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Semin Reprod Med 2010; 28(6): 493-499
DOI: 10.1055/s-0030-1265676
© Thieme Medical Publishers

Ovarian Hyperstimulation Syndrome Prevention Strategies: Use of Gonadotropin-Releasing Hormone Antagonists

Georg Griesinger1
  • 1Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
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Publication History

Publication Date:
16 November 2010 (online)

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ABSTRACT

The most serious complication of ovarian stimulation for in vitro fertilization is severe ovarian hyperstimulation syndrome (OHSS), a rare but potentially life-threatening condition. The present review discusses the place of gonadotropin-releasing hormone antagonists (GnRH-ant) in primary, secondary, and tertiary prevention of OHSS. Sound evidence indicates that the routine use of GnRH-ant instead of GnRH agonists (GnRHa) during ovarian stimulation drastically reduces the relative risk of OHSS. GnRH-ant are therefore useful for primary OHSS prevention, and an increased use of antagonists should help reduce the overall incidence of severe OHSS with its associated risks and complications. In patients on antagonist protocols identified to be at risk of developing severe OHSS, replacing human chorionic gonadotropin with GnRHa as a trigger of final oocyte maturation has been proposed as an effective measure of secondary prevention. A concept of combining GnRHa triggering with cryopreservation of all oocytes or embryos has yielded promising results as far as total avoidance of OHSS is concerned while providing a good chance of pregnancy for the patient in later frozen-thawed embryo transfers. In patients with early onset of OHSS, reinitiation of GnRH-ant in the luteal phase as a measure of tertiary prevention might lead to rapid regression of the syndrome; however only limited data on this new concept are available in the literature.

KEYWORDS

Ovarian hyperstimulation syndrome - GnRH antagonist - GnRH agonist - ovarian stimulation - OHSS prevention

