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Combination of cabergoline and embryo cryopreservation after GnRH agonist triggering prevents OHSS in patients with extremely high estradiol levels—a retrospective study

  • ASSISTED REPRODUCTION TECHNOLOGIES
  • Published:
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Abstract

Purpose

Embryo cryopreservation after triggering oocyte maturation with GnRH agonist (GnRHa) in GnRH antagonist protocols has been proposed to prevent ovarian hyperstimulation syndrome (OHSS). However, a small percentage of patients still developed severe OHSS. The purpose of the study was to investigate the efficacy of preventing OHSS in patients at very high risk when cabergoline was given in addition to elective cryopreservation after GnRHa triggering.

Methods

This is a retrospective observational study. The patients were stimulated with GnRH antagonist protocol. When serum E2 concentration was >6,000 pg/ml and there were more than 20 follicles ≥11 mm on the day of final oocyte maturation, GnRHa was used to trigger oocyte maturation. Cabergoline was given to augment the effect of preventing OHSS. The embryos were electively cryopreserved by vitrification and thawed in subsequent cycles. The primary outcome measure was the incidence of severe OHSS. The secondary outcome measure was the clinical pregnancy rate in the first frozen-thawed embryo transfer cycle.

Results

One hundred and ten patients underwent 110 stimulated cycles were included for analysis. No patients developed moderate/severe OHSS. Mean E2 concentration on the day of final oocyte maturation was 7,873 pg/ml, and an average of 22.7 oocytes was obtained from each patient. One hundred and ten thawing cycles were performed, resulting in 69 clinical pregnancies (62.7 %).

Conclusions

Combining cabergoline and embryo cryopreservation after GnRHa triggering in GnRH antagonist protocol could prevent OHSS in patients at very high risk.

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References

  1. Aboulghar M. Symposium: update on prediction and management of OHSS. Prevention of OHSS. Reprod Biomed Online. 2009;19:33–42.

    Article  PubMed  CAS  Google Scholar 

  2. Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, Abou-Setta AM. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011;CD001750.

  3. Alvarez C, Alonso-Muriel I, Garcia G, Crespo J, Bellver J, Simon C, et al. Implantation is apparently unaffected by the dopamine agonist cabergoline when administered to prevent ovarian hyperstimulation syndrome in women undergoing assisted reproduction treatment: a pilot study. Hum Reprod. 2007;22:3210–4.

    Article  PubMed  CAS  Google Scholar 

  4. Alvarez C, Marti-Bonmati L, Novella-Maestre E, Sanz R, Gomez R, Fernandez-Sanchez M, et al. Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction. J Clin Endocrinol Metab. 2007;92:2931–7.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    PubMed  CAS  Google Scholar 

  6. Babayof R, Margalioth EJ, Huleihel M, Amash A, Zylber-Haran E, Gal 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;21:1260–5.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. Castillo JC, Dolz M, Bienvenido E, Abad L, Casañ EM, Bonilla-Musoles F. Cycles triggered with GnRH agonist: exploring low-dose HCG for luteal support. Reprod BioMed Online. 2010;20:175–81.

    Article  PubMed  CAS  Google Scholar 

  9. Cerrillo M, Pacheco A, Rodriguez S, Gomez R, Delgado F, Pellicer A, et al. Effect of GnRH agonist and hCG treatment on VEGF, angiopoietin-2, and VE-cadherin: trying to explain the link to ovarian hyperstimulation syndrome. Fertil Steril. 2011;95:2517–9.

    Article  PubMed  CAS  Google Scholar 

  10. Delvigne A. Symposium: update on prediction and management of OHSS. Epidemiology of OHSS. Reprod Biomed Online. 2009;19:8–13.

    Article  PubMed  Google Scholar 

  11. Delvigne A, Rozenberg S. Preventive attitude of physicians to avoid OHSS in IVF patients. Hum Reprod. 2001;16:2491–5.

    Article  PubMed  CAS  Google Scholar 

  12. Desai N, Abdelhafez F, Bedaiwy MA, Goldberg J, Falcone T, Goldfarb J. Clinical pregnancy and live births after transfer of embryos vitrified on day 3. Reprod Biomed Online. 2010;20:808–13.

    Article  PubMed  Google Scholar 

  13. Devroey P, Polyzos NP, Blockeel C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod. 2011;26:2593–7.

    Article  PubMed  Google Scholar 

  14. Emperaire JC, Ruffie A. Triggering ovulation with endogenous luteinizing hormone may prevent the ovarian hyperstimulation syndrome. Hum Reprod. 1991;6:506–10.

    PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. Gomez R, Simon C, Remohi J, Pellicer A. Vascular endothelial growth factor receptor-2 activation induces vascular permeability in hyperstimulated rats, and this effect is prevented by receptor blockade. Endocrinology. 2002;143:4339–48.

    Article  PubMed  CAS  Google Scholar 

  19. Griesinger G, Berndt H, Schultz L, Depenbusch M, Schultze-Mosgau A. Cumulative live birth rates after GnRH-agonist triggering of final oocyte maturation in patients at risk of OHSS: a prospective, clinical cohort study. Eur J Obstet Gynecol Reprod Biol. 2010;149:190–4.

    Article  PubMed  CAS  Google Scholar 

  20. Griesinger G, Berndt H, Schultz L, Schultze-Mosgau A, Diedrich K, Otte S. Intensified ovarian stimulation in a GnRH antagonist protocol with agonist triggering: a prospective, clinical feasibility study. Reprod BioMed Online. 2011;22:133–9.

    Article  PubMed  CAS  Google Scholar 

  21. 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;12:159–68.

    Article  PubMed  CAS  Google Scholar 

  22. 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;95:2029–33.

    Google Scholar 

  23. 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;22:1348–52.

    Article  PubMed  CAS  Google Scholar 

  24. Griffin D, Benadiva C, Kummer N, Budinetz T, Nulsen J, Engmann L. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril. 2012;97:1316–20.

    Article  PubMed  CAS  Google Scholar 

  25. 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;95:1137–40.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. Humaidan P. Luteal phase rescue in high-risk OHSS patients by GnRHa triggering in combination with low-dose HCG: a pilot study. Reprod Biomed Online. 2009;18:630–4.

    Article  PubMed  CAS  Google Scholar 

  28. Humaidan P, Bredkjaer HE, Bungum L, Bungum M, Grondahl ML, Westergaard L, et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005;20:1213–20.

    Article  PubMed  CAS  Google Scholar 

  29. 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;13:173–8.

    Article  PubMed  CAS  Google Scholar 

  30. Humaidan P, Ejdrup Bredkjaer H, Westergaard LG, Yding Andersen C. 1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study. Fertil Steril. 2010;93:847–54.

    Article  PubMed  CAS  Google Scholar 

  31. Hwang J-L, Lin Y-H, Seow K-M. Failure of cabergoline to prevent severe ovarian hyperstimulation syndrome in patients with extremely high estradiol levels. Int J Gynaecol Obstet. 2010;108:159–60.

    Article  PubMed  CAS  Google Scholar 

  32. Hwang JL, Lin YH, Tsai YL. Pregnancy after immature oocyte donation and intracytoplasmic sperm injection. Fertil Steril. 1997;68:1139–40.

    Article  PubMed  CAS  Google Scholar 

  33. Itskovitz-Eldor J, Boldes R, Levron J, Erlik Y, Kahana L, Brandes JM. Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. Fertil Steril. 1991;56:213–20.

    Google Scholar 

  34. Kol S. A case of severe early-onset OHSS after GnRH-agonist triggering. Fertil Steril. 2011;96:e151. author reply e152.

    Article  PubMed  Google Scholar 

  35. Kol S, Lewit N, Itskovitz-Eldor J. Ovarian hyperstimulation: effects of GnRH analogues. Ovarian hyperstimulation syndrome after using gonadotrophin-releasing hormone analogue as a trigger of ovulation: causes and implications. Hum Reprod. 1996;11:1143–4.

    Article  PubMed  CAS  Google Scholar 

  36. Kolibianakis EM, Schultze-Mosgau A, Schroer A, van Steirteghem A, Devroey P, Diedrich K, 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;20:2887–92.

    Article  PubMed  CAS  Google Scholar 

  37. Levinsohn-Tavor O, Friedler S, Schachter M, Raziel A, Strassburger D, Ron-El R. Coasting-what is the best formula? Hum Reprod. 2003;18:937–40.

    Article  PubMed  CAS  Google Scholar 

  38. Lin YH, Wen YR, Chang Y, Seow KM, Hsieh BC, Hwang JL, et al. Safety and efficacy of mixing cetrorelix with follitropin alfa: a randomized study. Fertil Steril. 2010;94:179–83.

