ADVANCES IN IN-VIVO FERTILIZED AND MATURED HUMAN EMBRYOS AND CHARACTERIZATION BY PRE-IMPLANTATION GENETIC TESTING (PGT-A)

Abstract

Introduction Early work performed by Buster et al. (1985) demonstrated the recovery of embryos from the uteri using uterine lavage. The advancement in embryo cryopreservation, blastocyst culture and the development of comprehensive methods of PGT-A have refocused attention on uterine lavage as a possible nonsurgical minimally invasive approach for fertile individuals who desire PGT-A without utilization of in vitro fertilization (IVF). Materials and Methods Gonadotropin induced ovarian stimulation and insemination were performed followed by uterine lavage to recover the in vivo conceived embryos. Recovered embryos were characterized morphologically using the Gardner Scale, underwent trophectoderm (TE) biopsy, were then vitrified and stored in liquid nitrogen. Biopsies were analyzed using next-generation sequencing (NGS) technique. Results were compared with in vitro conceived embryos from other cycles of the same patients. Results Uterine lavage performed after insemination successfully recovered blastocysts providing a reliable and consistent means to capture in vivo conceived embryos. Results to date from this ongoing study (134 of 500 planned lavage cycles completed) show consistent improvement in successive cohorts with respect to the ability of the lavage system to recover embryos. Embryos of many stages were recovered in 42% (56/134) of the cycles, out of which, 71% (96/136) embryos were blastocyst stage embryos representing a most advanced stage of embryogenesis. The 63% of in vivo conceived embryos were euploid or low-mosaic ( A 73.7% (70/95, 1 blastocyst not graded) of recovered in vivo embryos were of good quality as determined by the Gardner Scale of Morphology compared to 178 of controls. Conclusions Although a nascent technology, studies indicate that Uterine Lavage may have the potential to provide a new tool to acquire genetic information on in vivo conceived embryos. The procedure has the potential to provide a low cost, minimally invasive, reproducible and effective way to acquire in-vivo conceived embryos. Uterine Lavage provides an alternative option to IVF for fertile couples who want to be proactive in the health of their future children. It offers a platform for genetic testing (PGT-A) prior to the establishment of pregnancy as well as the diagnosis and identification of genetic indications. From a research perspective, the study of in-vivo conceived embryos when compared to IVF-derived embryos may provide new scientific insights into embryo science by characterizing any difference between embryos conceived within and outside the uterus.