The effectiveness comparison between letrozole and clomiphene citrate as ovulation induction therapy in patients of polycystic ovarian syndrome (PCOS)
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Sep 9, 2023
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Abstract
Letrozole is an aromatase inhibitor that has been tested and proven to be superior to CC in terms of ovulation, pregnancy and birth rates. However, letrozole has the potential to be teratogenic to the fetus. To compare the effectiveness of Letrozole and Clomiphene Citrate as ovulation induction therapy in polycystic ovarian syndrome (PCOS) patients. Methods is Literature review of four databases; PubMed, DOAJ, Cochrane, and Google Scholar published within the last 5 years from 2018-2022. There were 11 studies reporting the effectiveness of Letrozole and Clomiphene Citrate as ovulation induction therapy in polycystic ovarian syndrome (PCOS) patients. Primary and secondary outcomes are used to evaluate outcomes. The key outcomes were the drug's impact on ovulation, birth, pregnancy, multiple pregnancies, miscarriages, and birth defects rates. The effectiveness of combination therapy and monotherapy was also contrasted in this literature study. Based on this literature review, it was found that Letrozole is superior to Clomiphene Citrate as an ovulation induction agent in PCOS patients. Letrozole is also associated with a better probability of pregnancy and birth and a lower chance of multiple pregnancies. The probability of miscarriage and the occurrence of congenital anomalies or defects in the newborn did not differ between the groups receiving letrozole or CC. In addition, the combination of letrozole and CC was superior to letrozole alone in increasing the ovulation rate in women with PCOS. Letrozole is also better and more acceptable than the combination of CC and metformin for inducing ovulation.
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How to Cite
Dhiya Prameswari Wiyono, P. (2023) “The effectiveness comparison between letrozole and clomiphene citrate as ovulation induction therapy in patients of polycystic ovarian syndrome (PCOS)”, Science Midwifery, 11(3), pp. 629-634. doi: 10.35335/midwifery.v11i3.1292.
References
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Danandjaja, J. (2014). Metode Penelitian Kepustakaan. Antropologi Indonesia, 0(52). https://doi.org/10.7454/ai.v0i52.3318
Hu, S., Yu, Q., Wang, Y., Wang, M., Xia, W., & Zhu, C. (2018). Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Archives of Gynecology and Obstetrics, 297(5), 1081–1088. https://doi.org/10.1007/s00404-018-4688-6
Joham, A. E., & Peña, A. S. (2022). Polycystic Ovary Syndrome in Adolescence. Seminars in Reproductive Medicine, 40(12). https://doi.org/10.1055/s-0042-1757138
Keevil. (2019). Steroid Mass Spectrometry for the Diagnosis of PCOS. Medical Sciences, 7(7). https://doi.org/10.3390/medsci7070078
Manique, M. E. S., & Ferreira, A. M. A. P. (2022). Polycystic Ovary Syndrome in Adolescence: Challenges in Diagnosis and Management. In Revista Brasileira de Ginecologia e Obstetricia (Vol. 44, Issue 4). https://doi.org/10.1055/s-0042-1742292
Mehdinejadiani, S., Amidi, F., Mehdizadeh, M., Barati, M., Safdarian, L., Aflatoonian, R., Alyasin, A., Aghahosseini, M., Pazhohan, A., Hayat, P., Mohammadzadeh kazorgah, F., & Sobhani, A. (2018). The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome. Gynecological Endocrinology, 34(9), 775–780. https://doi.org/10.1080/09513590.2018.1446934
Mejia, R. B., Summers, K. M., Kresowik, J. D., & Van Voorhis, B. J. (2019). A Randomized Controlled Trial of Combination Letrozole and Clomiphene Citrate or Letrozole Alone for Ovulation Induction in Women with Polycystic Ovary Syndrome. Obstetrical and Gynecological Survey, 74(6), 349–350. https://doi.org/10.1097/01.ogx.0000559835.21805.5b
Najafi, P. Z., Noghabi, S. P., Afzali, N., & Mohammadzadeh, S. (2020). Comparing the effect of clomiphene citrate and letrozole on ovulation induction in infertile women with polycystic ovary syndrome. Journal of the Pakistan Medical Association, 70(2), 268–271. https://doi.org/10.5455/JPMA.267607
Nylander, M., Frøssing, S., Clausen, H. V., Kistorp, C., Faber, J., & Skouby, S. O. (2017). Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial. Reproductive BioMedicine Online, 35(1). https://doi.org/10.1016/j.rbmo.2017.03.023
Park, C. H., & Chun, S. (2020). Influence of combined oral contraceptives on polycystic ovarian morphology-related parameters in Korean women with polycystic ovary syndrome. Obstetrics and Gynecology Science, 63(1). https://doi.org/10.5468/ogs.2020.63.1.80
Penzias, A., Bendikson, K., Falcone, T., Hansen, K., Hill, M., Jindal, S., Mersereau, J., Racowsky, C., Rebar, R., Steiner, A. Z., Stovall, D., Tanrikut, C., Kalra, S., Reindollar, R., & Hurd, W. (2020). Evidence-based treatments for couples with unexplained infertility: a guideline. Fertility and Sterility, 113(2). https://doi.org/10.1016/j.fertnstert.2019.10.014
Rezk, M., Shaheen, A. E., & Saif El-Nasr, I. (2018). Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial. Gynecological Endocrinology, 34(4), 298–300. https://doi.org/10.1080/09513590.2017.1395838
Saiyed, A., Jahan, N., Makbul, S. A. A., Ansari, M., Bano, H., & Habib, S. H. (2016). Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats. Integrative Medicine Research, 5(4). https://doi.org/10.1016/j.imr.2016.10.002
Sugiyono. (2017). Metode Penelitian Kuantitatif Kualitiatif dan R&D.
