Ovulation Induction in Unexplained Infertility: A Comparative Analysis of Letrozole, Clomiphene Citrate, and Gonadotropins

INTRODUCTION: To compare the effects of three different ovulation induction protocols (clomiphene citrate (CC), letrozole, and gonadotropin) on pregnancy outcomes in women diagnosed with unexplained infertility undergoing intrauterine insemination (IUI).
METHODS: This retrospective observational cohort study was conducted at the Infertility Unit, Department of Obstetrics and Gynecology, Etlik City Hospital, Ankara, Türkiye. A total of 156 women aged 18–42 years with unexplained infertility who underwent IUI between January 2022 and December 2024 were included. Patients received ovarian stimulation with CC, letrozole, or gonadotropins prior to IUI. Clinical pregnancy was confirmed by serum β-hCG and ultrasound. Independent predictors of pregnancy were evaluated using multivariate logistic regression analysis adjusted for age, FSH, AMH, and IUI protocol.
RESULTS: Pregnancy occurred in 21 patients (13.5%). The pregnancy group had significantly lower FSH levels compared to the non-pregnancy group (median 5.4 vs. 6.0 IU/L, p=0.046). Letrozole use was significantly higher among patients who conceived (76.2% vs. 44.4%, p=0.025). In multivariate analysis, letrozole remained an independent predictor of pregnancy (aOR: 3.589, 95% CI: 1.229–10.480, p=0.019), while higher FSH levels were negatively associated with pregnancy (aOR: 0.744, 95% CI: 0.557–0.996, p=0.047).
DISCUSSION AND CONCLUSION: In women with unexplained infertility, ovulation induction with letrozole prior to IUI is associated with higher pregnancy rates compared to other protocols. Considering its cost-effectiveness, lower risk of multiple pregnancies, and favorable endometrial effects, letrozole should be considered as a first-line treatment option in appropriate patients.

Keywords: Unexplained infertility, Ovulation induction, Letrozole, Clomiphene citrate, Gonadotropins, Intrauterine insemination