Discussion
Abdominal bloating, congenital anomalies, PCOS, infertility, ovulatory dysfunction
ADVERSE EFFECTS, MINOR, ANOVULATORY, SIDE EFFECT
This study aimed to compare the efficacy of a combination of CC and letrozole versus CC alone for ovulation induction in infertile women with ovulatory dysfunction. A previous study reported that women with PCOS had a significantly higher ovulation rate with combination therapy than with letrozole alone [From a theoretical standpoint, the local action of letrozole and the central influence of CC were anticipated to synergistically enhance ovulation induction. However, our study found comparable ovulation rates for the combination and CC-alone groups. Furthermore, the dose of CC was identical in both groups of our study, and a previous study reported a higher ovulation rate in a combination group than in a letrozole-alone group [Numerous studies have investigated the individual effects of letrozole and CC on the ovulation rate; however, studies examining the combined effect of these medications are limited. A study by Hajishafiha et al. investigated the combination of letrozole and CC in PCOS patients and reported a follicle development rate of 82.9% in the combination group. However, that study included patients who were refractory to CC or letrozole, and ovulation confirmation using follicle size alone (as was done by Hajishafiha et al.) is not always reliable [Previous meta-analyses have reported significant heterogeneity among randomized controlled trials investigating the ovulation rates achieved with letrozole and CC in the PCOS population, although letrozole significantly increased the ovulation rate compared to CC [The side effects of the 2 groups in our study were comparable, and all adverse effects from medication were minor and tolerable. Abdominal bloating was the most common side effect reported in both groups. We also found no evidence of congenital anomalies in the live births from either group. Taken together, these results indicate that both treatment regimens were safe and well tolerated.The observations made in this study represent a significant contribution to the literature. Notably, our study is the first to compare the efficacy of ovulation induction achieved with the combination of CC and letrozole versus CC alone in anovulatory women. Our study’s randomized controlled trial design minimized confounding factors and neutralized baseline characteristics between groups. Additionally, mid-luteal serum progesterone clearly defined the primary outcome, which was unaffected by operator and participant biases. To minimize interobserver variation, a single operator blinded to the study medications performed all transvaginal ultrasonographic investigations.Several limitations should be acknowledged in this study. First, the low pregnancy rate may limit the generalizability of our findings, as we did not evaluate all possible infertility factors that could have contributed to the low rate. Second, while we advised participants on the optimal timing of intercourse, we could not determine the degree of adherence to these instructions. Third, our study’s treatment and follow-up durations were relatively short, as we evaluated only one treatment cycle in each patient. Finally, the letrozole-only group for ovulation induction was not included in this study. Therefore, more treatment groups and long follow-up periods are needed to assess and compare the cumulative ovulatory rate between these ovulation induction regimens. As we know that live birth is the most meaningful outcome, the ovulation rate was a reasonable primary outcome for evaluating the efficacy of ovulation induction agents. This is because the rate minimizes confounding factors related to infertility factors beyond ovulation.