Efektivitas Metformin dalam Meningkatkan Kehamilan Klinis dan Angka Kelahiran Hidup pada Wanita dengan PCOS: Tinjauan Naratif dengan Implikasi bagi Kesehatan Masyarakat

Authors

  • Juwana Janu Institut Teknologi Sumatera
  • Reny Haryani Institut Teknologi Sumatera

DOI:

https://doi.org/10.54259/sehatrakyat.v4i3.5320

Keywords:

Metformin, Clinical Pregnancy, Live Birth Rate, Infertile, PCOS

Abstract

Infertility due to ovulatory disorders presents a significant challenge in reproductive health, with Polycystic Ovary Syndrome (PCOS) being one of the leading causes. Metformin has been widely used in clinical practice to manage ovulatory dysfunction in women with PCOS, either as monotherapy or in combination with other therapeutic approaches. This narrative review aims to evaluate the effectiveness of metformin on clinical pregnancy rate (CPR) and live birth rate (LBR) through a critical appraisal of nine scientific publications published in the past ten years. Relevant literature was gathered through the PubMed database using selected keywords and screened based on predefined inclusion and exclusion criteria. Findings indicate that metformin provides beneficial effects on improving CPR, particularly when used as an adjunct therapy prior to IVF protocols or in combination with non-pharmacological approaches such as acupuncture. However, evidence related to LBR demonstrates greater variability. Overall, these findings support the role of metformin as part of an individualized, evidence-based fertility treatment strategy. This review offers important clinical implications for optimizing infertility management in women with PCOS.

Downloads

Download data is not yet available.

References

Agrawal, A., Mahey, R., Kachhawa, G., Khadgawat, R., Vanamail, P., & Kriplani, A. (2019). Comparison of metformin plus myoinositol vs metformin alone in PCOS women undergoing ovulation induction cycles: Randomized controlled trial. Gynecological Endocrinology, 35(6), 511–514. https://doi.org/10.1080/09513590.2018.1549656

Arlt, W., Witchel, S. F., Tauber, M., Thilenius, M., & Homburg, R. (2022). Polycystic ovary syndrome. Nature Reviews Disease Primers, 8(1), 20. https://doi.org/10.1038/s41572-022-00361-1

Bäsian, L., et al. (2019). SANRA—a scale for the quality assessment of narrative review articles. Research Integrity and Peer Review. https://doi.org/10.1186/s41073-019-0064-8

Benmachiche, A., Benbouhedja, S., Zoghmar, A., & Humaidan, P. (2019). Supplementation with metformin improves clinical pregnancy rate in PCOS women undergoing ART. Frontiers in Endocrinology, 10, 681. https://doi.org/10.3389/fendo.2019.00681

Boomsma, C. M., Eijkemans, M. J., Hughes, E. G., Visser, G. H., Fauser, B. C., & Macklon, N. S. (2006). A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Human Reproduction Update, 12(6), 673–683. https://doi.org/10.1093/humupd/dml036

Bordewijk, E. M., Nahuis, M., Costello, M. F., van der Veen, F., Tso, L. O., Mol, B. W. J., & van Wely, M. (2017). Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome. Cochrane Database of Systematic Reviews, 2017(1), CD009090. https://doi.org/10.1002/14651858.CD009090.pub2

Chen, X., Lan, Y., Yang, L., Liu, Y., Li, H., Zhu, X., Zhao, Y., Long, C., Wang, M., Xie, Q., Li, Z., & Wu, J. (2022). Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis. Frontiers in Endocrinology, 13, 978280. https://doi.org/10.3389/fendo.2022.978280

Christ, J. P., & Cedars, M. I. (2023). Current guidelines for diagnosing PCOS. Diagnostics, 13(6), 1113. https://doi.org/10.3390/diagnostics13061113

