Abstract
Study question
Does use of Dual-trigger (GnRH-agonist with recombinant-hcg) improve the clinical outcome in women with diminished ovarian reserve as compared to Recombinant-hcg trigger?
Summary answer
Yes, the use of Dual-trigger (GnRH-agonist with recombinant-hcg) improve the clinical outcome in women with diminished ovarian reserve as compared to Recombinant-hcg trigger.
What is known already
The population of poor responders has grown exponentially over the years and their management of ovarian stimulation remains one of the most challenging aspects. In GnRH antagonist down-regulated IVF-ICSI cycles, dual triggering for the final oocyte maturation with GnRH-a and a reduced dose of hCG improves the rate of fertilization and clinical pregnancy in women with diminished ovarian reserve. Further more, the benefit of lowered cycle cancellation rate would also enable greater percentage of patients with diminished ovarian reserve to reach the final stage of their ART treatment, thereby enhancing their chances of achieving a successful pregnancy .
Study design, size, duration
This RCT included GnRH antagonist ICSI cycles from 2018-2019. 82 women with diminished ovarian reserve (AMH ≤ 1.1 ng/ml and AFC ≤5) were included. The primary outcome measured was the oocyte fertilization rate, implantation rate and clinical pregnancy rate per oocyte retrieval cycle. Secondary outcome measured was embryo transfer cancellation rate and abortion rate per oocyte retrieval cycle.
Participants/materials, setting, methods
82 women with diminished ovarian reserve undergoing fresh embryo transfer were included and randomly divided in two groups - Group-A (hCG trigger/control group: n = 41); and Group-B (dual trigger/study group: n = 41). Both patient groups underwent controlled ovarian stimulation using antagonist. The final oocyte maturation was triggered either by recombinant hCG (Group-A) or by a combination of recombinant hCG and GnRH-agonist (Dual trigger) (Group-B).
Main results and the role of chance
The dual-trigger group had significantly higher fertilization rate (62.8 vs. 37.6%), higher clinical pregnancy rate (31.4% vs. 18.1%) as compared to the recombinant-hCG trigger group. In addition, the abortion rate(12.1% vs. 21.3%) and embryo transfer cancellation rate (8.3% vs. 16.1%) were both significantly lower in the dual trigger group. The baseline characteristics for the control and the study group were similar and there was no significant difference in the patient age, serum AMH level, and cause of infertility. The total r-FSH dose, duration of stimulation, endometrial thickness, and serum hormone profile on the day of trigger were also similar between the control and the study group. The main advantage of triggering with GnRH-a is that it induces a mid-cycle FSH surge which resembles the natural ovulatory cycle hormonal changes. Study shows that in GnRH antagonist ART cycles, dual triggering with GnRH-a and hCG could significantly improve the rate of fertilization and clinical pregnancy in diminished ovarian reserve women. Furthermore, the benefit of lowered cycle cancellation rate would also enable greater percentage of patients with diminished ovarian reserve to reach the final stage of their ART treatment thereby enhancing their chance of achieving a successful pregnancy as well as reducing their mental stress.
Limitations, reasons for caution
The main limitation of our study is the low patient number. Triggering with GnRH-a has become a significant part of contemporary ART practice, especially in high responders, oocytes donors and oncology patients. However, more RCTs are required in order to justify the use of GnRH-agonists in poor responders in ART cycles.
Wider implications of the findings
Results of our study concurred with other studies of dual triggering, calls for a possible paradigm shift in ovulation-triggering agent for GnRH-antagonist cycles. Diminished ovarian reserve patients are constituting a large part of clinical ART practice and for such patients, obtaining maximum mature oocytes and good embryos is vitally important.
Trial registration number
not applicable
Comparison of hCG Versus Gonadotropin-Releasing Hormone Agonist to Induce Oocyte Maturation in Assisted Reproductive Technology Cycles: A Retrospective Study
