GnRH agonist trigger and ovarian hyperstimulation syndrome: relook at ‘freeze-all strategy’

Abstract

A case is reported of early onset ovarian hyperstimulation syndrome (OHSS) after gonadotrophin-releasing hormone agonist (GnRHa) trigger for final oocyte maturation in a GnRH antagonist protocol. The use of GnRHa in place of HCG as a trigger for final oocyte maturation in an antagonist IVF cycle has been proposed as a method for preventing OHSS in predicted high-responders. This approach, however, did not prevent the occurrence of OHSS in our case despite a freeze-all strategy. To the best of our knowledge, this is a possible index case of severe OHSS with GnRHa trigger for oocyte maturation without any luteal HCG rescue for a high responder, despite IVF cycle segmentation.

GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles—A Systematic PRISMA Review and Meta-analysis

“…However, despite the irrefutable OHSS risk reduction after GnRHa trigger followed by segmentation, even in GnRHa triggered segmented cycles, a few severe early-onset OHSS cases have been reported (27–29). Furthermore, the segmentation policy after GnRHa trigger in line with previous reports on health outcomes of children born as a result of cryopreserved thawed embryos is likely to increase the incidence of macrosomia and large for gestational age (30–32), the risk of placenta accreta (33, 34), and the risk of preeclampsia (35).…”

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

“…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).…”

“…Hence, the occurrence of a uniquely extreme ovarian response did not seem to be related with any unwarranted excessive stimulation and was, for this reason, otherwise unexpected. To this extent, Ling et al [17] postulated if extreme AMH levels could serve as a warning sign for this sort of complication, since they were the first to report that, in their case, the patient had an exceptionally high AMH level of 64.5 ng/mL (Beckman DSL, AMH Gen II assay kit).…”

“…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].…”

Does freeze all policy eliminate OHSS??? “It ain’t necessarily so…”

“…The main problem with the policy of using this approach is an incorrect sense of security, believing that indeed this policy has completely eliminated the risk of severe OHSS. However, it has not, as suggested by the five recent publications, including the present [1,[3][4][5][6], of OHSS necessitating hospitalization, despite GnRH agonist triggering instead of hCG. Retrospective evaluation of the patient's characteristics could have led to an appreciation of very high risk of OHSS due to PCOS, very high AMH of 18.28 ng/mL, and an antral follicle count of 40.…”