Gynäkologische Endokrinologie

, Volume 5, Issue 1, pp 39–48 | Cite as

Anwendung von Clomifen zur ovariellen Stimulation

CME Weiterbildung • Zertifizierte Fortbildung

Zusammenfassung

Clomifen stellt auch heute noch insbesondere bei hypothalamisch-hypophysären Funktionsstörungen in vielen Fällen das Therapeutikum der ersten Wahl bei der ovariellen Stimulation dar. Um seine therapeutische Potenz bei höchstmöglicher Sicherheit (Vermeidung von Mehrlingsschwangerschaften etc.) ausschöpfen zu können, bedarf es der Beurteilung der Zervix (außer bei geplanter Insemination) sowie eines sonographischen (evtl. auch hormonellen) Monitorings, das die weiteren Abläufe (evtl. HCG-Gabe, Geschlechtsverkehr etc.) terminiert und Nebenwirkungen (Endometriumdicke, polyfollikuläre Reaktion) erfasst. Nur dadurch kann einem suboptimalen Verlauf entgegengewirkt bzw. frühzeitig entschieden werden, ob Therapiealternativen diskutiert werden müssen.

Schlüsselwörter

Clomifen Endometrium Monitoring Ovarielle Stimulation Sterilität 

Application of clomiphene for ovarian stimulation

Abstract

Clomiphene is the first choice for ovarian stimulation, especially for patients with hypothalamic-hypophysis dysfunctions. To use its therapeutic potential with minimal risk (avoidance of multiples etc.), it is necessary to evaluate the cervical mucus (except in planned intrauterine insemination) and to perform sonographic, and sometimes also endocrinological, monitoring. This is necessary for the timing of later procedures (application of human chorionic gonadotrophin, intercourse, etc.), and to monitor possible problems such as endometrial thickness and polyfollicular reaction. If such details are known, we can try to compensate for a suboptimal procedure and decide whether therapeutic alternatives should be discussed.

