Ovulation Induction in PCOS

Chapter
First Online:

In the general population, ovarian dysfunction is the most common reason of fertility problems. About 20% of couples consulting a fertility clinic present with oligo- or amenorrea [1,2]. Occasionally, ovulatory cycles may be observed in oligomenorreic women, but the frequency of ovulations appears to decrease as cycle length progresses. Unfortunately, well-designed longitudinal follow-up studies regarding this issue are lacking.

Keywords

Follicle Stimulate Hormone Aromatase Inhibitor Polycystic Ovary Clomiphene Citrate Ovulation Induction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Hull MG. Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynaecol Endocrinol 1987; 235–245Google Scholar
  2. 2.
    Balen AH, Rutherford AJ. Managing anovulatory infertility and polycystic ovary syndrome. BMJ 2007. 335: 663–666PubMedCrossRefGoogle Scholar
  3. 3.
    Rowe PJ, Combaire FH, Hargreave TB, et al. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press, 2001Google Scholar
  4. 4.
    van Santbrink EJ, Hop WC, Fauser BC. Classification of nomogonadotrophic anovulatory infertility: Polycystic ovaries diagnosed by ultrasound versus endocrine characteristics of polycystic ovary syndrome. Fertil Steril 1997. 67: 453–458Google Scholar
  5. 5.
    Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935. 29: 181–191Google Scholar
  6. 6.
    Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine F, eds. Polycystic Ovary Syndrome. Boston: Blackwell Scientific, 1992: 377–384Google Scholar
  7. 7.
    PCOS consensus. The 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: 41–47CrossRefGoogle Scholar
  8. 8.
    PCOS consensus. The 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). Fertil Steril 2004. 81: 19–25Google Scholar
  9. 9.
    Azziz R. Diagnosis of polycystic ovarian syndrome: The Rotterdam criteria are premature. J Clin Endocrinol Metab 2007. 91: 781–785CrossRefGoogle Scholar
  10. 10.
    van Santbrink EJ, Eijkemans MJ, Laven SJ, et al. Patient-tailored conventional ovulation induction algorithms in anovulatory infertility. Trends Endocrinol Metab 2005. 16: 381–389PubMedCrossRefGoogle Scholar
  11. 11.
    Aboulghar MA, Mansour RT. Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Hum Reprod Update 2003. 9: 275–289PubMedCrossRefGoogle Scholar
  12. 12.
    Kiddy D, Sharp PS, White DM, et al. Differences in clinical and endocrine features between obese and non-obese subjects with PCOS: an analysis of 263 consecutive cases. Clin Endocrinol 1990; 213–220Google Scholar
  13. 13.
    Franks S, Kiddy D, Sharp P, et al. Obesity and polycystic ovary syndrome. Annals of the NY academy of Sciences 1991; 626:201–206CrossRefGoogle Scholar
  14. 14.
    Rich-Edwards JW, Spiegelman D, Garland M, et al. Physical activity, body mass index, and ovulatory disorder infertility. Epidemiology 2002. 13: 184–190PubMedCrossRefGoogle Scholar
  15. 15.
    Norman RJ, Davies MJ, Lord J, et al. The role of life-style modification in polycystic ovary syndrome. Trends Endocrinol Metab 2002. 13: 251–257PubMedCrossRefGoogle Scholar
  16. 16.
    Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obesity Research 2002. 10: 551–554PubMedCrossRefGoogle Scholar
  17. 17.
    Dietl J. Maternal obesity and complications during pregnancy. J Perinat Med 2005. 33: 100–105PubMedCrossRefGoogle Scholar
  18. 18.
    Boomsma CM, Fauser BC, Macklon NS. Pregnancy complications in women with PCOS. Semin Reprod Med 2008. 26: 72–84PubMedCrossRefGoogle Scholar
  19. 19.
    Valkenburg O, Steegers-Theunissen RP, Smedts HP, et al. A more atherogenic serum lipoprotein profile is present in women with polycystic ovary syndrome: a case-control study. J Clin Endocrinol Metab 2007; epub ahead of print.Google Scholar
  20. 20.
    Clark AM, Thornley B, Tomlinson L, et al. Weight loss in obese infertile women results in improvement of reproductive outcome for all forms of fertility treatment. Hum Reprod 1998. 13: 1502–1505PubMedCrossRefGoogle Scholar
