Recombinant hCG versus Dual Triggering for final oocyte maturation in ICSI Cycles among Poor Responders with Endometriosis

Abstract This double-blind randomized clinical trial compared recombinant human chorionic gonadotropin (rhCG) alone versus dual triggering (gonadotropin-releasing hormone agonist plus rhCG) for final oocyte maturation in women with endometriosis and poor ovarian response (Bologna criteria) undergoing intracytoplasmic sperm injection. A total of 152 eligible women were randomized (1:1) to receive either rhCG (250 µg) plus placebo (n=76) or rhCG (250 µg) plus GnRH agonist (0.2 mg; n=76). Ultimately, 128 participants completed the protocol through embryo transfer (per-protocol cohort: n=65 rhCG, n=63 dual-trigger). The primary outcome was retrieved metaphase II (MII) oocytes; secondary outcomes included embryo quality and pregnancy rates. The dual-trigger group yielded significantly more MII oocytes (6.53±4.61 vs. 4.14±2.91; effect size [ES]=0.63, 95% CI: 0.30–0.95; p<0.001) and Grade A embryos (0.66±0.82 vs. 0.37±0.62; ES=0.39, 95% CI: 0.05–0.73; p=0.023). Per-protocol chemical (38.1% vs. 15.4%; relative risk of success [RR]=2.48, 95% CI: 1.29–4.75; p=0.004) and clinical pregnancy rates (38.1% vs. 10.8%; RR=3.54, 95% CI: 1.64–7.62; p<0.001) were significantly superior following dual triggering, with consistent findings in intention-to-treat analyses. Dual triggering significantly enhances oocyte maturity, embryo quality, and clinical pregnancy outcomes compared to rhCG monotherapy in poor responders with endometriosis; larger multicenter trials are warranted to corroborate these findings. Lay Summary Women with endometriosis often face difficulty becoming pregnant, mainly when their ovaries produce only a small number of eggs. In assisted fertility treatments, hormones are used to help eggs mature before they are collected. One common method uses a hormone called hCG, while another approach, known as dual triggering, combines hCG with an additional hormone to better mimic the body’s natural process. In this study, we compared these two methods in 152 women with endometriosis and poor ovarian response undergoing fertility treatment. We found that women who received the two-hormone method produced more fully mature eggs, more good-quality embryos, and had higher chances of pregnancy than those who received hCG alone. These findings suggest that using both hormones may offer a better chance of success for some women with endometriosis undergoing fertility treatment and could help doctors tailor treatment to individual patient needs.