P-707 RCT of Dual-Triger (GnRH-Agonist &amp; hCG) versus hCG-Trigger alone for Normal Responders in IVF-ICSI Cycles
Authors: Singh M 
Published: June 2022

Abstract

Study question
Does Dual Triger with GnRH-Agonist with hCG in IVF-ICSI cycles in normal responders improve oocyte quality and pregnancy outcome compared to Triger with hCG alone?

Summary answer
Yes, Dual Triger with GnRH-Agonist with hCG in IVF-ICSI cycles in normal responders improve oocyte quality and pregnancy outcome compared to Triger with hCG alone.

What is known already
Dual-Triggering for final oocyte maturation combining GnRH-Agonist with hCG can improve clinical outcomes in high responders during IVF–ICSI cycles. .
However, there is insufficient evidence regarding the impact of a Dual-Trigger on the reproductive outcome in normal responders.
Some studies reported a significantly improved ongoing pregnancy rate and live-birth rate in fresh-embryo-transfer cycles for a dual-trigger group compared with the hCG-trigger group in normal responders . By contrast, several studies have demonstrated that dual trigger of oocyte maturation was not associated with a change in the live-birth rate in FET cycles for normal ovarian responders .

Study design, size, duration
RCT of 214 patients of IVF-ICSI Cycles between 2016 - 2020 were included in the study .The inclusion criteria in the study were: Age &lt; 40 years, AMH &gt;1 ng/ml, AFC : 07-20 and FSH &lt;10 IU/l.
The exclusion criteria were Poor-Ovarian-Reserve (Low-AMH &lt;1 ng/ml) and patients at high-risk of developing OHSS (High-AMH &gt;07 or AFC &gt;20). Recombinant-FSH dose was adjusted according to E2 levels and follicular monitoring along with a flexible GnRH-Antagonist-Protocol.

Participants/materials, setting, methods
RCT of 214 patients of IVF-ICSI Cycles between 2016-2020 were included in the study and were divided in two groups.
Administration of the GnRH-antagonist was initiated based on a flexible protocol and final oocyte-maturation was triggered either by hCG alone (contol group) or by combining GnRH-Agonist with hCG (2000 IU) (study group).Data on number of oocytes retrieved, number of mature (MII) oocytes, embryos and blastocysts and clinical pregnancy rate were assessed and compared.

Main results and the role of chance
The Implantation-Rate (16% versus 33%) and the Clinical-Pregnancy-Rate per patient (18% versus 38%) were significantly higher in the Dual Triger of GnRH-Agonist with hCG study group, compaired to contol group of Triger with hCG alone.
Dual-trigger approach appears superior to an hCG trigger alone with regard to the number of top-quality embryos produced.
Final oocyte maturation is the key step in ART cycles and Human-Chorionic-Gonadotropin (hCG) alone has been used for final oocyte maturation for many years and has been demonstrated to promote an increased pregnancy rate. However, the administration of hCG for final oocyte maturation results in supraphysiologic steroid levels in the luteal phase due to its long half-life and is consequently associated with an increased risk of OHSS. The hCG trigger may have negative impacts on endometrial receptivity and embryo quality .
The GnRH-Agonist trigger benefits the induction of both an FSH and an LH surge and the possibility of retrieving more mature MII oocytes than is expected with an hCG trigger . Drawback of a GnRHa trigger was LH depletion and the withdrawal of LH support of the corpus luteum , however this problem has been overcome with intensive luteal phase support (LPS) and luteal-phase hCG administration .

Limitations, reasons for caution
The present study did not include a third arm of patients who were triggered with GnRH-Agonist alone.
If we had added the third arm, we would have been able to test whether it was the administration of GnRH-Agonist or the co-administration of GnRH-Agonist and hCG that improved the outcome .

Wider implications of the findings
We conclude that using the dual trigger for final follicular maturation in normal responder increases the number of good quality mature MII oocytes and top-quality blastocysts compared to triggering with hCG alone.
The increase in the number of good quality blastocysts improved the outcome of the IVF-CSI cycle in normal responders.

Trial registration number
not applicable