The present randomized controlled study aims to investigate the effectiveness of a combined regimen of letrozole and gonadotropin with dose adjustments based on body mass index (BMI) compared to a conventional only gonadotropin regimen in intrauterine insemination (IUI) cycles for couples experiencing unexplained infertility. The study was conducted at a tertiary university hospital's Assisted Reproductive Technologies (ART) center from January 2023 to January 2024. Couples with unexplained infertility were enrolled based on comprehensive assessments, and randomization was performed based on national ID (odd or even). The Conventional Only Gonadotropin (COG) group received recombinant FSH based on body mass index (BMI), while the Combined Letrozole-Gonadotropin (CLG) group received letrozole followed by gonadotropin with dose adjustments based on BMI. Ovulation induction and IUI were performed according to standard protocols. Clinical outcomes, gonadotropin consumption, and pregnancy rates were compared between groups. Among 317 IUI cycles, 131 couples with unexplained infertility were randomized (CLG: 61, COG: 70). Demographic parameters were similar between groups. The CLG group had lower daily gonadotropin doses (67 ± 18 IU/D vs. 76 ± 11 IU/d, p=0.01) and total gonadotropin consumption (750 IU vs. 825 IU, p=0.01) with comparable ovulation and clinical pregnancy rates. The COG group exhibited higher multiple pregnancy rates, although not statistically significant (CLG vs. COG; 1/61 vs. 3/70, p=0.4). The study suggests that the combined letrozole and gonadotropin regimen with BMI-based dose adjustments in IUI cycles for unexplained infertility is associated with reduced gonadotropin consumption and potentially lower multiple pregnancy rates.

Inclusion Criteria:

• Couples with unexplained infertility
• Aged between 18-35

Exclusion Criteria:

• Male factor infertility
• Diminished ovarian reserve
• Patient refusion to participate

All data generated or analyzed during this study are included in this published article and are available from the corresponding author on reasonable request.

Patients were divided into two study arms based on the initial digits of their national IDs by ART nurses. Importantly, the IVF clinicians remained blinded to the patients' grouping throughout the study.