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• W4386804331 abstract "We read with interest the Letter to the Editor by Ingold and Bedoschi,1Ingold C. Bedoschi G. Safety and efficacy concerns of long-acting GnRHa trigger for ovulation induction in oncological patients undergoing oocyte cryopreservation: a call for caution and further investigation.ESMO Open. 2023; Abstract Full Text Full Text PDF Google Scholar raising relevant points regarding triggering ovulation with long-acting gonadotropin-releasing hormone agonist (GnRH) agonist (GnRHa) after controlled ovarian stimulation for oocyte cryopreservation, as we have proposed and reported.2Massarotti C, Stigliani S, Gazzo I, Lambertini M, Anserini P. Long-acting gonadotropin-releasing hormone agonist trigger in fertility preservation cycles before chemotherapy. ESMO Open. 20236;8(4):101597.Google Scholar We wholeheartedly concur with the appeal for the need for further investigations. As we stated in our conclusions, our aim was to report preliminary data on the feasibility of the option, but, akin to any potentially transformative innovation, sustained evidence from more expansive and randomized cohorts remains imperative before introduction in clinical practice. Rationally, the use of long-acting GnRHa trigger does not entail the complete eradication of the risk of ovarian hyperstimulation syndrome (OHSS), given that this risk is not absent even with the use of short-acting GnRHa trigger alone.3Fernández-Sánchez M. Fatemi H. García-Velasco J.A. Heiser P.W. Daftary G.S. Mannaerts B. Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in “freeze-all” approach.Gynecol Endocrinol. 2023; 392205952Crossref PubMed Scopus (0) Google Scholar Rather, its purpose is to reduce the increase in OHSS risk given by a second flare-up on recently stimulated ovaries, as it would happen with a long-acting GnRHa injection a few days after oocyte retrieval. Notably, the published cases of OHSS with the use of long-acting GnRHa before chemotherapy occurred under such circumstances.4Christ J. Herndon C.N. Yu B. Severe ovarian hyperstimulation syndrome associated with long-acting GnRH agonist in oncofertility patients.J Assist Reprod Genet. 2021; 38: 751-756Crossref PubMed Scopus (8) Google Scholar, 5Iorio G.G. Rovetto M.Y. Conforti A. et al.Severe ovarian hyperstimulation syndrome in a woman with breast cancer under letrozole triggered with GnRH agonist: a case report and review of the literature.Front Reprod Health. 2021; 3704153Crossref Google Scholar, 6Marin L. Vitagliano A. Capobianco G. Dessole F. Ambrosini G. Andrisani A. Which is the optimal timing for starting chemoprotection with gonadotropin-releasing hormone agonists after oocyte cryopreservation? Reflections on a critical case of ovarian hyperstimulation syndrome.J Gynecol Obstet Hum Reprod. 2021; 50101815Crossref PubMed Scopus (5) Google Scholar The biological rationale underlying this risk is readily apparent. A long-acting GnRHa injection after egg retrieval causes a second gonadotrophin flare-up before initiating ovarian suppression, as the pituitary regains its responsiveness not later than a week after the short-acting GnRHa trigger.7Porcu E. Dal Prato L. Seracchioli R. Fabbri R. Longhi M. Flamigni C. Comparison between depot and standard release triptoreline in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results.Fertil Steril. 1994; 62: 126-132Abstract Full Text PDF PubMed Google Scholar This flare-up stimulates recent corpora lutea: short-acting GnRHa trigger usually prompts a more rapid luteolysis than traditional human chorionic gonadotropin trigger,8Fatemi H.M. Polyzos N.P. van Vaerenbergh I. et al.Early luteal phase endocrine profile is affected by the mode of triggering final oocyte maturation and the luteal phase support used in recombinant follicle-stimulating hormone-gonadotropin-releasing hormone antagonist in vitro fertilization cycles.Fertil Steril. 2013; 100: 742-747Abstract Full Text Full Text PDF PubMed Google Scholar but the literature shows variability between patients regarding luteolysis kinetics, with cases of luteolysis as far as 8 days after trigger with short-acting GnRHa.9Kol S. Breyzman T. GnRH agonist trigger does not always cause luteolysis: a case report.Reprod Biomed Online. 2016; 32: 132-134Abstract Full Text Full Text PDF PubMed Google Scholar Moreover, if we consider that human corpus luteum functional recovery was described as far as after 7 days of deprivation,10Weissman A. Loumaye E. Shoham Z. Recovery of corpus luteum function after prolonged deprivation from gonadotrophin stimulation.Hum Reprod. 