Is the Co-administration of Metformin and Clomiphene Superior to Induce Ovulation in Infertile Patients With Poly Cystic Ovary Syndrome and Confirmed Insulin-Resistance: A Double Blind Randomized Clinical Trial

Overview

Journal J Family Reprod Health

Date 2023 Aug 4

PMID 37538230

Authors

Azam Azargoon

Human Mousavi Fatemi

Majid Mirmohammadkhani

Satinik Darzi

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to compare the effects of clomiphene citrate (CC) combined with metformin or placebo on infertile patients with poly cystic ovary syndrome (PCOS) and insulin resistance (IR).

Materials And Methods: We included 151 infertile women with PCOS and IR in a university hospital from November 2015 to April 2022 in this prospective, double-blind, randomized, placebo-controlled trial. Patients were randomized into two groups; group A: received CC plus metformin (n = 76) and group B: received CC plus placebo (n = 75). The ovulation rate was the main outcome measure. Clinical pregnancy, ongoing pregnancy, live birth and abortion rates were secondary outcome measures.

Results: There was no remarkable difference in ovulation rate in two groups. Moreover, no significant changes were observed in clinical pregnancy, ongoing pregnancy, live birth and abortion rates between two groups. A larger proportion of women in group A suffered from side effects of metformin (9.3% versus 1.4%; p=0.064), although this was not significant.

Conclusion: In IR infertile women with PCOS, metformin pre-treatment did not increase the ovulation, clinical pregnancy and live birth rates in patients on clomiphene citrate.

Citing Articles

Transvaginal ovarian drilling for polycystic ovary syndrome prior to in vitro fertilization dramatically improves embryo yield, implantation, and ongoing pregnancy rates.

Rubin S, Bibi M, Breborowicz A, Chau P, Keltz M J Assist Reprod Genet. 2024; .

PMID: 39718714 DOI: 10.1007/s10815-024-03362-9.

References

Moll E, van der Veen F, van Wely M . The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update. 2007; 13(6):527-37. DOI: 10.1093/humupd/dmm026. View

Nestler J, Jakubowicz D, Evans W, Pasquali R . Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med. 1998; 338(26):1876-80. DOI: 10.1056/NEJM199806253382603. View

Leanza V, Coco L, Grasso F, Leanza G, Zarbo G, Palumbo M . Ovulation induction with clomiphene citrate and metformin in women with polycystic ovary syndrome. Minerva Ginecol. 2014; 66(3):299-301. View

. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1):19-25. DOI: 10.1016/j.fertnstert.2003.10.004. View

Moll E, Bossuyt P, Korevaar J, Lambalk C, van der Veen F . Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ. 2006; 332(7556):1485. PMC: 1482338. DOI: 10.1136/bmj.38867.631551.55. View

Hosseinpanah F, Barzin M, Tehrani F, Azizi F . The lack of association between polycystic ovary syndrome and metabolic syndrome: Iranian PCOS prevalence study. Clin Endocrinol (Oxf). 2011; 75(5):692-7. DOI: 10.1111/j.1365-2265.2011.04113.x. View

March W, Moore V, Willson K, Phillips D, Norman R, Davies M . The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2009; 25(2):544-51. DOI: 10.1093/humrep/dep399. View

Legro R, Barnhart H, Schlaff W, Carr B, Diamond M, Carson S . Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007; 356(6):551-66. DOI: 10.1056/NEJMoa063971. View

Legro R, Schlaff W, Diamond M, Coutifaris C, Casson P, Brzyski R . Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism. J Clin Endocrinol Metab. 2010; 95(12):5305-13. PMC: 2999971. DOI: 10.1210/jc.2010-1123. View

10.

Hasegawa I, Murakawa H, Suzuki M, Yamamoto Y, Kurabayashi T, Tanaka K . Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome. Fertil Steril. 1999; 71(2):323-7. DOI: 10.1016/s0015-0282(98)00454-3. View

11.

Lebovitz H . Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes. 2001; 109 Suppl 2:S135-48. DOI: 10.1055/s-2001-18576. View

12.

Nestler J, Jakubowicz D . Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab. 1997; 82(12):4075-9. DOI: 10.1210/jcem.82.12.4431. View

13.

Liu K, Tataryn I, Sagle M . Use of metformin for ovulation induction in women who have polycystic ovary syndrome with or without evidence of insulin resistance. J Obstet Gynaecol Can. 2006; 28(7):595-599. DOI: 10.1016/S1701-2163(16)32202-2. View

14.

Kocak M, Caliskan E, Simsir C, Haberal A . Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril. 2002; 77(1):101-6. DOI: 10.1016/s0015-0282(01)02941-7. View

15.

Johnson N . Metformin is a reasonable first-line treatment option for non-obese women with infertility related to anovulatory polycystic ovary syndrome--a meta-analysis of randomised trials. Aust N Z J Obstet Gynaecol. 2011; 51(2):125-9. DOI: 10.1111/j.1479-828X.2010.01274.x. View

16.

Cooper T, Noonan E, von Eckardstein S, Auger J, Baker H, Behre H . World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2009; 16(3):231-45. DOI: 10.1093/humupd/dmp048. View

17.

Sharpe A, Morley L, Tang T, Norman R, Balen A . Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019; 12:CD013505. PMC: 6915832. DOI: 10.1002/14651858.CD013505. View

18.

SHEPARD M, Balmaceda J, Leija C . Relationship of weight to successful induction of ovulation with clomiphene citrate. Fertil Steril. 1979; 32(6):641-5. DOI: 10.1016/s0015-0282(16)44411-0. View

19.

Acbay O, Gundogdu S . Can metformin reduce insulin resistance in polycystic ovary syndrome?. Fertil Steril. 1996; 65(5):946-9. View

20.

Horowitz E, Weissman A . The stair-step approach in treatment of anovulatory PCOS patients. Ther Adv Reprod Health. 2020; 14:2633494120908818. PMC: 7254579. DOI: 10.1177/2633494120908818. View