Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-l4dxg Total loading time: 0 Render date: 2025-01-19T03:35:20.376Z Has data issue: false hasContentIssue false

Chapter 13 - Polycystic Ovary Syndrome: Ovulation Induction Strategies

from Section 3 - Difficulties and Complications of Ovarian Stimulation and Implantation

Published online by Cambridge University Press:  14 April 2022

By
Lina El-Taha ,
Botros Rizk ,
William Ledger ,
Raja Sayegh  and
Johnny Awwad
Edited by
Mohamed Aboulghar  and
Botros Rizk
Mohamed Aboulghar
Affiliation:
University of Cairo IVF Centre
Botros Rizk
Affiliation:
University of South Alabama
Get access

Summary

Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrinopathies affecting 5 to 10 percent of women of reproductive age [1;2]. Characteristic clinical features of PCOS include menstrual irregularity such as oligomenorrhea/amenorrhea and signs of hyperandrogenemia including hirsutism, acne, and/or obesity. The syndrome was first clearly described by Stein and Leventhal in 1935 [3]. While the primary etiology remains poorly defined [4], insulin resistance with compensatory hyperinsulinemia is a prominent feature of the condition and appears to be an underlying cause of hyperandrogenemia identified in both lean and obese women [5]. Hyperinsulinemia promotes increased ovarian androgen biosynthesis in vivo and in vitro [6;7]. It also decreases sex hormone-binding globulin production in the liver [8], which results in the increased bioavailability of free androgens and exacerbates the signs of androgen excess.

Type
Chapter
Information
Ovarian Stimulation , pp. 119 - 131
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Frank, S. Polycystic ovarian syndrome. N Engl J Med 1995;333:853–861.Google Scholar
Homburg, R. Polycystic ovary syndrome–from gynaecological curiosity to multisystem endocrinopathy. Hum Reprod 1996;11:29–39.Google Scholar
Stein, IF, Leventhal, ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181–191.CrossRefGoogle Scholar
Balen, A. The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best Pract Res Clin Obstet Gynaecol 2004;18:685–706.CrossRefGoogle ScholarPubMed
Dunaif, A, Segal, KR, Futterweit, W, Dobrjansky, A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165–1174.Google Scholar
Adashi, EY, Resnick, CE, D’Ercole, AJ, Svoboda, ME, Van Wyk, JJ. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr Rev 1985;6:400–420.Google Scholar
Barbieri, RL, Makris, A, Randall, RW, et al. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab 1986;62:904–910.Google Scholar
Nestler, JE, Powers, LP, Matt, DW, et al. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991;72:83–89.CrossRefGoogle ScholarPubMed
Zawadzki, JK, Dunaif, A. Diagnostic criteria for polycystic syndrome: towards a rational approach. In: Dunaif, A, Givens, JR, Haseltine, FP, et al., eds. Polycystic ovary syndrome. Boston: Blackwell Scientific; 1992:337–384.Google Scholar
Rotterdam ESHRE/ASRM‐Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19(1):41–47.Google Scholar
Lizneva, D, Suturina, L, Walker, W, et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 2016;106(1):6–15.Google Scholar
Erel, CT, Senturk, LM. The impact of body mass index on assisted reproduction. Curr Opin Obstet Gynecol 2009;21:228–235.Google Scholar
Balen, AH, Conway, GS, Kaltsas, G, et al. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod 1995;10:2107–2111.CrossRefGoogle ScholarPubMed
Kiddy, DS, Sharp, PS, White, DM, et al. Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases. Clin Endocrinol (Oxf) 1990;32:213–220.Google Scholar
Goldzieher, JW, Axelrod, LR. Clinical and biochemical features of polycystic ovarian disease. Fertil Steril 1963;14:631–653.Google Scholar
Moran, LJ, Pasquali, R, Teede, HJ, Hoeger, KM, Norman, RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril 2009;92(6):1966–1982.Google Scholar
Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril 2015;104(5):1116–1126.Google Scholar
National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. Clinical Guideline; London: RCOG Press; 2004.Google Scholar
Legro, RS, Kunselman, AR, Brzyski, RG, et al. The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials 2012;33(3):470–481.Google Scholar
