Benefits, Harms, and Costs
- 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).
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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- Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.J Clin Endocrinol Metab. 1998; 83: 3078-3082
- A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile.J Clin Endocrinol Metab. 1999; 84: 4006-4011
- A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.J Clin Endocrinol Metab. 2000; 85: 2434-2438
- Polycystic ovaries and associated clinical and biochemical features in young women.Clin Endocrinol (Oxf). 1999; 51: 779-786
- Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.Fertil Steril. 2004; 81: 19-25
- The effect of obesity on the outcome of infertility management in women with polycystic ovary syndrome.Arch Gynecol Obstet. 2004; 270: 205-210
- The role of lifestyle modification in polycystic ovary syndrome.Trends Endocrinol Metab. 2002; 13: 251-257
- Improving reproductive performance in overweight/obese women with effective weight management.Hum Reprod Update. 2004; 10: 267-280
- Obesity and lifestyle management in polycystic ovary syndrome.Clin Obstet Gynecol. 2007; 50: 277-294
- The impact of obesity on reproduction in women with polycystic ovary syndrome.BJOG. 2006; 113: 1148-1159
- Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome.Fertil Steril. 2011; 96: 1508-1513
- Evaluation of ovarian functionality after a dietary treatment in obese women with polycystic ovary syndrome.Eur J Obstet Gynecol Reprod Biol. 2005; 119: 87-93
- Effect of body weight reduction on plasma androgens in obese, infertile women.Fertil Steril. 1982; 38: 406-409
- Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment.Hum Reprod. 1998; 13: 1502-1505
- Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome.Clin Endocrinol (Oxf). 1992; 36: 105-111
- Clinical gynecologic endocrinology and infertility.Lippincott Williams & Wilkins, Pennsylvania2005
- Clinical and laboratory predictors of clomiphene response.Fertil Steril. 1982; 37: 168-174
- A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome.Fertil Steril. 2004; 81: 630-637
- Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2003; 88: 812-819
- Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone.J Clin Endocrinol Metab. 1999; 84: 1470-1474
- New advances in ovulation induction.Curr Opin Obstet Gynecol. 2007; 19: 248-252
- Modern use of clomiphene citrate in induction of ovulation.Hum Reprod Update. 1997; 3: 359-365
- The effect of therapy initiation day on clomiphene citrate therapy.Fertil Steril. 1989; 52: 564-568
- Product monograph, Clomid Revised: July 21, 2009.(Available at)http://products.sanofi.ca/en/clomid.pdfDate: 2006Date accessed: March 5, 2010
- ACOG practice bulletin. Management of infertility caused by ovulatory dysfunction. Number 34, February 2002. American College of Obstetricians and Gynecologists.Int J Gynaecol Obstet. 2002; 77: 177-188
- Single luteal phase serum progesterone assay as an indicator of ovulation.Am J Obstet Gynecol. 1972; 112: 1043-1046
- 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: 113-120
- A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test.Fertil Steril. 1982; 37: 161-167
- Monitoring plasma concentrations to individualize treatment with clomiphene citrate.Fertil Steril. 2004; 81: 1187-1193
- Transvaginal sonographic assessment of follicular and endometrial growth in spontaneous and clomiphene citrate cycles.Fertil Steril. 1991; 56: 208-212
- Relationship of endometrial thickness and pattern to fecundity in ovulation induction cycles: effect of clomiphene citrate alone and with human menopausal gonadotropin.Fertil Steril. 1993; 59: 756-760
- Endometrial thickness cannot predict ongoing pregnancy achievement in cycles stimulated with clomiphene citrate for intrauterine insemination.Reprod Biomed Online. 2004; 8: 115-118
- Development, pharmacology and clinical experience with clomiphene citrate.Hum Reprod Update. 1996; 2: 483-506
- An investigation of the visual disturbances experienced by patients on clomiphene citrate.Fertil Steril. 2010; 93: 1169-1172
- Ovarian tumors in a cohort of infertile women.N Engl J Med. 1994; 331: 771-776
- Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial.Fertil Steril. 2006; 86: 1447-1451
- Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate.Fertil Steril. 2001; 75: 305-309
- A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation.Fertil Steril. 2004; 82: 1561-1563
- Totongy M. Clomiphene citrate or aromatase inhibitors for superovulation in women with unexplained infertility undergoing intrauterine insemination: a prospective randomized trial.Fertil Steril. 2009; 92: 1355-1359
- Health Canada Endorsed Important Safety Information on Femara (letrozole).(Available at)http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2005/14326a-eng.phpDate: 2005Date accessed: July 31, 2007
- The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins.Fertil Steril. 2005; 84: S95
- Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate.Fertil Steril. 2006; 85: 1761-1765
- Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.N Engl J Med. 2014; 371: 119-129
- CFAS Position Statement on the Use of Letrozole for the Management of Infertility.2015
- Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.N Engl J Med. 1996; 335: 617-623
- Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.J Clin Endocrinol Metab. 2000; 85: 139-146
- Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.Obstet Gynecol. 1997; 90: 392-395
- Effects of short-term and long-term metformin treatment on menstrual cyclicity in women with polycystic ovary syndrome.Fertil Steril. 2006; 86: 230-232
- Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.N Engl J Med. 1998; 338: 1876-1880
- Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.Fertil Steril. 2002; 77: 101-106
- 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: 310-315
- Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin.Hum Reprod. 2002; 17: 2858-2864
- Metformin in polycystic ovary syndrome: systematic review and meta-analysis.BMJ. 2003; 327: 951-953
- Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis.BMJ. 2017; 356: j138
- Use of metformin in polycystic ovary syndrome: a meta-analysis.Obstet Gynecol. 2008; 111: 959-968
- Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.Cochrane Database Syst Rev. 2012; (CD003053)
- Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial.Hum Reprod. 2001; 16: 1625-1631
- Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.N Engl J Med. 2007; 356: 551-566
- The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome.Eur J Obstet Gynecol Reprod Biol. 2004; 113: 214-220
- Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome.Int J Gynaecol Obstet. 2005; 90: 39-43
- Is the addition of metformin efficacious in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome? A structured literature review.Fertil Steril. 2006; 86: 1432-1437
- Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?.Hum Reprod. 2008; 23: 1830-1834
- Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.J Clin Endocrinol Metab. 2002; 87: 524-529
- Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin.Fertil Steril. 2006; 85: 1002-1009
- Metformin reduces abortion in pregnant women with polycystic ovary syndrome.Gynecol Endocrinol. 2006; 22: 680-684
- Ovulation induction management of PCOS.Clin Obstet Gynecol. 2007; 50: 255-267
- Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open trial.BJOG. 2003; 110: 1072-1077
- A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.Hum Reprod Update. 2006; 12: 13-21
- Surgical treatment of bilateral polycystic ovaries – Amenorrhea and sterility.Am J Obstet Gynecol. 1939; 38: 465-480
- Post-ovarian wedge resection adhesive disease.Fertil Steril. 1975; 26: 874-876
- Laparoscopic “drilling” by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.Cochrane Database Syst Rev. 2007; (CD001122)
- Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial.BMJ. 2004; 328: 192
- Evaluation of ovarian adhesion formation after laparoscopic ovarian drilling by second-look minilaparoscopy.Fertil Steril. 2008; 89: 1229-1233
- Ovarian electrocautery in the treatment of women with polycystic ovary syndrome (PCOS). Factors affecting the results.Acta Obstet Gynecol Scand. 1994; 73: 407-412
- Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.Cochrane Database Syst Rev. 2012; (CD001122)
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