG genotype, the number of oocytes recovered after ovarian stimulation (COS) were significantly (p < 0.01) lower than in those bearing other genotypes in this or the -29G > A SNP. Analysis of the large scale database revealed that both allelic and genotype frequencies for the three SNPs were very similar to those detected in the IVF cohort (p ≥ 0.38) and that female carriers of the c.2039 G allele tended to present lower number of pregnancies than women bearing the AA genotype; this trend was stronger when women with more Native American ancestry was separately analyzed (OR = 2.0, C.I. 95% 1.03–3.90, p = 0.04). There were no differences or trends in the number of pregnancies among the different genotypes of the -29G > A SNP.ConclusionsThe frequency of the GG/GG combination genotype for the c.919 and c.2039 SNPs in Mexican hispanics is among the lowest reported. The GG genotype is associated with decreased number of oocytes recovered in response to COS as well as to lower pregnancy rates in Hispanic women from the general population. The absence of any effect of the -29AA genotype on the response to COS, indicates that there is no need to perform this particular genotype testing in Hispanic women with the purpose of providing an individually-tailored COS protocol.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0420-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry

García-Jiménez¹,

Zariñán

Rodríguez-Valentín

et al. 2018

Reprod Biol Endocrinol

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“…The quality of the included studies was assessed by 2 reviewers independently through a checklist derived from the Strengthening the Reporting of Genetic Association (STREGA) recommendations for reports on genetic association studies [16], which was widely employed in previous meta-analysis studies [17,18].…”

Section: Quality Assessment Of Included Studiesmentioning

confidence: 99%

The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis

et al. 2018

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Background The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study. Methods The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018. Results Fourteen related studies involving 1035 patients were finally included. Significant associations were found among 3 CYP2D6 phenotypes (NM, IM, and PM) and most pharmacokinetic parameters of venlafaxine. However, CYP2D6 phenotypes were not associated with Hamilton Depression Rating Scale response of venlafaxine. In addition, we also found no significant association between CYP2D6 phenotype and overall rate of adverse events. Conclusions CYP2D6 metabolizer status had significant influence on venlafaxine pharmacokinetics, but insufficient evidence demonstrated that CYP2D6 metabolizer status was associated with its therapeutic effects and overall rate of adverse events, which provided further evidence regarding the relationship between CYP2D6 metabolizer status and venlafaxine.

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“…FSHR overexpression may play a role in the early phase of EOC development [ 29 ]. However, the majority of studies are inconsistent and inconclusive results [ 8 , 15 , 30 ]. Our study showed the expression levels of FSHR mRNAs and proteins of FRBI-treated groups less than CG and FSH group.…”

Section: Discussionmentioning

confidence: 99%

“…The cAMP and IP3 further lead to the activation of the downstream cascade of protein kinases. FRBI is able to fully inhibit FSH-induced cAMP production, thereby inhibiting steroidogenesis [ 30 ]. Up to date, whether FRBI treatment of oocytes influences this signal transduction remains unknown [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway

et al. 2018

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The present study aimed to investigate FSHreceptor binding inhibitor (FRBI) effects on relative factors (K-Ras, c-Myc and Vascular endothelial growth factor (VEGF)) to ovarian cancer, and expression levels of FSH receptor (FSHR) mRNAs and proteins in the cumulus-oocyte complex (COCs), to determine changes of protein kinase A (PKA) in sheep granulosa cells, further to elucidate signaling pathway of FRBI action. COCs were cultured in vitro for 24h under supplementation of varying concentrations of FRBI (0, 10, 20, 30 and 40μg/mL) or FSH (10IU/mL). Concentrations of K-Ras, c-Myc, VEGF, cAMP and FSH were detected in IVM media fluids, respectively. The results showed that the concentrations of c-Myc, K-Ras and FSH of FRBI groups were gradually reduced with the increase of FRBI doses. VEGF level of the FRBI-4 group was significantly greater than control group (CG). Expression levels FSHR mRNA and protein and PKA of FRBI-3 and FRBI-4 groups were less than that of CG or FSH group (P<0.05 or P<0.01). Inositol trisphosphate (IP3) concentrations of FRBI-3 and FRBI-4 groups were less than FSH group (P<0.05). FRBI administration doses had significant negative correlations to levels or concentrations of K-Ras, c-Myc, VEGF, FSHR mRNA and protein and PKA protein. K-Ras had significant positive correlations with FSHR mRNA and protein and PKA protein. In conclusion, FRBI could promote the production of VEGF of sheep COCs. Higher doses of FRBI (30 and 40μg/mL) suppressed the production of c-Myc and K-Ras, and declined FSH concentrations in the IVM medium fluid, and decreased the expressions of FSHR at the gene and protein levels, additionally attenuated expression of PKA protein in the granulosa cells.

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Effect of follicle-stimulating hormone receptor Asn680Ser polymorphism on the outcomes of controlled ovarian hyperstimulation: an updated meta-analysis of 16 cohort studies

Abstract: FSHR Asn680Ser polymorphism might be a significant biomarker for predicting the number of retrieved oocytes and poor response, especially in Asian subjects. Other outcomes such as exogenous FSH dose, OHSS, and pregnancy rate were not influenced by FSHR Asn680Ser polymorphism.

Cited by 38 publications

References 37 publications

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry

The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis

FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway

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