Skip to main content

Advertisement

SpringerLink
Log in

Ovarian hyperstimulation syndrome after gonadotropin-releasing hormone agonist triggering and “freeze-all”: in-depth analysis of genetic predisposition

  • Case Report
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

We report on the results of the whole-genome analysis performed in a patient who developed severe ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone (GnRH) agonist triggering in a “freeze-all” protocol.

Methods

A 30-year-old patient with polycystic ovary syndrome who developed severe early-onset OHSS with clinical ascites, and slight renal and hepatic dysfunction was admitted for monitoring and treatment with cabergoline and intravenous albumin. Exome sequencing to assess for any known genetic predisposition for OHSS was performed.

Results

No known genetic variants associated with OHSS predisposition were found.

Conclusions

Case reports of severe OHSS following a “freeze-all” strategy are starting to arise, showing that OHSS has not been completely eliminated with this approach. Further studies should be conducted to confirm if such cases may be due to genetic predisposition or not.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Papanikolaou EG, Pozzobon C, Kolibianakis EM, Camus M, Tournaye H, Fatemi HM, 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):112–20. doi:10.1016/j.fertnstert.2005.07.1292.

    Article  CAS  PubMed  Google Scholar 

  2. Mathur RS, Akande AV, Keay SD, Hunt LP, Jenkins JM. Distinction between early and late ovarian hyperstimulation syndrome. Fertil Steril. 2000;73(5):901–7.

    Article  CAS  PubMed  Google Scholar 

  3. 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. doi:10.1016/j.fertnstert.2007.02.002.

    Article  CAS  PubMed  Google Scholar 

  4. Acevedo B, Gomez-Palomares JL, Ricciarelli E, Hernandez ER. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates. Fertil Steril. 2006;86(6):1682–7. doi:10.1016/j.fertnstert.2006.05.049.

    Article  CAS  PubMed  Google Scholar 

  5. Delvigne A, Rozenberg S. Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS). Hum Reprod Update. 2003;9(1):77–96.

    Article  CAS  PubMed  Google Scholar 

  6. Vloeberghs V, Peeraer K, Pexsters A, D’Hooghe T. Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol. 2009;23(5):691–709. doi:10.1016/j.bpobgyn.2009.02.006.

    Article  PubMed  Google Scholar 

  7. Humaidan P, Kol S, Papanikolaou EG. GnRH agonist for triggering of final oocyte maturation: time for a change of practice? Hum Reprod Update. 2011;17(4):510–24. doi:10.1093/humupd/dmr008.

    Article  CAS  PubMed  Google Scholar 

  8. Engmann L, Benadiva C. Agonist trigger: what is the best approach? Agonist trigger with aggressive luteal support. Fertil Steril. 2012;97(3):531–3. doi:10.1016/j.fertnstert.2011.12.020.

    Article  CAS  PubMed  Google Scholar 

  9. Garcia-Velasco JA. Agonist trigger: what is the best approach? Agonist trigger with vitrification of oocytes or embryos. Fertil Steril. 2012;97(3):527–8. doi:10.1016/j.fertnstert.2011.12.010.

    Article  PubMed  Google Scholar 

  10. Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update. 2006;12(2):159–68. doi:10.1093/humupd/dmi045.

    Article  CAS  PubMed  Google Scholar 

  11. Herrero L, Pareja S, Losada C, Cobo AC, Pellicer A, Garcia-Velasco JA. Avoiding the use of human chorionic gonadotropin combined with oocyte vitrification and GnRH agonist triggering versus coasting: a new strategy to avoid ovarian hyperstimulation syndrome. Fertil Steril. 2011;95(3):1137–40. doi:10.1016/j.fertnstert.2010.09.040.

    Article  CAS  PubMed  Google Scholar 

  12. Iliodromiti S, Blockeel C, Tremellen KP, Fleming R, Tournaye H, Humaidan P, et al. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support: a retrospective multicentre study. Hum Reprod. 2013;28(9):2529–36. doi:10.1093/humrep/det304.

    Article  CAS  PubMed  Google Scholar 

  13. Melo M, Busso CE, Bellver J, Alama P, Garrido N, Meseguer M, et al. GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized, prospective, controlled, assessor-blind study. Reprod Biomed Online. 2009;19(4):486–92. doi:10.1016/j.rbmo.2009.06.001.