  21. 21.
    Hoeger KM. Role of lifestyle modification in the management of polycystic ovary syndrome. Best Practice and research in Clin Endocrinol and Metab 2006. 20: 293–310CrossRefGoogle Scholar
  22. 22.
    Balen AH, Dresner M, Scott EM, et al. Should obese women with polycystic ovary syndrome receive treatment for infertility? BMJ 2006. 332: 434–435PubMedCrossRefGoogle Scholar
  23. 23.
    Nelson SM, Fleming RF. The preconceptual contraception paradigm: obesity and infertility. Hum Reprod 2007. 22: 912–915PubMedCrossRefGoogle Scholar
  24. 24.
    Stein IF, Cohen MR, Elson R. Results of bilateral ovarian wedge resection in 47 cases of sterility; 20 year end results; 75 cases of bilateral polycystic ovaries. Am J Obstet Gynecol 1949. 58: 267–274PubMedGoogle Scholar
  25. 25.
    Mahesh VB and Greenblatt RB. Urinary steroid excretion patterns in hirsutism. II. Effect of ovarian stimulation with human pituitary FSH on urinary 17-ketosteroids. J Clin Endocrinol Metab 1964. 24: 1293–1302PubMedCrossRefGoogle Scholar
  26. 26.
    Pildes RB. Induction of ovulation with clomiphene. Am J Obstet Gynecol 1965. 15: 466–479Google Scholar
  27. 27.
    Greenblatt EM, Casper RF. Laparoscopic ovarian drilling in women with polycystic ovarian syndrome. Prog Clin Biol Res 1993. 381: 129–138PubMedGoogle Scholar
  28. 28.
    Farquhar C, Lilford RJ, Marjoribanks J, et al. Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev 2007; 18: CD001122Google Scholar
  29. 29.
    Youssef H, Atallah MM. Unilateral ovarian drilling in polycystic ovarian syndrome: a prospective randomized study. Reprod Biomed Online 2007. 15: 457–462PubMedCrossRefGoogle Scholar
  30. 30.
    Saleh AM, Khalil HS. Review of non-surgical and surgical treatment and the role of insulin-sensitizing agents in the management of infertile women with PCOS. Acta Obstet Gynecol Scand 2004. 83: 614–621PubMedGoogle Scholar
  31. 31.
    Seow KM, Juan CC, Hwang JL, et al. Laparoscopic surgery in polycystic ovary syndrome: reproductive and metabolic effects. Semin Reprod Med 2008. 26: 101–110PubMedCrossRefGoogle Scholar
  32. 32.
    Boostanfar R. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril 2001; 75:1024–1026PubMedCrossRefGoogle Scholar
  33. 33.
    Imani B, Eijkemans MJ, te Velde ER, et al. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1999. 84: 1617–1622PubMedCrossRefGoogle Scholar
  34. 34.
    Dehbashi S, Vafaei H, Persanezhad M et al. Time of initiation of clomiphene citrate and pregnancy rate in polycystic ovary syndrome. Int J Gynaecol Obstet 2006. 93: 44–48PubMedCrossRefGoogle Scholar
  35. 35.
    Imani B, Eijkemans MJ, te Velde ER, et al. Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1998. 83: 2361–2365PubMedCrossRefGoogle Scholar
  36. 36.
    Koustra E, White DM, Franks S. Modern use of CC in induction of ovulation. Hum Reprod Update 1997. 3: 359–365CrossRefGoogle Scholar
  37. 37.
    Imani B, Eijkemans MJ, te Velde ER, et al. A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertil Steril 2002. 77: 91–97PubMedCrossRefGoogle Scholar
  38. 38.
    Fauser BC, van Heusden AM. Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev 1997. 18: 71–106.PubMedCrossRefGoogle Scholar
  39. 39.
    Bayram N, van Wely M, van Der Veen F. Recombinant FSH versus urinary gonadotrophins or recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev 2001; 2:CD002121PubMedGoogle Scholar
  40. 40.
    White DM, Polson DW, Kiddy D, et al. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. J Clin Endocrinol Metab 1996. 81: 3821–3824PubMedCrossRefGoogle Scholar
  41. 41.
    van Santbrink EJ, Fauser BC. Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: Prospective, randomized comparison between low-dose step-up and step-down dose regimens. J Clin Endocrinol Metab 1997. 82: 3597–3602PubMedCrossRefGoogle Scholar
  42. 42.
