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Journal of Assisted Reproduction and Genetics

Published in:

15-09-2023 | Ovarian Hyperstimulation Syndrome | Assisted Reproduction Technologies

The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization

Authors: I. Feferkorn, S. Santos-Ribeiro, F. M. Ubaldi, J. G. Velasco, B. Ata, C. Blockeel, A. Conforti, S. C. Esteves, H. M. Fatemi, L. Gianaroli, M. Grynberg, P. Humaidan, G.T Lainas, A. La Marca, L. B. Craig, R. Lathi, R. J. Norman, R. Orvieto, R. Paulson, A. Pellicer, N. P. Polyzos, M. Roque, S. K. Sunkara, S. L. Tan, B. Urman, C. Venetis, A. Weissman, H. Yarali, M. H. Dahan

Published in: Journal of Assisted Reproduction and Genetics | Issue 11/2023

Abstract

Purpose

To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS)

Methods

A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other.

Results

A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15–19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus).

Conclusion

These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research.

Available only for authorised users

Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod [Internet]. 2011;26:1768–74. [cited 2022 Mar 16] Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/21558332/PubMedCrossRef

Polyzos NP, Drakopoulos P, Parra J, Pellicer A, Santos-Ribeiro S, Tournaye H, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including ∼15,000 women. Fertil Steril [Internet]. 2018;110:661–670.e1. [cited 2021 Mar 4]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/30196963/PubMedCrossRef

Bosdou JK, Venetis CA, Tarlatzis BC, Grimbizis GF, Kolibianakis EM. Higher probability of live-birth in high, but not normal, responders after first frozen-embryo transfer in a freeze-only cycle strategy compared to fresh-embryo transfer: a meta-analysis. Hum Reprod [Internet]. 2019;34:491–505. [cited 2022 Mar 17]; Available from: https://academic.oup.com/humrep/article/34/3/491/5303709PubMedCrossRef

Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update [Internet]. 2019;25:2–14. [cited 2022 Jun 25] Available from: https://academic.oup.com/humupd/article/25/1/2/5155324PubMedCrossRef

Boynukalin FK, Turgut NE, Gultomruk M, Ecemis S, Yarkiner Z, Findikli N, et al. Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders? PLoS One. 2020;15 [cited 2022 Mar 17]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/32589634/

Ioannidou PG, Bosdou JK, Lainas GT, Lainas TG, Grimbizis GF, Kolibianakis EM. How frequent is severe ovarian hyperstimulation syndrome after GnRH agonist triggering in high-risk women? A systematic review and meta-analysis. Reprod Biomed Online [Internet]. 2021;42:635–50. [cited 2022 Jun 21]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33483281/PubMedCrossRef

Orvieto R. Can we eliminate severe ovarian hyperstimulation syndrome? Hum Reprod [Internet]. 2005;20:320–2. [cited 2023 Mar 16]; Available from: https://pubmed.ncbi.nlm.nih.gov/15567876/PubMedCrossRef

Committee of the American Society for Reproductive Medicine P, Pfeifer S, Butts MSCES, Dumesic D, Fossum G, Gracia MSCEC, et al. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril [Internet]. 2016;106:1634–47. https://doi.org/10.1016/j.fertnstert.2016.08.048.CrossRef

Feferkorn I, Ata B, Esteves SC, La Marca A, Paulson R, Blockeel C, et al. The HERA (Hyper-response Risk Assessment) Delphi consensus definition of hyper-responders for in-vitro fertilization. J Assist Reprod Genet. 2023; [cited 2023 Mar 21]; Available from: https://pubmed.ncbi.nlm.nih.gov/36933094/

10.

Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, et al. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014;101:967–73.PubMedCrossRef

11.

12.

Magnusson Å, Källen K, Thurin-Kjellberg A, Bergh C. The number of oocytes retrieved during IVF: a balance between efficacy and safety. Hum Reprod [Internet]. 2018;33:58–64. [cited 2022 Apr 27]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/29136154/PubMedCrossRef

13.

Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfers in high responders. Fertil Steril [Internet]. 2011;96:516–8. [cited 2022 Jun 25]; Available from: https://pubmed.ncbi.nlm.nih.gov/21737071/PubMedCrossRef

14.

Chen Z-J, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. New Engl J Med [Internet]. 2016;375:523–33. [cited 2022 Apr 20]; Available from: https://www.nejm.org/doi/10.1056/NEJMoa1513873PubMedCrossRef

15.