Costello, M. F., Misso, M. L., Balen, A., Legro, R. S., Bhattacharya, S., Norman, R. J., & Teede, H. J. (2019). A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome. Australian and New Zealand Journal of Obstetrics and Gynaecology, 59(6), 867–873. https://doi.org/10.1111/ajo.13051

Escobar-Morreale, H. F., Roldán-Valadez, E., Chacín-Bodereau, C., López-Yacó, Y., & San Miguel, G. (2020). Insulin resistance in polycystic ovary syndrome across various tissues. Journal of Ovarian Research, 13(1), 123. https://doi.org/10.1186/s13048-020-00699-5

Ferrari, R. (2015). Writing narrative style literature reviews. Medical Writing, 24(4), 230–235. https://doi.org/10.1179/2047480615Z.000000000329

Ghazeeri, G., Rahme, M., Fahed, M., Semaan, A. B., & Meshel, H. (2022). Markers of insulin resistance in polycystic ovary syndrome women. Journal of Ovarian Research, 15(1), 1–18. https://doi.org/10.1186/s13048-022-01091-0

Himpunan Endokrinologi Reproduksi dan Fertilitas Indonesia (HIFERI), Perkumpulan Fertilisasi In Vitro Indonesia (PERFITRI), Ikatan Ahli Urologi Indonesia (IAUI), Perhimpunan Dokter Spesialis Andrologi Indonesia (PERSANDI), & Perkumpulan Obstetri dan Ginekologi Indonesia (POGI). (2019). Konsensus penanganan infertilitas (Edisi ke-2). Departemen Obstetri dan Ginekologi, Fakultas Kedokteran Universitas Indonesia/RSUPN dr. Cipto Mangunkusumo.

Kar, S., & Sanchita, S. (2015). Clomiphene citrate, metformin or a combination of both as the first line ovulation induction drug for Asian Indian women with polycystic ovarian syndrome: A randomized controlled trial. Journal of Human Reproductive Sciences, 8(4), 197–201. https://doi.org/10.4103/0974-1208.170373

Kementerian Kesehatan Republik Indonesia. (2022, Mei 23). Kemandulan (infertil): Stigma negatif pada wanita Indonesia. https://keslan.kemkes.go.id/view_artikel/12/kemandulan-infertil-stigma-negatif-pada-wanita-indonesia

Lord, J. M., Flight, I. H., & Norman, R. J. (2003). Metformin in polycystic ovary syndrome: Systematic review and meta-analysis. BMJ, 327(7421), 951–953. https://doi.org/10.1136/bmj.327.7421.951

Maheshwari, A., Bell, J., Bhide, P., Brison, D., Bhattacharya, S., Burleigh, A., et al. (2017). Toward a standardization of live birth rate as an outcome measure for clinical trials in assisted reproduction: A consensus statement. Fertility and Sterility, 108(2), 255–260.e3. https://doi.org/10.1016/j.fertnstert.2017.05.027

Naseem, H. S., Rehman, R., & Habib, S. (2021). Induction of ovulation. Obstetrics, Gynaecology and Reproductive Medicine, 31(5), 127–130. https://doi.org/10.1016/j.ogrm.2021.02.004

Palomba, S., Orio, F., Falbo, A., Manguso, F., Russo, T., Cascella, T., Tolino, A., Carmina, E., Colao, A., & Zullo, F. (2005). Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 90(7), 4068–4074. https://doi.org/10.1210/jc.2005-0110

Palomba, S., Santagni, S., & La Sala, G. B. (2015). Complications and challenges associated with polycystic ovary syndrome: Current perspectives. International Journal of Women's Health, 7, 745–763. https://doi.org/10.2147/IJWH.S70314

Prabhakar, P., Mahey, R., Gupta, M., Khadgawat, R., Kachhawa, G., Sharma, J. B., Vanamail, P., Kumari, R., & Bhatla, N. (2021). Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles: Randomized controlled trial. Gynecological Endocrinology, 37(4), 332–336. https://doi.org/10.1080/09513590.2020.1810657

