Comparative efficacy of modified antagonist protocols combining clomiphene citrate or letrozole for ovarian stimulation in patients with normal ovarian reserve.

BACKGROUND

To compare the efficacy of modified gonadotropin-releasing hormone (GnRH) antagonist protocols combining clomiphene citrate (CC) or letrozole (LE) versus a conventional antagonist protocol in patients with normal ovarian reserve, aiming to reduce gonadotropin (Gn) consumption and ovarian hyperstimulation syndrome (OHSS) risk.

METHODS

This retrospective cohort study included 565 in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Patients were divided into three groups based on the stimulation protocol: CC group (n = 217; CC 50 mg/day throughout stimulation), LE group (n = 148; LE 2.5 mg/day for 5 days), and Control group (n = 200; conventional antagonist protocol). The primary outcome was clinical pregnancy rate (CPR). Secondary outcomes included live birth rate, implantation rate, miscarriage rate, and laboratory parameters.

RESULTS

Baseline characteristics were similar among groups. Both CC and LE groups required significantly shorter Gn duration and lower total Gn dose than the control group (both P < 0.001). GnRH antagonist consumption was lowest in the LE group (P < 0.001). On the trigger day, estradiol (E2) levels were significantly lower in the LE group than in the CC and control groups (P < 0.001). Although the LE group was associated with a lower oocyte yield than the control group (P < 0.05), it had a significantly higher day-3 top-quality embryo rate (52.9% vs. 44.1%, P < 0.001). The CC group exhibited a higher cycle-specific top-quality embryo rate after blastocyst culture (55.7% vs. 45.9%, P < 0.001). In fresh transfer cycles, CPR was comparable between the LE and control groups (60.0% vs. 48.3%, P = 0.172). Live birth rates were comparable among the three groups in FET cycles (40.2%, 40.2%, and 45.2%, respectively; P = 0.709). In frozen-thawed embryo transfer (FET) cycles, no significant differences were observed in CPR, implantation rate, miscarriage rate, or live birth rate among the three groups.

CONCLUSIONS

Modified GnRH antagonist protocols with CC or LE were associated with reduced Gn and antagonist consumption and decrease oocyte yield but were associated with higher embryo quality metrics and achieve comparable clinical pregnancy outcomes in normal ovarian reserve patients. These protocols are associated with reduced medication costs to conventional stimulation.