Toftager M, Bogstad J, Bryndorf T, Løssl K, Roskær J, Holland T, et al. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod [Internet]. 2016;31:1253–64. [cited 2022 Jul 10]; Available from: https://academic.oup.com/humrep/article/31/6/1253/1749630PubMedCrossRef

16.

Ovarian Stimulation TEGGO, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI†. Hum Reprod Open [Internet]. 2020;2020:1–13. [cited 2022 Mar 23]; Available from: https://academic.oup.com/hropen/article/2020/2/hoaa009/5827574

17.

Oudshoorn SC, van Tilborg TC, Eijkemans MJC, Oosterhuis GJE, Friederich J, van Hooff MHA, et al. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: the predicted hyper responder. Hum Reprod [Internet]. 2017;32:2506–14. [cited 2022 Apr 30]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/29121269/PubMedCrossRef

18.

Lensen SF, Wilkinson J, Leijdekkers JA, la Marca A, Mol BWJ, Marjoribanks J, et al. Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI). Cochrane Database Syst Rev. 2018;2 [cited 2022 Jun 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/29388198/

19.

Friis Petersen J, Løkkegaard E, Andersen LF, Torp K, Egeberg A, Hedegaard L, et al. A randomized controlled trial of AMH-based individualized FSH dosing in a GnRH antagonist protocol for IVF. Hum Reprod Open [Internet]. 2019;2019 [cited 2022 Jun 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/30895268/

20.

Mannaerts BMJL, Rombout F, Out HJ, Bennink HC. Clinical profiling of recombinant follicle stimulating hormone (rFSH; Puregon): relationship between serum FSH and efficacy. Hum Reprod Update [Internet]. 1996;2:153–61. [cited 2022 Jun 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/9079410/PubMedCrossRef

21.

Rose TH, Röshammar D, Erichsen L, Grundemar L, Ottesen JT. Population pharmacokinetic modelling of FE 999049, a recombinant human follicle-stimulating hormone, in healthy women after single ascending doses. Drugs R D [Internet]. 2016;16:173–80. [cited 2022 Jun 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/27003895/PubMedPubMedCentralCrossRef

22.

Rose TH, Röshammar D, Erichsen L, Grundemar L, Ottesen JT. Characterisation of population pharmacokinetics and endogenous follicle-stimulating hormone (FSH) levels after multiple dosing of a recombinant human FSH (FE 999049) in healthy women. Drugs RD [Internet]. 2016;16:165–72. [cited 2022 Jun 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/27139012/CrossRef

23.

Ledger WL, Fauser BCJM, Devroey P, Zandvliet AS, BMJL M. Corifollitropin alfa doses based on body weight: clinical overview of drug exposure and ovarian response. Reprod Biomed Online [Internet]. 2011;23:150–9. [cited 2022 Jun 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/21665541/PubMedCrossRef

24.

Leijdekkers JA, van Tilborg TC, Torrance HL, Oudshoorn SC, Brinkhuis EA, Koks CAM, et al. Do female age and body weight modify the effect of individualized FSH dosing in IVF/ICSI treatment? A secondary analysis of the OPTIMIST trial. Acta Obstet Gynecol Scand [Internet]. 2019;98:1332–40. [cited 2022 Jun 24]; Available from: https://onlinelibrary-wiley-com.proxy3.library.mcgill.ca/doi/full/10.1111/aogs.13664PubMedCrossRef

25.

Lainas GT, Lainas TG, Sfontouris IA, Venetis CA, Bosdou JK, Chatzimeletiou A, et al. Association between body mass index and oocyte maturation in patients triggered with GnRH agonist who are at high risk for severe ovarian hyperstimulation syndrome: an observational cohort study. Reprod Biomed Online [Internet]. 2020;40:168–75. [cited 2022 Jun 21]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/31839394/PubMedCrossRef

26.

Aboulghar MA, Mansour RT, Serour GI, Rhodes CA, Amin YM. Reduction of human menopausal gonadotropin dose before coasting prevents severe ovarian hyperstimulation syndrome with minimal cycle cancellation. J Assist Reprod Genet [Internet]. 2000;17:298. [cited 2022 Aug 26]; Available from: /pmc/articles/PMC3455203/PubMedPubMedCentralCrossRef

27.

Fatemi H, Bilger W, Denis D, Griesinger G, la Marca A, Longobardi S, et al. Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007-2017). Reprod Biol Endocrinol [Internet]. 2021;19 [cited 2022 Aug 26] Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33975610/

28.