Legro, RS, Brzyski, RG, Diamond, MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014;371:119–129.Google Scholar
Caserta, D, Adducchio, G, Picchia, S, et al. Metabolic syndrome and polycystic ovary syndrome: an intriguing overlapping. Gynecol Endocrinol 2014;30(6):397–402.CrossRefGoogle ScholarPubMed
Salehi, M, Bravo-Vera, R, Sheikh, A, Gouller, A, Poretsky, L. Pathogenesis of polycystic ovary syndrome: what is the role of obesity? Metabolism 2004;53(3):358–376.CrossRefGoogle ScholarPubMed
Douchi, T, Kuwahata, R, Yamamoto, S, et al. Relationship of upper body obesity to menstrual disorders. Acta Obstet Gynecol Scand 2002;81:147–150.Google Scholar
Hartz, AJ, Rupley, DC, Rimm, AA. The association of girth measurements with disease in 32,856 women. Am J Epidemiol 1984;119:71–80.Google Scholar
Pasquali, R, Pelusi, C, Genghini, S, Cacciari, M, Gambineri, A. Obesity and reproductive disorders in women. Hum Reprod Update 2003;9:359–372.CrossRefGoogle ScholarPubMed
Norman, RJ, Masters, SC, Hague, W, et al. Metabolic approaches to the subclassification of polycystic ovary syndrome. Fertil Steril 1995;63(2):329–335.Google Scholar
Gesink Law, DC, Maclehose, RF, Longnecker, MP. Obesity and time to pregnancy. Hum Reprod 2007;22:414–420.CrossRefGoogle ScholarPubMed
Fedorcsak, P, Dale, PO, Storeng, R, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod 2004;19:2523–2528.Google Scholar
Cedergren, MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol 2004;103:219–224.Google Scholar
Weiss, JL, Malone, FD, Emig, D, et al. FASTER Research Consortium. Obesity, obstetric complications and cesarean delivery rate: a population-based screening study. Am J Obstet Gynecol 2004;190:1091–1097.Google Scholar
Metwally, M, Ledger, WL, Li, TC. Reproductive endocrinology and clinical aspects of obesity in women. Ann N Y Acad Sci 2008;1127:140–146.Google Scholar
Lintsen, AM, Pasker-de Jong, PC, De Boer, EJ, et al. Effects of subfertility cause, smoking and body weight on the success rate of IVF. Hum Reprod 2005;20(7):1867–1875.Google Scholar
Loveland, JB, McClamrock, HD, Malinow, AM, Sharara, FI. Clinical assisted reproduction: increased body mass index has a deleterious effect on in vitro fertilization outcome. J Assist Reprod Genet 2001;18(7):382–386.Google Scholar
Dechaud, H, Anahory, T, Reyftmann, L, et al. Obesity does not adversely affect results in patients who are undergoing in vitro fertilization and embryo transfer. Eur J Obstet Gynecol Reprod Biol 2006;127:88–93.Google Scholar
Lashen, H, Ledger, W, Bernal, AL, Barlow, D. Extremes of body mass do not adversely affect the outcome of superovulation and in-vitro fertilization. Hum Reprod 1999;14:712–715.CrossRefGoogle Scholar
Martinuzzi, K, Ryan, S, Luna, M, Copperman, AB. Elevated body mass index (BMI) does not adversely affect in vitro fertilization outcome in young women. J Assist Reprod Genet 2008;25:169–175.Google Scholar
MacKenna, A, Schwarze, JE, Crosby, JA, Zegers-Hochschild, F. Outcome of assisted reproductive technology in overweight and obese women. JBRA Assist Reprod 2017;21(2):79–83.Google Scholar
Balaban, B, Urman, B. Effect of oocyte morphology on embryo development and implantation. Reprod Biomed Online 2006;12:608–615.Google Scholar
Carrell, DT, Jones, KP, Peterson, CM, et al. Body mass index is inversely related to intrafollicular HCG concentrations, embryo quality and IVF outcome. Reprod Biomed Online 2001;3:109–111.CrossRefGoogle ScholarPubMed
Esinler, I, Bozdag, G, Yarali, H. Impact of isolated obesity on ICSI outcome. Reprod Biomed Online 2008;17:583–587.Google Scholar
Wittemer, C, Ohl, J, Bailly, M, et al. Does body mass index of infertile women have an impact on IVF procedure and outcome? J Assist Reprod Genet 2000;17:547–552.CrossRefGoogle ScholarPubMed
Jungheim, ES, Moley, KH. Current knowledge of obesity’s effects in the pre- and periconceptional periods and avenues for future research. Am J Obstet Gynecol 2010;203(6):525–530.Google Scholar
Pandey, S, Pandey, S, Maheshwari, A, Bhattacharya, S. The impact of female obesity on the outcome of fertility treatment. J Hum Reprod Sci 2010;3(2):62–67.Google Scholar
Metwally, M, Cutting, R, Tipton, A, et al. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online 2007;15:532–538.Google Scholar
