Ovulation induction in polycystic ovarian syndrome - basics for gynecologist

Punita Yadav


Polycystic ovarian syndrome (PCOS) is the most common problem related to infertility among women. This review looked into the evidence and options available for ovulation induction. The management protocol and their respective efficacy was looked into during the write up of the review. Weight reduction, along with metformin therapy are the initial and efficient way to regain ovulation among obese female. This should be complemented by use of first line medicine like aromatase inhibitors and selective estrogen receptor modulators. The first line is effective in significant proportion of female to induce ovulation and increase live birth rate. However, for those not responding should initially undergo the use of gonadotropins and ovarian drilling. Finally, controlled ovarian stimulation and in vitro fertilization should be considered as it is an invasive, expensive and there are risks of ovarian hyperstimulation and multiple gestation.


PCOS, Ovulation induction, Gonadotropins, Live birth

Full Text:



Balaji S, Amadi C, Prasad S, Bala Kasav J, Upadhyay V, Singh AK, et al. Urban rural comparisons of polycystic ovary syndrome burden among adolescent girls in a hospital setting in India. Biomed Res Int. 2015;2015.

Joshi B, Mukherjee S, Patil A, Purandare A, Chauhan S, Vaidya R. A cross-sectional study of polycystic ovarian syndrome among adolescent and young girls in Mumbai, India. Indian J Endocrinol. 2014;18(3):317–24.

Clayton RN, Ogden V, Hodgkinson J, Worswick L, Rodin DA, Dyer S, et al. How common are polycystic ovaries in normal women and what is their significance for the fertility of the population? Clin Endocrinol. 1992;37(2):127–34.

Taylor AE, McCourt B, Martin KA, Anderson EJ, Adams JM, Schoenfeld D, et al. Determinants of Abnormal Gonadotropin Secretion in Clinically Defined Women with Polycystic Ovary Syndrome1. J Clin Endocrinol Metab. 1997;82(7):2248–56.

Dutta D. Amenorrhoea. Konar HL, Dutta D, Textbook of Gynecology. 6th ed. Jaypee Brothers; 2013:477.

Nahuis MJ, Oosterhuis GJE, Hompes PGA, Van Wely M, Mol BWJ, Van Der Veen F. The basic fertility workup in women with polycystic ovary syndrome: A systematic review. Fertil Steril. 2013;100(1):219–25.

Legro RS, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, et al. Randomized controlled trial of preconception interventions in infertile women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015;100(11):4048–58.

Palomba S, Falbo A, La Sala GB. Metformin and gonadotropins for ovulation induction in patients with polycystic ovary syndrome: A systematic review with meta-analysis of randomized controlled trials. 2014;12.

Huber-Buchholz MM, Carey DGP, Norman RJ. Restoration of Reproductive Potential by Lifestyle Modification in Obese Polycystic Ovary Syndrome: Role of Insulin Sensitivity and Luteinizing Hormone1. J Clin Endocrinol Metab. 1999;84(4):1470–4.

Al-Azemi M, Omu FE, Omu AE. The effect of obesity on the outcome of infertility management in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2004;270(4):205–10.

Robinson S, Kiddy D, Gelding S V., Willis D, Niththyananthan R, Bush A, et al. The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries. Clin Endocrinol (Oxf). 1993;39(3):351–5.

Nestler JE, Jakubowicz DJ. Decreases in Ovarian Cytochrome P450c17α Activity and Serum Free Testosterone after Reduction of Insulin Secretion in Polycystic Ovary Syndrome. N Engl J Med. 1996;335(9):617–23.

Fleming R, Hopkinson ZE, Michael Wallace A, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002;87(2):569–74.

Johnson NP, Stewart AW, Falkiner J, Farquhar CM, Milsom S, Singh VP, et al. PCOSMIC: A multi-centre randomized trial in women with PolyCystic Ovary syndrome evaluating metformin for infertility with clomiphene. Hum Reprod. 2010;25(7):1675–83.

Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Vol. 2017, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2017.

Lashen H. Review: Role of metformin in the management of polycystic ovary syndrome [Internet]. Vol. 1, Therapeutic Advances in Endocrinology and Metabolism. SAGE Publications; 2010;117–28.