Mahony MC, Hayward B, Mottla GL, Richter KS, Beall S, Ball GD, et al. Recombinant human follicle-stimulating hormone alfa dose adjustment in US clinical practice: an observational, retrospective analysis of a real-world electronic medical records database. Front Endocrinol (Lausanne) [Internet]. 2021;12 [cited 2022 Aug 26]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/34956077/

29.

D’Angelo A, Brown J, Amso NN. Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev [Internet]. 2011; [cited 2022 Aug 26]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/21678336/

30.

D’Angelo A, Amso NN, Hassan R. Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev [Internet]. 2017;5 [cited 2022 Aug 26]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/28535578/

31.

Palomba S, Falbo A, Russo T, Orio F, Tolino A, Zullo F. Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response. Hum Reprod. 2010;25:1005–13. [cited 2022 Aug 28]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/20106839/PubMedCrossRef

32.

Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2020;12 [cited 2022 Jun 23] Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33347618/

33.

Wu Y, Tu M, Huang Y, Liu Y, Zhang D. Association of metformin with pregnancy outcomes in women with polycystic ovarian syndrome undergoing in vitro fertilization: a systematic review and meta-analysis. JAMA Netw Open [Internet]. 2020;3:e2011995. [cited 2022 Jun 23]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/32744629/PubMedPubMedCentralCrossRef

34.

Siristatidis CS, Basios G, Pergialiotis V, Vogiatzi P. Aspirin for in vitro fertilisation. Cochrane Database Syst Rev. 2016;11 [cited 2022 Aug 26]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/27807847/

35.

Orvieto R. Prediction of ovarian hyperstimulation syndrome. Challenging the estradiol mythos. Human Reproduction [Internet]. 2003;18:665–7. [cited 2022 Apr 4]; Available from: https://academic.oup.com/humrep/article/18/4/665/596582PubMedCrossRef

36.

Orvieto R. Controlled ovarian hyperstimulation - an inflammatory state. J Soc Gynecol Investig. 2004;11:424–6.PubMedCrossRef

37.

Orvieto R, Ben-Rafael Z. Ovarian hyperstimulation syndrome: a new insight into an old enigma. J Soc Gynecol Investig [Internet]. 1998;5:110–3. [cited 2023 Mar 16]; Available from: https://pubmed.ncbi.nlm.nih.gov/9614638/PubMedCrossRef

38.

Ata B, Tulandi T. Pathophysiology of ovarian hyperstimulation syndrome and strategies for its prevention and treatment. Expert Rev Obstet Gynecol. 2014;4:299–311. https://doi.org/10.1586/eog.09.10.CrossRef

39.

Levy T, Orvieto R, Homburg R, Peleg D, Dekel A, Ben-Rafael Z. Severe ovarian hyperstimulation syndrome despite low plasma oestrogen concentrations in a hypogonadotrophic, hypogonadal patient. Human Reproduction [Internet]. 1996;11:1177–9. [cited 2022 Apr 29]; Available from: https://academic.oup.com/humrep/article/11/6/1177/772241PubMedCrossRef

40.

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.PubMedCrossRef

41.

Tarlatzi TB, Venetis CA, Devreker F, Englert Y, Delbaere A. What is the best predictor of severe ovarian hyperstimulation syndrome in IVF? A cohort study. J Assist Reprod Genet [Internet]. 2017;34:1341.PubMedPubMedCentralCrossRef

42.

Kahnberg A, Enskog A, Brännström M, Lundin K, Bergh C. Prediction of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Acta Obstet Gynecol Scand [Internet]. 2009;88:1373–81. [cited 2022 Aug 26]; Available from: https://onlinelibrary.wiley.com/doi/full/10.3109/00016340903287482PubMedCrossRef

43.

Griesinger G, Verweij PJM, Gates D, Devroey P, Gordon K, Stegmann BJ, et al. Prediction of ovarian hyperstimulation syndrome in patients treated with Corifollitropin alfa or rFSH in a GnRH antagonist protocol. PLoS One [Internet]. 2016;11:e0149615. https://doi.org/10.1371/journal.pone.0149615.CrossRefPubMed

44.

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 [Internet]. 2006;147:5400–11. [cited 2022 Jul 2]; Available from: https://academic.oup.com/endo/article/147/11/5400/2500695PubMedCrossRef

45.

Mourad S, Brown J, Farquhar C. Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;1 [cited 2022 Apr 30]. Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/28111738/

46.

