O-242 A randomized controlled trial exploring the effect of different timings of luteal hCG support on luteal phase serum progesterone levels in GnRHa triggered IVF cycles
Authors: Svenstrup L 
Published: June 2022

Study question

Will sequential luteal phase hCG support in GnRHa triggered IVF cycles result in a more optimal progesterone profile compared to single dose luteal hCG dosing?

Summary answer

Sequential hCG support after GnRHa trigger provides the most optimal progesterone (P4) level during the luteal phase.

What is known already

The luteal progesterone level at peri- implantation and during the late luteal phase is pivotal to establish and maintain pregnancy.

In OHSS risk patients, co-treated with a GnRH antagonist (GnRHant), final oocyte maturation is commonly triggered with a GnRHa, followed by a “freeze all” policy to avoid OHSS. However, in non OHSS risk patients, fresh embryo transfer can still be performed after GnRHa trigger with excellent reproductive outcomes, provided that an optimized luteal phase support (LPS) is used.

Study design, size, duration

A randomized controlled 3-arm study with 96 enrolled patients from January 2015 until September 2019, at the Fertility Clinic at Odense University Hospital, Denmark.

Participants/materials, setting, methods

IVF patients in GnRHant co-treatment, with 12-25 follicles ≥12 mm, were randomized into: Group 1: 6500 IU hCG for trigger. Group 2: 0.5 mg GnRHa for trigger followed by 1500 IU hCG on OPU. Group 3: 0.5 mg GnRHa for trigger followed by 1000 IU hCG on OPU and 500 IU hCG on OPU+5. All patients received similar vaginal progesterone as LSP. Eight blood-samples were drawn and analyzed for progesterone during the luteal phase.

Main results and the role of chance

In total, 69 patients completed the study. The final groups included 25, 22, and 22 patients, respectively. Baseline data were similar between the groups and were comparable in number of retrieved, fertilized, and cleaved oocytes. P4 peaked on OPU+4 in groups 1 (6500 IU hCG) and 2 (GnRHa+ 1500 IU hCG), whereas in group 3 (GnRHa+1000 IU hCG +500 IU hCG) P4 showed a stady increase with a peak on OPU+6. On OPU+6, the P4 level in group 2 (GnRHa+1500 IU HCG) was significantly lower (p = 0.03) compared to the other groups. Further, on OPU+8, the P4 level in Group 3 (GnRHa+1000 IU hCG+500 IU hCG) was significantly higher compared to the other groups (p &lt; 0.001). The area under the curve of P4 were significantly higher in group 3 (GnRHa+1000 IU hCG +500 IU hCG) from OPU+6 until OPU+14, compared individually to each of the other groups. Furthermore, significant inverse association between BMI and P4 level was observed (p = 0.038).

Limitations, reasons for caution

This study was powered for P4 values, and not the reproductive outcome. The result is restricted to normal/high responder patients, and limits the generalization of the results. Further, the study was un-blinded.

Wider implications of the findings

Dividing the 1.500 IU hCG for additional support in GnRHa triggered cycles into two administrations of 1000 and 500 IU on day OPU and OPU+5 improves P4 output and is likely to augment pregnancy rates.

Trial registration number

EudraCT 2013-003304-39