    Article  CAS  PubMed  Google Scholar 

  14. Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod. 2011;26(10):2593–7. doi:10.1093/humrep/der251.

    Article  PubMed  Google Scholar 

  15. Bodri D, Guillén JJ, Trullenque M, Schwenn K, Esteve C, Coll O. Early ovarian hyperstimulation syndrome is completely prevented by gonadotropin releasing-hormone agonist triggering in high-risk oocyte donor cycles: a prospective, luteal-phase follow-up study. Fertil Steril. 2010;93(7):2418–20. doi:10.1016/j.fertnstert.2009.08.036.

    Article  CAS  PubMed  Google Scholar 

  16. Griesinger G, Schultz L, Bauer T, Broessner A, Frambach T, Kissler S. Ovarian hyperstimulation syndrome prevention by gonadotropin-releasing hormone agonist triggering of final oocyte maturation in a gonadotropin-releasing hormone antagonist protocol in combination with a “freeze-all” strategy: a prospective multicentric study. Fertil Steril. 2011;95(6):2029–33. doi:10.1016/j.fertnstert.2011.01.163.

  17. Ling LP, Phoon JW, Lau MS, Chan JK, Viardot-Foucault V, Tan TY, et al. GnRH agonist trigger and ovarian hyperstimulation syndrome: relook at ‘freeze-all strategy’. Reprod Biomed Online. 2014;29(3):392–4. doi:10.1016/j.rbmo.2014.05.012.

    Article  CAS  PubMed  Google Scholar 

  18. Gurbuz AS, Gode F, Ozcimen N, Isik AZ. Gonadotrophin-releasing hormone agonist trigger and freeze-all strategy does not prevent severe ovarian hyperstimulation syndrome: a report of three cases. Reprod Biomed Online. 2014. doi:10.1016/j.rbmo.2014.07.022.

    PubMed  Google Scholar 

  19. Fatemi HM, Popovic-Todorovic B, Humaidan P, Kol S, Banker M, Devroey P, et al. Severe ovarian hyperstimulation syndrome after gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze-all” approach in GnRH antagonist protocol. Fertil Steril. 2014;101(4):1008–11. doi:10.1016/j.fertnstert.2014.01.019.

    Article  CAS  PubMed  Google Scholar 

  20. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989;44(6):430–40.

    Article  CAS  PubMed  Google Scholar 

  21. Kol S. A case of severe early-onset OHSS after GnRH-agonist triggering. Fertil Steril. 2011;96(3):e151. doi:10.1016/j.fertnstert.2011.06.057. author reply e152.

    Article  PubMed  Google Scholar 

  22. Abu-Louz SK, Ahmed AA, Swan RW. Spontaneous ovarian hyperstimulation syndrome with pregnancy. Am J Obstet Gynecol. 1997;177(2):476–7.

    Article  CAS  PubMed  Google Scholar 

  23. Ayhan A, Tuncer ZS, Aksu AT. Ovarian hyperstimulation syndrome associated with spontaneous pregnancy. Hum Reprod. 1996;11(8):1600–1.

    Article  CAS  PubMed  Google Scholar 

  24. Di Carlo C, Bruno P, Cirillo D, Morgera R, Pellicano M, Nappi C. Increased concentrations of renin, aldosterone and Ca125 in a case of spontaneous, recurrent, familial, severe ovarian hyperstimulation syndrome. Hum Reprod. 1997;12(10):2115–7.

    Article  PubMed  Google Scholar 

  25. group E-A-sPcw. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–7.

    Article  Google Scholar 

  26. Altmae S, Hovatta O, Stavreus-Evers A, Salumets A. Genetic predictors of controlled ovarian hyperstimulation: where do we stand today? Hum Reprod Update. 2011;17(6):813–28. doi:10.1093/humupd/dmr034.

    Article  CAS  PubMed  Google Scholar 

  27. Moron FJ, de Castro F, Royo JL, Montoro L, Mira E, Saez ME, et al. Bone morphogenetic protein 15 (BMP15) alleles predict over-response to recombinant follicle stimulation hormone and iatrogenic ovarian hyperstimulation syndrome (OHSS). Pharmacogenet Genomics. 2006;16(7):485–95. doi:10.1097/01.fpc.0000215073.44589.96.