Provost, MP, Acharya, KS, Acharya, CR, et al. Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008–2010 Society for Assisted Reproductive Technology registry. Fertil Steril 2016;105(3):663–669.CrossRefGoogle Scholar
Provost, MP, Acharya, KS, Acharya, CR, et al. Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008–2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry. Fertil Steril 2016;105(2):364–368.Google Scholar
Rittenberg, V, Seshadri, S, Sunkara, SK, et al. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online 2011;23(4):421–439.CrossRefGoogle ScholarPubMed
Escobar-Morreale, HF, Luque-Ramírez, M, González, F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and meta analysis. Fertil Steril 2011;95(3):1048–1058.Google Scholar
Paepegaey, AC, Genser, L, Bouillot, JL, et al. High levels of CRP in morbid obesity: the central role of adipose tissue and lessons for clinical practice before and after bariatric surgery. Surg Obes Relat Dis 2015;11(1):148–154.Google Scholar
Faucher, G, Guénard, F, Bouchard, L, et al. Genetic contribution to C-reactive protein levels in severe obesity. Mol Genet Metab 2012;105(3):494–501.Google Scholar
Kadowaki, T. Yamauchi, T. Adiponectin and adiponectin receptors. Endocr Rev 2005;26:439–451.Google Scholar
Yuan, G, Zhou, L, Tang, J, et al. Serum CRP levels are equally elevated in newly diagnosed type 2 diabetes and impaired glucose tolerance and related to adiponectin levels and insulin sensitivity. Diabetes Res clin Pract 2006;72(3):244–250.CrossRefGoogle ScholarPubMed
Sieminska, L, Marek, B, Kos-Kudla, B, et al. Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters. J Endocrinol Investig 2004;27(6):528–534.CrossRefGoogle ScholarPubMed
Kopp, HP, Krzyzanowska, K, Möhlig, M, et al. Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women. Int J Obes 2005;29(7):766–771.CrossRefGoogle ScholarPubMed
Esposito, K, Pontillo, A, Di Palo, C, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003;289(14):1799–1804.Google Scholar
Woelnerhanssen, B, Peterli, R, Steinert, RE, et al. Effects of postbariatric surgery weight loss on adipokines and metabolic parameters: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy – a prospective randomized trial. Surg Obes Relat Dis 2011;7(5):561–568.Google Scholar
Wadden, TA, Foster, GD. Behavioral treatment of obesity. Med Clin N Am 2000;84(2):441–461.Google Scholar
Wadden, TA, Webb, VL, Moran, CH, Bailer, BA. Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation 2012;125(9):1157–1170.Google Scholar
Pucci, A, Finer, N. New medications for treatment of obesity: metabolic and cardiovascular effects. Can J Cardiol 2015;31(2):142–152.Google Scholar
Apovian, CM, Aronne, LJ, Bessesen, DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100(2):342–362.CrossRefGoogle ScholarPubMed
Keating, GM, Jarvis, B. Orlistat: in the prevention and treatment of type 2 diabetes mellitus. Drugs 2001;61:2107–2119.Google Scholar
Inge, TH, Jenkins, TM, Zeller, M, et al. Baseline BMI is a strong predictor of nadir BMI after adolescent gastric bypass. J Pediatr 2010;156(1):103–108.Google Scholar
Deitel, M, Stone, E, Kassam, HA, Wilk, EJ, Sutherland, DJ. Gynecologic-obstetric changes after loss of massive excess weight following bariatric surgery. J Am Coll Nutr 1988;7:147–153.Google Scholar
Abiad, F, Abbas, HA, Hamadi, C, Ghazeeri, G. Bariatric surgery in the management of adolescent and adult obese patients with polycystic ovarian syndrome. J Obes Weight Loss Ther 2016;6:303.Google Scholar
Abiad, F, Khalife, D, Safadi, B, et al. The effect of bariatric surgery on inflammatory markers in women with polycystic ovarian syndrome. Diabetes Metab Syndr 2018;12(6):999–1005.CrossRefGoogle ScholarPubMed
Sheiner, E, Levy, A, Silverberg, D, et al. Pregnancy after bariatric surgery is not associated with adverse perinatal outcome. Am J Obstet Gynecol 2004;190:1335–1340.Google Scholar
Printen, KJ, Scott, D. Pregnancy following gastric bypass for the treatment of morbid obesity. Am Surg 1982;48:363–365.Google Scholar
Marceau, P, Kaufman, D, Biron, S, et al. Outcome of pregnancies after biliopancreatic diversion. Obes Surg 2004;14:318–324.Google Scholar
Mutsaerts, MA, van Oers, AM, Groen, H, et al. Randomized trial of a lifestyle program in obese infertile women. N Engl J Med 2016;374:1942–1953.Google Scholar