Leitao VMS, Moroni RM, Seko LMD, Nastri CO, Martins WP. Cabergoline for the prevention of ovarian hyperstimulation syndrome: systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2014;101:664–675.e7.PubMedCrossRef

47.

Tang H, Mourad SM, Wang A, Zhai S di, Hart RJ. Dopamine agonists for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev [Internet]. 2021 2021 [cited 2022 Aug 20]. Available from: /pmc/articles/PMC8092425/.

48.

Shrem G, Steiner N, Balayla J, Volodarsky-Perel A, Tannus S, Son WY, et al. Use of cabergoline and post-collection GnRH antagonist administration for prevention of ovarian hyperstimulation syndrome. Reprod Biomed Online. 2019;39:433–8.PubMedCrossRef

49.

Seow KM, Lin YH, Bai CH, Chen HJ, Hsieh BC, Huang LW, et al. Clinical outcome according to timing of cabergoline initiation for prevention of OHSS: a randomized controlled trial. Reprod Biomed Online. 2013;26:562–8.PubMedCrossRef

50.

The ESHRE Guideline Group on Ovarian Stimulation, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI†. Hum Reprod Open [Internet]. 2020;2020:1–13. [cited 2022 Mar 17]; Available from: https://academic.oup.com/hropen/article/2020/2/hoaa009/5827574

51.

Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021;2 [cited 2022 Aug 20]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33539543/

52.

Revelli A, Dolfin E, Gennarelli G, Lantieri T, Massobrio M, Holte JG, et al. Low-dose acetylsalicylic acid plus prednisolone as an adjuvant treatment in IVF: a prospective, randomized study. Fertil Steril. 2008;90:1685–91.PubMedCrossRef

53.

Várnagy Á, Bódis J, Mánfai Z, Wilhelm F, Busznyák C, Koppán M. Low-dose aspirin therapy to prevent ovarian hyperstimulation syndrome. Fertil Steril. 2010;93:2281–4.PubMedCrossRef

54.

Asimakopoulos B, Nikolettos N, Nehls B, Diedrich K, Al-Hasani S, Metzen E. Gonadotropin-releasing hormone antagonists do not influence the secretion of steroid hormones but affect the secretion of vascular endothelial growth factor from human granulosa luteinized cell cultures. Fertil Steril [Internet]. 2006;86:636–41. [cited 2022 Aug 23]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/16904114/PubMedCrossRef

55.

Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Kolibianakis EM. Management of severe early ovarian hyperstimulation syndrome by re-initiation of GnRH antagonist. Reprod Biomed Online [Internet]. 2007;15:408–12. [cited 2022 Aug 23]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/17908403/PubMedCrossRef

56.

Lainas GT, Kolibianakis EM, Sfontouris IA, Zorzovilis IZ, Petsas GK, Tarlatzi TB, et al. Outpatient management of severe early OHSS by administration of GnRH antagonist in the luteal phase: an observational cohort study. Reprod Biol Endocrinol. 2012;10 [cited 2022 Aug 23]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/22938051/

57.

Mills G, Dahan MH. Gonadotropin releasing hormone (GnRH) antagonist administration to decrease the risk of ovarian hyperstimulation syndrome in GNRH agonist cycles triggered with human chorionic gonadotropin. Arch Gynecol Obstet [Internet]. 2022; [cited 2022 Aug 31]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/35932297/

58.

VTE, thrombophilia, antithrombotic therapy, and pregnancy - antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest [Internet]. 2012;141:e691S–736S. [cited 2022 Aug 23]; Available from: http://journal.chestnet.org/article/S0012369212601366/fulltext

59.

Castillo JC, Dolz M, Bienvenido E, Abad L, Casan EM, Bonilla-Musoles F. Cycles triggered with GnRH agonist: exploring low-dose HCG for luteal support. Reprod Biomed Online [Internet]. 2010;20:175–81. [cited 2022 Aug 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/20113955/PubMedCrossRef

60.

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 [Internet]. 2009;18:630–4. [cited 2022 Aug 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/19549440/PubMedCrossRef

61.

Humaidan P, Ejdrup Bredkjær 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 [Internet]. 2010;93:847–54. [cited 2022 Aug 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/19200959/PubMedCrossRef

62.

Humaidan P, Bungum L, Bungum M, Andersen CY. 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 [Internet]. 2006;13:173–8. [cited 2022 Aug 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/16895629/PubMedCrossRef

63.

