A prospective open label randomized controlled trial comparing the effect of letrozole and mifepristone pre-treatment in medical termination of pregnancy up to 9 weeks

Sangeeta Raman Jogi; Dipika Singh; Anju Garhewal

doi:10.18203/2320-1770.ijrcog20251753

Authors

Sangeeta Raman Jogi Department of Obstetrics and Gynaecology, Chhattisgarh Institute of Medical Science, Bilaspur, Chhattisgarh, India
Dipika Singh Department of Obstetrics and Gynaecology, Chhattisgarh Institute of Medical Science, Bilaspur, Chhattisgarh, India
Anju Garhewal Department of Obstetrics and Gynaecology, Chhattisgarh Institute of Medical Science, Bilaspur, Chhattisgarh, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20251753

Keywords:

Mifepristone, Letrozole, Medical termination of pregnancy

Abstract

Background: Mifepristone for medical termination of pregnancy (MTP) has been shown to increase the success rate. mifepristone followed by misoprostol for the medical management of first trimester pregnancy in previous clinical trials has ranged from 79% to 87%. As access to mifepristone is restricted in some countries, and some patients may have contraindications to the use of mifepristone, we propose that letrozole may be a good alternative.

Methods: This was a hospital based open label randomized controlled trial study carried out year 2023 to 2024 in the department of obstetrics and gynecology at CIMS Bilaspur, total sample was 100.

Results: In present study both groups received a single dose of their respective drug, with a slightly higher proportion of mifepristone users receiving two doses (14%) compared to letrozole users (6%) and in gestational sac expulsion 84% of participants from both groups expelled the sac in 2 days, mifepristone users had a slightly higher rate of incomplete expulsion (6%) compared to letrozole users (4%) (p=0.041).

Conclusions: The comparison between letrozole and mifepristone users highlights several key differences. Mifepristone users experienced a higher frequency of irregular menstrual cycles, incomplete expulsion of the gestational sac, and a greater need for dilation and curettage (D and C) procedures compared to those using letrozole.

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References

Cameron S. Recent advances in improving the effectiveness and reducing the complications of abortion. F1000Res. 2018:7:F1000 Faculty Rev-1881. DOI: https://doi.org/10.12688/f1000research.15441.1

Zhang J, Zhou K, Shan D, Luo X. Medical methods for first trimester abortion. Cochrane Database Syst Rev. 2022;2022(5):CD002855. DOI: https://doi.org/10.1002/14651858.CD002855.pub5

Lemmers M, Verschoor MA, Kim BV, Hickey M, Vazquez JC, Mol BWJ. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev. 2019;6(6):CD002253. DOI: https://doi.org/10.1002/14651858.CD002253.pub4

Autry BM, Wadhwa R. Mifepristone. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2025.

Alabiad MA, Elhasadi I, Alnasser SM, Alorini M, Alshaikh ABA, Jaber FA, et al. Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study. Iran J Med Sci. 2024;49(1):46-56.

Zhang J, Gilles JM, Barnhart K. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med. 2005;353:761-9. DOI: https://doi.org/10.1056/NEJMoa044064

Stockheim D, Machtinger R, Wiser. A randomized prospective study of misoprostol or mifepristone followed by misoprostol when needed for the treatment of women with early pregnancy failure. Fertil Steril. 2006;86:956-60. DOI: https://doi.org/10.1016/j.fertnstert.2006.03.032

Torky HA, Marie H, ElDesouky E, Letrozole vs. placebo pretreatment in the medical management of first trimester missed miscarriage: a randomized controlled trial. Geburtshilfe Frauenheilkd. 2018;78:63-9. DOI: https://doi.org/10.1055/s-0043-122499

Abbasalizadeh F, Sahhaf F, Sadeghi-Shabestari P, Comparison between effect of letrozole plus misoprostol and misoprostol alone in terminating non-viable first trimester pregnancies: a single blind randomized trial. J Family Report Health. 2018;12:27-33.

