USE OF LETROZOLE PRETREATMENT WITH MISOPROSTOL FOR FIRST-TRIMESTER MEDICAL MISCARRIAGE: A RANDOMIZED CONTROLLED TRIAL

Abstract

Miscarriage is the most common complication of pregnancy, occurring in 10-20% of clinically recognized pregnancies(Bagratee et al., 2004). Estrogen is important in the maintenance of pregnancy. Aromatase inhibitors such as letrozole, suppress the peripheral conversion of androgen to estrogen, the use of letrozole combined with vaginal misoprostol was more effective than misoprostol alone in termination of pregnancy up to nine weeks’ gestation(Yeung et al., 2012). Letrozole seven and halfmilligram given daily for two days and then followed by 800 microgram of vaginal misoprostol induce complete abortion in 80% of patients(Kallner, 2012). This clinical trial was conducted at Ain Shams University Maternity Hospital in the period between October 2014 and April 2015. Patients that seem to be fulfilling the inclusion criteria were recruited, then, an informed written consent was taken from every patient before starting the examination to confirm fulfilling all inclusion and exclusion criteria. Followed by Careful and detailed history and examination of all the patients. Hemoglobin, hematocrit, Blood group, RH, and Trans-vaginal ultrasound were done for all patients before the study. Patients fulfilling inclusion and exclusion criteria were divided into two groups. 160 patients received misoprostol with letrozole, and the other 160 patients received misoprostol with placebo. Group (A): Women received three tablets of letrozole as a single dose, each tablet 2.5 milligram for three days followed by four tablets of vaginal misoprostol (200 microgram) every three hours up to maximum two doses. Group (B): Women received three tablets of placebo as a single dose, each tablet 2.5 milligram for three days followed by four tablets of vaginal misoprostol (200 mcg) every three hours up to maximum two doses. Temperature, blood pressure and pulse were recorded hourly. Side effects, presence of vaginal bleeding and the time of expulsion of tissue mass were recorded too. If the vaginal bleeding affects patient`s general condition surgical evacuation was done immediately. The follow-up visit on day seven during which a trans-vaginal ultrasound was performed and blood sample was taken for hemoglobin level. In participants with incomplete or missed miscarriage on day seven surgical evacuationwas performed under general anesthesia. Surgical evacuation was also done at any time over the seven days follow up period if there was heavy bleeding or on patient’s request. If no emergency or elective curettage was necessary over the seven days, the outcome of treatment was classified as “complete miscarriage”. This study demonstrated that 7.5mg letrozole for threedays followed by 800 micrograms of vaginal misoprostolismore effective than misoprostol alone for firsttrimesterabortion. In the total of 320 women were recruited. The complete miscarriage rate of the letrozole group was significantly higher than that of the placebo group (82.6% compared with 68.2%).