Embryo Transfer Strategies For Patients With Polycystic Ovary Syndrome

Research background and purpose:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that mainly manifests as abnormal levels of basal hormones,insulin resistance,obesity,ovulation dysfunction,infertility,etc.In recent years,with the development of ovulation induction and assisted reproductive technology,the pregnancy rate of PCOS patients has improved significantly,but the pregnancy outcome is still worse than that of non-PCOS patients.The endometrial receptivity and embryo quality are key factors affecting the success of embryo transfer.This study aims to explore the embryo transfer strategy for PCOS patients,and to investigate the application of endometrial receptivity testing and non-invasive embryo assessment in PCOS patients.The goal is to establish an effective individualized embryo transfer protocol,which can increase the clinical pregnancy rate and implantation rate of PCOS patients,reduce the biochemical pregnancy rate and early miscarriage rate,and improve the assisted pregnancy outcome.Materials and Methods:1.Traditional Embryo Transfer Strategy StudyA retrospective analysis was conducted on PCOS infertile patients who underwent controlled ovarian hyperstimulation with gonadotrophin releasing hormone antagonist(Gn RH-ant)protocol and IVF/ICSI(In vitro fertilization/Intracytoplasmic sperm injection)treatment at the Reproductive Medicine Center of Sichuan Provincial Maternal and Child Health Hospital from January 2017 to January 2022 as the study group(A1-A3): among them,58 patients who transferred cleavage-stage embryos in the first thawing cycle after complete embryo freezing(A1 group),66 patients who transferred cleavage-stage embryos in fresh cycles(A2 group),and 145 patients who transferred blastocysts in the first thawing cycle after complete embryo freezing(A3group);213 patients who underwent IVF/ICSI treatment for tubal factor infertility or male factor infertility at this center during the same period,using antagonist protocol for ovarian stimulation,complete embryo freezing and blastocyst transfer in the first thawing cycle were selected as the control group(B group).The patients’ general information,embryo transplantation status,and pregnancy outcomes were compared.SPSS 26.0 was used for statistical analysis.Quantitative data were expressed as mean± standard deviation(normal distribution)or median with interquartile range(non-normal distribution),and count data were expressed by rate(%).T-test or rank sum test was used for intra-group comparison,ANOVA test or rank sum test was used for inter-group comparison,and chi-square test was used for comparison of rates among groups,p<0.05 was considered statistically significant.2.Personal Embryo Transfer Strategy Based on Endometrial Receptivity and Non-invasive Embryo EvaluationThis part is a single-center,prospective,randomized controlled study.Patients with PCOS who underwent IVF/ICSI treatment at the Reproductive Medicine Center of Sichuan Provincial Maternal and Child Health Hospital from March 2022 to December2022 were selected as the study subjects.According to a completely random principle,they were divided by a random number table into study group 1(n=11): personalized embryo transfer(p ET)group guided by endometrial receptivity analysis(ERA)combined with non-invasive preimplantation potential assessment of embryo(EMBRACE);study group 2(n=12): embryo transfer group guided by EMBRACE alone;study group 3(n=17): control group,conventional morphological selection of embryos and conventional transfer time.All subjects voluntarily participated in this study and signed informed consent forms.The trial was registered in the Chinese Clinical Trial Registry with the number Chi CTR2100053824.The general information,superovulation and embryo transplantation status,and pregnancy outcomes of the three groups were compared.SPSS 26.0 was used for statistical analysis.Quantitative data were expressed as mean ± standard deviation(normal distribution)or median with interquartile range(non-normal distribution),and count data were expressed by rate(%).T-test or rank sum test was used for intra-group comparison,ANOVA test or rank sum test was used for inter-group comparison,and the chi-square test or Fisher exact probability method was used to compare rates among groups,p<0.05 was considered statistically significant.Result:1.Traditional Embryo Transfer Strategy Study1.1 Comparison of Frozen-Thawed and Fresh Transfer in PCOS Patients(Cleavage Stage Embryos)1.1.1 General Information: Patients in group A1 and group A2 were consistent in age,infertility duration,body mass index(BMI),antral follicle count(AFC),follicle