Use of letrozole versus clomiphene citrate for superovulation in patients undergoing intrauterine insemination : a systematic review

Abstract

Background: Intrauterine Insemination (IUI)is one of the common first-line assisted reproductive technologies (ART) for couples suffering infertility. Controlled ovarian stimulation (COH) with clomiphene citrate (CC) or aromatase inhibitor (like Letrozole) is often used in adjunct to IUI to increase the pregnancy outcome. Both CC and letrozole can be given alone as a single ovulation induction agent or they can be combined with injectable gonadotropin for purpose of superovulation. Study objectives: To systematically review the efficacy and adverse outcomes of letrozole and CC for supervulation in infertility patients undergoing IUI. Method: Systematic review of pertinent randomised controlled trials (RCT) using the bibliographic databases EMBASE, PubMed, Cochrane, Medline (OVID), Academic Search Premier and CINAHL. References of selected articles identified were hand-searched for additional relevant citations. RCTs that have compared the pharmacological performance of CC and letrozole as a single agent or combination with equal dose of gonadotropins were included. Results: Ten published randomized controlled trials were included in this review. The mean age, infertility diagnosis and duration of infertility of the recruited participants were comparable. Pregnancy rate was found to be comparable in clomiphene citrate (CC) group and letrozole (L) group. Higher peak estrogen concentration and greater number of dominant follicles were reported in CC group. Endometrial thickness was found significantly greater in L group. Adverse outcomes of rate of miscarriage, multiple pregnancies, ectopic pregnancies, OHSS and fetal anomalies were not significantly different between the two intervention groups. Conclusion: Letrozole and CC, considered equally patient-friendly agent due to oral route administration. Both agents achieved similar pregnancy rates without any increased risk of adverse events in either group. Letrozole can be used as alternative first-line OI agent to CC in reproductive treatments. Drug selection for patients should be done according to the cost effectiveness, duration of therapy, characteristics and compliance of patients.