Clinical efficacy of the use of myoinositol alone compared with clomiphene citrate alone and the combined use of both medications as regards the conception rates of patients with PCOS: A systematic review and meta‑analysis

Saadia,Zaheera; Memon,Muhammad Munir; Memon,Mushhood

doi:10.3892/wasj.2025.360

Clinical efficacy of the use of myoinositol alone compared with clomiphene citrate alone and the combined use of both medications as regards the conception rates of patients with PCOS: A systematic review and meta‑analysis

Authors:
- Zaheera Saadia
- Muhammad Munir Memon
- Mushhood Memon
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Affiliations: Department of Obstetrics and Gynecology, College of Medicine, Qassim University, Buraydah, Al‑Qassim 52571, Kingdom of Saudi Arabia, Department of Medicine, SBH Health System, Bronx, NY 10457, USA
Published online on: June 12, 2025 https://doi.org/10.3892/wasj.2025.360
Article Number: 72
Copyright : © Saadia et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Myoinositol and clomiphene citrate have been investigated for improving conception rates in patients with polycystic ovary syndrome (PCOS). However, the comparative efficacy of these treatments remains uncertain. The present study performed a systematic review and meta‑analysis in an aim to examine the efficacy of myoinositol and clomiphene citrate (CC), both as standalone treatments compared with a combination of myoinositol and CC, in enhancing fertility rates among patients with PCOS. For this purpose, a random‑effects model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals for the efficacy of myoinositol alone, CC alone, compared with the combination of myoinositol and clomiphene citrate, in improving conception rates in patients with PCOS. The pooled OR indicated no significant differences in conception rates between myoinositol and CC. However, myoinositol treatment was associated with improvements in other parameters, such as weight control and insulin resistance. On the whole, the present study demonstrates that myoinositol alone or in combination with CC does not improve the conception rates in patients with PCOS compared to the use of CC alone. However, myoinositol provides additional benefits in terms of weight control and insulin resistance.