REFERENCES

  • 1 Serour G I, Aboulghar M, Mansour R, Sattar M A, Amin Y, Aboulghar H. Complications of medically assisted conception in 3,500 cycles.  Fertil Steril. 1998;  70(4) 638-642
    CrossrefPubMedGoogle Scholar
  • 2 Arya R, Shehata H A, Patel R K et al. Internal jugular vein thrombosis after assisted conception therapy.  Br J Haematol. 2001;  115(1) 153-155
    CrossrefPubMedGoogle Scholar
  • 3 Klemetti R, Sevón T, Gissler M, Hemminki E. Complications of IVF and ovulation induction.  Hum Reprod. 2005;  20(12) 3293-3300
    CrossrefPubMedGoogle Scholar
  • 4 Mára M, Koryntová D, Rezábek K et al. Thromboembolic complications in patients undergoing in vitro fertilization: retrospective clinical study [in Czech].  Ceska Gynekol. 2004;  69(4) 312-316
    PubMedGoogle Scholar
  • 5 Brinsden P R, Wada I, Tan S L, Balen A, Jacobs H S. Diagnosis, prevention and management of ovarian hyperstimulation syndrome.  Br J Obstet Gynaecol. 1995;  102(10) 767-772
    PubMedGoogle Scholar
  • 6 Papanikolaou E G, Pozzobon C, Kolibianakis E M et al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.  Fertil Steril. 2006;  85(1) 112-120
    CrossrefPubMedGoogle Scholar
  • 7 Borm G, Mannaerts B. Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial.  Hum Reprod. 2000;  15(7) 1490-1498
    CrossrefPubMedGoogle Scholar
  • 8 European and Middle East Orgalutran Study Group . Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation.  Hum Reprod. 2001;  16(4) 644-651
    CrossrefPubMedGoogle Scholar
  • 9 Fluker M, Grifo J, Leader A. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation.  Fertil Steril. 2001;  75(1) 38-45
    CrossrefPubMedGoogle Scholar
  • 10 Kolibianakis E M, Collins J, Tarlatzis B C, Devroey P, Diedrich K, Griesinger G. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis.  Hum Reprod Update. 2006;  12(6) 651-671
    CrossrefPubMedGoogle Scholar
  • 11 Al-Inany H G, Abou-Setta A M, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review.  Reprod Biomed Online. 2007;  14(5) 640-649
    CrossrefPubMedGoogle Scholar
  • 12 Ragni G, Vegetti W, Riccaboni A, Engl B, Brigante C, Crosignani P G. Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome.  Hum Reprod. 2005;  20(9) 2421-2425
    CrossrefPubMedGoogle Scholar
  • 13 Felberbaum R E, Reissmann T, Küpker W et al. Preserved pituitary response under ovarian stimulation with HMG and GnRH antagonists (Cetrorelix) in women with tubal infertility.  Eur J Obstet Gynecol Reprod Biol. 1995;  61(2) 151-155
    CrossrefPubMedGoogle Scholar
  • 14 Fauser B C, de Jong D, Olivennes F et al. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization.  J Clin Endocrinol Metab. 2002;  87(2) 709-715
    CrossrefPubMedGoogle Scholar
  • 15 Humaidan P, Bungum L, Bungum M, Yding Andersen C. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study.  Reprod Biomed Online. 2006;  13(2) 173-178
    CrossrefPubMedGoogle Scholar
  • 16 Babayof R, Margalioth E J, Huleihel M et al. Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF treatment: a prospective randomized trial.  Hum Reprod. 2006;  21(5) 1260-1265
    CrossrefPubMedGoogle Scholar
  • 17 Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study.  Fertil Steril. 2008;  89(1) 84-91
    CrossrefPubMedGoogle Scholar
  • 18 Galindo A, Bodri D, Guillén J J, Colodrón M, Vernaeve V, Coll O. Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.  Gynecol Endocrinol. 2009;  25(1) 60-66
    CrossrefPubMedGoogle Scholar
  • 19 Bodri D, Guillén J J, Galindo A, Mataró D, Pujol A, Coll O. Triggering with human chorionic gonadotropin or a gonadotropin-releasing hormone agonist in gonadotropin-releasing hormone antagonist-treated oocyte donor cycles: findings of a large retrospective cohort study.  Fertil Steril. 2009;  91(2) 365-371
    CrossrefPubMedGoogle Scholar
  • 20 Griesinger G, Diedrich K, Tarlatzis B C, Kolibianakis E M. GnRH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polycystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis.  Reprod Biomed Online. 2006;  13(5) 628-638
    CrossrefPubMedGoogle Scholar
  • 21 Kol S. Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to prevention of ovarian hyperstimulation syndrome.  Fertil Steril. 2004;  81(1) 1-5
    PubMedGoogle Scholar
  • 22 Gonen Y, Balakier H, Powell W, Casper R F. Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization.  J Clin Endocrinol Metab. 1990;  71(4) 918-922
    CrossrefPubMedGoogle Scholar
  • 23 Nevo O, Eldar-Geva T, Kol S, Itskovitz-Eldor J. Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin.  Fertil Steril. 2003;  79(5) 1123-1128
    CrossrefPubMedGoogle Scholar