    Article  CAS  PubMed  Google Scholar 

  28. Rizk B. Symposium: Update on prediction and management of OHSS. Genetics of ovarian hyperstimulation syndrome. Reprod Biomed Online. 2009;19(1):14–27.

    Article  CAS  PubMed  Google Scholar 

  29. O’Brien TJ, Kalmin MM, Harralson AF, Clark AM, Gindoff I, Simmens SJ, et al. Association between the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) rs4073366 polymorphism and ovarian hyperstimulation syndrome during controlled ovarian hyperstimulation. Reprod Biol Endocrinol RB&E. 2013;11(1):71. doi:10.1186/1477-7827-11-71.

    Article  Google Scholar 

  30. Achrekar SK, Modi DN, Desai SK, Mangoli VS, Mangoli RV, Mahale SD. Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women. Fertil Steril. 2009;91(2):432–9. doi:10.1016/j.fertnstert.2007.11.093.

    Article  CAS  PubMed  Google Scholar 

  31. Daelemans C, Smits G, de Maertelaer V, Costagliola S, Englert Y, Vassart G, et al. Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism. J Clin Endocrinol Metab. 2004;89(12):6310–5. doi:10.1210/jc.2004-1044.

    Article  CAS  PubMed  Google Scholar 

  32. Dulitzky M, Cohen SB, Inbal A, Seidman DS, Soriano D, Lidor A, et al. Increased prevalence of thrombophilia among women with severe ovarian hyperstimulation syndrome. Fertil Steril. 2002;77(3):463–7.

    Article  PubMed  Google Scholar 

  33. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31(13):3812–4. doi:10.1093/nar/gkg509.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–9. doi:10.1038/nmeth0410-248.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011;5:CD001750. doi:10.1002/14651858.CD001750.pub3.

    PubMed  Google Scholar 

  37. Humaidan P. Agonist trigger: what is the best approach? Agonist trigger and low dose hCG. Fertil Steril. 2012;97(3):529–30. doi:10.1016/j.fertnstert.2011.11.016.

    Article  CAS  PubMed  Google Scholar 

  38. Griesinger G, von Otte S, Schroer A, Ludwig AK, Diedrich K, Al-Hasani S, 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):1348–52. doi:10.1093/humrep/dem006.

    Article  CAS  PubMed  Google Scholar 

  39. Seyhan A, Ata B, Polat M, Son WY, Yarali H, Dahan MH. Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG. Hum Reprod. 2013;28(9):2522–8. doi:10.1093/humrep/det124.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have nothing to disclose

Funding

This case report was financially supported by the Willy Gepts Fund of the Universitair Ziekenhuis Brussel

Author information

Authors and Affiliations

  1. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium

    Samuel Santos-Ribeiro, Nikolaos P. Polyzos, Michel De Vos, Herman Tournaye & Christophe Blockeel

  2. Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Universitário de Santa Maria, Avenida Professor Egas Moniz, 1649-035, Lisbon, Portugal

    Samuel Santos-Ribeiro

  3. Department of Clinical Medicine, Faculty of Health, University of Aarhus, Incuba/Skejby, bld.2, Palle Juul-Jensens Boulevard 82, Aarhus N, 8200, Aarhus, Denmark

    Nikolaos P. Polyzos

  4. Centre for Medical Genetics, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium

    Katrien Stouffs & Sara Seneca

Authors
  1. Samuel Santos-Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolaos P. Polyzos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katrien Stouffs
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michel De Vos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sara Seneca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Herman Tournaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christophe Blockeel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christophe Blockeel.

Additional information

Capsule Whole-genome sequencing performed in a patient who developed early-onset severe OHSS following a freeze-all strategy with GnRH agonist triggering did not reveal any known genetic predisposition for this ART-related complication.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santos-Ribeiro, S., Polyzos, N.P., Stouffs, K. et al. Ovarian hyperstimulation syndrome after gonadotropin-releasing hormone agonist triggering and “freeze-all”: in-depth analysis of genetic predisposition. J Assist Reprod Genet 32, 1063–1068 (2015). https://doi.org/10.1007/s10815-015-0498-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-015-0498-y

Keywords

Search

Navigation