Severe ovarian hyperstimulation syndrome after gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze-all” approach in GnRH antagonist protocol

Ovarian hyperstimulation syndrome after gonadotropin-releasing hormone agonist triggering and “freeze-all”: in-depth analysis of genetic predisposition

“…In view of this, elective cryopreservation of embryos has been proposed for women undergoing IVF/ICSI who develop ≥18 follicles with a diameter of at least 10-14 mm [39] to minimize the risk of the development of severe OHSS. OHSS in a GnRH agonist triggered Bfreeze-all^has been, until now, such a unique event that some have considered it to be likely limited to women genetically prone to develop this complication [19]. Since 2014, an increasing amount of clinicians have reported on cases of severe (grade 4 or 5) early-onset OHSS following a Bfreeze-all^protocol.…”

“…Since 2014, an increasing amount of clinicians have reported on cases of severe (grade 4 or 5) early-onset OHSS following a Bfreeze-all^protocol. These cases have come from all over the globe, including India, the United Arab Emirates [19], Singapore [17], Turkey [18], and now Belgium. In all instances, the patients were administered total doses of exogenous FSH within the normal ranges that one could expect for ovarian stimulation during a conventional IVF treatment (between 775 and 2025 IU).…”

“…In a GnRH antagonist co-treated cycle, the GnRH agonist causes the displacement of the GnRH antagonist from the pituitary receptors, resulting in a LH flare-up/Bsurget hat lasts for approximately 24-36 h [7]. This approach, combined with the elective cryopreservation of all oocytes/embryos, referred to by some as the BOHSS-free clinic^ [14], had effectively abolished the incidence of severe early OHSS [14,15,10] until recently, when the first cases of OHSS requiring hospitalization were reported [16][17][18][19]. These cases include both patients with either grade 4 (3 cases) and grade 5 (4 patients) severe early-onset OHSS according to the OHSS classification proposed by Golan et al [adopted by the European Society of Human Reproduction and Embryology (ESHRE)] [20].…”

“…These cases include both patients with either grade 4 (3 cases) and grade 5 (4 patients) severe early-onset OHSS according to the OHSS classification proposed by Golan et al [adopted by the European Society of Human Reproduction and Embryology (ESHRE)] [20]. However, it has been questioned if the first case report did indeed represent a bona fide case of severe OHSS [21] and if OHSS after a Bfreeze-all^protocol may not be limited to extremely rare genetically-prone women [19]. In fact, evidence of genetic predisposition for OHSS has been previously described, namely through reports of familial and isolated cases of severe OHSS in women with natural conceptions [22][23][24].…”

The state of “freeze-for-all” in human ARTs

“…Following the introduction of the antagonist protocols, complementary measures came along to avoid the risk of OHSS even more, like triggering ovulation induction with GnRH agonists instead of human chorionic gonadotropin (HCG) [30][31][32][33]. Still, this approach is not 100 % safe as a few anecdotal cases of severe OHSS following GnRH agonist triggering with no luteal supplementation have been reported [34][35][36]. GnRH agonist triggering has been associated with luteal phase defects, presumably due to excessive negative steroid feedback [37][38][39].…”