1996; 11: 943-949Crossref PubMed Scopus (16) Google Scholar it becomes evident that the risk for a renewed surge in oestrogens and progesterone exists, prompted by the gonadotropin flare-up caused by the long-acting GnRHa injection before chemotherapy. This scenario aligns with the cases documented in the literature of OHSS in fertility-preservation patients.4Christ J. Herndon C.N. Yu B. Severe ovarian hyperstimulation syndrome associated with long-acting GnRH agonist in oncofertility patients.J Assist Reprod Genet. 2021; 38: 751-756Crossref PubMed Scopus (8) Google Scholar, 5Iorio G.G. Rovetto M.Y. Conforti A. et al.Severe ovarian hyperstimulation syndrome in a woman with breast cancer under letrozole triggered with GnRH agonist: a case report and review of the literature.Front Reprod Health. 2021; 3704153Crossref Google Scholar, 6Marin L. Vitagliano A. Capobianco G. Dessole F. Ambrosini G. Andrisani A. Which is the optimal timing for starting chemoprotection with gonadotropin-releasing hormone agonists after oocyte cryopreservation? Reflections on a critical case of ovarian hyperstimulation syndrome.J Gynecol Obstet Hum Reprod. 2021; 50101815Crossref PubMed Scopus (5) Google Scholar In clinical practice, the risk may discourage gynaecologists and oncologists to start GnRHa before chemotherapy in cases of abundant ovarian response. These patients are those who would especially benefit from the use of long-acting GnRH trigger before oocyte retrieval. Ingold and Bedoschi also advocate for a better understanding of the advantages of ovarian suppression with long-acting GnRHa in different patients. We wholeheartedly agree with the need to bridge this gap in our knowledge. Indeed, while we have compelling evidence for breast cancer,11Lambertini M. Moore H.C.F. Leonard R.C.F. et al.Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data.J Clin Oncol. 2018; 36: 1981-1990Crossref PubMed Scopus (223) Google Scholar there is still uncertainty regarding its efficacy in patients affected by other neoplasms.12Demeestere I. Brice P. Peccatori F.A. et al.No evidence for the benefit of gonadotropin-releasing hormone agonist in preserving ovarian function and fertility in lymphoma survivors treated with chemotherapy: final long-term report of a prospective randomized trial.J Clin Oncol. 2016; 34: 2568-2574Crossref PubMed Scopus (166) Google Scholar,13Hoyos-Martinez A. Scheurer M.E. Allen-Rhoades W. Okcu M.F. Horne V.E. Leuprolide protects ovarian reserve in adolescents undergoing gonadotoxic therapy.J Adolesc Young Adult Oncol. 2023; (In press)https://doi.org/10.1089/jayao.2022.0128Crossref PubMed Scopus (0) Google Scholar Based on recent guidelines, GnRHa use during chemotherapy is a standard approach in women with cancer receiving cytotoxic therapy who wish to mitigate the risk of developing premature ovarian insufficiency.14Anderson R.A. Amant F. Braat D. et al.ESHRE Guideline Group on Female Fertility PreservationESHRE guideline: female fertility preservation.Hum Reprod Open. 2020; 2020hoaa052Crossref Google Scholar However, this approach should not be considered a fertility-preservation strategy per se and should not replace but should follow a cryopreservation procedure.14Anderson R.A. Amant F. Braat D. et al.ESHRE Guideline Group on Female Fertility PreservationESHRE guideline: female fertility preservation.Hum Reprod Open. 2020; 2020hoaa052Crossref Google Scholar Consequently, prioritizing research into the optimal methods for safely and effectively providing oocyte/embryo cryopreservation followed by the use of GnRHa during chemotherapy is paramount. In conclusion, we concur that our proposal to trigger ovulation with long-acting GnRHa is promising, but, as we concluded in our report, further research is needed to better describe its efficacy and safety before affirming it should be the standard in clinical practice. This research should take place as a prospective, randomized controlled collaborative effort to maximize the number of patients and reduce biases. PA acknowledges the support by the Italian Ministry of Health - Ricerca Corrente (no grant number). ML acknowledges the support by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant number MFAG 2020 ID 24698). None declared." @default.
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• W4386804331 title "Re: Safety and efficacy concerns of long-acting GnRH agonist trigger for ovulation induction in oncological patients undergoing oocyte cryopreservation: a call for caution and further investigation" @default.
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