Comparison Between Effect of Letrozole Plus Misoprostol and Misoprostol Alone in Terminating Non-Viable First Trimester Pregnancies: A Single Blind Randomized Trial
AbstractObjective: To evaluate the effect of letrozole plus misoprostol to terminate non-viable pregnancies in first trimester compared with the use of misoprostol alone.Materials and methods: In a single-blind clinical trial, 128 women over 18 years old referred to Educational-Medical centers of Tabriz University of Medical Science (Tabriz, Iran), for abortion in first trimester of non-viable pregnancies, were randomly selected in two intervention and control groups using Rand list (version 1.2) software. To complete abortion both groups received 600 mcg of misoprostolorally. The intervention group received letrozole 10 mg daily for 3 days before receiving misoprostolorally. Complete abortion rate and the side effects of both groups were recorded.Results: Mean pregnancy age based on LMP in intervention group and control group were 7.74 ± 0.95 and 8.52 ± 1.29 weeks respectively. Complete abortion rate in the intervention group was 93.7%, and in control group was 68.7% which was significantly higher in intervention group (p = 0.001). Abdominal pain in the intervention group is also significantly lower than that of the control group (p = 0.013). Intervention group also had significantly lower duration of bleeding rather than control group (p = 0.006).Conclusion: Based on the findings of this study, letrozole pretreatment with misoprostol for first-trimester medical abortion can increase complete abortion rate significantly without increasing side effects compared to use of misoprostol alone.
Henshaw SK, Singh S, Haas T. The incidence of abortion worldwide. Int Fam Plann Persp 1999; 25:S30-8.
Sedgh G, Henshaw S, Singh S, Åhman E, Shah IH. Induced abortion: estimated rates and trends worldwide. Lancet 2007;370:1338-45.
Creinin MD. Medical abortion regimens: historical context and overview.Am J Obstet Gynecol. 2000;183:S3-S9.
Virk J, Zhang J, Olsen J. Medical abortion and the risk of subsequent adverse pregnancy outcomes.N Engl J Med 2007;357:648-53.
Hamoda H, Templeton A. Medical and surgical options for induced abortion in first trimester.Best Pract Res Clin Obstet Gynaecol 2010;24:503-16.
Ngai SW, Chan YM, Tang OS, Ho PC. Vaginal misoprostol as medical treatment for first trimester spontaneous miscarriage.Hum Reprod 2001;16:1493-6.
Sahin H, Sahin H, Kocer M. Randomized outpatient clinical trial of medical evacuation and surgical curettage in incomplete miscarriage.Eur J Contracept Reprod Health Care 2001;6:141-4.
Dalenda C, Ines N, Fathia B, Malika A, Bechir Z, Ezzeddine S, et al. Two medical abortion regimens for late first-trimester termination of pregnancy: a prospective randomized trial. Contraception 2010;81:323-7.
Cunningham FG, Leveno KJ, Bloom SL, Hauth J, Gilstrap L, Wenstrom K. Williams obstetrics. 24nd. NewYork: McGRAW Hill Medical Publishing Division 2014;987:1007.
Weeks A, Alia G, Blum J, Winikoff B, Ekwaru P, Durocher J, et al. A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion. Obstet Gynecol 2005;106:540-7.
Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome.Int J Womens Health 2011;3:25-35.
Kopp Kallner H, Ho PC, Gemzell-Danielsson K. Effect of letrozole on uterine tonus and contractility: a randomized controlled trial. Contraception 2012;86:419-24.
Gibson L, Lawrence D, Dawson C, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2009;4: CD003370.
Shi L, Shi S-Q, Given RL, von Hertzen H, Garfield RE. Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy. Steroids 2003;68:1077-84.
Yeung TWY, Lee VCY, Ng EHY, 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;86:763-9.
Petitet PH, Ith L, Cockroft M, Delvaux T. Towards safe abortion access: an exploratory study of medical abortion in Cambodia.Reprod Health Matters 2015;22:47-55.
You JH, Chung TK. Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis.Hum Reprod 2005;20:2873-8.
Lee VCY, Tang OS, Ng EHY, Yeung WSB, Ho PC. A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days. Contraception 2011;83:62-7.
Jain JK, Dutton C, Harwood B, Meckstroth KR, Mishell DR Jr. A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. Hum Reprod 2002;17:1477-82.
Gemzell-Danielsson K, Ho P, de León RGP, Weeks A, Winikoff B. Misoprostol to treat missed abortion in the first trimester.Int J Gynaecol Obstet 2007;99:S182-S5.
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;171:291-4.
Lee VC, Ng EH, Yeung WS, Ho PC. Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial.Obstet Gynecol 2011;117:317-23.
Lee VC, Tang OS, Ng EH, Yeung WS, Ho PC. A prospective double-blinded, randomized, placebo-controlled trial on the use of letrozole pretreatment with misoprostol for second-trimester medical abortion. Contraception 2011;84:628-33.
Lee VC, Gao J, Lee KF, Ng EH, Yeung WS, Ho PC. The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta. Hum Reprod 2013: 28:2912-9.
American College of Obstetricians and Gynecologists. Practice bulletin no.143: medical management of first-trimester abortion. Obstet Gynecol 2014;123:676-92.
Rodriguez MI, Mendoza WS, Guerra-Palacio C, Guzman NA, Tolosa JE. Medical abortion and manual vacuum aspiration for legal abortion protect women’s health and reduce costs to the health system: findings from Colombia.Reprod Health Matters 2015;22:
27.Sanhueza Smith P, Peña M, Dzuba IG, García Martinez ML, Aranguré Peraza AG,
Bousiéguez M, et al. Safety, efficacy and acceptability of outpatient mifepristone-misoprostol medical abortion through 70 days since last menstrual period in public sector facilities in Mexico City. Reprod Health Matters 2015;22:75-82.