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

I Feferkorn¹, S Santos-Ribeiro², F M Ubaldi³, J G Velasco⁴, B Ata^{5

6}, C Blockeel⁷, A Conforti⁸, S C Esteves^{9

10

11}, H M Fatemi¹², L Gianaroli¹³, M Grynberg¹⁴, P Humaidan¹⁵, G T Lainas¹⁶, A La Marca¹⁷, L B Craig¹⁸, R Lathi¹⁹, R J Norman^{20

21

22

23}, R Orvieto^{24

25

26}, R Paulson²⁷, A Pellicer^{28

29}, N P Polyzos³⁰, M Roque^{31

32}, S K Sunkara³³, S L Tan³⁴, B Urman³⁵, C Venetis^{36

37

38}, A Weissman³⁹, H Yarali⁴⁰, M H Dahan⁴¹

Affiliations

¹ IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. idofeferkon@gmail.com.
² IVI-RMA Lisboa, 1800-282, Lisbon, Portugal.
³ GeneraLife Centers for Reproductive Medicine, Rome, Italy.
⁴ IVI RMA Madrid, Madrid, Spain.
⁵ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey.
⁶ ART Fertility Clinics, Dubai, United Arab Emirates.
⁷ Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Jette, Belgium.
⁸ Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy.
⁹ ANDROFERT, Andrology and Human Reproduction Clinic, Av. Dr. Heitor Penteado 1464, Campinas, SP, 13075-460, Brazil.
¹⁰ Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, SP, Brazil.
¹¹ Faculty of Health, Aarhus University, C, 8000, Aarhus, Denmark.
¹² ART Fertility Clinics, Abu Dhabi, United Arab Emirates.
¹³ Società Italiana Studi di Medicina della Riproduzione, S.I.S.Me.R. Reproductive Medicine Institute, Bologna, Emilia-Romagna, Italy.
¹⁴ Department of Reproductive Medicine, Hôpital Antoine-Béclère, University Paris-Sud (Paris XI), Le Kremlin-Bicêtre, Clamart, France.
¹⁵ The Fertility Clinic, Skive Regional Hospital, Faculty of Health, Aarhus University, Resenvej 25, 7800, Skive, Denmark.
¹⁶ Eugonia IVF Unit, Athens, Greece.
¹⁷ Obstetrics, Gynecology and Reproductive Medicine, University of Modena and Reggio Emilia, Policlinico di Modena, via del Pozzo 71, 41124, Modena, Italy.
¹⁸ Section of Reproductive Endocrinology & Infertility, Department of Obstetrics & Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
¹⁹ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
²⁰ Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
²¹ FertilitySA, Adelaide, South Australia, Australia.
²² Monash Centre for Health Research and Implementation MCHRI, Monash University, Melbourne, Australia.
²³ NHMRC Centre of Research Excellence in Women's Health in Reproductive Life (CRE-WHiRL), Melbourne, Australia.
²⁴ Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.
²⁵ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁶ Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
²⁷ University of Southern California, Los Angeles, CA, 90033, USA.
²⁸ Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain.
²⁹ IVI Roma Parioli, IVI-RMA Global, Rome, Italy.
³⁰ Department of Reproductive Medicine, Dexeus Mujer, Hospital Universitario Dexeus, Barcelona, Spain.
³¹ Department of Reproductive Medicine, ORIGEN-Center for Reproductive Medicine, Rio de Janeiro, RJ, Brazil.
³² Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
³³ Department of Women and Children's Health, King's College London, London, UK.
³⁴ OriginElle Fertility Clinic 2110 Boul. Decarie, Montreal, QC, Canada.
³⁵ Department of Obstetrics and Gynecology and Assisted Reproduction, American Hospital, Istanbul, Koc University School of Medicine, Istanbul, Turkey.
³⁶ Unit for Human Reproduction, 1st Dept of OB/Gyn, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
³⁷ Centre for Big Data Research in Health, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
³⁸ Virtus Health, Sydney, Australia.
³⁹ In Vitro Fertilization Unit, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴⁰ Division of Reproductive Endocrinology and Infertility, Dept. of Obstetrics and Gynecology, Hacettepe University, School of Medicine, Anatolia IVF and Women's Health Center, Ankara, Turkey.
⁴¹ Division of Reproductive Endocrinology and Infertility, McGill University Health Care Center, 888 Boul. de Maisonneuve E #200, Montreal, QC, H2L 4S8, Canada.

