Comparative study of two ovulation induction therapies and laparoscopic ovarian drilling on clinical outcomes in women with clomiphene citrate-resistant polycystic ovary syndrome

OBJECTIVE: Clomiphene citrate (CC) is the first-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS), yet a substantial proportion exhibit CC resistance. This study compares clinical outcomes following treatment with gonadotropins, letrozole, or unilateral laparoscopic ovarian drilling (LOD) in women with CC-resistant PCOS. METHODS: In this prospective, randomized clinical trial conducted at the infertility clinic of the Maternity Hospital from May 2021 to May 2024 (Clinical Trial No. NCT06486870), 183 middle-aged, anovulatory infertile women with CC-resistant PCOS, diagnosed using the Rotterdam criteria, were included. Participants were randomly assigned to one of three groups: letrozole (n=61), gonadotropins (n=61), or unilateral LOD (n=61). The primary outcome was the cumulative pregnancy rate over 6 months. Statistical analyses were performed using IBM SPSS Statistics ver. 24. RESULTS: Baseline demographics were comparable across groups. The gonadotropin-treated cohort achieved the highest cumulative pregnancy rate (41%), followed by letrozole (32.8%) and LOD (18%). Gonadotropin therapy also yielded the highest ovulation rate and the lowest incidence of oligo/amenorrhea. In contrast, LOD produced greater reductions in luteinizing hormone, anti-Müllerian hormone, and antral follicle count, and more patients attained menstrual regularity. Although LOD was associated with a lower pregnancy rate, it conferred a reduced risk of multiple gestations and ovarian hyperstimulation syndrome (OHSS). CONCLUSION: Gonadotropins and letrozole are more effective than unilateral LOD for inducing ovulation and achieving pregnancy in women with CC-resistant PCOS. Nevertheless, LOD remains a viable alternative, offering the advantage of lower rates of multiple pregnancy and OHSS.