Comparison of ART outcome in 0.2 mg GnRH agonist trigger vs Dual trigger trigger in Poor ovarian reserve females, a randomized clinical trial

Back ground :Human chorionic gonadotrophin (HCG) has been successfully used for decades as a surrogate for the natural LH surge for oocyte maturation during IVF cycles. Gonadotrophin releasing hormone agonist as the trigger was introduced for IVF in high responders to minimize the risk of OHSS but with a compromised pregnancy rate because of luteolytic action. The addition of a reduced dose of hCG at oocyte retrieval showed promising results in improvement of pregnancy rate. Subsequently, the concept of “dual-trigger†(GnRH-a plus a reduced dose of hCG) was proposed as another mean to rescue the corpus luteal function. Despite being molecularly similar, hCG and LH elicit different gene expressions. LH helps in cellular growth, which supports embryo development and survival, whereas hCG enhances apoptosis.hCG administration alone also does not produce FSH activity, while GnRH-agonist releases an endogenous FSH and LH surge, resulting in a more physiologic response. GnRH agonist trigger induces FSH surge along with a surge in LH, which mimics the phenomenon that in a natural cycle.  Being more physiological the agonist trigger seems to produce well-matured oocytes than the hCG trigger only. These promising results were mainly attributed to the simultaneous FSH surge induced by a trigger with GnRHa.

 Related Work : Li et.al studied a total of 427 completed GnRH-antagonist downregulated IVF cycles with fresh embryo transfer (ET) in a retrospective analysis in decreased ovarian reserve (DOR) defined as antral follicle count ≤5 and serum anti-Müllerian hormone level ≤ 1.1 ng/mL. The control group (n = 130) used a 6500 IU of recombinant hCG for trigger, and the study group (n = 297) used 0.2 mg of triptorelin plus 6500 IU of recombinant hCG for trigger. The dual-trigger group had significantly higher oocyte fertilization rate (73.1% vs. 58.6%), clinical pregnancy rate (33.0% vs. 20.7%) and live birth rate (26.9% vs. 14.5%) when compared to the hCG trigger group.

A retrospective cohort study by chen et.al. investigated 384 cycles fulfilling the POSEIDON group 4 criteria who underwent IVF using the gonadotropin-releasing hormone (GnRH) antagonist protocol. The study group received dual-trigger (human chorionic gonadotropin [hCG] plus GnRH-agonist) for final oocyte maturation & the control group included 114 cycles where final oocyte maturation was performed with only hCG. The results showed 4.30-fold increase in clinical pregnancy (95% CI 1.38–13.43, p = 0.012) and a 3.16-fold increase in live birth (95% CI 1.06–9.38, p = 0.039) in the POSEIDON group 4 patients with dual trigger compared to those using hCG trigger alone.(7)

Objective of the study : Toexplore whether a Dual trigger (0.2 mg triptorelin acetate + 1500 IU urinary-hCG)for final oocyte maturation could improve the maturationrate of retrieved oocytesand subsequently the IVF outcomes of patients with POR as compared to that of0.2 mg Triptorelin acetate.

Methodology: This is a prospective, open-label, multicenter, randomized, parallel group study to be conducted in 654 women in the age group of 25 to 40 years (both inclusive), who are indicated to undergo COS as part of ART. Each woman will participate in the study for a maximum duration of approximately 28 weeks after signing the informed consent form (ICF). This will include a screening period, single cycle of COS and ART procedures, and post-ART follow-up for ongoing pregnancy till 12 completed wks of gestation.