Rajasekaran, K., Malhotra, N., Mahey, R., Khadgawat, R., & Kalaivani, M. (2021). Myoinositol versus metformin pretreatment in GnRH-antagonist cycle for women with PCOS undergoing IVF: A double-blinded randomized controlled study. Gynecological Endocrinology, 38(2), 140–147. https://doi.org/10.1080/09513590.2021.1981282

Taheripanah, R., Kazemi, S. N., Taheripanah, A., & Fereidoonjah, S. (2024). A randomized controlled trial comparing pioglitazone and metformin prior to in vitro fertilization in polycystic ovary syndrome-associated infertile women: Impact on pregnancy rates. Annals of Medicine and Surgery, 86(5), 2696–2701. https://doi.org/10.1097/MS9.0000000000001816

Tang, T., Lord, J. M., Norman, R. J., Yasmin, E., & Balen, A. H. (2012). Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews, (5), CD003053. https://doi.org/10.1002/14651858.CD003053.pub5

Teede, H. J., Misso, M. L., Costello, M. F., Dokras, A., Laven, J., Moran, L. J., et al. (2018). Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertility and Sterility, 108(3), 393–406. https://doi.org/10.1016/j.fertnstert.2017.06.005

Teede, H. J., Misso, M. L., Costello, M. F., Dokras, A., Laven, J., Moran, L. J., ... & Norman, R. J. (2023). Recommendations from the international evidence-based guideline for the assessment and management of PCOS. Human Reproduction, 38(1), 14–29. https://doi.org/10.1093/humrep/deac049

Tso, L. O., Costello, M. F., Albuquerque, L. E. T., Andriolo, R. B., & Macedo, C. R. (2020). Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews, 2020(12), CD006105. https://doi.org/10.1002/14651858.CD006105.pub4

Unanyan, A., Pivazyan, L., Krylova, E., Eskin, A., Zakaryan, A., Sarkisova, A., & Ishchenko, A. (2022). Effectiveness of inositol, metformin and their combination in women with PCOS undergoing assisted reproduction: Systematic review and meta-analysis. Gynecological Endocrinology, 38(12), 1035–1046. https://doi.org/10.1080/09513590.2022.2136160

Wang, R., Mol, B. W., & Legro, R. S. (2023). Role of metformin in the treatment of polycystic ovary syndrome. Lancet Diabetes & Endocrinology, 11(2), 98–109. https://doi.org/10.1016/S2213-8587(22)00301-9

Wang, J., Wang, B., Li, C., Meng, T., Liu, C., Chen, J., & Guo, Y. (2025). Evolving global trends in PCOS burden: A three-decade analysis (1990–2021) with projections to 2036 among adolescents and young adults. Frontiers in Endocrinology, 16, 1569694. https://doi.org/10.3389/fendo.2025.1569694

World Health Organization. (2023). Infertility – Diagnosis and treatment. World Health Organization. Retrieved July 26, 2025, from https://www.who.int/health-topics/infertility#tab=tab_3

Zegers-Hochschild, F., Adamson, G. D., Dyer, S., Racowsky, C., de Mouzon, J., Sokol, R., et al. (2017). The International Glossary on Infertility and Fertility Care, 2017. Fertility and Sterility, 108(3), 393–406. https://doi.org/10.1016/j.fertnstert.2017.06.005

Downloads

Published

2025-08-10

How to Cite

Juwana Janu, & Reny Haryani. (2025). Efektivitas Metformin dalam Meningkatkan Kehamilan Klinis dan Angka Kelahiran Hidup pada Wanita dengan PCOS: Tinjauan Naratif dengan Implikasi bagi Kesehatan Masyarakat. Sehat Rakyat: Jurnal Kesehatan Masyarakat, 4(3), 478–492. https://doi.org/10.54259/sehatrakyat.v4i3.5320