Sugiyono. (2018). Metode Penelitian Kuantitatif, Kualitatig, dan R&D. 456.
Sugiyono. (2019). Metode Penelitian Kuantitatif, Kualitatif, dan R&D (1st ed.). Penerbit Alfabeta.
Tsiami, A. P., Goulis, D. G., Sotiriadis, A. I., & Kolibianakis, E. M. (2021). Higher ovulation rate with letrozole as compared with clomiphene citrate in infertile women with polycystic ovary syndrome: a systematic review and meta-analysis. Hormones, 20(3), 449–461. https://doi.org/10.1007/s42000-021-00289-z
Wang, L., Lv, S., Li, F., Bai, E., & Yang, X. (2021). Letrozole Versus Clomiphene Citrate and Natural Cycle: Endometrial Receptivity During Implantation Window in Women With Polycystic Ovary Syndrome. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.532692
Wang, L., Wen, X., Lv, S., Zhao, J., Yang, T., & Yang, X. (2019). Comparison of endometrial receptivity of clomiphene citrate versus letrozole in women with polycystic ovary syndrome: a randomized controlled study. Gynecological Endocrinology, 35(10), 862–865. https://doi.org/10.1080/09513590.2019.1612358
Witchel, S. F., Oberfield, S. E., & Peña, A. S. (2019). Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment with Emphasis on Adolescent Girls. In Journal of the Endocrine Society (Vol. 3, Issue 8). https://doi.org/10.1210/js.2019-00078
Xi, W., Liu, S., Mao, H., Yang, Y., Xue, X., & Lu, X. (2015). Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: A prospective study. Drug Design, Development and Therapy, 9. https://doi.org/10.2147/DDDT.S83259
Xu, X. L., Deng, S. L., Lian, Z. X., & Yu, K. (2021). Estrogen receptors in polycystic ovary syndrome. In Cells (Vol. 10, Issue 2). https://doi.org/10.3390/cells10020459
Yan, Q., Qiu, D., Liu, X., Xing, Q., Liu, R., & Hu, Y. (2022). The incidence of gestational diabetes mellitus among women with polycystic ovary syndrome: a meta-analysis of longitudinal studies. BMC Pregnancy and Childbirth, 22(1). https://doi.org/10.1186/s12884-022-04690-3
Yu, Y., Fang, L., Zhang, R., He, J., Xiong, Y., Guo, X., Du, Q., Huang, Y., & Sun, Y. (2017). Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: A network meta-analysis. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-03803-9
Bansal, S., Goyal, M., Sharma, C., & Shekhar, S. (2021). Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: A randomized controlled trial. International Journal of Gynecology and Obstetrics, 152(3), 345–350. https://doi.org/10.1002/ijgo.13375
Danandjaja, J. (2014). Metode Penelitian Kepustakaan. Antropologi Indonesia, 0(52). https://doi.org/10.7454/ai.v0i52.3318
Hu, S., Yu, Q., Wang, Y., Wang, M., Xia, W., & Zhu, C. (2018). Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Archives of Gynecology and Obstetrics, 297(5), 1081–1088. https://doi.org/10.1007/s00404-018-4688-6
Joham, A. E., & Peña, A. S. (2022). Polycystic Ovary Syndrome in Adolescence. Seminars in Reproductive Medicine, 40(12). https://doi.org/10.1055/s-0042-1757138
Keevil. (2019). Steroid Mass Spectrometry for the Diagnosis of PCOS. Medical Sciences, 7(7). https://doi.org/10.3390/medsci7070078
Manique, M. E. S., & Ferreira, A. M. A. P. (2022). Polycystic Ovary Syndrome in Adolescence: Challenges in Diagnosis and Management. In Revista Brasileira de Ginecologia e Obstetricia (Vol. 44, Issue 4). https://doi.org/10.1055/s-0042-1742292
Mehdinejadiani, S., Amidi, F., Mehdizadeh, M., Barati, M., Safdarian, L., Aflatoonian, R., Alyasin, A., Aghahosseini, M., Pazhohan, A., Hayat, P., Mohammadzadeh kazorgah, F., & Sobhani, A. (2018). The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome. Gynecological Endocrinology, 34(9), 775–780. https://doi.org/10.1080/09513590.2018.1446934
Mejia, R. B., Summers, K. M., Kresowik, J. D., & Van Voorhis, B. J. (2019). A Randomized Controlled Trial of Combination Letrozole and Clomiphene Citrate or Letrozole Alone for Ovulation Induction in Women with Polycystic Ovary Syndrome. Obstetrical and Gynecological Survey, 74(6), 349–350. https://doi.org/10.1097/01.ogx.0000559835.21805.5b
