GnRH Agonist Triggering of Final Oocyte Maturation: Improving Safety without Compromising Success

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About this Research Topic

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Background

The use of GnRH agonists to trigger final oocyte maturation has gained momentum recently over the use of hCG in women at high risk for OHSS. Because of the shorter duration of the agonist-induced LH surge, earlier demise of the corpus luteum (CL) is associated with a significant reduction in OHSS at the peril of decreased embryo implantation and increased pregnancy loss. For this reason, the effectiveness of GnRHa triggering was placed under scrutiny in fresh cycles while the quest for the most optimal strategies of luteal phase support (LPS) remains unresolved.



The adoption of a GnRH agonist trigger protocol with segmentation of the IVF cycle is one way of ensuring reproductive success without compromising patient safety. Approval of this management approach however is subject to patients’ values and financial resources. It is also dependent on the success of the cryopreservation program.

When a fresh embryo transfer is planned, alternative strategies to improve the profoundly deficient luteal phase have been suggested. The use of intensive hormonal supplementation has been inadequately investigated. Whether standardized or individualized protocols are more suitable in this context remain inconclusive. The administration of low dose hCG to prevent corpus luteum demise was found to be successful in restoring reproductive outcome. These protocols nonetheless are very heterogenous and differ in the dose and timing of hCG administration. Their safety when used in high responders has not been fully confirmed. On another note, incidents of partial and/or complete failure of oocyte collection have also been reported after agonist triggering. Risk factors have been poorly explored, while preventive and corrective measures remain largely erratic.

Some of the research challenges we face today include the following topics:



§ In fresh IVF cycles using a GnRH agonist for triggering of final oocyte maturation,

- Does LPS protocols utilized for frozen embryo transfer (FET) work equally well?

- Which intensive LPS strategy is more cost effective: standardized or individualized?

- Does patients’ characteristics and/or follicular dynamics influence the reproductive success with intensive LPS?

- What is the risk benefit analysis for low-dose hCG LPS protocols?

- Does the molecular structure of an agonist influence LH characteristics and CL function?

- Can we manipulate the mode of administration of an agonist to prolong the LH surge and optimize reproductive outcomes?

- Do low-dose hCG LPS protocols differ in terms of risk benefit profile?

- Can we predict and prevent complete and/or partial empty follicle syndrome?

§ How does the cost-effectiveness analysis look like for cycle segmentation/FET versus Intensive luteal phase/fresh ET?

§ When hCG tiggering is associated with persistently low rates of oocyte collection, fertilization, and maturation, is dual triggering beneficial?

§ Is there any role for GnRH agonist triggering in ovulation induction IUI cycles?

§ Does dual triggering improve the reproductive outcome of poor responders undergoing IVF?

§ Should a dual trigger be used routinely in all normal responders undergoing IVF?

§ What clinical algorithms may be useful to determine the most appropriate LPS management: segmentation versus intensive luteal supplementation versus hCG luteal support?



Details for authors:

This Research Topic intends to gather the most recent basic and translational research on the use of GnRH agonists for the triggering of final oocyte maturation. The goal is to fill knowledge gaps in the literature over the benefits and risks of agonist triggering strategies, with emphasis on developing best practice models for an OHSS-free IVF clinic.



We welcome contributions of any type (review articles, original papers, case discussions, clinical opinions) on the following topics around GnRH agonist triggering of final oocyte maturation:



Physiology of the agonist triggered LH surge.

Endocrinology of the corpus luteum.

Molecular imprints of the secretory endometrium.

Oocyte and embryo dynamics.

Intensive luteal supplementation for fresh embryo transfer.

LH/hCG support of the luteal phase.

Individualized versus standardized luteal support.

Complete and/or partial empty follicle syndrome.

Dual triggering in normal and poor responders.

Dual triggering for persistently low rates of oocyte yield, fertilization and/or maturation.

OHSS risk assessment.

Keywords: GnRH agonist, ovulation triggering, controlled ovarian stimulation, assisted reproduction, ovarian hyperstimulation syndrome.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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