Einarsson, S, Bergh, C, Friberg, B, et al. Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. Hum Reprod 2017;32:1621–1630.Google Scholar
Norman, RJ, Mol, BWJ. Successful weight loss interventions before in vitro fertilization: fat chance? Fertil Steril 2018;110:581–586.CrossRefGoogle ScholarPubMed
Greenblatt, RB, Barfield, WE, Jungck, EC, Ray, AW. Induction of ovulation with MRL/41. Preliminary report. J Am Med Assoc 1961;178:101–104.Google Scholar
Ecklund, LC, Usadi, RS. Endocrine and reproductive effects of polycystic ovarian syndrome. Obstet Gynecol Clin North Am 2015;42(1):55–65.CrossRefGoogle ScholarPubMed
Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril 2013;100(2):341–348.CrossRefGoogle Scholar
Hammond, MG. Monitoring techniques for improved pregnancy rates during clomifene ovulation induction. Fertil Steril 1984;42:499–508.Google Scholar
Dickey, RP, Taylor, SN, Curole, DN, et al. Incidence of spontaneous abortion in clomifene pregnancies. Hum Reprod 1996;11:2623–2628.Google Scholar
Gysler, M, March, CM, Mishell, DR Jr., Bailey, EJ. A decade’s experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril 1982;37:161–167.CrossRefGoogle ScholarPubMed
Eden, JA, Place, J, Carter, GD, et al. The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Fertil Steril 1989;73:187–190.Google Scholar
Bonhoff, AJ, Naether, OG, Johannisson, E. Effects of clomiphene citrate stimulation on endometrial structure in infertile women. Hum Reprod 1996;11(4):844–849.Google Scholar
Dehbashi, S, Parsanezhad, ME, Alborzi, S, Zarei, A. Effect of clomiphene citrate on endometrium thickness and echogenic patterns. Int J Gynaecol Obstet 2003;80(1):49–53.Google Scholar
Thompson, LA, Barratt, CL, Thornton, SJ, Bolton, AE, Cooke, ID. The effects of clomiphene citrate and cyclofenil on cervical mucus volume and receptivity over the periovulatory period. Fertil Steril 1993;59(1):125–129.Google Scholar
Kousta, E, White, DM, Franks, S. Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update 1997;3(4):359–365.Google Scholar
Hull, MG, Savage, PE, Bromham, DR, Ismail, AA, Morris, AF. The value of a single serum progesterone measurement in the midluteal phase as a criterion of a potentially fertile cycle (‘ovulation’) derived from treated and untreated conception cycles. Fertil Steril 1982;37(3):355–360.Google Scholar
Talbert, LM. Clomiphene citrate induction of ovulation. Fertil Steril 1983;39(6):742–743.Google Scholar
Chaabane, S, Sheehy, O, Monnier, P, et al. Ovarian stimulation, intrauterine insemination, multiple pregnancy and major congenital malformations: a systematic review and meta-analysis-The ART_Rev Study. Curr Drug Saf 2016;11(3):222–261.CrossRefGoogle Scholar
Senturk, LM, Erel, CT. Thin endometrium in assisted reproductive technology. Curr Opin Obstet Gynecol 2008;20:221–228.Google Scholar
Oliveira, JB, Baruffi, RL, Mauri, AL, et al. Endometrial ultrasonography as a predictor of pregnancy in an in-vitro fertilization programme after ovarian stimulation and gonadotrophin-releasing hormone and gonadotrophins. Hum Reprod 1997;12(11):2515–2518.Google Scholar
Schild, RL, Knobloch, C, Dorn, C, et al. Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow. Fertil Steril 2001;75:361–366.Google Scholar
Wu, Y, Gao, X, Lu, X, et al. Endometrial thickness affects the outcome of in vitro fertilization and embryo transfer in normal responders after GnRH antagonist administration. Reprod Biol Endocrinol 2014;12(1):96.Google Scholar
Wang, Y, Zhu, Y, Sun, Y, et al. Ideal embryo transfer position and endometrial thickness in IVF embryo transfer treatment. Int J Gynecol Obstet 2018;143(3):282–288.CrossRefGoogle ScholarPubMed
Lobo, RA, Gysler, M, March, CM, Goebelsmann, U, Mishell, DR Jr. Clinical and laboratory predictors of clomiphene response. Fertil Steril 1982;37(2):168–174.Google Scholar
Douchi, T, Oki, T, Yamasaki, H, et al. Body fat patterning in polycystic ovary syndrome women as a predictor of the response to clomiphene. Acta Obstet Gynecol Scand 2004;83:838–841.Google Scholar
Imani, B, Eijkemans, MJ, te Velde, ER, Habbema, JD, Fauser, BC. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1999;84(5):1617–1622.Google Scholar
