Abstract BACKGROUND: Abortion is one of the most common complications of pregnancy. One type of abortion; missed abortion, occurs in 15%–20% of clinically diagnosed pregnancies and is the retention of pregnancy products in the uterus for several days or weeks after death of the fetus. Many medications registered had been described to terminate pregnancy replacing the surgical procedure avoiding considerable perioperative complications.  
AIM: This study aimed to evaluate the effect of letrozole plus misoprostol to terminate non-viable pregnancies in first trimester compared with the use of misoprostol alone.   
METHODS: This study included two groups: Group I, (Misoprostol group) received 600 micrograms of misoprostol (Misotac®, Tab. 200 mcg, Sigma company, Egypt) administered sublingual on the 1st day of enrolment (3 tablets twice, 4 hours apart).Group II, (Letrozole + Misoprostol group) received letrozole 2.5mg (Femara®, Tab. 2.5- mg, Novartis company, Egypt) , one dose 10 mg (4 tablets) on the 1st day of enrolment followed by 600 micrograms of misoprostol (Misotac®, Tab. 200 mcg, Sigma company, Egypt) administered sublingual on the 2nd day of enrolment (3 tablets twice, 4 hours apart). All women underwent detailed history, physical examination including local examination to assess the cervix. Investigations included: Complete blood count, Blood group analysis, Rh typing, Ultrasound.
RESULTS: 90 women were enrolled, divided into 45 women in letrozole + Misoprostol and 45 women in Misoprostol group. Four women from Misoprostol group and 2 women from Letrozole + Misoprostol group were lost to follow-up. Baseline characteristics regarding age, parity, gestational age and BMI revealing non significant difference between studied groups. The mean interval time of start of bleeding, induction to expulsion interval and abortion time were significantly lower in Letrozole + Misoprostol women compared to Misoprostol group. The most common side-effects in both groups were abdominal pain and headache. The incidence of side-effects was comparable for the two groups (P > 0.05), also the severity of side-effects was not significantly different between groups (P > 0.05). Complete abortion was observed in 36 subjects in Letrozole +Misoprostol group which was significantly more frequent than 26 subjects in Misoprostol subjects (83.7% and 63.4%, respectively, P < 0.05). No statistical significance was seen regarding Hb levels before and after treatment, while Hct levels showed significant difference before and after treatment concerning women underwent complete abortion only in the 2 studied groups.  
CONCLUSION: The use of letrozole in addition to misoprostol was associated with shorter induction to complete expulsion interval, higher complete abortion rate and less curettage rate compared to misoprostol group in patients undergoing induction of first trimesteric missed abortion (less than 14 weeks). Further larger studies are needed to determine the optimum treatment protocol to achieve the highest success rate, and the lowest rate of side effects and the most cost-effective.