RECURRENT IMPLANTATION FAILURE – ROLE OF PGT AND ERA TO OPTIMIZE REPRODUCTIVE OUTCOMES?

Abstract

To assess the role of Pre-Implantation Genetic Testing for Aneuploidy (PGT-A) and Endometrial Receptivity Assay (ERA) in couples with Recurrent Implantation failure (RIF) to optimize reproductive outcomes. This is retrospective data of couples at our private fertility clinic during January 2014 to July 2019. Study population was divided into three groups; All women with history of RIF were only recruited or this study. Group A – Both PGT-A and ERA done (n=79) Group B – only PGT-A done, no ERA done – (n=54) Group C – No PGT-A / No ERA done (n=189) INCLUSION CRITERIA Women with at least two fresh/frozen embryos transfers with minimum 4 blastocysts transferred in total and never conceived were considered as RIF. Only women with one euploid embryo, who underwent frozen embryo transfers (FET) were recruited in this study in group A&B. Women of all age groups who had Blastocysts available for transfer were included in Group- C. Only self-gamete cycles were considered in this study. All the women with RIF underwent controlled ovarian stimulation and oocyte retrieval as per our clinic’s standard operating protocol (SOP). ICSI was the choice of insemination considering history of failed implantation, fertilized oocytes were cultured till blastocysts and freeze all policy was adopted. Blastocysts were biopsied and trophectoderm tissue was subjected to genetic testing through Next-Generation Sequencing (NGS). ERA was done as per our institutes SOP. The biopsy was done using a endometrial biopsy pipette supplied by the company at 120 hours (day 5) of the start of the progesterone supplementation. This procedure was repeated at 144 hours (day 6) also. This was done to cater for the reduction in the error that could occur due to the extrapolation of results in cases of pre-receptive samples. The samples that were collected were stored and transported in the prescribed method of the company. The same conditions were replicated in the (FET) transfer cycle. Group A women underwent elective Single Euploid Blastocyst transfer (eSET) in an artificial cycle as per the ERA timing. Group B underwent eSET of a Euploid Blastocyst in a FET cycle on 6th day post progesterone support, no ERA was done. Group C women underwent transfer with un-screened double Blastocyst Transfer (DET) in a FET cycle. Primary Outcome was Implantation Rate (IR). Mean of IR of all subjects were calculated: Group A - 53% Group B - 47% Group C - 42% Odds ratio and p value was calculated for IR between the groups and showed no statistical significance. Though Group A had the best implantation rates, there was no statistical significance with the other two groups. Role of PGT-A and ERA as an intervention to improve reproductive outcomes is still debatable and needs well designed RCTs to further infer. PGT-A and ERA for RIF couples do not seem to offer beneficial reproductive outcomes. Couples need to be counselled appropriately while offering treatment options for RIF.