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1	Bellver J, Rodríguez-Tabernero L, Robles A, Muñoz E, Martínez F, Landeras J, García-Velasco J, Fontes J, Álvarez M, Álvarez C, et al: Polycystic ovary syndrome throughout a woman's life. J Assist Reprod Genet. 35:25–39. 2018.PubMed/NCBI View Article : Google Scholar
2	Tanbo T, Mellembakken J, Bjercke S, Ring E, Åbyholm T and Fedorcsak P: Ovulation induction in polycystic ovary syndrome. Acta Obstet Gynecol Scand. 97:1162–1167. 2018.PubMed/NCBI View Article : Google Scholar
3	Palomba S, Falbo A, Russo T and Zullo F: Ovulation induction in anovulatory patients with polycystic ovary syndrome. Current Drug Therapy. 1:91–105. 2006.
4	Escobar-Morreale HF: Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 14:270–284. 2018.
5	Zahra M, Shah M, Ali A and Rahim R: Effects of metformin on endocrine and metabolic parameters in patients with polycystic ovary syndrome. Horm Metab Res. 49:103–108. 2017.PubMed/NCBI View Article : Google Scholar
6	Morley LC, Tang T, Yasmin E, Norman RJ and Balen AH: Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for patients with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 11(CD003053)2017.PubMed/NCBI View Article : Google Scholar
7	Cataldo NA, Barnhart HX, Legro RS, Myers ER, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, et al: Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome. J Clin Endocrinol Metab. 93:3124–3127. 2008.PubMed/NCBI View Article : Google Scholar
8	Chen X, He S and Wang D: Effects of metformin on body weight in polycystic ovary syndrome patients: Model-based meta-analysis. Expert Rev Clin Pharmacol. 14:121–130. 2021.PubMed/NCBI View Article : Google Scholar
9	Abu Hashim H: Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence? Reprod Biomed Online. 32:44–53. 2016.PubMed/NCBI View Article : Google Scholar
10	Malik M, Tasnim N and Mahmud G: Effect of metformin alone compared with metformin plus simvastatin on polycystic ovarian syndrome in Pakistani women. J Coll Physicians Surg Pak. 28:184–187. 2018.PubMed/NCBI View Article : Google Scholar
11	DiNicolantonio JJ and O'Keefe JH: Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes. Open Heart. 9(e001989)2022.PubMed/NCBI View Article : Google Scholar
12	Chandrasekaran S and Sagili H: Metabolic syndrome in patients with polycystic ovary syndrome. Obstet Gynaecol. 20:245–252. 2018.
13	Caprio F, D'Eufemia MD, Trotta C, Campitiello MR, Ianniello R, Mele D and Colacurci N: Myo-inositol therapy for poor-responders during IVF: A prospective controlled observational trial. J Ovarian Res 8: Article. 8(37)2015.PubMed/NCBI View Article : Google Scholar
14	Zain MM, Jamaluddin R, Ibrahim A and Norman RJ: Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: A randomized controlled trial. Fertil Steri. 91:514–521. 2009.PubMed/NCBI View Article : Google Scholar
15	Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, et al: RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 366(l4898)2019.PubMed/NCBI View Article : Google Scholar
16	Kamenov Z, Kolarov G, Gateva A, Carlomagno G and Genazzani AD: Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol. 31:131–135. 2015.PubMed/NCBI View Article : Google Scholar
17	Parveen S, Iram N, Saeed BZ, Yaqub U and Niazi NK: Clomiphene supported ovulation induction in subfertile polycystic ovary syndrome women: Role of different insulin sensitizers. Pak Armed Forces Med J. 73(810)2023.
18	Rolland AL, Peigné M, Plouvier P, Dumont A, Catteau-Jonard S and Dewailly D: Could myo-inositol soft gel capsules outperform clomiphene in inducing ovulation? Results of a pilot study. Eur Rev Med Pharmacol Sci. 21 (Suppl 2):S10–S14. 2017.PubMed/NCBI
19	Taş M and Özçelik B: Does the combination of myo-inositol improve pregnancy outcomes in obese polycystic ovary syndrome women undergoing ovarian stimulation with clomiphene citrate? J Surg Med. 3:707–710. 2019.
20	Nakamura Y, Ono M, Yoshida Y, Sugino N, Ueda K and Kato H: Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium. Fertil Steril. 67:256–260. 1997.PubMed/NCBI View Article : Google Scholar
21	ESHRE Capri Workshop Group. Health and fertility in World Health Organization group 2 anovulatory women. Hum Reprod Update. 18:586–599. 2012.PubMed/NCBI View Article : Google Scholar
22	Palomba S, Piltonen TT and Giudice LC: Endometrial function in women with polycystic ovary syndrome: A comprehensive review. Hum Reprod Update. 27:584–618. 2021.PubMed/NCBI View Article : Google Scholar
23	Hamilton-Fairley D, Kiddy D, Watson H, Paterson C and Franks S: Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. Br J Obstet Gynaecol. 99:128–131. 1992.PubMed/NCBI View Article : Google Scholar
24	Kumar P, Nawani N, Malhotra N, Malhotra J, Patil M, Jayakrishnan K, Kar S, Jirge PR and Mahajan N: Assisted reproduction in polycystic ovarian disease: A multicentric trial in India. J Hum Reprod Sci. 6:49–53. 2013.PubMed/NCBI View Article : Google Scholar
25	Siristatidis CS, Maheshwari A, Vaidakis D and Bhattacharya S: In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction. Cochrane Database Syst Rev: CD006606, 2013.
26	Pundir J, Psaroudakis D, Savnur P, Bhide P, Sabatini L, Teede H, Coomarasamy A and Thangaratinam S: Inositol treatment of anovulation in women with polycystic ovary syndrome: A meta-analysis of randomised trials. BJOG. 125:299–308. 2018.PubMed/NCBI View Article : Google Scholar
27	Kousta E, White DM and Franks S: Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update. 3:359–365. 1997.PubMed/NCBI View Article : Google Scholar
28	Massai MR, de Ziegler D, Lesobre V, Bergeron C, Frydman R and Bouchard P: Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment. Fertil Steril. 59:1179–1186. 1993.PubMed/NCBI View Article : Google Scholar
29	Emekçi Özay Ö, Özay AC, Çağlıyan E, Okyay RE and Gülekli B: Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: A prospective, controlled, randomized trial. Gynecol Endocrinol. 33:524–528. 2017.PubMed/NCBI View Article : Google Scholar
30	Benelli E, Del Ghianda S, Di Cosmo C and Tonacchera M: A combined therapy with Myo-Inositol and D-Chiro-Inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. Int J Endocrinol. 2016(3204083)2016.PubMed/NCBI View Article : Google Scholar
31	Gerli S, Mignosa M and Di Renzo GC: Effects of inositol on ovarian function and metabolic factors in women with PCOS: A randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci. 7:151–159. 2023.PubMed/NCBI
32	Etrusco A, Laganà AS, Chiantera V, Buzzaccarini G and Unfer V: Myo-inositol in assisted reproductive technology from bench to bedside. Trends Endocrinol Metab. 35:74–83. 2024.PubMed/NCBI View Article : Google Scholar