The Use of Letrozole or Mifepristone for Pretreatment of Medical Termination of Pregnancy

Summary

Medical termination of pregnancy (mTOP) generally involves using either a combined regimen consisting of mifepristone and misoprostol, or a misoprostol-only regimen. Complete abortion rates of first trimester mTOP with the use of misoprostol-only regimen varies between 74-88%. With the addition of mifepristone as pre-treatment drug, this improves success rates to 93-97%. Mifepristone, an anti-progesterone, is relatively expensive and is subject to stringent regulations for usage in addition to restricted access in many countries. Therefore, there is a need to find a cheaper and more readily available, yet effective alternative. The use of letrozole (an aromatase inhibitor) in mTOP is postulated to suppress estradiol levels (an important factor in the maintenance of early pregnancy), therefore enhancing the effect of misoprostol in inducing abortion. Studies have shown that pre-treatment with letrozole achieves a complete abortion rate of 77-98%, similar to that in mifepristone-Misoprostol studies. 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: 1. Oral letrozole 10mg daily for 3 days, followed by vaginal misoprostol on Day 3 (Intervention group) 2. Oral mifepristone 200mg once on Day 1, followed by vaginal misoprostol 800mcg on Day 3. Then, 4 hours later, another dose of 400mcg PV misoprostol if no signs of abortion (Control group - current practice). The investigators aim to include a total of 144 patients, 72 in each arm, to detect a non-inferiority margin of 15% with a power of 80% at 5% significance. The investigators primary outcome will be rate of complete abortion by Day 21-28 of mTOP. This pilot RCT will provide preliminary data and preparation for larger grant application which will provide necessary evidence to enhance the care of women undergoing mTOP, with enhanced cost-savings and availability.

Timeline

Start

2022-11-22

Primary completion

2025-08

Completion

2025-11

Publications

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• Background Blum J, Raghavan S, Dabash R, Ngoc Nt, Chelli H, Hajri S, Conkling K, Winikoff B. Comparison of misoprostol-only and combined mifepristone-misoprostol regimens for home-based early medical abortion in Tunisia and Vietnam. Int J Gynaecol Obstet. 2012 Aug;118(2):166-71. doi: 10.1016/j.ijgo.2012.03.039. Epub 2012 Jun 8.
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• Background Allen R, O'Brien BM. Uses of misoprostol in obstetrics and gynecology. Rev Obstet Gynecol. 2009 Summer;2(3):159-68.
• Background Chai J, Ho PC. A pilot study on the combined use of letrozole, mifepristone and misoprostol in termination of first trimester pregnancy up to 9 weeks' gestation. Eur J Obstet Gynecol Reprod Biol. 2013 Dec;171(2):291-4. doi: 10.1016/j.ejogrb.2013.09.017. Epub 2013 Sep 25.
• Background Yeung TW, Lee VC, Ng EH, Ho PC. A pilot study on the use of a 7-day course of letrozole followed by misoprostol for the termination of early pregnancy up to 63 days. Contraception. 2012 Dec;86(6):763-9. doi: 10.1016/j.contraception.2012.05.009. Epub 2012 Jun 18.
• Background (Power Analysis and Sample Size Software (2015). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass.)
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• Teong ACA, Wong TTC, Soe NN, Lau HCQ, Ang CYX, Loy SL, Ku CW, Chan JKY, Mohamed Siraj SH, Mathur M, Seet MJ. The use of letrozole or mifepristone for pre-treatment of medical termination of pregnancy: A randomized, non-inferiority trial. Int J Gynaecol Obstet. 2026 Jun 16. doi: 10.1002/ijgo.71104. Online ahead of print.

Drugs

Indications

No indication recorded.