Letrozole versus clomiphene citrate for unexplained infertility: A systematic review and meta‐analysis

Abstract

The objective of this study is to investigate and compare the effectiveness of letrozole and clomiphene citrate for improving fertility outcomes, including pregnancy rate, miscarriage rate, multiple pregnancy rate, and incidence rate of adverse events, number of dominant follicles, endometrial thickness at hCG day and serum E2 on hCG day. MEDLINE, EMBASE, CENTRAL, CNKI and CBMdisc databases were searched up to March 2013. Randomized controlled trials comparing letrozole with clomiphene in women with unexplained infertility were included. Pooled relative risk, mean difference and 95% confidence intervals were calculated. We found that there are no differences in pregnancy, miscarriage and multiple pregnancy rates, incidence rate of adverse events, number of dominant follicles (>18 mm) and endometrial thickness at hCG day in women with unexplained infertility between letrozole and clomiphene regimens. The mean (±standard deviation) concentration of serum E2 on hCG day was lower in those treated with letrozole than those with clomiphene. The subgroup of 2.5 mg letrozole displayed a statistically significant higher rate of clinical pregnancy as compared with 100 mg of clomiphene. The results of this study conclude that letrozole is as effective as clomiphene in women with unexplained infertility. Letrozole at a dose of 2.5 mg seems more effective. Further high-quality studies assessing the possible effectiveness of letrozole in selected groups of patients are warranted.

What is the optimal protocol for Intrauterine Insemination (IUI)? A Mini Review and A Retrospective Study to Evaluate Effective Factors Influencing Pregnancy after IUI

“…Based on data from 7 randomised controlled trials (RCTs), Hughes et al [30] described similar live birth and clinical pregnancy rate per woman in IUI treatment with CC or placebo for unexplained subfertility. However, letrozole (2.5 mg) displayed a statistically significantly higher CPR in couples with unexplained infertility than CC (100 mg) [31]. In our study CC and letrozole showed similar effects on CPR in unexplained infertility couples.…”

Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A prospective randomized trial

“…Letrozole is a third-generation aromatase inhibitor which has been successfully used for ovulation induction in patients with polycystic ovary syndrome (PCOS) (11). Mitwally et al had reported acceptable pregnancy outcomes and lower rate of multiple gestation in letrozole group for ovarian stimulation (12).…”

“…It has a short half-life (45 hr), so it would be eliminated from the body rapidly (13). Although clomiphene is the standard drug for ovulation stimulation, clomiphene-resistance has been discovered in 15-20% of the patients (11). …”

Oral Drugs for Unexplained Infertility

“…Recent studies have found that aromatase inhibitors including letrozole may be safe and useful agents for ovulation induction in patients with unexplained infertility [10][11][12]. Letrozole has been used for ovarian stimulation by fertility doctors since 2001 because it has fewer side effects than clomiphene citrate and less chance of multiple gestations [10][11][12]. A detailed ovulation induction follow-up study found that letrozole, compared with a control group of clomiphene, had significantly lower congenital malformations and chromosomal abnormalities at an overall rate of 2.4 % (1.2 % major malformations) compared with clomiphene 4.8 % (3.0 % major malformations) [13].…”

“…However, empirical ovarian stimulation (with clomiphene or particularly with gonadotropin) is frequently complicated by the ovarian hyperstimulation syndrome and by multiple gestations, with an increased risk of preterm birth and associated neonatal morbidity and costs [4][5][6][7][8][9]. Recent studies have found that aromatase inhibitors including letrozole may be safe and useful agents for ovulation induction in patients with unexplained infertility [10][11][12]. Letrozole has been used for ovarian stimulation by fertility doctors since 2001 because it has fewer side effects than clomiphene citrate and less chance of multiple gestations [10][11][12].…”