Meirow D, Laufer N, Schenker JG. Ovulation induction in polycystic ovary syndrome: A review of conservative and new treatment modalities. Eur J Obstet Gynecol Reprod Biol. 1993;50(2):123–31.

Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. Clomiphene and anti-oestrogens for ovulation induction in PCOS [Internet]. Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2009.

Kousta E, White DM, Franks S. Modern use of clomiphene citrate in induction of ovulation [Internet]. Vol. 3, Human Reproduction Update. Oxford University Press. 1997;359–65.

Balen AH, Morley LC, Misso M, Franks S, Legro RS, Wijeyaratne CN, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: An analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22(6):687–708.

Gysler M, March CM, Mishell DR, Bailey EJ. A decade’s experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril. 1982;37(2):161–7.

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.

Rossing MA, Daling JR, Weiss NS, Moore DE, Self SG. Ovarian tumors in a cohort of infertile women. N Engl J Med; 1995;8L25–6.

Racette L, Casson PR, Claman P, Zackon DH, Casson EJ. An investigation of the visual disturbances experienced by patients on clomiphene citrate. Fertil Steril. 2010;93(4):1169–72.

Cole PA, Robinson CH. Mechanism and Inhibition of Cytochrome P-450 Aromatase. J Med Chem. 1990;33(11):2933–42.

Lee VCY, Ledger W. Aromatase inhibitors for ovulation induction and ovarian stimulation. Clin Endocrinol. 2011;74:537–46.

Franik S, Eltrop SM, Kremer JAM, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Databa Systemat Rev. 2018;2018.

Rahmani E, Ahmadi S, Motamed N, Maneshi HO. Clinical Study Dosage Optimization for Letrozole Treatment in Clomiphene-Resistant Patients with Polycystic Ovary Syndrome: A Prospective Interventional Study. Obstet Gynecol Int. 2012;2012.

Diamond MP, Legro RS, Coutifaris C, Alvero R, Robinson RD, Casson P, et al. Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility. N Engl J Med. 2015;373(13):1230–40.

Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P, et al. Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2014;371(2):119–29.

Dale PO, Tanbo T, Lunde O, Åbyholm T. Ovulation induction with low‐dose follicle‐stimulating hormone in women with the polycystic ovary syndrome. Acta Obstet Gynecol Scand. 1993;72(1):43–6.

Fauser BCJM, van Heusden AM. Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences*. Endocr Rev. 1997;18(1):71–106.

Homburg R, Howles CM. Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: Rationale, results, reflections and refinements. In: Human Reproduction Update. Hum Reprod Update. 1999;493–9.

Tarlatzis BC, Fauser BCJM, Legro RS, Norman RJ, Hoeger K, Pasquali R, et al. Consensus on infertility treatment related to polycystic ovary syndrome. In: Human Reproduction. Oxford University Press. 2008;462–77.

Balasch J, Tur R, Peinado JA. The safety and effectiveness of stepwise and low-dose administration of follicle stimulating hormone in WHO group II anovulatory infertile women: Evidence from a large multicenter study in Spain. J Assist Reprod Genet. 1996;13(7):551–6.

Kumar P, Sait SF, Sharma A, Kumar M. Ovarian hyperstimulation syndrome. J Hum Reprod Sci. 2011;4:70–5.

Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Freitas V. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2009.

Armar NA, McGarrigle HHG, Honour J, Holownia P, Jacobs HS, Lachelin GCL. Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: Endocrine changes and clinical outcome. Fertil Steril. 1990;53(1):45–9.

Agarwal S, Trolice MP. Pregnancy rates after laparoscopic ovarian drilling in polycystic ovary syndrome patients following unsuccessful ovulation induction. Fertil Steril. 2019;112(3):e414.

Bordewijk EM, Nahuis M, Costello MF, Van der Veen F, Tso LO, Mol BWJ, et al. Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome. Cochra Databa Systemat Rev. 2017;2017.

Guzick DS. Ovulation induction management of PCOS. Clin Obstet Gynecol. 2007;50(1):255–67.