The effect of ovarian stimulation on aneuploidy of early aborted tissues and preimplantation blastocysts: comparison of the GnRH agonist long protocol with the GnRH antagonist protocol

Purpose To compare aneuploidy rates in early aborted tissues or blastocysts between in vitro fertilization (IVF) cycles after the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol or the GnRH agonist (GnRH-a) long protocol. Methods This was a retrospective cohort study from a university-affiliated fertility center. In total, 550 early miscarriage patients who conceived through IVF/intracytoplasmic sperm injection (ICSI) after receiving the GnRH-ant or GnRH-a long protocol were analyzed to compare aneuploidy rates in early aborted tissues. To compare aneuploidy rates in blastocysts, 404 preimplantation genetic testing for aneuploidy (PGT-A) cycles with the GnRH-ant protocol or GnRH-a long protocol were also analyzed. 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 (48.51% vs. 64.19%). Regarding PGT-A cycles, the rate of blastocyst aneuploidy was significantly higher in the GnRH-ant protocol group than the GnRH-a long protocol group (39.69% vs. 52.27%). After stratification and multiple linear regression, the GnRH-ant regimen remained significantly associated with an increased risk of aneuploidy in early aborted tissues and blastocysts [OR (95% CI) 1.81 (1.21, 2.71), OR (95% CI) 1.65 (1.13, 2.42)]. Furthermore, the blastocyst aneuploidy rate in the GnRH-ant protocol group was significantly higher but only in young and normal ovarian responders [OR (95% CI) 5.07 (1.99, 12.92)]. Conclusion Compared to the GnRH-a long protocol, the GnRH-ant protocol is associated with a higher aneuploidy rate in early aborted tissues and blastocysts. These results should be confirmed in a multicenter, randomized controlled trial.