Gindoff, PR, Jewelewicz, R. Reproductive potential in the older woman. Fertil Steril 1986;46(6):989–1001.Google Scholar
Rossing, MA, Daling, JR, Weiss, NS, et al. Ovarian tumors in a cohort of infertile women. N Engl J Med 1994;331:771–776.CrossRefGoogle Scholar
Balen, A. Anovulatory infertility and ovulation induction. Policy and Practice subcommittee of the British Fertility Society. Hum Reprod 1997;12 (11 Suppl):83–87.Google Scholar
Balen, AH, Morley, LC, Misso, M, 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.Google Scholar
Palomba, S. Aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab 2015;100(5):1742–1747.Google Scholar
Holzer, H, Casper, R, Tulandi, T. A new era in ovulation induction. Fertil Steril 2006;85(2):277–284.Google Scholar
Kar, S. Current evidence supporting “letrozole” for ovulation induction. J Hum Reprod Sci 2013;6(2):93–98.Google Scholar
Mitwally, MF, Biljan, MM, Casper, RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005;192(2):381–386.Google Scholar
Franik, S, Eltrop, SM, Kremer, JA, Kiesel, L, Farquhar, C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev 2018;5:CD010287.Google Scholar
Biljan, MM, Hemmings, R, Brassard, N. The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins. Fertil Steril 2005;84:S95.Google Scholar
Tulandi, T, Martin, J, Al-Fadhli, R, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril 2006;85(6):1761–1765.Google Scholar
American College of Obstetricians and Gynecologists. Polycystic ovary syndrome. ACOG practice bulletin no. 194. Obstet Gynecol 2018;11:131.Google Scholar
Velazquez, EM, Mendoza, S, Hamer, T, Sosa, F, Glueck, CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994;43:647–654.Google Scholar
Williamson, DF, Pamuk, E, Thun, M, et al. Prospective study of intentional weight loss and mortality in never-smoking overweight US white women aged 40–64 years. Am J Epidemiol 1995;141:1128–1141.Google Scholar
Kiddy, DS, Hamilton-Fairley, D, Bush, A, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol 1992;36:105–111.Google Scholar
Crosignani, PG, Colombo, M, Vegetti, W, et al. Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet. Hum Reprod 2003;18:1928–1932.Google Scholar
Harborne, L, Fleming, R, Lyall, H, Norman, J, Sattar, N. Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. Lancet 2003;361:1894–1901.Google Scholar
Nawaz, FH, Khalid, R, Naru, T, Rizvi, J. Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome? J Obstet Gynaecol Res 2008;34(5):832–837.Google Scholar
Morley, LC, Tang, TM, Balen, AH. Metformin therapy for the management of infertility in women with polycystic ovary syndrome: Scientific Impact Paper No. 13. BJOG 2017;124(12):E306–E313.Google Scholar
Legro, RS, Barnhart, HX, Schlaff, WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007;356(6):551–566.Google Scholar
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):527–537.Google Scholar
Palomba, S, Pasquali, R, Orio, JF, Nestler, JE. Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis. Clin Endocrinol 2009;70:311–321.Google Scholar
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. Cochrane Database Syst Rev 2017;11:CD003053.Google Scholar
Practice Committee of the American Society for Reproductive Medicine. Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertil Steril 2017;108(3):426–441.Google Scholar
Elnashar, A, Abdelmageed, E, Fayed, M, Sharaf, M. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod 2006;21(7):1805–1808.Google Scholar
Esmaeilzadeh, S, Amiri, MG, Basirat, Z, Shirazi, M. Does adding dexamethasone to clomiphene citrate improve ovulation in PCOS patients? A triple-blind randomized clinical trial study. Int J Fertil Steril 2011;5(1):9–12.Google Scholar
Shabana, AA, Al-Halby, AE, Abd Hamid, ES, El-Naggar, AM. Letrozole with dexamethasone versus clomiphene citrate with dexamethasone for induction of ovulation in polycystic ovary. Menoufia Med J 2018;31(1):38–45.Google Scholar
Badawy, A, State, O, Abdelgawad, S. N-acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand 2007;86(2):218–222.Google Scholar
Lak, TB, Hajshafiha, M, Nanbakhsh, F, Oshnouei, S. N-acetyl cysteine in ovulation induction of PCOS women underwent intrauterine insemination: An RCT. Int J Reprod Biomed 2017;15(4):203–206.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×