The GnRH Antagonist Protocol is Associated with a Higher Embryo Aneuploidy Rate Than the GnRH Agonist Long Protocol in Chinese Women

Background: Studies in oocytes have suggested increased aneuploidy rates after ovulation induction in mammals and humans. Conversely, some studies have shown that ovarian stimulation does not significantly increase the embryo aneuploidy rate in humans compared with an unstimulated cycle. In addition, the potential effect of the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol and GnRH agonist (GnRH-a) long protocol on embryo aneuploidy remains unknown.Methods: This is the retrospective cohort study from university-affiliated fertility center. In total, 578 early miscarriage patients who conceived through IVF/intracytoplasmic sperm injection (ICSI) after receiving the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol or the GnRH agonist (GnRH-a) long protocol were analyzed to compare the aneuploidy rates in early aborted tissues. In addition, a total of 466 preimplantation genetic testing for aneuploidy (PGT-A) cycles undergoing GnRH-ant protocol or GnRH-a long protocol were also analyzed to compare the aneuploidy rates in embryo.Results: For early miscarriage patients who conceived through IVF/ICSI, compared to the GnRH-a long protocol group, the GnRH-ant protocol group had a significantly higher rate of aneuploidy in early aborted tissues (48.70% vs. 64.52%), and increased aneuploidy was associated with a significantly higher incidence of trisomy 13, 18, and 21 (p<0.01). Regarding PGT-A cycles, compared to the GnRH-a long protocol group, the rate of embryo aneuploidy was also significantly higher in the GnRH-ant protocol group (48.01% vs. 58%). After stratification and multiple linear regression, the GnRH-ant regimen remained significantly associated with an increased risk of aneuploidy in early aborted tissues and embryos [OR (95% CI) 1.767 (1.174, 2.661), OR (95% CI) 1.465 (1.020, 2.102)]. Furthermore, the embryo aneuploidy rate in the GnRH-ant protocol group was significantly higher than that in the GnRH-a long protocol group but only in young and normal ovarian responders [OR (95% CI) 3.54 (1.48, 8.46)].Conclusions: The GnRH-ant protocol is associated with a higher aneuploidy rate in early aborted tissues and embryos than the GnRH-a long protocol in Chinese women. A multicenter, randomized controlled trial would be the optimal strategy to confirm these results.