PMID: 37713144
PMCID: PMC10643792
DOI: 10.1007/s10815-023-02918-5

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

I Feferkorn et al. J Assist Reprod Genet. 2023 Nov.

. 2023 Nov;40(11):2681-2695.

doi: 10.1007/s10815-023-02918-5. Epub 2023 Sep 15.

Authors

Affiliations

¹ IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. idofeferkon@gmail.com.
² IVI-RMA Lisboa, 1800-282, Lisbon, Portugal.
³ GeneraLife Centers for Reproductive Medicine, Rome, Italy.
⁴ IVI RMA Madrid, Madrid, Spain.
⁵ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey.
⁶ ART Fertility Clinics, Dubai, United Arab Emirates.
⁷ Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Jette, Belgium.
⁸ Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy.
⁹ ANDROFERT, Andrology and Human Reproduction Clinic, Av. Dr. Heitor Penteado 1464, Campinas, SP, 13075-460, Brazil.
¹⁰ Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, SP, Brazil.
¹¹ Faculty of Health, Aarhus University, C, 8000, Aarhus, Denmark.
¹² ART Fertility Clinics, Abu Dhabi, United Arab Emirates.
¹³ Società Italiana Studi di Medicina della Riproduzione, S.I.S.Me.R. Reproductive Medicine Institute, Bologna, Emilia-Romagna, Italy.
¹⁴ Department of Reproductive Medicine, Hôpital Antoine-Béclère, University Paris-Sud (Paris XI), Le Kremlin-Bicêtre, Clamart, France.
¹⁵ The Fertility Clinic, Skive Regional Hospital, Faculty of Health, Aarhus University, Resenvej 25, 7800, Skive, Denmark.
¹⁶ Eugonia IVF Unit, Athens, Greece.
¹⁷ Obstetrics, Gynecology and Reproductive Medicine, University of Modena and Reggio Emilia, Policlinico di Modena, via del Pozzo 71, 41124, Modena, Italy.
¹⁸ Section of Reproductive Endocrinology & Infertility, Department of Obstetrics & Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
¹⁹ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
²⁰ Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
²¹ FertilitySA, Adelaide, South Australia, Australia.
²² Monash Centre for Health Research and Implementation MCHRI, Monash University, Melbourne, Australia.
²³ NHMRC Centre of Research Excellence in Women's Health in Reproductive Life (CRE-WHiRL), Melbourne, Australia.
²⁴ Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.
²⁵ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁶ Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
²⁷ University of Southern California, Los Angeles, CA, 90033, USA.
²⁸ Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain.
²⁹ IVI Roma Parioli, IVI-RMA Global, Rome, Italy.
³⁰ Department of Reproductive Medicine, Dexeus Mujer, Hospital Universitario Dexeus, Barcelona, Spain.
³¹ Department of Reproductive Medicine, ORIGEN-Center for Reproductive Medicine, Rio de Janeiro, RJ, Brazil.
³² Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
³³ Department of Women and Children's Health, King's College London, London, UK.
³⁴ OriginElle Fertility Clinic 2110 Boul. Decarie, Montreal, QC, Canada.
³⁵ Department of Obstetrics and Gynecology and Assisted Reproduction, American Hospital, Istanbul, Koc University School of Medicine, Istanbul, Turkey.
³⁶ Unit for Human Reproduction, 1st Dept of OB/Gyn, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
³⁷ Centre for Big Data Research in Health, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
³⁸ Virtus Health, Sydney, Australia.
³⁹ In Vitro Fertilization Unit, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴⁰ Division of Reproductive Endocrinology and Infertility, Dept. of Obstetrics and Gynecology, Hacettepe University, School of Medicine, Anatolia IVF and Women's Health Center, Ankara, Turkey.
⁴¹ Division of Reproductive Endocrinology and Infertility, McGill University Health Care Center, 888 Boul. de Maisonneuve E #200, Montreal, QC, H2L 4S8, Canada.

