Clomiphene citrate alone versus combined metformin and clomiphene citrate versus combined metformin and clomiphene citrate and drilling versus metformin alone in infertile Indian women with PCOS: a prospective cross-sectional study
Keywords:Clomiphene, Hyperinsulinemia, Infertility, Metformin, Ovarian drilling, Polycystic ovarian syndrome
Background: Polycystic ovary syndrome (PCOS) is a common cause of infertility and is associated with chronic anovulation and hyperandrogenemia. With associated features like irregular menses, acne and hirsuitism. It is seen in approximately 6% of women in reproductive age group and is one of the most common reproductive abnormality and endocrinopathy. Clomiphene Citrate remains the mainstay of this disorder however addition of metformin to it has been known to improve ovulation and pregnancy. The aim and objectives of the present study were to diagnose the patients with PCOS out of all patients who present with complaints of infertility, to compare ovulation and conception rates with Clomiphene Citrate alone V/S Combined Metformin and Clomiphene Citrate V/S Combined Metformin and Clomiphene Citrate and Drilling V/S metformin alone in Infertile Indian Women with PCOS.
Methods: A total of 50 cases with PCOS, in women of age group between 20 to 35 years was studied from June 2017 to December 2017. All of them having chief complain of infertility. Endocrino-histologic correlation and laparoscopic evaluation was confirmed by history, clinical manifestations, USG, laboratory investigations (LH, FSH, Insulin levels etc.) and laparoscopy was done.
Results: After administration of Insulin sensitizing agent, Tab. Metformin, 500mg 1 TDS, in management of PCOS who have hyperinsulinemic insulin resistance, there was ovulation with regular menstrual cycles, followed by pregnancy and full term deliveries. Thus, metformin definitely has a role in treatment of PCOS.
Conclusions: Metformin down regulated the hyperstimulated reproductive axis and allows for reversal to normoandrogenic state. Hence adding metformin to CC leads to increased ovulatory and conception rates as compared to either of them alone. In cases of laproscopic ovarian drilling spontaneous pregnancy rates showed no statistically significant correlation between the degree of fall in AMH but the chances of successful conception may improve after Ovarian drilling.
Heard MJ, Pierce A, Carson SA, Buster JE. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril 2002;77(4):669-73.
National Collaborating Centre for Women’s and Children’s Health/National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. In:RCOGPress; 2004;11:57-8.
Beck JI, Boothroyd C, Proctor M, Farquhar C, Hughes E. Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev 2005;1(3):CD002249.
Randall JM, Templeton A. Cervical mucus score and in vitro sperm mucus interaction in spontaneous and CC citrate cycles. Fertil Steril 1991;56(3):465-8.
Nakamura Y, Ono M, Yoshida Y, Sugino N, Ueda K, Kato H. Effects of CC on the endometrial thickness and echogenic pattern of the endometrium. Fertil Steril 1997;67(2):256-60.
Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv 2004;59(2):141-54.
Siebert TI, Kruger TF, Steyn DW, Nosarka S. Is the addition of metformin efficacious in the treatment clomiphene citrate-resistant patients with polycystic ovary syndrome? A structured literature review. Fertil Steril 2006;86(5):1432-7.
Malkawi HY, Qublan HS. The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome. Saudi Med J 2002;23(6):663-6.
Vandermolen DT, Ratts V, Evans WS, Stovall DW, Kauma SW, Nester JE. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patient with polycystic ovary syndrome who is resistant to clomiphene citrate alone. Fertil Steril 2001;75(2):310-5.
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.
Mumford SL, Legro RS, Diamond MP, Coutifaris C, Steiner AZ, Schlaff WD et al. Baseline AMH Level Associated With Ovulation Following Ovulation Induction in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2016;101(9):3288-96.
La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010;16(2):113-30.
Maria JI, Nestler JE. Insulin-lowering drugs in polycystic ovary syndrome. Obstet Gynecol Clin North Am. 2001;28(1):153-64
Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kauma SW, Nestler JE. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril. 2001;75(2):310-5.
Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: Systematic review and meta-analysis. Br Med J. 2003;327(7421):951-3.
Malkawi HY, Qublan HS. The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome. Saudi Med J. 2002;23(6):663-6.
Labo RA, Granger LR, Davajan V, Mishell DR., Jr An extended regimen of clomiphene citrate in women unresponsive to standard therapy. Fertil Steril. 1982;37(6):462-6.
Batukan C, Baysal B. Metformin improves ovulation and pregnancy rates in patients with polycystic ovarian syndrome. Arch Gynecol Obstet. 2001;265(3):124-7.
Boostanfar R, Jain JK, Mishell DR, Jr, Paulson RJ. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril. 2001;75(5):1024-6.
Memon Z, Karim N, Agha F. Effect of metformin versus clomiphene citrate on ovulation and conception rate in polycystic ovarian syndrome patients. J Basic Appl Sci. 2011;7:55-9.
Katsiki N, Georgiadou E, Hatzitolios AI. The role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Drugs. 2009;69(11):1417-31.
Zain MM, Jamaluddin R, Ibrahim A, 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 Steril. 2009;91(2):514-21.
Pasquali R, Gambineri A. Insulin-sensitizing agents in polycystic ovary syndrome. Eur J Endocrinol. 2006;154:763-75.
Dasari P, Pranahita GK. The efficacy of metformin and clomiphene citrate combination compared with clomiphene citrate alone for ovulation induction in infertile patients with PCOS. J Hum Reprod Sci. 2009;2(1):18-22.
Neveu N, Granger L, St-Michel P, Lavoie HB. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertil Steril. 2007;87(1):113-20.
Jungheim ES, Odibo AO. Fertility treatment in women with polycystic ovary syndrome: A decision analysis of different oral ovulation induction agents. Fertil Steril. 2010;94(7):2659-64.