  • 24 Humaidan P, Bredkjaer H E, Bungum L et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study.  Hum Reprod. 2005;  20(5) 1213-1220
    CrossrefPubMedGoogle Scholar
  • 25 Erb T M, Vitek W, Wakim A N. Gonadotropin-releasing hormone agonist or human chorionic gonadotropin for final oocyte maturation in an oocyte donor program.  Fertil Steril. 2010;  93(2) 374-378
    CrossrefPubMedGoogle Scholar
  • 26 Galindo A, Bodri D, Guillén J J, Colodrón M, Vernaeve V, Coll O. Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.  Gynecol Endocrinol. 2009;  25(1) 60-66
    CrossrefPubMedGoogle Scholar
  • 27 Acevedo B, Gomez-Palomares J L, Ricciarelli E, Hernández E R. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates.  Fertil Steril. 2006;  86(6) 1682-1687
    CrossrefPubMedGoogle Scholar
  • 28 Shapiro B S, Daneshmand S T, Garner F C, Aguirre M, Ross R. Comparison of human chorionic gonadotropin and gonadotropin-releasing hormone agonist for final oocyte maturation in oocyte donor cycles.  Fertil Steril. 2007;  88(1) 237-239
    CrossrefPubMedGoogle Scholar
  • 29 Griesinger G, Kolibianakis E M, Papanikolaou E G et al. Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin. Live birth after frozen-thawed embryo replacement cycles.  Fertil Steril. 2007;  88(3) 616-621
    CrossrefPubMedGoogle Scholar
  • 30 Erden H F, Akman M A, Çiray N, Bahçeci M. The results of fresh and frozen thaw embryo transfer cycles of PCOS patients in which GnRH-ant were used together with GnRHa for LH surge.  Fertil Steril. 2005;  84 (Suppl 1) S164 (P-36)
    PubMedGoogle Scholar
  • 31 Eldar-Geva T, Zylber-Haran E, Babayof R et al. Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation.  Reprod Biomed Online. 2007;  14(2) 148-154
    CrossrefPubMedGoogle Scholar
  • 32 Kolibianakis E M, Schultze-Mosgau A, Schroer A et al. A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.  Hum Reprod. 2005;  20(10) 2887-2892
    CrossrefPubMedGoogle Scholar
  • 33 Youssef M, Griesinger G, Van Wely M, AL-Inany H, Van der Veen F. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist ART cycles. A systematic review and metaanalysis. Abstracts of the 25th Annual Meeting of ESHRE, Amsterdam, the Netherlands, 28 June–1 July, 2009.  Hum Reprod. 2009;  24(Suppl) 1241-1530
    CrossrefPubMedGoogle Scholar
  • 34 Yding Andersen C, Humaidan P. Characteristics of follicular fluid from women receiving either Buserelin or hCG to induce ovulation.  Hum Reprod. 2005;  20(Suppl 1) 65
    PubMedGoogle Scholar
  • 35 Engmann L, Siano L, Schmidt D, Nulsen J, Maier D, Benadiva C. GnRH agonist to induce oocyte maturation during IVF in patients at high risk of OHSS.  Reprod Biomed Online. 2006;  13(5) 639-644
    CrossrefPubMedGoogle Scholar
  • 36 Kol S, Solt I. GnRH agonist for triggering final oocyte maturation in patients at risk of ovarian hyperstimulation syndrome: still a controversy?.  J Assist Reprod Genet. 2008;  25(2–3) 63-66
    CrossrefPubMedGoogle Scholar
  • 37 Griesinger G, von Otte S, Schroer A et al.. Elective cryopreservation of all pronuclear oocytes after GnRH-agonist triggering of final oocyte maturation in patients at risk of developing OHSS: a prospective, observational proof-of-concept study.  Hum Reprod. 2007;  22(5) 1348-1352
    CrossrefPubMedGoogle Scholar
  • 38 Manzanares M A, Gómez-Palomares J L, Ricciarelli E, Hernández E R. Triggering ovulation with gonadotropin-releasing hormone agonist in in vitro fertilization patients with polycystic ovaries does not cause ovarian hyperstimulation syndrome despite very high estradiol levels.  Fertil Steril. 2010;  93(4) 1215-1219
    CrossrefPubMedGoogle Scholar
  • 39 Lainas T G, Sfontouris I A, Zorzovilis I Z, Petsas G K, Lainas G T, Kolibianakis E M. Management of severe early ovarian hyperstimulation syndrome by re-initiation of GnRH antagonist.  Reprod Biomed Online. 2007;  15(4) 408-412
    CrossrefPubMedGoogle Scholar
  • 40 Lainas T G, Sfontouris I A, Zorzovilis I Z et al. Management of severe OHSS using GnRH antagonist and blastocyst cryopreservation in PCOS patients treated with long protocol.  Reprod Biomed Online. 2009;  18(1) 15-20
    CrossrefPubMedGoogle Scholar
  • 41 Lainas T G, Sfontouris I A, Zorzovilis I Z et al. Live births after management of severe OHSS by GnRH antagonist administration in the luteal phase.  Reprod Biomed Online. 2009;  19(6) 789-795
    CrossrefPubMedGoogle Scholar

Georg GriesingerM.D. M.Sc. Ph.D. 

Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Campus Luebeck

Ratzeburger Allee 160, 23538 Luebeck, Germany

Email: griesing@uni-luebeck.de

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