A prospective randomised controlled study (RCT) evaluating the effect of early hcg trigger on pregnancy rates in patients undergoing IVF-ICSI cycles using GNRH-antagonists

Study question: Does an early Administration Of Human Chorionic Gonadotropin (hCG) Improve Pregnancy rates In IVF‐ICSI Cycles With GnRH Antagonists? Summary answer: Yes: Early HCG‐triggering of final oocyte maturation result in an improved probability of pregnancy by leading to a less deranged and more receptive endometrium. What is known already: The criteria used for hCG administration in GnRH ‐ Antagonist cycles (hCG triggering for the final oocyte maturation as soon as ≥ 3 follicles ≥ 17 mm) have not been evidence‐based, and their importance for the probability of pregnancy was unknown until recently. Studies have shown that delaying hCG administration is associated with a decreased probability of ongoing pregnancy because of premature closure of the Implantation‐Window. Early HCG‐triggering is expected to result in lower progesterone levels on the day of hCG and this intervention might result in an improved pregnancy rates by leading to less deranged and more receptive endometrium. Study design, size, duration: The purpose of this randomized controlled trial of 416 infertile patients between 2006 to 2016, below 42 yrs of age, was to evaluate whether triggering of final oocyte maturation as soon as ≥ 3 follicles ≥ 16 mm present on ultrasound or one/two day later affects the probability of pregnancy in patients stimulated with GnRH‐antagonists in IVF‐ICSI‐cycles. PRIMARY OUTCOME: pregnancy rate SECONDARY OUTCOME: number of MII oocytes, endometrial‐thickness, progesterone levels and complications like OHSS Participants/materials, setting, methods: Patients were randomized by a computer‐generated list and after proper consent were divided into two groups of 208 patients each (group one ‐ Early HCG and group two ‐ Late HCG). Main results and the role of chance: Significant differences were observed between the groupOne(early‐hCG) and group Two (the late‐hCG group) regarding ‐ Pregnancy Rates (33% Vs 21%, respectively) and Progesterone Levels (0. 7 ± 0. 5 Vs 1. 1 ± 0. 4 ng/mL, respectively) on the day of hCG administration and Endometrial Thickness (10. 8 +/‐ 2. 3 mm Vs 7. 3 +/‐ 2. 5 mm) on day of embryo transfer. the number of Metaphase II Oocytes (6. 1 ± 4. 1 Vs 9. 1 ± 4. 8, respectively). and less Complications like OHSS (3 % Vs 7%) More similar multicentric trials are needed to assess its potential in improving the implantation chances in IVF‐ICSI cycles, thereby improving pregnancy rates and reducing the complications of ART. Limitations, reasons for caution: Why delaying HCG administration leads to an increased incidence of endometrial advancement is not clear? The adverse effect of Progesterone elevation on the day of hCG is explained by the induction of differences at the histological level and gene expression level between endometrial samples exposed to high concentrations of progesterone. Wider implications of the findings: Our study suggests that prolongation of follicular phase is associated with a higher incidence of premature secretory changes of the endometrium due to Progesterone elevation and supraphysiological E2 levels in late‐hCG group. Since earlier hcg‐ triggering results in lower progesterone levels, such an intervention might give better pregnancy rates.