    Mulders AG, Eijkemans MJ, Imani B, et al. Prediction of chances for success or complications in gonadotrophin ovulation induction in normogonadotrophic anovulatory infertility. Reprod BioMed Onl 2003. 7: 48–56Google Scholar
  43. 43.
    Fauser BC, Devroey P, Macklon NS. Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet 2005. 365: 1807–1816PubMedCrossRefGoogle Scholar
  44. 44.
    Eijkemans MJ, Imani B, Mulders AG, et al. High singleton live birth rate following classical ovulation induction in normogonadotropic anovulatory infertility. Hum Reprod 2003. 18: 2357–2362PubMedCrossRefGoogle Scholar
  45. 45.
    Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for pathogenesis. Endocr Rev 1997. 18: 774–800PubMedCrossRefGoogle Scholar
  46. 46.
    Coffler MS, Patel K, Dahan MH, et al. Enhanced granulosa cell responsiveness to FSH during insulin infusion in women with PCOS treated with Pioglitazone. J Clin Endocrinol Metab 2003. 88: 5624–5631PubMedCrossRefGoogle Scholar
  47. 47.
    Nestler JE, Jakubowicz DJ, Evans WS, et al. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. NEJM 1998. 338: 1876–1880PubMedCrossRefGoogle Scholar
  48. 48.
    Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with PCOS. Diabetes Care 1999. 22: 141–146PubMedCrossRefGoogle Scholar
  49. 49.
    Sinawat S, Buppasiri P, Lumbiganon P, et al. Long versus short course treatment with Metformin and Clomiphene Citrate for ovulation induction in women with PCOS. Cochrane Database Syst Rev. 2008; Jan 23;(1):CD006226Google Scholar
  50. 50.
    Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. Br Medical J 2003. 327: 951–953CrossRefGoogle Scholar
  51. 51.
    Tang T, Glanville J, Hayden CJ, et al. Combined life-style modification and metformin in obese patients with PCOS. A randomized, placebo-controlled, double-blind, multi center study. Hum Reprod 2006. 21: 80–89PubMedCrossRefGoogle Scholar
  52. 52.
    Moll E, Bossuyt PM, Korevaar JC, et al. Effect of clomiphene citrate plus metformin and clomiphene citrate plus placebo on induction of ovulation in women with newly diagnosed PCOS: randomised double-blind clinical trial. BMJ 2006. 332: 1485PubMedCrossRefGoogle Scholar
  53. 53.
    Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, Metformin, or both for Infertility in the PCOS. N Engl J Med 2007. 356: 551–566PubMedCrossRefGoogle Scholar
  54. 54.
    The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group March 2–3, 2007, Thessaloniki, Greece. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008 Feb 1 [Epub ahead of print]Google Scholar
  55. 55.
    Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001. 75: 305–309PubMedCrossRefGoogle Scholar
  56. 56.
    Fisher SA, Reid RL, van Vught DA, et al. A randomized double blind comparison of the effects of CC and the aromatase inhitor Letrozole on the ovulatory function in normal women. Fertil Steril 2002. 78: 280–285PubMedCrossRefGoogle Scholar
  57. 57.
    Mitwally MFM, Casper RF. Aromatase inhibitors for the treatment of infertility. Expert Opin Investig Drugs 2003. 12: 353–371PubMedCrossRefGoogle Scholar
  58. 58.
    Fatemi HM, Kolibianakis E, Tournaye H, et al. Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study. Reprod Biomed Online 2003. 7: 543–546PubMedCrossRefGoogle Scholar
  59. 59.
    Bayar U, Basaran M, Kiran S, et al. Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertil Steril 2006. 86: 1447–1451PubMedCrossRefGoogle Scholar
  60. 60.
    Biljan MM, Hemmings R, Brassard N. The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins. Fertil Steril 2005; 84 (supp. 1), O-231 Abstract 1033Google Scholar
  61. 61.
    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; 85:1761–1765PubMedCrossRefGoogle Scholar
  62. 62.
    Forman R, Gill S, Moretti M, et al. Fetal safety of letrozole and clomiphene citrate for ovulation induction. J Obstet Gynaecol Can 2007. 29: 668–671PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus Medical CenterSenior consultant in Reproductive MedicineThe Netherlands

Personalised recommendations