Association Between Polycystic Ovarian Syndrome And Embryo Chromosomal Abnormalities

Background:Polycystic ovarian syndrome(PCOS)is a common endocrine and metabolic disease in female and the most important cause of anovulatory infertility.It is characterized by ovulatory dysfunction,polycystic ovaries,hyperandrogenism accompanied by other endocrine metabolic disorders.Most women diagnosed with PCOS could get pregnancy after ovulation induction or in-vitro fertilization(IVF).However,some studies reported a higher early miscarriage rate in PCOS women compared with non-PCOS women.Some postulated that PCOS women may produce embryos with abnormal chromosomes so that inducing a higher miscarriage rate.Nevertheless,until now,few studies have investigated the embryonic aneuploid rate in PCOS women.Moreover,most of them were indirect evidence which was analyzed from chorionic villi tissue of miscarried conceptuses rather than embryos.Also,conclusions among these studies were disputable.Thus,embryo evidence was needed to better demonstrate the association between PCOS and embryo ploidy.Objective:To determine the association between PCOS and embryo ploidy.Also,to further evaluate the relationship between PCOS phenotypes and embryo ploidy.Methods:A secondary analysis of multi-center randomized controlled trial which was conducted from July 2017 to June 2018.The original intent was to identify whether preimplantation genetic test for aneuploidy(PGT-A)improves the live birth rate as compared with IVF.In this study,we enrolled all 190 PCOS patients based on Rotterdam Criteria(Patients had at least 2 of the following criteria and excluded other causes of hyperandrogenism and ovulation dysfunction:(1)oligo-anovulation(OA);(2)clinical and/or biochemical hyperandrogenism(HA);(3)polycystic ovarian morphology(PCOM)and 1:1 age-matched(±1 year)190 non-PCOS patients from PGT-A group.In sub-analysis,PCOS patients were divided into 4 groups according to phenotype(18):Phenotype A included OA+HA+PCOM;phenotype B included OA+HA;phenotype C included HA+PCOM;and phenotype D included OA+PCOM.Three embryos of the highest grade were chosen from every patient for trophectodenm biopsy and then analyzed by PGT-A using next-generation sequencing.Every embryo was numbered.A model combined generalized estimating equation(GEE)with binomial logistic regression was performed to identify the difference in embryo aneuploidy and mosaicism between PCOS and control groups,as well as different PCOS subgroups.Results:The rate of embryonic aneuploidy in PCOS group was comparable with control group[embryonic aneuploid rate PCOS group:14.0%vs control group:18.3%,adjusted OR(95%CI):0.78(0.54,1.12),P=0.19].Embryonic mosaic rate in PCOS group has non-significant difference with control group as well[embryonic mosaic rate 10.9%vs 10.1%,adjusted OR(95%CI):0.91(0.59,1.40),P=0.66].The rate of aneuploid and mosaic embryos were comparable between each of PCOS phenotype and control group,as well as within different PCOS phenotype groups,reespectively.There was still no significant difference of embryonic aneuploid and embryo mosaic rates within four phenotypes.Conclusions:The risk of aneuploid and mosaic embryos was not increased in PCOS women.Other maternal factors(e.g.endometrial dysfunction,luteal deficiency,chronic inflammation,immune imbalance,etc)may contribute to miscarriage in PCOS women.