Which factors are correlated with embryo euploidy in PGT-A cycles? - A multivariate logistic regression analysis of 3054 embryos

Abstract

Introduction Aneuploidy is generally accepted as one of the main causes of IVF/ICSI treatment failures worldwide. For this reason, increasing number of clinics & infertility specialists seek and promote preimplantation genetic testing for aneuploidy (PGT-A) to improve the clinical outcome for indications advanced maternal age (AMA), repeated implantation failure (RIF), recurrent miscarriage (RM), severe male factor infertility. Once an euploid embryo is found, elective single euploid blastocyst transfer (eSEBT) has been shown to improve the overall clinical outcome by providing high implantation rates and lower multiple pregnancy rates. Although It is well known that aneuploidy is strongly correlated with maternal biologic age, the possibility of finding an euploid embryo in a given cycle remains largely unknown and association of aneuploidy with many patient or cycle-related parameters remain controversial. The aim of this study was to evaluate which patient, cycle or laboratory factors have an impact on aneuploidy rate in euploidy for blastocyst stage human embryos. Material & Methods This retrospective study compiled 1362 ICSI cycles of 1136 patients undergoing PGT-A with clinical indications recurrent implantation failure (RIF), recurrent miscarriage (RM) and advanced maternal age (AMA) between January 2016 and December 2018. Trophectoderm(TE) biopsy was performed and next generation sequencing (NGS) was used for comprehensive chromosomal screening (CCS). We checked the possible influence of patient characteristics, treatment history, ovarian stimulation variables, embryo scores and day on aneuploidy. To identify characteristics that may be associated with the euploidy rate multivariate logistic regression analysis was performed. Generalized estimating equations were used after we had taken into account the patient effect. Results The mean age of patients was 38.1±4.7 years. Of these 1136 patients 187(16,5%) have male factor, 256(22,5%) diminished ovarian reserve, 83(7,3%) PCOS, (9,4%) 131(11.5%) endometriosis, 89(7,8%) tubal factor, 277(24,3%) unexplained infertility, and 113(9,9%) male and female factor. Clinical indications of PGT-A these of 1136 patients were RIF in 552(48,5%), RM in 162(14,2%), AMA in 270(23,7%), RIF+AMA in 152(13,4%). Out of 3084 embryos that were biopsied at blastocyst stage, 3054 concluded with valid result (99.02%). After analysis of biopsied materials by NGS, 1327 (43.5%) were found to be euploid and 1727(56,5%) were aneuploid. Severe male factor infertility, duration of ovarian stimulation, total dose of gonadotropins used, number of oocytes retrieved, serum estradiol level on the day of hCG trigger, serum progesterone level on the day of trigger, trophectoderm and inner cell mass scores have been found to be the parameters which significantly affect euploidy in univariate analysis (p Conclusions Due to the limited number of embryos available for embryo biopsy, relative estimation of finding a euploid embryo, which is one of the most frustrating issue for both patients and clinicians, remains a challenge in PGT-A cycles. Our study and results shed light on the nature as well as the magnitude of the patient-, cycle- or laboratory-related parameters that can be used to predict the probability of euploidy before a PGT-A is planned.