ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025†

Abstract

STUDY QUESTION: What is the recommended management of ovarian stimulation, based on the best available evidence in the literature? SUMMARY ANSWER: This updated ESHRE guideline on ovarian stimulation for IVF/ICSI provides 121 recommendations, answering 21 key questions on ovarian stimulation for IVF/ICSI. WHAT IS KNOWN ALREADY?: Before the ESHRE guideline on ovarian stimulation for IVF/ICSI was published in 2019, ovarian stimulation for IVF/ICSI had only been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems and in a statement by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for ESHRE guidelines. The 18 key questions from the 2019 version of the guideline were revised by the Guideline Development Group (GDG). This resulted in the addition of one new key question, the splitting of the key question on fertility preservation in three separate key questions (fertility preservation for women facing gonadotoxic treatment, elective oocyte cryopreservation, and oocyte donation) and several new interventions being added to the existing key questions. Papers published between 31 October 2018 and 2 February 2025 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS). PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the available evidence, recommendations were formulated and discussed until consensus was reached within the GDG. Following stakeholder review of the initial draft, the final version was approved by the GDG and ultimately by the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides a total of 121 recommendations: 42 recommendations remained unchanged in 2019, 4 recommendations were reworded for better understanding, 29 recommendations were updated in view of new evidence, and 46 new recommendations for 2025 have been formulated. The guideline provides 4 recommendations on pre-stimulation evaluation, 7 recommendations on pre-treatment therapies, 50 recommendations on pituitary suppression and ovarian stimulation, 17 recommendations on monitoring, 18 recommendations on triggering of final oocyte maturation and luteal support, and 8 recommendations on the prevention of OHSS. In addition, the guideline provides 17 recommendations on fertility preservation, both oncologic and elective, and oocyte donation. These include 90 evidence-based recommendations, of which only 42 were formulated as strong recommendations and 48 as conditional, as well as 29 good practice points and 2 research-only recommendations. Of the evidence-based recommendations, none were supported by high-quality evidence, 6 by moderate-quality evidence, 36 by low-quality evidence, and 148 by very low-quality evidence. To support future research on ovarian stimulation for IVF/ICSI, a list of research recommendations was provided. LIMITATIONS, REASONS FOR CAUTION: Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): The guideline was developed by ESHRE, who funded the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive any financial incentives; all work was provided voluntarily. BA reports speaker's fees from Gedeon-Richter, Ferring, IBSA, Intas, Merck, Organon, consulting fees from Merck, Organon, Oxolife, stock options from Global Fertility Solutions LLC (employee co-investment), and was chair of the Turkish Society of Reproductive Medicine. EB reports research grants from Roche Diagnostics and IBSA, consulting fees from MSD, Abbot, Gedeon-Richter, Roche, speaker's fees from IBSA, MSD, Ferring Pharmaceuticals, Abbot, Gedeon-Richter, Merck, Roche, participation in the advisory board of Ferring Pharmaceuticals, IBSA and Merck, and ownership interest from IVI-RMS Valencia. GG was part of the ESHRE working group on Recurrent Implantation Failure and the ESHRE working group on clinical KPISs, reports travel support from Merck, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, consulting fees from Organon, Ferring, Merck, Gedeon-Richter, Theramex, Abbott, ReproNovo, Igyxos, OxoLife, Philipps, ReprodWissen, PregLem, Guerbet, Roche, IBSA, and Besins, speaker's fees from Organon, Ferring, Merck, Gedeon-Richter, Theramex, Abbott, ReproNovo, Igyxos, OxoLife, Philipps, ReprodWissen, PregLem, Guerbet, Roche, IBSA, and Besins, and research grants from Besin, Merck, Abbott, Ferring, Theramex. MG reports speaker's fees from Merck Serono, Ferring, and Gedeon Richter. EK reports travel/hotel expenses from Ferring, Merck SERONO, Vianex, speaker's fees from Ferring, Merck SERONO, Vianex, and is chair of the Greek Society of Fertility and Sterility. MK reports travel support and speaker's fees from Ferring. ALM reports research grants from Merck, Ferring, IBSA, Roche, Organon, Theramex, Beckman Coulter, and Gedeon-Richter, consulting fees from Merck, Ferring, IBSA, Roche, Organon, Theramex, Beckman Coulter, and Gedeon-Richter, speaker's fees from Merck, Ferring, IBSA, Roche, Organon, Theramex, Beckman Coulter, Gedeon-Richter, and participation on an advisory board of Merck, Organon, Ferring, Theramex, Gedeon Richter, and IBSA. GL reports consulting fees from Ferring and Merck, speaker's fees from Ferring, Merck, Gedeon-Richter, Organon, and Vianex, expert testimony fees from Cook, travel support from ESHRE, Ferring, Merck, Gedeon-Richter, Organon, and Vianex, is on the advisory board of Merck and Ferring, and participated in an ESHRE committee and on the Greek Fertility and Sterility Committee. NM reports research grants from IBSA, Organon, consulting fees from Organon, Merck, GE, Ferring, Abbott, and Cooper, and speaker's fees from Ferring, GE, Organon, IBSA, Merck, Theramex. NPP reports research grants from Besins Healthcare, Ferring Pharmaceutical, Merck Serono, Organon, Roche Diagnostics, and Theramex, consulting fees from Besins Healthcare, Alife, Ferring, IBSA, Merck Serono, Organon, Abbott, FertilAI, and speaker's fees from Besins Healthcare, Roche Diagnostics, Ferring Pharmaceuticals, Gedeon-Richter, IBSA, Merck Serono, Organon, and Theramex. SKS reports a research grant from Ferring, travel support from Merck and INTAS, consulting fees from Merck, and speaker's fees from Merck, MSD, INTAS, and Ferring. TT reports travel support from Merck, speaker's fees from Merck, Organon, MSD and is editor-in-chief of a Bulgarian journal, Reproductive Health. MT reports travel support from IBSA, Ferring, and Merck, consulting fees from Abbott and is a member of the board of the Finnish Endocrine Society. JU is a member of the Steering Committee of Richter Reproduction Network and received travel support from IBSA. FB reports a research grant from Besins, is on the advisory board of Merck and Abbott, reports speaker's fees from Ferring, Merck, Besins, Intas Fermaceuticals, PREIS School; he is the owner of FRANKSCHOOL RforL. The other authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained.Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (The full disclaimer is available at www.eshre.eu/guidelines.).