PMID: 37713144
PMCID: PMC10643792
DOI: 10.1007/s10815-023-02918-5

Erratum in

Correction to: The HERA (Hyper‑response Risk Assessment) Delphi consensus for the management of hyper‑responders in in vitro fertilization.
Feferkorn I, Santos-Ribeiro S, Ubaldi FM, Velasco JG, Ata B, Blockeel C, Conforti A, Esteves SC, Fatemi HM, Gianaroli L, Grynberg M, Humaidan P, Lainas GT, La Marca A, Craig LB, Lathi R, Norman RJ, Orvieto R, Paulson R, Pellicer A, Polyzos NP, Roque M, Sunkara SK, Tan SL, Urman B, Venetis C, Weissman A, Yarali H, Dahan MH. Feferkorn I, et al. J Assist Reprod Genet. 2024 Feb;41(2):519-520. doi: 10.1007/s10815-023-03003-7. J Assist Reprod Genet. 2024. PMID: 38079078 Free PMC article. No abstract available.

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.

Keywords: Hyper-response; Ovarian hyperstimulation syndrome; Ovarian stimulation.

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Conflict of interest statement

All declarations of interest are outside the submitted work. Peter Humaidan reports reception of lecture honoraria from Merck, Gedeon Richter, and IBSA. Antonio La Marca reports reception of consulting fees from Merck, Organon, Ferring, Gedeon Richter, Theramex, Beckman Coulter, and Roche. Samuel Santos-Ribeiro reports reception of research funding from Roche Diagnostics, Organon, and Theramex; reception of consulting fees from Organon, MSD, and Ferring; honoraria for lectures from Ferring, Besins, MSD/Organon, Theramex, and Gedeon Richter; reception of equipment materials or other services from Roche Diagnostics and Ferring; and is deputy of the SQART SIG in ESHRE. Alessandro Conforti reports reception of grants from the University of Naples Federico II; reception honoraria from Medea, Event Planet, and Merck. Baris Ata reports reception of consulting fees from Merck GmBH–Turkey; reception of payment or honoraria from Abbott, Merck GmBH, and Ferring; reception of support for attending meetings or travel from IBSA; is president of the Turkish Society of Reproductive Medicine; and is an executive committee member of ESHRE. Juan Garcia Velasco reports reception of payment or honoraria for lectures or educational events from Merck, Ferring, MSD, Organon, Theramex, and Gedeon Richter. George Lainas reports reception of payment or honoraria for lectures or educational events from Merck and Ferring, payment for expert testimony from Merck, and support for attending meetings from ESHRE. He also participated in data safety monitoring or advisory board of Merck. Filippo Maria Ubaldi is the scientific director of GeneraLife and minority shareholder of the company. He is also the president of SIFES-MR (the Italian Society of Fertility, Sterility and Reproductive Medicine) and a member of the scientific board of Medea. In the last 3 years, F.M. Ubaldi has received honoraria or consultation fees from Merck, MSD, Ferring, Gedeon Richter, Organon, and IBSA. Sesh Sunkara reports reception of payment or honoraria for lectures from Merck Ferring and MSD. Raoul Orvieto reports reception of consulting fees from Merck and Ferring and payment or honoraria for lectures from Merck and Ferring. Nikolaos Polyzos reports reception of grants or contracts from Merck Serono, IBSA, Organon, Ferring, Roche, Theramex, Besins Healthcare, and Gedeon Richter and reception of consulting fees from Merck Serono, IBSA, Organon, Ferring, Besins Healthcare, and Gedeon Richter. Hakan Yarali reports unrestricted grants from Merck, honoraria for lectures from Merck and IBSA, and support for attending meetings from Merck, IBSA, and Ferring. Human Fatemi reports receiving research grants from Merck Serono and Organon; consulting fees from Ferring Global; speaker honoraria from Organon, Merck Serono, and Ferring; and participation in data safety monitoring or advisory board for Ferring. Sandro Esteves reports unrestricted research grants from Merck KGaA; reception of consulting fees from Merck, MeD.E.A, and event planet; reception of honoraria for lectures from Merck, MeD.E.A, and event planet; has a patent on the ART calculator, is an unpaid advisory board member for Nature Reviews and for Urology, Is the Head, Department of Education and Research, Brazilian Society of Urology (São Paulo section; unpaid), and is the Co-chair, Male Infertility Special Interest Group, WHO Infertility Guidelines (unpaid). Craig LaTasha is a site investigator for Ferring Pharmaceuticals. He was an advisory board member for Ferring Pharmaceuticals. Ariel Weissman, Christophe Blockeel, Christos Venetis, Seang Lin Tan, Michael Dahan, Bulent Urman, RJ Norman, Richard Paulson, and Ido Feferkorn report no conflicts of interest.

Figures

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References

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources