Pharmacogeneitcs Study Of Asn680Ser And-29A>G Of FSHR Gnen In Controlled Ovary Hyper-Stimulation

BackgroundThe various and unpredictable outcome of controlled ovarian hyperstimulation (COH), which is a critical step of Assisted Reproductive Technology(ART) has been puzzled clinicians for years. Several single-nucleotide polymorphisms (SNP) in the follicle-stimulation hormone receptor (FSHR) gene have been reported to have pharmacogenetic potential to predict the outcome of COH. According to several previous studies, two SNPs, namely Asn680Ser and -29A/G are most potential polymorphisms that may have pharmacogenetic value. Previous studies on Asn680Ser have got to inconsistent conclusion. On the other hand, there are just a few studies on-29A/G, and are of small sample sizes. The associations of these two SNP with the ovarian are still unclear.MethodsThe present study evaluated the association of genotype ofAsn680Ser and-29A/G, with ovary response separately and in combination.416 Chinese women undergoing IVF-ET (in vitro fertilization and embryo transfer) were included in this study. The admission criteria also include:first cycle of ovarian stimulation, normal menstrual cycle; basal FSH level below 12 mIU/ml; BMI range from 15 to 38kg/m2; Normal karyotype and Age range from 20 to 40. Women who have History of ovary ovarian surgery, other diseases that affect fertility (PCOS, endometriosis), Abnormal AFC such as PCO or poor ovary reserve were excluded. The endocrine parameters, ovarian stimulation progress and outcome of each participant are recorded. The genotypes of the mentioned SNPs were identified by High-resolution melting-curve (HRM). The value of exogenous follicle stimulatinghormone (FSH) dosage per oocyte divided by body surface area(Dosage/Oocyte X Surface) were calculated for each patient as an indicator of ovarian response.ResultsThe result of statistic analysis showed no association between genotype of Asn680Ser and ovary response as well as clinical parameters. When it comes to-29A/G, the heterozygotes had higher number of oocyte retrieved (p=0.034) and were more likely to be good responders. Combination analysis shows that women with genotype A/G-Asn/Asn appears to have lower basal-FSH and have more oocytes retrieved. Analysis of association of genotype with ovarian response only revealed that A/G-Asn/Asn has a significant higher risk of developing hyper respond (OR=7.86;95%CI1.31-9.43).ConclusionThe present study demonstrated that the combination of the rs6166 (Asn680Ser) and rs1394205 (-29G>A) genotypes has an association with the ovary response. However, the prediction of COH outcome based on the genotype of Asn680Ser and-29A/G lacks sensitivity and specificity. As COH is a complicated process, the inclusions of other genes and pharmacogenomics studies are also needed to elucidate the pharmcogenetic mechanism in depths. In the meantime, other parameters such as age and AMH should also be taken into consideration in clinical practice.