Journal of Assisted Reproduction and Genetics

, Volume 27, Issue 2–3, pp 121–128 | Cite as

Ovarian hyperstimulation syndrome: pathophysiology and prevention

  • Carolina O. Nastri
  • Rui A. Ferriani
  • Isa A. Rocha
  • Wellington P. Martins
Gonad Physiology and Disease

Abstract

Purpose

To review and discuss the pathophysiology and prevention strategies for ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in up to 20% of the high risk women submitted to assisted reproductive technology cycles.

Methods

The English language literature on these topics were reviewed through PubMed and discussed with emphasis on recent data.

Results

The role of estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory mediators, the renin-angiotensin system and vascular endothelial growth factor is discussed in the pathophysiology of OHSS. In addition we consider the prevention strategies, including coasting, administration of albumin, renin-angiotensin system blockage, dopamine agonist administration, non-steroidal anti-inflammatory administration, GnRH antagonist protocols, reducing hCG dosage, replacement of hCG and in vitro maturation of oocytes (IVM).

Conclusions

Among the many prevention strategies that have been discussed, the current evidence points to the replacement of hCG by GnRH agonists in antagonist cycles and the performance of IVM procedures as the safest approaches.

Keywords

Ovarian hyperstimulation syndrome Ovulation induction Assisted reproductive techniques 