Keywords

Clomiphene Endometrium Monitoring Ovarian stimulation Sterility 

Notes

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Literatur

  1. 1.
    Agarwal SK, Buyalos RP (1995) Corpus luteum function and pregnancy rates with clomiphene citrate therapy: comparison of human chorionic gonadotrophin-induced versus spontaneous ovulation. Hum Reprod 10: 328–331PubMedGoogle Scholar
  2. 2.
    Al-Fozan H, Al-Khadouri M, Tan SL, Tulandi T (2004) A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertil Steril 82: 1561–1563CrossRefPubMedGoogle Scholar
  3. 3.
    Bayar U, Tanriverdi HA, Barut A et al. (2006) Letrozole vs. clomiphene citrate in patients with ovulatory infertility. Fertil Steril 85: 1045–1048CrossRefPubMedGoogle Scholar
  4. 4.
    Beckers NG, Macklon NS, Eijkemans MJ et al. (2003) Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment. J Clin Endocrinol Metab 88: 4186–4192CrossRefPubMedGoogle Scholar
  5. 5.
    Beckers NG, Platteau P, Eijkemans MJ et al. (2006) The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women. Eur J Endocrinol 155: 355-363CrossRefPubMedGoogle Scholar
  6. 6.
    Branigan EF, Estes MA (2003) A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment. Am J Obstet Gynecol 188: 1424–1428CrossRefPubMedGoogle Scholar
  7. 7.
    Cantineau AE, Cohlen BJ, Heineman M (2006) The search for an optimal stimulation protocol for intrauterine insemination (IUI): a Cochrane systematic review. Fertil Steril 86 [Suppl 2]: S422Google Scholar
  8. 8.
    Check JH, Dietterich C, Lurie D (2004) The effect of consecutive cycles of clomiphene citrate therapy on endometrial thickness and echo pattern. Obstet Gynecol 86: 341–345CrossRefGoogle Scholar
  9. 9.
    Daya S, Gunby J (2004) Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev 3: CD004830PubMedGoogle Scholar
  10. 10.
    Dehbashi S, Parsanezhad ME, Alborzi S, Zarei A (2003) Effect of clomiphene citrate on endometrium thickness and echogenic patterns. Int J Gynaecol Obstet 80: 49–53CrossRefPubMedGoogle Scholar
  11. 11.
    Dickey RP, Taylor SN, Curole DN et al. (1997) Relationship of clomiphene dose and patient weight to successful treatment. Hum Reprod 12: 449–453CrossRefPubMedGoogle Scholar
  12. 12.
    Elkind-Hirsch KE, Darensbourg C, Creasy G, Gipe D (2005) Conception rates in clomiphene citrate cycles with and without hormone supplementation: a pilot study. Curr Med Res Opin 21: 1035–1040CrossRefPubMedGoogle Scholar
  13. 13.
    Elnashar A, Abdelmageed E, Fayed M, Sharaf M (2006) Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod 21: 1805–1808CrossRefPubMedGoogle Scholar
  14. 14.
    Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P (2005) Laparoscopic „drilling“ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev 3: CD001122PubMedGoogle Scholar
  15. 15.
    Glueck CJ, Aregawi D, Agloria M et al. (2006) Sustainability of 8% weight loss, reduction of insulin resistance, and amelioration of atherogenic-metabolic risk factors over 4 years by metformin-diet in women with polycystic ovary syndrome. Metabolism 55: 1582–1589CrossRefPubMedGoogle Scholar
  16. 16.
    Greenblatt RB, Barfield WE, Jungck EC, Ray AW (1961) Induction of ovulation with MRL/41. Preliminary report. J Am Med Assoc 178: 101–104Google Scholar
  17. 17.
    Hendriks DJ, Mol BW, Bancsi LF et al. (2006) The clomiphene citrate challenge test for the prediction of poor ovarian response and nonpregnancy in patients undergoing in vitro fertilization: a systematic review. Fertil Steril 86: 807–818CrossRefPubMedGoogle Scholar
  18. 18.
    Homburg R (2005) Clomiphene citrate – end of an era? A mini-review. Hum Reprod 20: 2043–2051CrossRefPubMedGoogle Scholar
  19. 19.
    Hughes E, Collins J, Vandekerckhove P (2000) Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea. Cochrane Database Syst Rev 2: CD000056 PubMedGoogle Scholar
  20. 20.
    Hughes E, Collins J, Vandekerckhove P (2000) Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev 3: CD000057 PubMedGoogle Scholar
  21. 21.
    Imani B, Eijkemans MJ, te Velde ER et al. (2002) A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertil Steril 77: 91–97CrossRefPubMedGoogle Scholar
  22. 22.
    Kolibianakis EM, Zikopoulos KA, Fatemi HM et al. (2004) Endometrial thickness cannot predict ongoing pregnancy achievement in cycles stimulated with clomiphene citrate for intrauterine insemination. Reprod Biomed Online 8: 115–118PubMedGoogle Scholar
  23. 23.
    Legro RS, Myers ER, Schlaff WD, Carr BR, Diamond MP (2006) Improvement in live births with clomiphene citrate and metformin, alone and in combination, in infertile women with polycystic ovary syndrome. Fertil Steril 86 [Suppl 2]: S1Google Scholar
  24. 24.
    Lewis V, Queenan J Jr, Hoeger K et al. (2006) Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial. Fertil Steril 85: 401–406CrossRefPubMedGoogle Scholar
  25. 25.
    Moll E, Bossuyt PM, Korevaar JC et al. (2006) Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. Brit Med J 332: 1485–1488CrossRefPubMedGoogle Scholar
  26. 26.
    Nakamura Y, Ono M, Yoshida Y et al. (1997) Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium. Fertil Steril 67: 256–260CrossRefPubMedGoogle Scholar
  27. 27.
    Ness RB, Cramer DW, Goodman MT et al. (2002) Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol 155: 217–224CrossRefPubMedGoogle Scholar
  28. 28.
    Neveu N, Granger L, St-Michel P, Lavoie HB (2007) 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 87: 113–120CrossRefPubMedGoogle Scholar
  29. 29.
    Palomba S, Orio F Jr, Falbo A et al. (2005) Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab 90: 4068–4074CrossRefPubMedGoogle Scholar
  30. 30.
    Parsanezhad ME, Alborzi S, Motazedian S, Omrani G (2002) Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. Fertil Steril 78: 1001–1004CrossRefPubMedGoogle Scholar
  31. 31.
    Richter KS, Bugge KR, Bromer JG, Levy MJ (2007) Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril 87: 53–59CrossRefPubMedGoogle Scholar
  32. 32.
    Rostami-Hodjegan A, Lennard MS, Tucker GT, Ledger WL (2004) Monitoring plasma concentrations to individualize treatment with clomiphene citrate. Fertil Steril 81: 1187–1193CrossRefPubMedGoogle Scholar
  33. 33.
    Siebert TI, Kruger TF, Steyn DW, Nosarka S (2006) Is the addition of metformin efficacious in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome? A structured literature review. Fertil Steril 86: 1432–1437CrossRefPubMedGoogle Scholar
  34. 34.
    Steiner AZ, Terplan M, Paulson RJ (2005) Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod 20: 1511–1515CrossRefPubMedGoogle Scholar
  35. 35.
    Unfer V, Costabile L, Gerli S et al. (2001) Low dose of ethinyl estradiol can reverse the antiestrogenic effects of clomiphene citrate on endometrium. Gynecol Obstet Invest 51: 120–123CrossRefPubMedGoogle Scholar
  36. 36.
    Vlahos NF, Coker L, Lawler C et al. (2005) Women with ovulatory dysfunction undergoing ovarian stimulation with clomiphene citrate for intrauterine insemination may benefit from administration of human chorionic gonadotropin. Fertil Steril 83: 1510–1516CrossRefPubMedGoogle Scholar
  37. 37.
    Wilcox AJ, Weinberg CR, Baird DD (1995) Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 333: 1517–1521CrossRefPubMedGoogle Scholar
  38. 38.
    Wingfield M, Fitzgerald J, Milne P (2006) Is it safe to prescribe clomiphene citrate without ultrasound monitoring facilities? Hum Reprod 21 [Suppl 1]: i101Google Scholar
  39. 39.
    Wu CH, Winkel CA (1989) The effect of therapy initiation day on clomiphene citrate therapy. Fertil Steril 52: 564–568PubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2007

Authors and Affiliations

  1. 1.Zentrum für Hormon- und Stoffwechselerkrankungen, Reproduktionsmedizin und Gynäkologische EndokrinologieENDOKRINOLOGIKUM HamburgHamburgDeutschland

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