Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles

Abstract

EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. Trial registration date: 18 September 2008. Date of first patient's enrolment: 14 January 2009.

Calcium infusion plus or minus cabergoline for prevention of ovarian hyperstimulation syndrome: Randomized double-blind placebo-controlled trial

“…Severe OHSS takes maximal concern of infertility clinicians as it may complicate up to 8.9% of crude IVF/ICSI women who were stimulated by long agonist protocol (LAP) and ovulation was triggered with conventional HCG regimen [8] as well as if not timely and efficiently treated, may be associated with severe morbidity and even mortality [1,2,3,4] . All tried preventive modalities, for OHSS occurrence, up till now didn't achieve complete prevention rather than reduce the incidence of overall all as well as severe OHSS [25] .…”

“…from OPU day for 4 days in combination with oral cabergoline 0.5 mg from the day of HCG triggering is superior to calcium infusion alone. The OHSS protective effect of antagonists protocol (AP) was recently demonstrated in adequately powered randomized clinical trial [8] (RCT) in crude IVF/ICSI population, where the incidence of severe OHSS in AP versus LAP 5.1% vs 8.9% with p = 0.02 ; while moderate OHSS was 10.2 vs. 15.6% with p = 0.01 and rate of hospital admission due to OHSS was lower in AP when compared with LAP (1.7% vs 3.6%, P = 0.06) as well as there is no ascetic tap in AP compared to 2% in LAP (P < 0.01). In analysis of subgroup with irregular anovulatory cycle PCOS, authors reported a development of more severe OHSS when compared to less risk, women with regular ovulatory cycles [8] , so there is a need for adequate powered RCT to explore the antagonist protocol OHSS sparing effect in women at high risk for OHSS development; namely, with high basal Antimullerian hormone (AMH), Antral follicular count (AFC) and high SE2 at ovulation triggering.…”

“…OHSS incidence varies greatly in literatures, owning to existence of several OHSS grading systems with a vague definition of different stages, without specific cut-off values as well as incorporating of subjective and objective parameters [5,6,7] . According to Toftager et al [8] depended on Golen criteria in long agonist protocol (LAP), the incidence of mild, moderate and severe OHSS was 31.9%, 15.6% and 8.9%, respectively, in broad largely unselected ART candidates (n = 495) with varying ages, infertility causes as well as OHSS risks. OHSS manifested clinically by groups of symptoms and signs related to increased vascular permeability with serous sacs fluid collection as ascites, pleural effusion, abdominal discomfort and enlarged ovaries [2] .…”

“…A lot of preventive strategies have been accessed targeting different points in OHSS pathophysiologic cascade to lower the incidence and the severity of OHSS including cycle cancellation [10] , coasting [11] , freeze all [10,15] , intravenous fluids infusion as calcium infusion [12] , albumin [13] , hydroxyethyl starch [14] , replacing HCG triggering by GnRH agonist in antagonist protocol [15] , utilizing antagonist protocol in risky ART population of OHSS instead of classic agonist protocol [8] as well as replacing against by antagonist during COH if there is anticipated hyper-response [16] and dopamine agonist as cabergoline [9,17,18] . However, all these evaluated strategies did not wholly eliminate OHSS especially after HCG administration in the course of COH in context of ART cycles.…”

Prevention and management of ovarian hyperstimulation syndrome

“…Notably many of the trials included in the meta-analysis were done in high-risk patients. However, recent confirmation of the efficacy of GnRH antagonists for a reduction in OHSS was obtained by an RCT of 1050 unselected women having their first treatment cycle (OR 0.43, 95% CI 0.33, 0.57) [9]. That live-birth rates were similar for both treatment arms would suggest that a GnRH antagonist protocol would be the treatment of choice for the first IVF cycle in women <40years old [9].…”