References

  1. 1.
    Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Updat. 2002;8:559–77.CrossRefGoogle Scholar
  2. 2.
    Vlahos NF, Gregoriou O. Prevention and management of ovarian hyperstimulation syndrome. Ann N Y Acad Sci. 2006;1092:247–64.CrossRefPubMedGoogle Scholar
  3. 3.
    Gera PS, Tatpati LL, Allemand MC, Wentworth MA, Coddington CC. Ovarian hyperstimulation syndrome: steps to maximize success and minimize effect for assisted reproductive outcome. Fertil Steril. 2009.Google Scholar
  4. 4.
    Michaelson-Cohen R, Altarescu G, Beller U, Reens R, Halevy-Shalem T, Eldar-Geva T. Does elevated human chorionic gonadotropin alone trigger spontaneous ovarian hyperstimulation syndrome? Fertil Steril. 2008;90:1869–74.CrossRefPubMedGoogle Scholar
  5. 5.
    ASRM. Ovarian hyperstimulation syndrome. Fertil Steril. 2008;90:S188–93.Google Scholar
  6. 6.
    Aboulghar MA, Mansour RT. Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Hum Reprod Updat. 2003;9:275–89.CrossRefGoogle Scholar
  7. 7.
    Goldsman MP, Pedram A, Dominguez CE, Ciuffardi I, Levin E, Asch RH. Increased capillary permeability induced by human follicular fluid: a hypothesis for an ovarian origin of the hyperstimulation syndrome. Fertil Steril. 1995;63:268–72.PubMedGoogle Scholar
  8. 8.
    Tollan A, Holst N, Forsdahl F, Fadnes HO, Oian P, Maltau JM. Transcapillary fluid dynamics during ovarian stimulation for in vitro fertilization. Am J Obstet Gynecol. 1990;162:554–8.PubMedGoogle Scholar
  9. 9.
    Asch RH, Li HP, Balmaceda JP, Weckstein LN, Stone SC. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups. Hum Reprod. 1991;6:1395–9.PubMedGoogle Scholar
  10. 10.
    Pellicer A, Miro F, Sampaio M, Gomez E, Bonilla-Musoles FM. In vitro fertilization as a diagnostic and therapeutic tool in a patient with partial 17, 20-desmolase deficiency. Fertil Steril. 1991;55:970–5.PubMedGoogle Scholar
  11. 11.
    Soares SR, Gomez R, Simon C, Garcia-Velasco JA, Pellicer A. Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome. Hum Reprod Updat. 2008;14:321–33.CrossRefGoogle Scholar
  12. 12.
    Rizk B, Aboulghar M, Smitz J, Ron-El R. The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome. Hum Reprod Updat. 1997;3:255–66.CrossRefGoogle Scholar
  13. 13.
    Navot D, Margalioth EJ, Laufer N, Birkenfeld A, Relou A, Rosler A, et al. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril. 1987;48:57–61.PubMedGoogle Scholar
  14. 14.
    Blankestijn PJ, Derkx FH, Van Geelen JA, De Jong FH, Schalekamp MA. Increase in plasma prorenin during the menstrual cycle of a bilaterally nephrectomized woman. Br J Obstet Gynaecol. 1990;97:1038–42.PubMedGoogle Scholar
  15. 15.
    Fernandez LA, Tarlatzis BC, Rzasa PJ, Caride VJ, Laufer N, Negro-Vilar AF, et al. Renin-like activity in ovarian follicular fluid. Fertil Steril. 1985;44:219–23.PubMedGoogle Scholar
  16. 16.
    Morris RS, Paulson RJ. Increased angiotensin-converting enzyme activity in a patient with severe ovarian hyperstimulation syndrome. Fertil Steril. 1999;71:562–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Manno M, Tomei F. Renin-angiotensin system activation during severe OHSS: cause or effect? Fertil Steril. 2008;89:488.CrossRefPubMedGoogle Scholar
  18. 18.
    McClure N, Healy DL, Rogers PA, Sullivan J, Beaton L, Haning Jr RV, et al. Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome. Lancet. 1994;344:235–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Gomez R, Simon C, Remohi J, Pellicer A. Administration of moderate and high doses of gonadotropins to female rats increases ovarian vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression that is associated to vascular hyperpermeability. Biol Reprod. 2003;68:2164–71.CrossRefPubMedGoogle Scholar
  20. 20.
    Wang TH, Horng SG, Chang CL, Wu HM, Tsai YJ, Wang HS, et al. Human chorionic gonadotropin-induced ovarian hyperstimulation syndrome is associated with up-regulation of vascular endothelial growth factor. J Clin Endocrinol Metab. 2002;87:3300–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Villasante A, Pacheco A, Ruiz A, Pellicer A, Garcia-Velasco JA. Vascular endothelial cadherin regulates vascular permeability: Implications for ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 2007;92:314–21.CrossRefPubMedGoogle Scholar
  22. 22.
    Rodewald M, Herr D, Duncan WC, Fraser HM, Hack G, Konrad R, et al. Molecular mechanisms of ovarian hyperstimulation syndrome: paracrine reduction of endothelial claudin 5 by hCG in vitro is associated with increased endothelial permeability. Hum Reprod. 2009;24(5):1191–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Nardo LG, Cheema P, Gelbaya TA, Horne G, Fitzgerald CT, Pease EH, et al. The optimal length of ‘coasting protocol’ in women at risk of ovarian hyperstimulation syndrome undergoing in vitro fertilization. Hum Fertil (Camb). 2006;9:175–80.CrossRefGoogle Scholar
  24. 24.
    Ho Yuen B, Nguyen TA, Cheung AP, Leung PC: Clinical and endocrine response to the withdrawal of gonadotropin-releasing hormone agonists during prolonged coasting. Fertil Steril. 2008.Google Scholar
  25. 25.
    Moon HS, Joo BS, Moon SE, Lee SK, Kim KS, Koo JS. Short coasting of 1 or 2 days by withholding both gonadotropins and gonadotropin-releasing hormone agonist prevents ovarian hyperstimulation syndrome without compromising the outcome. Fertil Steril. 2008;90:2172–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Yilmaz N, Uygur D, Ozgu E, Batioglu S: Does coasting, a procedure to avoid ovarian hyperstimulation syndrome, affect assisted reproduction cycle outcome? Fertil Steril. 2009.Google Scholar
