Towards an optimal luteal support modality in agonist triggered cycles: a randomized clinical trial.

STUDY QUESTION: In ICSI patients with high risk of ovarian hyperstimulation syndrome (OHSS), are antagonist cycles triggered by gonadotropin releasing hormone (GNRH) agonist with a specialized luteal support regimen associated with comparable ongoing pregnancy rate (OPR) and less OHSS than those triggered by hCG?

SUMMARY ANSWER: In antagonist ICSI cycles, GnRH agonist triggering with a specialized luteal support regimen is associated with comparable OPR to those triggered by hCG but may be less likely to be associated with OHSS.

WHAT IS KNOWN ALREADY: In IVF/ICSI protocols, exogenous hCG was used for years as a substitute of the endogenous LH surge. However, because of its longer half life, hCG is associated with more risk of OHSS, especially in high risk women. For this reason, GnRH agonist triggering was introduced. There is, however, no consensus on the best protocol for luteal support on agonist triggered cycles.

STUDY DESIGN, SIZE, DURATION: Randomized controlled open label trial including 190 participants recruited from June 2015 to March 2016 in a private fertility center. Participants were divided into 2 equal groups; GnRH agonist trigger and hCG trigger. Randomization was done using identical sealed envelope technique.

PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred ninety women, predicted to have high response, were randomized on the day of final oocyte maturation into two equal groups: group (A), GnRH agonist trigger followed by specialized regimen (1500 IU hCG) at time of oocyte retrieval plus oral estradiol and intramuscular progesterone during luteal phase; and group (B), 5000 IU of hCG with luteal support (oral estradiol and vaginal progesterone).

MAIN RESULTS AND THE ROLE OF CHANCE: The 2 groups were comparable in baseline characteristics. OPR per randomized patient was comparable in the 2 groups {49/95 (51.6%) in group A, and 50/95 (52.6%) in group B ((P = 0.88); RR = 0.980, 95% CI: 0.75-1.29)}. Considerable (moderate + severe) OHSS was higher in group B (13/95 [14%] versus 5/95 [5%] P = 0.047; uncorrected Chi-square test). Upon performing multivariate regression analysis for predicting OHSS, number of follicles ≥11 mm on trigger day was the only independent predictor (P = 0.0004).

LIMITATIONS, REASONS FOR CAUTION: Strict selection criteria limit generalization of results. The study was powered for pregnancy rate not OHSS, so that the strength of evidence on OHSS prediction is weak.

WIDER IMPLICATIONS OF THE FINDINGS: We recommend the use of GnRH agonist plus the specialized luteal phase support in high responders with high risk of OHSS undergoing IVF/ICSI cycles. This protocol achieved a similar ongoing pregnancy to hCG triggering and may be less likely to result in moderate to severe OHSS.

STUDY FUNDING/COMPETING INTEREST(S): None.

TRIAL REGISTRATION NUMBER: PACTR 201506001132105.

TRIAL REGISTRATION DATE: 24/6/2015.

DATE OF FIRST PATIENT’S ENROLLMENT: 26/6/2015.