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JOGC

No. 362-Ovulation Induction in Polycystic Ovary Syndrome

      Abstract

      Objective

      To review current non-pharmacologic and pharmacologic options for ovulation induction in women with polycystic ovary syndrome (PCOS).

      Options

      This guideline reviews the evidence for the various options for ovulation induction in PCOS.

      Outcomes

      Ovulation, pregnancy and live birth rates, risks, and side effects are the outcomes of interest.

      Evidence

      Published literature was retrieved through searches of Medline using appropriate controlled vocabulary and key words spanning from 2000 to 2016. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and of health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

      Values

      The evidence gathered was reviewed and evaluated by the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was quantified using the Canadian Task Force on Preventive Health Care.

      Benefits, Harms, and Costs

      Benefits include weight reduction and improvements in ovulation, pregnancy, and live birth rates. Potential harms include medication side effects and multiple pregnancies.

      Validation

      These guidelines have been reviewed and approved by the Reproductive Endocrinology and Infertility Committee of the SOGC.

      Conclusion

      First line management of infertility once a diagnosis of PCOS is made should include weight loss and exercise with goals to below class 2 obesity (BMI <35 kg/m2) as applicable. Subsequently, first line medical therapy for ovulation induction should include aromatase inhibitors (now considered both safe and effective) and selective estrogen receptor modulators as available. Insulin sensitizers should not be used as first line therapy but as adjuncts as appropriate. Referral to a reproductive endocrinologist should be considered if there is failure or resistance to these approaches to consider ovulation induction with gonadotropins or IVF as appropriate.

      Sponsor

      The Society of Obstetricians and Gynaecologists of Canada.

      Recommendations

      • 1.
        Weight loss, with a target of BMI <35 kg/m2 and/or 5% to 10% of bodyweight if overweight, through exercise and lifestyle modifications have been shown to be effective in restoring ovulatory cycles and achieving pregnancy in overweight individuals with polycystic ovary syndrome and should be the first-line option. However, the evidence is limited and not yet demonstrated in high-quality studies (II-3A). Morbidly obese (body mass index ≥40) individuals should seek expert advice through referral to qualified providers about safe weight loss strategies and pregnancy risk in this condition (III-A).
      • 2.
        Clomiphene citrate has been proven effective in ovulation induction for women with polycystic ovary syndrome and, where available, should be considered the first-line medical therapy. Patients should be informed that there is an increased risk of twin pregnancy or higher order multiples with ovulation induction using clomiphene citrate (I-A).
      • 3.
        Recent research has demonstrated both effectiveness and safety of aromatase inhibitors in their use for ovulation induction in polycystic ovary syndrome patients, particularly in the obese population. Where clomiphene citrate is not available, letrozole should be considered as an oral ovulation-induction agent after counselling patients on its classification as off-label use by Health Canada (I-B).
      • 4.
        Metformin combined with clomiphene citrate may increase ovulation and pregnancy rates but does not significantly improve the live birth rate over that of clomiphene citrate alone (I-A). Metformin may be added to clomiphene citrate in women with clomiphene resistance who are both older (age >28) and have visceral obesity (waist to hip ratio >0.85) (I-A).
      • 5.
        In cases of polycystic ovary syndrome with anovulatory cycles, gonadotropins should be considered second-line therapy for fertility. Gonadotropin treatment requires ultrasound and laboratory monitoring and is associated with high cost, high risk of cancellation due to higher than acceptable follicular development, risk of multiple births, and ovarian hyperstimulation syndrome (II-2A).
      • 6.
        When there are other indications for laparoscopy, laparoscopic ovarian drilling may be considered in cases of clomiphene and/or letrozole resistant polycystic ovary syndrome (I-A). The risks of surgery and decreased ovarian reserve should be considered (III-A).
      • 7.
        In vitro fertilization should be reserved for women with polycystic ovary syndrome who fail gonadotropin therapy or who have other indications for in vitro fertilization treatment (II-2A).

      Key Words

      Abbreviations:

      BMI (body mass index), CC (clomiphene citrate), CI (confidence interval), FSH (follicle stimulating hormone), IVF (in vitro fertilization), LH (luteinizing hormone), LOD (laparoscopic ovarian drilling), LTZ (letrozole), OR (odds ratio), PCOS (polycystic ovary syndrome)
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