  27. 27.
    Garcia-Velasco JA, Zuniga A, Pacheco A, Gomez R, Simon C, Remohi J, et al. Coasting acts through downregulation of VEGF gene expression and protein secretion. Hum Reprod. 2004;19:1530–8.CrossRefPubMedGoogle Scholar
  28. 28.
    D’Angelo A, Amso N: “Coasting” (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev. 2002;CD002811.Google Scholar
  29. 29.
    Huddleston HG, Racowsky C, Jackson KV, Fox JH, Ginsburg ES. Coasting vs. cryopreservation of all embryos for prevention of ovarian hyperstimulation syndrome in in vitro fertilization. Fertil Steril. 2008;90:1259–62.CrossRefPubMedGoogle Scholar
  30. 30.
    Aboulghar M, Evers JH, Al-Inany H. Intravenous albumin for preventing severe ovarian hyperstimulation syndrome: a Cochrane review. Hum Reprod. 2002;17:3027–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Isikoglu M, Berkkanoglu M, Senturk Z, Ozgur K. Human albumin does not prevent ovarian hyperstimulation syndrome in assisted reproductive technology program: a prospective randomized placebo-controlled double blind study. Fertil Steril. 2007;88:982–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Bellver J, Munoz EA, Ballesteros A, Soares SR, Bosch E, Simon C, et al. Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study. Hum Reprod. 2003;18:2283–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Ando H, Furugori K, Shibata D, Harata T, Murata Y, Mizutani S. Dual renin-angiotensin blockade therapy in patients at high risk of early ovarian hyperstimulation syndrome receiving IVF and elective embryo cryopreservation: a case series. Hum Reprod. 2003;18:1219–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Ata B, Yakin K, Alatas C, Urman B. Dual renin-angiotensin blockage and total embryo cryopreservation is not a risk-free strategy in patients at high risk for ovarian hyperstimulation syndrome. Fertil Steril. 2008;90:531–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Gomez R, Gonzalez-Izquierdo M, Zimmermann RC, Novella-Maestre E, Alonso-Muriel I, Sanchez-Criado J, et al. Low-dose dopamine agonist administration blocks vascular endothelial growth factor (VEGF)-mediated vascular hyperpermeability without altering VEGF receptor 2-dependent luteal angiogenesis in a rat ovarian hyperstimulation model. Endocrinology. 2006;147:5400–11.CrossRefPubMedGoogle Scholar
  36. 36.
    Carizza C, Abdelmassih V, Abdelmassih S, Ravizzini P, Salgueiro L, Salgueiro PT, et al. Cabergoline reduces the early onset of ovarian hyperstimulation syndrome: a prospective randomized study. Reprod Biomed Online. 2008;17:751–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Varnagy A, Bodis J, Manfai Z, Wilhelm F, Busznyak C, Koppan M: Low-dose aspirin therapy to prevent ovarian hyperstimulation syndrome. Fertil Steril. 2009.Google Scholar
  38. 38.
    Quintana R, Kopcow L, Marconi G, Young E, Yovanovich C, Paz DA. Inhibition of cyclooxygenase-2 (COX-2) by meloxicam decreases the incidence of ovarian hyperstimulation syndrome in a rat model. Fertil Steril. 2008;90:1511–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod Biomed Online. 2007;14:640–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Schmidt DW, Maier DB, Nulsen JC, Benadiva CA. Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization. Fertil Steril. 2004;82:841–6.CrossRefPubMedGoogle Scholar
  41. 41.
    Nargund G, Hutchison L, Scaramuzzi R, Campbell S. Low-dose HCG is useful in preventing OHSS in high-risk women without adversely affecting the outcome of IVF cycles. Reprod Biomed Online. 2007;14:682–5.PubMedGoogle Scholar
  42. 42.
    Group TERLS. Human recombinant luteinizing hormone is as effective as, but safer than, urinary human chorionic gonadotropin in inducing final follicular maturation and ovulation in in vitro fertilization procedures: results of a multicenter double-blind study. J Clin Endocrinol Metab. 2001;86:2607–18.CrossRefGoogle Scholar
  43. 43.
    Bodri D, Guillen JJ, Galindo A, Mataro 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;91:365–71.CrossRefPubMedGoogle Scholar
  44. 44.
    Galindo A, Bodri D, Guillen JJ, Colodron 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;25:60–6.CrossRefPubMedGoogle Scholar
  45. 45.
    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;89:84–91.CrossRefPubMedGoogle Scholar
  46. 46.
    Manzanares MA, Gomez-Palomares JL, Ricciarelli E, Hernandez ER: 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. 2009.Google Scholar
  47. 47.
    Lanzendorf SE. Developmental potential of in vitro- and in vivo-matured human oocytes collected from stimulated and unstimulated ovaries. Fertil Steril. 2006;85:836–7.CrossRefPubMedGoogle Scholar
  48. 48.
    Suikkari AM. In-vitro maturation: its role in fertility treatment. Curr Opin Obstet Gynecol. 2008;20:242–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Son WY, Chung JT, Demirtas E, Holzer H, Sylvestre C, Buckett W, et al. Comparison of in-vitro maturation cycles with and without in-vivo matured oocytes retrieved. Reprod Biomed Online. 2008;17:59–67.PubMedGoogle Scholar
  50. 50.
    Son WY, Chung JT, Chian RC, Herrero B, Demirtas E, Elizur S, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008;23:2010–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Carolina O. Nastri
    • 1
    • 2
  • Rui A. Ferriani
    • 1
  • Isa A. Rocha
    • 1
  • Wellington P. Martins
    • 1
    • 2
  1. 1.Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (DGO-HC-FMRP-USP)Ribeirão PretoBrazil
  2. 2.Escola de Ultra-Sonografia e Reciclagem Médica de Ribeirão Preto (EURP)Ribeirão PretoBrazil

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