Letrozole Compared With Clomiphene Citrate for Unexplained Infertility

Abstract

To estimate the clinical effectiveness, as determined by positive pregnancy test, of letrozole compared with clomiphene citrate for ovarian stimulation in patients with unexplained infertility. DATA SOURCES: We conducted a systematic review and meta-analysis of data from electronic databases including Ovid-MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and ClinicalTrials.gov. METHODS: We searched for concepts of unexplained infertility, letrozole, clomiphene citrate, and clinical outcomes including pregnancy and live birth. Studies were included if they were randomized controlled trials (RCTs) comparing clomiphene citrate with letrozole in patients with unexplained infertility. Eight RCTs including 2,647 patients with unexplained infertility were included. Primary outcome was positive pregnancy test per patient. Secondary outcomes included positive pregnancy test per cycle, clinical pregnancy, live birth, spontaneous miscar-riage, twin gestation, mean serum estradiol (E2), endometrial thickness, and number of dominant follicles. The Cochrane Q test and Higgin's I 2 were used to assess heterogeneity. Random effects models were used to obtain pooled relative risks (RR) and 95% CIs.

Evidence-based treatments for couples with unexplained infertility: a guideline

“…This guideline includes two randomized trials (26,33) and two systematic reviews of RCTs (28,30) that assessed aromatase inhibitors with intercourse as treatment for couples with unexplained infertility. In one high-quality RCT which included 996 patients, clinical pregnancy rate was no different between letrozole cycles with timed intercourse vs. medically unassisted age-matched controls who conceived (11.1% vs. 7.0%, respectively, P¼NS) (26).…”

“…Both systematic reviews demonstrated no difference in outcomes including clinical pregnancy, live-birth, miscarriage, and multiple pregnancy rates comparing letrozole to clomiphene citrate. However, both noted significant heterogeneity in the data and included some studies which added IUI to the ovarian stimulation (28,30). Pregnancy rates in an earlier trial were equivalent (and low) across doses of letrozole ranging from 2.5 to 7.5 mg (pregnancy rate/cycle: 2.5 mg, 4.8%; 5 mg, 4.3%; 7.5 mg, 6.5%), P¼NS) (33).…”

A review of the physiology behind letrozole applications in infertility: are current protocols optimal?

“…Letrozole dose and timing Selected literature references Oral ovulation induction for fertility enhancement in the ovulatory patient Letrozole 2.5 to 7.5 mg on days 3 through 7 of menstrual cycle [5][6][7] IVF in patients with breast cancer needing fertility preservation Letrozole 5 mg per day starting on day 2 or 3 of menstrual cycle followed by gonadotropins 2 days later until triggered for maturation [8,9] IVF in patients with diminished ovarian reserve 2.5 to 5 mg for 5 days starting simultaneously with high dose FSH during antagonist IVF cycle [10,11] Priming for in vitro maturation (IVM) patients 2.5 to 5 mg on days 3-7 of menstrual cycle with low dose FSH started on day 5 [12,13] Androgen production is not directly increased by letrozole. In the pre-menopausal woman, intra-ovarian androgen levels are increased, primarily because less androgen substrate is used for estrogen biosynthesis.…”

“…The mechanism used is to increase a patient's ovarian follicles' exposure to FSH by decreasing the negative feedback impact of estradiol production by the ovary. Typically, treatment consists of 2.5 to 7.5 mg of letrozole taken by the patient on days 3 through 7 of their menstrual cycle [5][6][7]. Adjunctive therapies often used with letrozole include intra-uterine insemination (IUI) and ovarian hyperstimulation with gonadotropins.…”

Comparative Analysis of Effectiveness of Clomiphene Citrate and Letrozole Combined with Low Dose Human Menopausal Gonadotropin for Controlled Ovarian Stimulation in Intrauterine Insemination Cycles

“…6 In a systematic review with meta-analysis of 8 randomized trials, similar pregnancy rate was seen with both letrozole and clomiphene in unexplained infertility. 7 Clomiphene and letrozole are often used in combination with human menopausal gonadotropin (hMG) for controlled ovarian stimulation in IUI cycles. Ovarian stimulation with low dose gonadotropin is always preferred due to a low risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies.…”