Comparison of Letrozole and Mifepristone pre-treatment in first trimester medication abortion- a non-inferiority randomized controlled trial.

Letrozole, an oral aromatase inhibitor that can inhibit oestrogen synthesis and has been shown to be useful when combined with misoprostol in medical abortion as a potential substitute for mifepristone, may be a good alternative. Mifepristone is unavailable in many countries and is a costly drug compared to letrozole. Recently, WHO abortion care guideline 2022 has suggested use of letrozole plus misoprostol as a safe and effective option for medication abortion <12 weeks, with a remark that further evidence is needed to determine the safety, effectiveness and acceptability of the letrozole plus misoprostol combination regimen, especially in comparison with that of the mifepristone plus misoprostol combination regimen (the available evidence focused on comparison with the use of misoprostol alone). Therefore, a comparative study between two drugs is essential before accepting this newly recommended drug in clinical practice.

Novelty: So far, no study has been done comparing mifepristone and letrozole pretreatment in inducing first trimester abortions

Expected outcome and application: Letrozole can be used as an alternative for mifepristone in pretreatment for inducing first trimester abortions

Aim: To compare the outcomes of pretreatment with letrozole and mifepristone in first trimester medication abortions.

 Objectives:

Ø  To estimate the proportion of complete expulsion rate with mifepristone and letrozole

Ø   To compare the time of expulsion of product of conception

Ø  To assess whether surgical evacuation needed or not

Study procedure: The study will be conducted in the Department of Obstetrics & Gynaecology after ethical approval. Eligible patients attending GOPD and meeting inclusion criteria will be included in the study. Informed written consent will be obtained from all participants. The women will be allowed to withdraw from the study for any reason at any time, and will receive the standard medical care in such case.

Eligible women will be randomly assigned to either the mifepristone or letrozole pretreatment group. Randomisation will be done using computer generated randomization table in blocks. The vouchers showing the assigned arms according to the randomisation list will be sealed in opaque envelopes which will be opened on recruitment of each patient in sequence.

Participants in the mifepristone group will get a single oral dosage of 200 mg mifepristone, and then, 48 hours later, 800 mg of misoprostol sublingually. According to the protocol employed in a prior trial on medical abortion, patients in the letrozole group will get 10 mg of letrozole orally three days in a row, followed by 800 mg of misoprostol given sublingually on the morning of the third day. The participants will remain in the hospital for at least 3-6 hours following misoprostol treatment to observe for serious negative consequences, tissue passage, and hemorrhage. Baseline demographic information, medical history, obstetric history, timing of drug administration, side effects, timing of tissue ejection, intensity of abdominal pain, and vaginal bleeding will be recorded on a standard data form. Other adverse effects including headaches, fever, diarrhoea, nausea, and vomiting will also be recorded.

Participants will be called for evaluation seven days later. Passage of tissue, persistent severe vaginal bleeding, and clinical infections symptoms will be assessed. Women who will not have the gestational sac released by day 7 might elect to get a second dosage 400 μg misoprostol sublingually, Or to undergo suction and evacuation. Those who will opt for an additional misoprostol dose or expectant therapy will be reevaluated in another week. Suction evacuation will be done if, one week after the second dose of misoprostol, the gestational sac will still be present. Following the use of misoprostol, all participants will be called for follow up after 15 days to get information on any subsequent treatments or negative side effects. In the interim, if there is significant vaginal bleeding, fever, or severe abdominal pain, patient can come back to the hospital. On day 15, ultrasound scan will be carried out to direct subsequent therapy in the event that there is persistent bleeding. If there will be no gestational sac or fetal structure, complete abortion will be taken into account. Persistent vaginal bleeding, and the presence of intrauterine material with a thickness greater than 15 mm will be treated surgically or expectantly according to the patient’s informed choice. The indications for suction evacuation will be persistent presence of a pregnancy sac 7–15 days after the first or second misoprostol administration, heavy vaginal bleeding, or incomplete abortion after 15 days following misoprostol administration. This will be an informed decision by the patient after explanation about the alternative options of expectant and repeat medical management