Humaidan P, Polyzos NP, Alsbjerg B, Erb K, Mikkelsen AL, Elbaek HO, et al. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod [Internet]. 2013;28:2511–21. [cited 2022 Aug 26]; Available from: https://academic.oup.com/humrep/article/28/9/2511/597543PubMedCrossRef

64.

Santos-Ribeiro S, Mackens S, Popovic-Todorovic B, Racca A, Polyzos NP, van Landuyt L, et al. The freeze-all strategy versus agonist triggering with low-dose hCG for luteal phase support in IVF/ICSI for high responders: a randomized controlled trial. Hum Reprod [Internet]. 2020;35:2808–18. [cited 2023 Mar 24]; Available from: https://pubmed.ncbi.nlm.nih.gov/32964939/PubMedCrossRef

65.

Humaidan P, Polyzos NP, Alsbjerg B, Erb K, Mikkelsen AL, Elbaek HO, et al. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod [Internet]. 2013;28:2511–21. [cited 2022 Aug 26]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/23753114/PubMedCrossRef

66.

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 [Internet]. 2013;28:2529–36. [cited 2022 Aug 26]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/23873146/PubMedCrossRef

67.

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 [Internet]. 2013;28:2522–8. [cited 2023 Feb 22]; Available from: https://pubmed.ncbi.nlm.nih.gov/23633553/PubMedCrossRef

68.

Orvieto R, Kirshenbaum M, Gleicher N. Is embryo cryopreservation causing macrosomia-and what else? Front Endocrinol (Lausanne) [Internet]. 2020;11 [cited 2023 Mar 16]; Available from: https://pubmed.ncbi.nlm.nih.gov/32047479/

69.

Glujovsky D, Pesce R, Sueldo C, Quinteiro Retamar AM, Hart RJ, Ciapponi A. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev. 2020;10 [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33112418/

70.

Vinsonneau L, Labrosse J, Porcu-Buisson G, Chevalier N, Galey J, Ahdad N, et al. Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles). Hum Reprod Open [Internet]. 2022;2022 [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/35274060/

71.

Gan J, Rozen G, Polyakov A. Treatment outcomes of blastocysts thaw cycles, comparing the presence and absence of a corpus luteum: a systematic review and meta-analysis. BMJ Open [Internet]. 2022;12:e051489. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/35473741/PubMedPubMedCentralCrossRef

72.

Wu H, Zhou P, Lin X, Wang S, Zhang S. Endometrial preparation for frozen-thawed embryo transfer cycles: a systematic review and network meta-analysis. J Assist Reprod Genet. 2021;38:1913–26. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33829375/PubMedPubMedCentralCrossRef

73.

Rosalik K, Carson S, Pilgrim J, Luizzi J, Levy G, Heitmann R, et al. Effects of different frozen embryo transfer regimens on abnormalities of fetal weight: a systematic review and meta-analysis. Hum Reprod Update [Internet]. 2021;28:1–14. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/34865039/PubMedCrossRef

74.

Asserhøj LL, Spangmose AL, Aaris Henningsen AK, Clausen TD, Ziebe S, Jensen RB, et al. Adverse obstetric and perinatal outcomes in 1,136 singleton pregnancies conceived after programmed frozen embryo transfer (FET) compared with natural cycle FET. Fertil Steril [Internet]. 2021;115:947–56. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33461756/PubMedCrossRef

75.

Busnelli A, Schirripa I, Fedele F, Bulfoni A, Levi-Setti PE. Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis. Hum Reprod [Internet]. 2022;37 [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/35553678/

76.

RESULTS - Frozen-Thawed Embryo Transfer - IVF-Worldwide [Internet]. [cited 2022 Aug 24]. Available from: https://ivf-worldwide.com/survey/frozen-thawed-embryo-transfer/results-frozen-thawed-embryo-transfer.html.

77.

Huang J, Lu X, Xie Q, Lin J, Cai R, Kuang Y. Timing of frozen-thawed embryo transfer after controlled ovarian stimulation in a non-elective freeze-all policy. Ann Transl Med [Internet]. 2019;7:752–2.PubMedPubMedCentralCrossRef

78.

Santos-Ribeiro S, Siffain J, Polyzos NP, van de Vijver A, van Landuyt L, Stoop D, et al. To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt? Fertil Steril [Internet]. 2016;105:1202–1207.e1. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/26806686/PubMedCrossRef

79.