stimulating hormone(FSH),estradiol(E2),progesterone(P),luteinizing hormone(LH),testosterone(T),prolactin(PRL),LH/FSH,and infertility type(p>0.05);AMH(anti-Miillerian hormone)in group A1 was higher than that in group A2(p<0.05);1.1.2 Embryo Transplantation Status: There was no statistical difference in the average number of transferred embryos between group A1 and group A2(p>0.05);The endometrial thickness on transfer day was lower in group A1 than in group A2(p<0.01);The average rate of transferring high-quality embryos in group A1 was significantly lower than that in group A2(p<0.05);1.1.3 Pregnancy Outcome: The biochemical pregnancy rate of group A1 was significantly lower than that of group A2(p<0.05);There were no significant differences between the two groups in pregnancy rate,embryo implantation rate,clinical pregnancy rate,ectopic pregnancy rate,early abortion rate,live birth rate,average birth weight and length of fetuses(p>0.05).1.2 Comparison of the First Frozen-Thawed Blastocyst Transfer cycle in PCOS Patients and the Control Group1.2.1 General Information: There was no significant difference in female age,E2,P,PRL between group A3 and group B(p>0.05).BMI,AFC,LH,T,AMH,LH/FSH of group A3 were significantly higher than those of group B(p<0.05).FSH of group A3 was lower than that of group B(p<0.05);1.2.2 Embryo Transplantation Status: There was no significant difference in the average number of transferred embryos between patients in group A3 and group B(p>0.05);The endometrial thickness on transfer day was lower in group A3 than in group B,and the average rate of transferring high-quality embryos was significantly higher than that in group B(p<0.01);1.2.3 Pregnancy Outcomes: There were no statistically significant differences between patients in group A3 and group B in pregnancy rate,embryo implantation rate,clinical pregnancy rate,ectopic pregnancy rate,biochemical pregnancy rate,early abortion rate,live birth rate,average birth weight and length(p>0.05).2.Personal Embryo Transfer Strategy Based on Endometrial Receptivity and Non-invasive Embryo Evaluation2.1 General information: The three groups of patients showed consistency in age,infertility duration,BMI,AFC,FSH,E2,P,LH,T,PRL,LH/FSH and infertility type.There was no statistically significant difference(p>0.05);2.2 Superovulation and Embryo Transplantation Status: The three groups of patients showed consistency in gonadotropin(Gonadotropin,Gn)dosage,Gn days,start Gn amount,HCG day hormone level,number of eggs obtained,normal fertilization rate,D3 high-quality embryo rate,balloon formation rate,high-quality balloon rate,transfer day endometrial thickness,average transfer high-quality balloon rate.There was no statistically significant difference(p>0.05);2.3 Pregnancy Outcomes: There was no statistically significant difference among the three groups and between-group pairwise comparisons in pregnancy rate,embryo implantation rate,clinical pregnancy rate,biochemical pregnancy rate(p>0.05),but the clinical pregnancy rate of the study group showed a trend higher than that of the control group,and the biochemical pregnancy rate showed a trend lower than that of the control group;2.4 Results of EMBRACE and ERA testing: A total of 27 patients in the study group(group 1 + group 2)underwent EMBRACE testing with a aneuploidy embryos rate of 48.75%.Among them,2 people did not undergo embryo transfer,and 2 people dropped out.A total of 11 patients in study group 1 underwent ERA testing at the same time,of which 7 were in receptive phase,4 were in pre-receptive phase,non-receptive phase ratio was 36.36%;all four patients adjusted their transfer time according to test results and became pregnant,of which three reached clinical pregnancy and one was biochemical pregnancy;After 12 cycles of embryo thawing and transfer based solely on EMBRACE test results in study group 2,a total of 9 cycles were pregnant,of which 7cycles reached clinical pregnancy and 2 cycles were biochemical pregnancy.No adverse medical events occurred during the follow-up period.Conclusion:1.The strategy of frozen-thawed embryo transfer can effectively reduce the biochemical pregnancy rate in PCOS patients.2.The decreased receptivity of the endometrium caused by abnormal endocrine metabolism in PCOS patients may be the reason for the poor pregnancy outcomes compared to non-PCOS patients.3.Personalized embryo transfer guided by ERA and/or EMBRACE testing may help lower the biochemical pregnancy rate of PCOS patients and improve their pregnancy outcome.4.Personalized embryo transfer guided by ERA in combination with EMBRACE testing may be the optimal personalized transfer strategy for PCOS patients in ART.