Abstract
The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm). CRD42016051091.
Highlights
GnRH agonist (GnRHa) trigger for final oocyte maturation significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS) in both fresh transfer and segmentation IVF/ICSI cycles [1, 2]
In fresh transfer cycles triggered with either GnRHa or hCG, LBR is comparable, regardless of the trigger strategy, provided that GnRHa trigger is followed by luteal phase support (LPS)
Evidence suggest that individualized LPS could further improve LBR following GnRHa trigger
Summary
GnRH agonist (GnRHa) trigger for final oocyte maturation significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS) in both fresh transfer and segmentation IVF/ICSI cycles [1, 2]. The pathophysiological mechanism behind the luteal phase insufficiency was low-circulating endogenous LH levels after the GnRHa trigger, leading to corpus luteum demise and suboptimal progesterone levels at peri-implantation [5,6,7] This finding led to the development of a modified LPS, which has proven to be mandatory to obtain reproductive outcomes comparable to those seen after hCG trigger [5]. Two different modified LPS strategies have been proposed to overcome the aforementioned luteal phase deficiency [7] One of these approaches has been called the “European approach” in which the endogenous steroid (progesterone and estradiol) production by the corpora lutea is boosted by exogenous LH activity, i.e., LH or hCG after GnRHa trigger. The other approach has been called the “American approach” in which luteal progesterone and estradiol are administered exogenously, disregarding the function of the corpora lutea [7]
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