Horowitz E, Mizrachi Y, Farhi J, Shalev A, Raziel A, Weissman A. Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle? Reprod Biomed Online [Internet]. 2019;39:439–45. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/31307924/PubMedCrossRef

80.

Santos-Ribeiro S, Polyzos NP, Lan VTN, Siffain J, Mackens S, van Landuyt L, et al. The effect of an immediate frozen embryo transfer following a freeze-all protocol: a retrospective analysis from two centres. Hum Reprod [Internet]. 2016;31:2541–8. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/27609984/PubMedCrossRef

81.

Lattes K, Checa MA, Vassena R, Brassesco M, Vernaeve V. There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Hum Reprod [Internet]. 2017;32:368–74. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/27986819/PubMedCrossRef

82.

Bourdon M, Santulli P, Maignien C, Pocate-Cheriet K, Alwohaibi A, Marcellin L, et al. The interval between oocyte retrieval and frozen-thawed blastocyst transfer does not affect the live birth rate and obstetrical outcomes. PLoS One. 2018;13 [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/30339700/

83.

Ozgur K, Bulut H, Berkkanoglu M, Humaidan P, Coetzee K. Frozen embryo transfer can be performed in the cycle immediately following the freeze-all cycle. J Assist Reprod Genet [Internet]. 2018;35:135–42. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/28939988/PubMedCrossRef

84.

Higgins C, Healey M, Jatkar S, Vollenhoven B. Interval between IVF stimulation cycle and frozen embryo transfer: is there a benefit to a delay between cycles? Aust N Z J Obstet Gynaecol [Internet]. 2018;58:217–21. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/28905357/PubMedCrossRef

85.

He Y, Zheng H, Du H, Liu J, Li L, Liu H, et al. Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing. Reprod Biol Endocrinol [Internet]. 2020;18

86.

Yildiz S, Turkgeldi E, Kalafat E, Keles I, Gokyer D, Ata B. Do live birth rate and obstetric outcomes vary between immediate and delayed embryo transfers following freeze-all cycles? J Gynecol Obstet Hum Reprod. 2021;50 [cited 2023 Mar 16]; Available from: https://pubmed.ncbi.nlm.nih.gov/34506996/

87.

Bergenheim SJ, Saupstad M, Pistoljevic N, Andersen AN, Forman JL, Løssl K, et al. Immediate versus postponed frozen embryo transfer after IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update [Internet]. 2021;27:623–42. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33594441/PubMedCrossRef

88.

Song JY, Dong FY, Li L, Zhang XX, Wang AJ, Zhang Y, et al. Immediate versus delayed frozen embryo transfer in women following a failed IVF-ET attempt: a multicenter randomized controlled trial. Reprod Biol Endocrinol. 2021;19 [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/34461950/

89.

Li H, Sun X, Yang J, Li L, Zhang W, Lu X, et al. Immediate versus delayed frozen embryo transfer in patients following a stimulated IVF cycle: a randomised controlled trial. Hum Reprod [Internet]. 2021;36:1832–40. [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/33885131/PubMedCrossRef

90.

Zuo N, Gao Y, Zhang N, Li D, Wang X. Effects of immediate versus delayed frozen embryo transfer in high responder patients undergoing freeze-all cycles. BMC Pregnancy Childbirth [Internet]. 2021;21 [cited 2022 Aug 24]; Available from: https://pubmed-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/34182954/

91.

Timmons D, Montrief T, Koyfman A, Long B. Ovarian hyperstimulation syndrome: a review for emergency clinicians. Am J Emerg Med. 2019;37:1577–84.PubMedCrossRef

Title: The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization
Authors: I. Feferkorn
S. Santos-Ribeiro
F. M. Ubaldi
J. G. Velasco
B. Ata
C. Blockeel
A. Conforti
S. C. Esteves
H. M. Fatemi
L. Gianaroli
M. Grynberg
P. Humaidan
G.T Lainas
A. La Marca
L. B. Craig
R. Lathi
R. J. Norman
R. Orvieto
R. Paulson
A. Pellicer
N. P. Polyzos
M. Roque
S. K. Sunkara
S. L. Tan
B. Urman
C. Venetis
A. Weissman
H. Yarali
M. H. Dahan
Publication date: 15-09-2023
Publisher: Springer US
Keywords: Ovarian Hyperstimulation Syndrome
Dopamine Agonist
GnRH Agonists
Published in: Journal of Assisted Reproduction and Genetics / Issue 11/2023
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-023-02918-5

At a glance: The STEP trials

Springer Medicine

The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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