Gonadotropin-releasing hormone agonist for ovulation trigger - OHSS prevention and use of modified luteal phase support for fresh embryo transfer

Juan Carlos Castillo, Thor Haahr, María Martínez-Moya, Peter Humaidan, Juan Carlos Castillo, Thor Haahr, María Martínez-Moya, Peter Humaidan

Abstract

The introduction of gonadotrophin-releasing hormone agonist (GnRHa) trigger greatly impacted modern IVF treatment. Patients at low risk of ovarian hyperstimulation syndrome (OHSS) development, undergoing fresh embryo transfer and GnRHa trigger can be offered a virtually OHSS-free treatment with non-inferior reproductive outcomes by using a modified luteal phase support in terms of small boluses of human chorionic gonadotrophin (hCG), daily recombinant luteinizing hormone LH (rLH) or GnRHa. In the OHSS risk patient, GnRHa trigger can safely be performed, followed by a 'freeze-all' policy with a minimal risk of OHSS development and high live birth rates in the subsequent frozen embryo transfer cycle. Importantly, GnRHa trigger opened the 'black box' of the luteal phase, promoting research in the most optimal steroid levels during the luteal phase. GnRHa trigger allows high-dose gonadotropin stimulation to achieve the optimal number of oocytes and embryos needed to ensure the highest chance of live birth. This review thoroughly discusses how the GnRHa trigger concept adds safety and efficacy to modern IVF in terms of OHSS prevention. Furthermore, the optimal luteal phase management after GnRHa trigger in fresh embryo transfer cycles is discussed.

Keywords: GnRHa trigger; IVF; hCG; ovarian hyperstimulation syndrome; ovulation trigger.

Conflict of interest statement

Not related to this manuscript, T.H. received honoraria for lectures from Ferring, IBSA, Besins, and Merck. P.H. received unrestricted research grants from MSD, Merck, and Ferring as well as honoraria for lectures from MSD, Merck, Gedeon-Richter, Theramex, and IBSA. P.H. and T.H. are listed as inventors in an international patent application (PCT/UK2018/040882). The remaining authors have no disclosures.

Figures

Figure 1.
Figure 1.
Comparison of ovulation triggers. Schematic graphic showing LH activity of different types of trigger agents when compared with natural mid-cycle surge. GnRHa: gonadotrophin-releasing hormone agonist; hCG: human chorionic gonadotropin. Adapted from Hoff et al. (6) and Casper (7).

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