Association of Thr307Ala and Asn680Ser of Follicle-Stimulating Hormone Receptor Gene Polymorphisms with Gonadotropin Administration during Controlled Ovarian Hyperstimulation

Objective:This study is to investigate the effect of different single-nucleotide polymorphisms of follicle-stimulating hormone receptor(FSHR)gene on gonadotropin(Gn)administration dosage during controlled ovarian hyperstimulation(COH)protocol of in vitro fertilization and embryo transfer.Methods:This retrospective study included 184 Chinese infertile women in Center for Reproduction and Genetics of Suzhou Municipal Hospital from June 2012 to 2014.All of the enrolled patients were homogeneous in some basal characteristics,and they all met the eligibility criteria.Blood tests were conducted on day 3 of menstrual cycle or the day of human chorionic gonadotropin administration for hormonal profile analysis and DNA extraction.DNA sequencing was performed for polymorphism analysis.The participants were classified into threonine(Thr)/Thr,Thr/alanine(Ala),and Ala/Ala groups according to genotype at position 307,and asparagine/asparagine(Asn/Asn),Asn/serine(Ser),and Ser/Ser groups according to genotype at position 680.Logistic regression and correlation analyses were performed to identify the effect of these two polymorphisms on Gn consumption.Results:The frequency of Thr307Ala and Asn680Ser distribution was consistent with Hardy-Weinberg equilibrium(P>0.05).No significant difference was found in age,basal hormone levels for different genotype groups.Logistic regression analysis results revealed that patients with Ser680Ser genotype have a higher risk of requiring a high dose of Gn compared with patients with Asn680Asn genotype,while polymorphism of Thr307 Ala has no such effect.Conclusion:This study suggested that FSHR genotype Asn680Ser would be helpful in determining the dosage of Gn in COH;patients with Ser680Ser genotype may require higher dose of Gn.

Pharmacogenetic study of Asn680Ser and-29A>G in FSHR gene in Chinese women undergoing controlled ovarian hyperstimulation

The outcome of controlled ovarian hyperstimulation(COH)is various and unpredictable.According to previous studies,2 single nucleotide polymorphisms,Asn680Ser and-29A/G,have a pharmacogenetic association with ovarian response to COH.However,studies on the Asn680Ser polymorphism have yielded inconsistent conclusions and only a few studies with small sample sizes have been performed on-29A/G.The association of these 2 polymorphisms with ovarian response remains unclear.The present study evaluated the association of Asn680Ser and-29A/G genotypes with COH.A total of 414 Chinese women undergoing in vitro fertilization-embryo transfer were included.Genotypes for these single nucleotide polymorphisms were identified by high-resolution melting-curve analysis.The value of exogenous follicle-stimulating hormone dosage per oocyte divided by the body surface area(Dosage/Oocyte
Surface)was calculated for each patient as an indicator of ovarian response.The results of statistical analyses showed no association between Asn680Ser genotype and ovarian response.As for-29A/G,heterozygote individuals had more oocytes retrieved(P=0.034).Combinatorial analysis of these 2 single nucleotide polymorphisms showed that genotype A/G-Asn/Asn had lower basal-follicle-stimulating hormone and more oocytes retrieved.Analysis of genotype association with ovarian response also revealed this genotype had a significantly higher risk of developing hyper response(OR=7.86;95%CI:1.31-9.43).To some extent,there were associations between the studied polymorphisms and ovarian response;however,the power of this link is weak and has limited value for clinical prediction.

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China

Background:More and more scholars have called for the cumulative live birth rate(CLBR)of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology.This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.Methods:Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI)cycles performed between January 2013 to December 2014.A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included.The study was followed up for 4 years to observe the CLBR.The multivariable logistic regression model was used to analyze the prognosis factor,P value of<0.05 was considered statistically significant.Results:The cumulative pregnancy rate was 58.14%(10,452/17,978),and the CLBR was 49.66%(8928/17,978).The female age was younger in the live birth group when compared with the non-live birth group(30.81±4.05 vs.33.09±5.13,P<0.001).The average duration of infertility was shorter than the non-live birth cohort(4.22±3.11 vs.5.06±4.08,P<0.001).The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group(both P<0.001).Meanwhile,the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group(15.35±7.98 vs.11.35±7.60,P<0.001;6.66±5.19 vs.3.62±3.51,P<0.001,respectively).Conclusions:The women's age,body mass index,duration of infertility years,infertility factors,controlled ovarian hyperstimulation protocol,the number of acquired oocytes,and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.

Effects of Transcutaneous Electrical Acupoint Stimulation on Ovarian Responses and Pregnancy Outcomes in Patients Undergoing IVF-ET:A Randomized Controlled Trial

Objective:To evaluate the influence of different transcutaneous electrical acupoint stimulation(TEAS)modes on ovarian responses and pregnancy outcomes in patients with infertility undergoing in vitro fertilization and embryo transfer(IVF-ET).Methods:Two hundred infertility patients undergoing IVF-ET were divided randomly into experimental groups(TEAS groups:E-Ⅰ,E-Ⅱ,E-Ⅲ,and E-Ⅳ,40 cases each group)and a control group(mock TEAS group,40 patients)using the random number method.The patients in the experimental groups received TEAS treatment of 20,30,40 and 50 m A for the E-Ⅰ,E-Ⅱ,E-Ⅲand E-Ⅳgroups,respectively.The control group received a treatment of 5 m A.TEAS was applied at acupoints of Guanyuan(RN 4),Zhongji(RN 3),Sanyinjiao(SP 6),Zigong(EX-CA 1),and Taixi(KI 13),once a day for 30 min each time for a treatment period of 10-13 d.Treatment effect was assessed using the following indicators:endometrial thickness on the 6 th day of gonadotropin treatment(GN6 day),endometrial thickness on the day on chorionic gonadotropin administration(HCG day),number of ovarian follicles on HCG day,number of ova captured,amount of estrogen required for each harvested ova,number of mature ova divided by the total number of ova,percentage of high-quality embryos,and clinical pregnancy.Results:Endometrial thickness in the experimental groups on the HCG day was significantly better than that of the control group after TEAS stimulation(P=0.01).TEAS exhibited a greater impact on the number of ova captured(P=0.003).However,the effect of TEAS stimulation on the high-quality embryo rate and clinical pregnancy in patients was not statistically significant(P>0.05).Conclusions:TEAS is an effective method in improving the ovarian state.When the stimulus intensity was at 40 m A and above,it could be helpful to improve the patient’s endometrial condition and endometrial receptivity and to retrieve more oocytes.(Trial registration No.Chi CTR-TRC-11001780)