Comparing Letrozole and Mifepristone pretreatment for medical management of first trimester miscarriages.

This will be a randomized control interventional trial. The investigators hypothesise that letrozole is equivalent to mifepristone for the pre-treatment of mTOP and propose to conduct a randomised, non-inferiority trial for mTOP up to 10 weeks gestation with two arms as detailed below:

(i)    Oral letrozole 10mg daily for 3 days, followed by vaginal misoprostol on Day 3 (Intervention group)

(ii)  Oral mifepristone 200mg once on Day 1, followed by vaginal misoprostol 800mcg on Day 3. (current practise)

The investigators aim to include 150 patients with 75 in each arm, to detect a non inferiority margin of 15% with a power of 80% with 5% significance.

The primary outcome is complete abortion rates(by day 7-10). Secondary outcomes include time-to-abortion interval, the number of misoprostol doses required, healthcare resource utilisation and side effects.

Letrozole priming before mTOP has been proposed as an alternative to the use of mifepristone. The proposed mechanism is a reduction in serum estrogen levels, leading to a concomitant reduction in progesterone receptor concentration necessary for the maintenance of pregnancy. Several randomised controlled trials (RCTs) have been performed by comparing the effectiveness of using letrozole for mTOP priming before misoprostol versus misoprostol alone. The combination of letrozole with misoprostol has shown to be effective in improving the success rates of complete abortion up to 10 weeks gestation, compared with misoprostol alone. Given its low price, ready availability worldwide and common usage in the fields of ovulation induction and breast cancer, letrozole may be a potential alternative to mifepristone in mTOP priming. While medication costs vary from country to country, the cost of a course of letrozole is largely cheaper than mifepristone. To address the aforementioned knowledge gaps, this study aims to conduct a non-inferior RCT to investigate whether pre-treatment with letrozole before misoprostol is comparable to mifepristone pre-treatment before misoprostol mTOP in patients up to 10 weeks gestation.