    Article  PubMed  CAS  Google Scholar 

  39. Manno M, Tomei F, Marchesan E, Adamo V. An important new adaption of a specific drug? Fertil Steril. 2007;88:533.

    Article  PubMed  Google Scholar 

  40. Mansour R, Aboulghar M, Serour G, Amin Y, Abou-Setta AM. Criteria of a successful coasting protocol for the prevention of severe ovarian hyperstimulation syndrome. Hum Reprod. 2005;20:3167–72.

    Article  PubMed  Google Scholar 

  41. 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. 2010;93:1215–9.

    Article  PubMed  CAS  Google Scholar 

  42. Mukaida T, Nakamura S, Tomiyama T, Wada S, Oka C, Kasai M, et al. Vitrification of human blastocysts using cryoloops: clinical outcome of 223 cycles*. Hum Reprod. 2003;18:384–91.

    Article  PubMed  CAS  Google Scholar 

  43. 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;85:112–20.

    Article  PubMed  CAS  Google Scholar 

  44. Radesic B, Tremellen K. Oocyte maturation employing a GnRH agonist in combination with low-dose hCG luteal rescue minimizes the severity of ovarian hyperstimulation syndrome while maintaining excellent pregnancy rates. Hum Reprod. 2011;26:3437–42.

    Article  PubMed  CAS  Google Scholar 

  45. Roque M, Lattes K, Serra S, Sola I, Geber S, Carreras R, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013;99:156–62.

    Article  PubMed  Google Scholar 

  46. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Comparison of “triggers” using leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin. Fertil Steril. 2011;95:2715–7.

    Article  PubMed  CAS  Google Scholar 

  47. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Thomas S. Gonadotropin-releasing hormone agonist combined with a reduced dose of human chorionic gonadotropin for final oocyte maturation in fresh autologous cycles of in vitro fertilization. Fertil Steril. 2008;90:231–3.

    Article  PubMed  CAS  Google Scholar 

  48. Shapiro BS, Daneshmand ST, Restrepo H, Garner FC, Aguirre M, Hudson C. Efficacy of induced luteinizing hormone surge after “trigger” with gonadotropin-releasing hormone agonist. Fertil Steril. 2011;95:826–8.

    Article  PubMed  CAS  Google Scholar 

  49. 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.

    Article  CAS  Google Scholar 

  50. Ulug U, Bahceci M, Erden HF, Shalev E, Ben-Shlomo I. The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles. Hum Reprod. 2002;17:310–3.

    Article  PubMed  Google Scholar 

  51. Yang YS, Hwang JL, Ho HN, Kuo YS, Lien YR, Lee TY. Pregnancy following oocyte donation and tubal embryo transfer in patients with premature ovarian failure: report of two cases. J Formos Med Assoc. 1991;90:688–92.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Shin Kong Wu Ho-Su Memorial Hospital (SKH-8302-99- DR- 27).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wen Chang Road, Shih Lin District, Taipei, Taiwan

    Yu-Hung Lin, Jiann-Loung Hwang, Heng-Ju Chen, Bih-Chwen Hsieh, Lee-Wen Huang & Kok-Min Seow

  2. School of Medicine, Fu Jen Catholic University, Taipei, Taiwan

    Yu-Hung Lin, Heng-Ju Chen, Bih-Chwen Hsieh & Lee-Wen Huang

  3. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Hsinchu, Taiwan

    Yu-Hung Lin

  4. Department of Obstetrics and Gynecology, Taipei Medical University, Taipei, Taiwan

    Yu-Hung Lin, Jiann-Loung Hwang & Chii-Ruey Tzeng

  5. Department of Nursing, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Mei-Zen Huang

  6. Graduate Institute of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan

    Mei-Zen Huang

  7. Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan

    Kok-Min Seow

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  1. Yu-Hung Lin
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Correspondence to Kok-Min Seow.

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Capsule Combination of cabergoline and embryo cryopreservation after GnRH agonist triggering prevents OHSS in patients with extremely high estradiol levels.

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Lin, YH., Huang, MZ., Hwang, JL. et al. Combination of cabergoline and embryo cryopreservation after GnRH agonist triggering prevents OHSS in patients with extremely high estradiol levels—a retrospective study. J Assist Reprod Genet 30, 753–759 (2013). https://doi.org/10.1007/s10815-013-9997-x

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  • DOI: https://doi.org/10.1007/s10815-013-9997-x

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