Letrozole vs. Placebo Pretreatment in the Medical Management of First Trimester Missed Miscarriage: a Randomized Controlled Trial

Abstract

Introduction Misoprostol is used for the medical management of miscarriage as it is more effective in the early stages of pregnancy. Letrozole has an anti-estrogen effect and is used for the pretreatment of miscarriage with misoprostol. Aim The aim of this study was compare the efficacy and safety of letrozole with placebo pretreatment in the medical management of first trimester missed miscarriage. Design This was a prospective randomized case-control study. Patients and Methods Four hundred and thirty-eight women were randomly divided into two groups of 219; the placebo group received placebo tablets twice daily for 3 days, followed by 800 micrograms of misoprostol vaginally on the fourth day of enrolment, while the letrozole group received letrozole 10 mg twice daily for three days followed by 800 micrograms misoprostol administered vaginally. Symptoms and side effects were recorded, and the women advised to return to hospital if they experienced severe pain or bleeding or intolerable side effects and to report to hospital for a check-up one week after misoprostol administration. Ultrasound was done seven days after misoprostol administration to monitor outcomes. Surgical evacuation was carried out if medical management failed. Results There were significant differences between the two groups, with better outcomes found for the letrozole group in terms of rates of complete miscarriage, onset of vaginal bleeding, and interval between induction and onset of expulsion (p < 0.001). A higher rate of nausea and vomiting was reported for the letrozole group (p = 0.002). Differences between groups with regard to pre- and post-termination hemoglobin levels, fever, severe pain and severe bleeding needing evacuation were not statistically significant. Conclusion Adding letrozole to misoprostol improves the success rate and decreases the interval between induction and expulsion in cases of first trimester miscarriage; however, nausea and vomiting is higher with letrozole.

A Comparative Study between Methotrexate versus Letrozole Prior to Misoprostol in Induction of First Trimester Missed Miscarriage

“…Success rate in the current study was higher than the reported by Torky et al, [16] who found that Letrozole + Misoprostol achieved a success rate of 78.0% in complete miscarriage versus a success rate of 39.0% that was achieved by Misoprostol alone (P<0.001), and also higher than Javanmanesh et al, [18] compared the use of Misoprostol with or with no Letrozole in management of miscarriage, they found that the rate of success was significantly high in the group received Letrozole+ Misoprostol than that of the group receiving Misoprostol only (78.3% vs. 13.0%; p=0.001). The variations between findings may explain by different doses and gestational age in studied women, duration of letrozole, and differrent doses of administration.…”

“…The sample size was calculated with 208 subjects in each arm of the study, using the formula for comparison of proportion with alpha = 0.01, beta = 0.05, and power = 95%, and 15% dropout rate during follow up. Sample size calculation was done using the results of a recent randomized clinical trial designed to compare the efficacy and safety of letrozole with placebo pretreatment in the medical management of first trimester missed miscarriage [16] . We calculated the effect size that was 0.3, alpha error was 0.01 and power of 0.95 was used.…”

Effect of misoprostol with and without letrozole on the induction of abortion for women with first‐trimester missed abortion

“…Torky et al 19 reported a rate of complete abortion of 78% after the administration of 10 mg of letrozole twice daily for 3 days followed by 800 μg of vaginal misoprostol, as compared with a rate of 39% after the administration of misoprostol alone ( P <0.05). In a study of 46 women with a gestation of less than 20 weeks, Javanmanesh et al 20 found that 3 days of administration of 10 mg of letrozole followed by oral misoprostol led to a significantly higher rate of complete abortion as compared with misoprostol plus placebo.…”

Prospective open-label non-inferiority randomised controlled trial comparing letrozole and mifepristone pretreatment in medical management of first trimester missed miscarriage: study protocol

“…The interval between induction and abortion in the letrozole group was 1.42 days which was shorter than that in the placebo group (3.09 days). 29 Another RCT showed a complete abortion rate of 93.7% in the letrozole plus misoprostol group compared with 68.7% in the misoprostol alone group for the treatment of first trimester non-viable pregnancies. 30 The above randomised controlled studies suggested that pretreatment with either mifepristone or letrozole followed by misoprostol are both effective in the management of first-trimester missed miscarriage.…”