Najafi, P. Z., Noghabi, S. P., Afzali, N., & Mohammadzadeh, S. (2020). Comparing the effect of clomiphene citrate and letrozole on ovulation induction in infertile women with polycystic ovary syndrome. Journal of the Pakistan Medical Association, 70(2), 268–271. https://doi.org/10.5455/JPMA.267607
Nylander, M., Frøssing, S., Clausen, H. V., Kistorp, C., Faber, J., & Skouby, S. O. (2017). Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial. Reproductive BioMedicine Online, 35(1). https://doi.org/10.1016/j.rbmo.2017.03.023
Park, C. H., & Chun, S. (2020). Influence of combined oral contraceptives on polycystic ovarian morphology-related parameters in Korean women with polycystic ovary syndrome. Obstetrics and Gynecology Science, 63(1). https://doi.org/10.5468/ogs.2020.63.1.80
Penzias, A., Bendikson, K., Falcone, T., Hansen, K., Hill, M., Jindal, S., Mersereau, J., Racowsky, C., Rebar, R., Steiner, A. Z., Stovall, D., Tanrikut, C., Kalra, S., Reindollar, R., & Hurd, W. (2020). Evidence-based treatments for couples with unexplained infertility: a guideline. Fertility and Sterility, 113(2). https://doi.org/10.1016/j.fertnstert.2019.10.014
Rezk, M., Shaheen, A. E., & Saif El-Nasr, I. (2018). Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial. Gynecological Endocrinology, 34(4), 298–300. https://doi.org/10.1080/09513590.2017.1395838
Saiyed, A., Jahan, N., Makbul, S. A. A., Ansari, M., Bano, H., & Habib, S. H. (2016). Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats. Integrative Medicine Research, 5(4). https://doi.org/10.1016/j.imr.2016.10.002
Sugiyono. (2017). Metode Penelitian Kuantitatif Kualitiatif dan R&D.
Sugiyono. (2018). Metode Penelitian Kuantitatif, Kualitatig, dan R&D. 456.
Sugiyono. (2019). Metode Penelitian Kuantitatif, Kualitatif, dan R&D (1st ed.). Penerbit Alfabeta.
Tsiami, A. P., Goulis, D. G., Sotiriadis, A. I., & Kolibianakis, E. M. (2021). Higher ovulation rate with letrozole as compared with clomiphene citrate in infertile women with polycystic ovary syndrome: a systematic review and meta-analysis. Hormones, 20(3), 449–461. https://doi.org/10.1007/s42000-021-00289-z
Wang, L., Lv, S., Li, F., Bai, E., & Yang, X. (2021). Letrozole Versus Clomiphene Citrate and Natural Cycle: Endometrial Receptivity During Implantation Window in Women With Polycystic Ovary Syndrome. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.532692
Wang, L., Wen, X., Lv, S., Zhao, J., Yang, T., & Yang, X. (2019). Comparison of endometrial receptivity of clomiphene citrate versus letrozole in women with polycystic ovary syndrome: a randomized controlled study. Gynecological Endocrinology, 35(10), 862–865. https://doi.org/10.1080/09513590.2019.1612358
Witchel, S. F., Oberfield, S. E., & Peña, A. S. (2019). Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment with Emphasis on Adolescent Girls. In Journal of the Endocrine Society (Vol. 3, Issue 8). https://doi.org/10.1210/js.2019-00078
Xi, W., Liu, S., Mao, H., Yang, Y., Xue, X., & Lu, X. (2015). Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: A prospective study. Drug Design, Development and Therapy, 9. https://doi.org/10.2147/DDDT.S83259
Xu, X. L., Deng, S. L., Lian, Z. X., & Yu, K. (2021). Estrogen receptors in polycystic ovary syndrome. In Cells (Vol. 10, Issue 2). https://doi.org/10.3390/cells10020459
Yan, Q., Qiu, D., Liu, X., Xing, Q., Liu, R., & Hu, Y. (2022). The incidence of gestational diabetes mellitus among women with polycystic ovary syndrome: a meta-analysis of longitudinal studies. BMC Pregnancy and Childbirth, 22(1). https://doi.org/10.1186/s12884-022-04690-3
Yu, Y., Fang, L., Zhang, R., He, J., Xiong, Y., Guo, X., Du, Q., Huang, Y., & Sun, Y. (2017). Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: A network meta-analysis. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-03803-9