Low dose human chorionic gonadotropin administration at the time of gonadotropin releasing-hormone agonist trigger versus 35 h later in women at high risk of developing ovarian hyperstimulation syndrome – a prospective randomized double-blind clinical trial

Abstract

BackgroundOvarian hyperstimulation syndrome remains a serious complication during in vitro fertilization cycles if high dose human chorionic gonadotropin (hCG) is used to trigger ovulation in high responder patients. Though much of this risk is mitigated with trigger using gonadotropin releasing-hormone (GnRH) agonist alone, it may result in lower birth rates. GnRH-agonist trigger and adjuvant low dose hCG has been proposed to improve birth rates, but timing of this hCG support to corpus luteum function has never been fully described. In this randomized, prospective trial, we explore differences in live birth rates and incidence of ovarian hyperstimulation syndrome (OHSS) in high-responder patients undergoing in vitro fertilization (IVF) receiving low dose hCG at the time of GnRH-agonist (dual trigger) or hCG adjuvant at the time of oocyte retrieval. Does the timing of hCG support make a difference?ResultsThirty-four subjects high-responder patients were randomized to receive low-dose hCG at the time of GnRH-agonist trigger (Group 1) and 37 received low-dose hCG at the time of oocyte retrieval (Group 2). There were no differences in the baseline characteristics and outcome of ovarian stimulation between the two groups. There were no differences in the live birth rates between Group 1 and Group 2 by intention-to-treat (14/34, 41.2% versus 21/37, 56.8%, p = 0.19) or per-protocol (14/26, 53.8% versus 19/31, 61.3%, p = 0.57) analyses. There was a slightly higher incidence of OHSS in Group 2 compared to Group 1 although the difference was not statistically significant (3/31, 9.7% versus 1/26, 3.8%). All the cases of OHSS in Group 2 were moderate while the one case of OHSS in Group 1 was mild.ConclusionsFor high responder patients receiving GnRH-agonist trigger, low dose hCG supplementation allowed high pregnancy rates after fresh embryo transfer, regardless of whether it was given at the time of trigger or at oocyte retrieval. Dual trigger may be preferable to reduce the risk of OHSS.

Dual trigger protocol is an effective in vitro fertilization strategy in both normal and high responders without compromising pregnancy outcomes in fresh cycles

“…In addition, it is important to note that both study groups exceeded expectations for both CPR and LBR compared with our center’s overall success rate in women <35 years old undergoing fresh autologous ET. This finding correlates with multiple research studies that showed that dual trigger improves IVF outcomes ( 38 , 39 , 40 , 41 , 42 , 43 ). Included in these studies was a double-blind, randomized, controlled trial that showed that the use of dual trigger had a significantly higher number of M2 oocytes retrieved, CPR, and LBR compared with those of hCG only trigger ( 40 ).…”

“…In addition, it is important to note that both study groups exceeded expectations for both CPR and LBR compared with our center's overall success rate in women <35 years old undergoing fresh autologous ET. This finding correlates with multiple research studies that showed that dual trigger improves IVF outcomes (38)(39)(40)(41)(42)(43). Included in these studies was TABLE 2 Clinical characteristics of cycles that did and did not achieve a live birth.…”

Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin‐releasing hormone agonist in high‐responder patients

“…25,26 In the modern patient-tailored IVF treatment, the selection of the ovulation trigger strategy remains relevant, because no ovulation trigger agent can be generally recommended for the universal use. 27,28 Furthermore, according to the European Society of Human Reproduction and Embryology guideline: ovarian stimulation for IVF/ICSI recommended future research focus on GnRHa trigger with adjusted luteal support compared to full dose hCG trigger with freeze-all in observed high responder. 29 The aim of this prospective observational study was to evaluate levels of angiogenic cytokines either as a low-dose bolus or dual trigger in high-risk patients after GnRHa agonist triggering and hCG co-administration versus the standard hCG trigger.…”

Different Timing of Adjuvant Low Dose hCG and GnRH Agonist Trigger Protocol, in OHSS High-Risk Patient with Peak E2 Level <4000 pg/mL

“…A new single-center prospective study demonstrates no significant differences in pregnancy rates between the two protocols comparing 1,000 vs 1,500 IU of hCG, with no statistically significant higher incidence of OHSS in the group of hCG ap-plied on OPU day compared to the group of Dual trigger. This demonstrates that either protocol may be a reliable option for patients at risk of OHSS who desire a fresh transfer (23).…”