Gatter M, Cleland K, Nucatola DL. Efficacy and safety of medical abortion using mifepristone and buccal misoprostol through 63 days. Contraception. 2015;91(4):269-73. DOI: https://doi.org/10.1016/j.contraception.2015.01.005

NA. ACOG Clinical Practice Update: Rh D Immune Globulin Administration After Abortion or Pregnancy Loss at Less Than 12 Weeks of Gestation. Obstetr Gynecol. 2024;144(6):e140-3. DOI: https://doi.org/10.1097/AOG.0000000000005733

World Health Organization (WHO). Safe abortion: Technical and policy guidance for health systems. World Health Organization. Available at: https://iris.who.int/bitstream/handle/10665/173586/WHO_RHR_15.04_eng.pdf. Accessed on 10 April 2025.

Kapp N, Eckersberger E, Lavelanet A, Rodriguez MI. Medical abortion in the late first trimester: a systematic review. Contraception. 2019;99(2):77-86. DOI: https://doi.org/10.1016/j.contraception.2018.11.002

Du L, Li RHW, Gemzell-Danielsson K, Du YH, Zhang L, Diao WY. Prospective open-label non-inferiority randomised controlled trial comparing letrozole and mifepristone pretreatment in medical management of first trimester missed miscarriage: study protocol. BMJ Open. 2022;12(1):e052192. DOI: https://doi.org/10.1136/bmjopen-2021-052192

Zhuo Y, Cainuo S, Chen Y, Sun B. The efficacy of letrozole supplementation for medical abortion: a meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2021;34(9):1501-7. DOI: https://doi.org/10.1080/14767058.2019.1638899

Nofal AM, Abd El All NK, El Deen Fathallah El Halaby A, Mahmoud FF, El-Kelani OA. Efficacy of Adjunctive Use of Letrozole and Misoprostol in the Medical Induction of First Trimester Abortion. Egypt J Hospital Med. 2024;95(1):2112- 8. DOI: https://doi.org/10.21608/ejhm.2024.358273

Simpson D, Curran MP, Perry CM. Letrozole: a review of its use in postmenopausal women with breast cancer. Drugs. 2004;64(11):1213-30. DOI: https://doi.org/10.2165/00003495-200464110-00005

Abbasalizadeh F, Sahhaf F, Sadeghi-Shabestari P, Mirza-Aghazadeh-Attari M, Naghavi-Behzad M. Comparison Between Effect of Letrozole Plus Misoprostol and Misoprostol Alone in Terminating Non-Viable First Trimester Pregnancies: A Single Blind Randomized Trial. J Family Reprod Health. 2018;12(1):27-33.

Xiao B, von Hertzen H, Zhao H, Piaggio G. Menstrual induction with mifepristone and misoprostol. Contraception. 2003;68(6):489-94. DOI: https://doi.org/10.1016/j.contraception.2003.09.009

Kumar A, Singh S, Abichandani R, Dey M, Nair VG, Kaur EJ. A Prospective Comparative Study of Mifepristone Combined with Misoprostol vs Letrozole Combined with Misoprostol for First-trimester Medical Abortion. Int J Infertil Fetal Med. 2025;1-4.

Joyce Chai, Pak-Chung Ho. 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 Obstetr Gynecol Reproduct Biol. 2013;171(2):291-4. DOI: https://doi.org/10.1016/j.ejogrb.2013.09.017

Shochet T, Turok D, Frye LJ, Sexsmith CD, Gawron LM, Kaiser JE. Single dose letrozole and misoprostol for termination of pregnancy through 63 days’ gestation: A pilot study. Contraception. 2023;120:109924. DOI: https://doi.org/10.1016/j.contraception.2022.109924

Newhall EP, Winikoff B. Abortion with mifepristone and misoprostol: regimens, efficacy, acceptability and future directions. Am J Obstet Gynecol. 2000;183(2):S44-53. DOI: https://doi.org/10.1067/mob.2000.107950

Du L, Li H, Danielsson K. Comparing letrozole and mifepristone pre-treatment in medical management of first trimester missed miscarriage: a prospective open-label non-inferiority randomised controlled trial. BJOG. 2024;131(3):319-26. DOI: https://doi.org/10.1111/1471-0528.17646