The Effect of Insemination Methods on Embryo Mosaicism in Preimplantation Genetic Testing for Aneuploidy (PGT-A) Cycles

Presented at: ASRM Scientific Congress, 2021

Authors: Jennifer Matucha, BS, Robert Colver, MD, Bradford Bopp, MD, Matthew Will, MD, Erica Anspach Will, MD, Glen Adaniya, PhD

Materials and Methods:  This exempt retrospective chart review was evaluated and approved by the Eastern Virginia Medical School Institutional Review Board. Cycle data were collected for 545 IVF cycles with PGT-A between July 2018 to October 2020 with one of the following methods of insemination: all ICSI (N = 369), all conventional insemination (IVF; N = 103), or a combination of both ICSI and IVF (COMBO; N = 73). A total of 2,672 embryos were biopsied from these cycles, and samples were sent to a single genetics facility for testing with next generation sequencing. Rates of euploid, aneuploid and mosaic embryos were compared between insemination methods by analyzing the aggregate data by two proportional z-tests. Secondary outcomes – including embryos fertilized, good day 3 development, total blastocyst development, mosaic embryo anomalies, clinical uterine gestation (CIG), and implantation rate – were analyzed by two proportional z-tests, and the Pearson chi-square test was used to compare outcomes for frozen embryo transfers (FET). Statistical analysis was performed using Intellectus Statistics software, and a p-value of less than 0.05 was defined as statistically significant, with a 95% confidence interval.

Results:  Rates of mosaicism were similar between ICSI and conventional insemination when examining total aggregate data (11% vs. 11%), COMBO cycles, intra-cohort comparison, oocyte age groups, and normal and oligospermic semen samples. A significant difference was only found between embryos from testicular cycles and oligospermic cycles (17% vs. 9%, p=0.019).  Occurrences of increased aneuploidy with ICSI, when compared to conventional insemination, were found from aggregate data (p=0.006), COMBO cycles (p<0.001), all IVF vs. IVF embryos from COMBO cycles (p=0.007), maternal age ≥38 (p=0.033), and in cycles with normal sperm concentration (p=0.001). However, FET outcomes, including pregnancy loss and implantation, did not differ between insemination methods. Within mosaic embryos, significantly higher percentages were seen of low-level compared to high-level (p=<0.001) and whole chromosome vs. segmental (p<0.001) mosaicism, but there were no differences found for the same comparisons by insemination type.

Conclusions:  Conventional insemination did not have a significant impact on levels of embryo mosaicism, and the only significant increase in mosaicism resulted from testicular samples.  Although more research is needed, this study did observe a significant increase in aneuploidy from ICSI-derived embryos, which may suggest the use of ICSI preferably for cycles with male infertility only.

Impact Statement: As the use of conventional insemination increases, and current research remains inconclusive regarding its impact on mosaicism, this study helped our clinic determine that conventional insemination does not lead to a higher incidence of mosaicism.