COMPARING TWO PROTOCOLS FOR FINAL OOCYTE MATURATION IN POOR RESPONDERS UNDERGOING GnRH-ANTAGONIST ICSI CYCLES
NCT ID: NCT05397795
Last Updated: 2022-05-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE3
160 participants
INTERVENTIONAL
2022-06-01
2023-01-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
In fact the live birth rate in the entire POR category is poor (about 6 % per cycle). However patients \<40 years have a significantly better prognosis compared to older patients, mainly due to better oocyte quality.Attempts to improve IVF cycle outcomes for poor responders included modifying the steps of ovarian stimulation protocols , such as different luteal phase pretreatments, increasing ovarian stimulation doses, as well as addition of various supplements. So far, most of the modifications had limited success, therefore, optimal protocol for poor responders has remained elusive.
Final oocyte maturation trigger is one of the most important key success factors in assisted reproductive technologies (ARTs). Oocyte maturation refers to a release of meiotic arrest that allows oocytes to advance from prophase I to metaphase II of meiosis. Luteinizing Hormone (LH) surge by dismantling the gap junctions between granulosa cells and oocyte inhibits the flow of maturation inhibitory factors into ooplasm and causes drop in concentration of cAMP. Decreased concentration of cyclic AMP (cAMP) in turn increases concentration of Ca and maturation-promoting factor (MPF), which are essential for the resumption of meiosis in oocyte and disruption of oocyte-cumulus complex triggering follicular rupture and ovulation about 36 h the LH surge.
The aim of the study is to compare the oocyte yield , oocyte quality and the ongoing pregnancy rate between dual trigger treatment (combination of gonadotrophin-releasing hormone (GnRH) agonist and human chorionic gonadotrophin) and human chorionic gonadotrophin alone in PORs undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles using a GnRH-antagonist protocol.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In fact the live birth rate in the entire POR category is poor (about 6 % per cycle).(4,5) however patients \<40 years have a significantly better prognosis compared to older patients, mainly due to better oocyte quality.(6) Attempts to improve IVF cycle outcomes for poor responders included modifying the steps of ovarian stimulation protocols , such as different luteal phase pretreatments, increasing ovarian stimulation doses, as well as addition of various supplements. So far, most of the modifications had limited success, therefore, optimal protocol for poor responders has remained elusive.(7)
ESHRE in 2019 stated GnRH antagonists and GnRH agonists are equally recommended for predicted low responders. (8)
Final oocyte maturation trigger is one of the most important key success factors in assisted reproductive technologies (ARTs). Oocyte maturation refers to a release of meiotic arrest that allows oocytes to advance from prophase I to metaphase II of meiosis. Luteinizing Hormone (LH) surge by dismantling the gap junctions between granulosa cells and oocyte inhibits the flow of maturation inhibitory factors into ooplasm and causes drop in concentration of cyclic AMP (cAMP) . Decreased concentration of cAMP in turn increases concentration of Ca and maturation-promoting factor (MPF), which are essential for the resumption of meiosis in oocyte and disruption of oocyte-cumulus complex triggering follicular rupture and ovulation about 36 h the LH surge.(9)
Until now, administering 5000 IU to 10,000 IU of hCG 34-36 h prior to oocyte retrieval remained the standard protocol for the induction of final oocyte maturation in IVF cycles worldwide. Traditionally, human chorionic gonadotropin (hCG) has been the trigger of choice for oocyte maturation due to its molecular and biological similarity with LH.(10)
Gonadotropin-releasing hormone (GnRH) agonists were first suggested for final oocyte maturation by Gonen et al. in 1990, as it is able to trigger endogenous release of both FSH and LH.(11) With a shorter mean duration of LH surge of about 34 hours, it is similar to the natural cycle duration of 48 hours,(12) effectively reducing the incidence of Ovarian Hyperstimulation Syndrome (OHSS) in high responders.(13,14) However, some problems surfaced with the substitution of GnRH-agonists as trigger. The risk of empty follicle syndrome was reported to be increased following isolated GnRH-agonist trigger due to a suboptimal LH surge(15) ,in addition, increased early pregnancy loss and decreased rates of ongoing pregnancy were noted by multiple studies.(16,17) As such, the idea of a dual trigger was developed.(18) Indeed, the hCG component of dual trigger could serve as a rescue trigger in case of poor response to GnRH-agonist, which occurs in about 2.71% of a study population.(19) In combining GnRH-agonist and hCG for the final oocyte maturation , we get the benefits of both. HCG administration alone also does not produce Follicle Stimulating Hormone(FSH) activity, while GnRH-agonist releases an endogenous FSH and LH surge, resulting in a more physiologic response.
In addition, another proposed advantage with dual trigger is potential enhancement of endometrial receptivity by the GnRH-a component. Significant elevation of both isoforms of human GnRH messenger Ribonucleic Acid (mRNA) expression have been detected in the secretory phase of the human menstrual cycle,(20-22) indicating the possible role of these hormones in regulation of endometrial receptivity.(20,23) Specifically, in vitro studies with human extra-villous cytotrophoblasts and decidual stroma cells have demonstrated the ability of GnRH to activate urokinase type plasminogen activator, a key component in decidualization and trophoblast invasion.(24,25) Therefore, inclusion of GnRH-a as part of luteal support regimen has been explored as a mean to improve the implantation rate.
Since its development, multiple investigations have shown the benefits of using a dual trigger for final oocyte maturation in normal responders,(16,26) including an improvement in total number of retrieved oocytes, MII oocytes, rates of embryo implantation, clinical pregnancy, and live birth rates.(27) Evidence from available meta-analysis in 2018 involving four studies including 527 patients found a significantly improved clinical pregnancy rate following dual trigger.(28) However, for poor ovarian responders (PORs), the situation is less clear cut.
ESHRE in 2019 stated that dual triggering is not recommended in normal ovarian responders. However, there was no clear recommendation regarding PORs, giving rise to the need to perform a well-designed randomized controlled trial for the evaluation of dual triggering in PORs. .(29,30)
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
All included women will undergo a fixed GnRH antagonist protocol of COH.
At the day of triggering, number of follicles and the number of oocytes expected to be retrieved will be documented and women will be given the trigger according to the randomization done at the enrollment.
Two main groups will be created depending on the trigger protocol used:
Group A: 80 subjects will be triggered by 10000 IU of hCG (Choriomon5000 IU; IBSA) given intramuscularly.
Group B: 80 subjects will be triggered by 10000 IU of hCG (Choriomon5000 IU; IBSA) intramuscular injection in addition to the GnRH agonist triptorelin 0.2 mg (Decapeptyl 0.1 mg; Ferring) subcutaneously.
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Group(A)
subjects will be triggered by 10000 IU of hCG (Choriomon5000 IU; IBSA) given intramuscularly.
10000 IU hCG (Choriomon5000 IU; IBSA)
10000 IU of hCG (Choriomon5000 IU; IBSA) given intramuscularly
Group(B)
subjects will be triggered by 10000 IU of hCG (Choriomon5000 IU; IBSA) intramuscular injection in addition to the GnRH agonist triptorelin 0.2 mg (Decapeptyl 0.1 mg; Ferring) subcutaneously.
10000 IU hCG (Choriomon5000 IU; IBSA)
10000 IU of hCG (Choriomon5000 IU; IBSA) given intramuscularly
Triptorelin 0.2 mg (Decapeptyl 0.1 mg; Ferring)
GnRH agonist triptorelin 0.2 mg (Decapeptyl 0.1 mg; Ferring) subcutaneously.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
10000 IU hCG (Choriomon5000 IU; IBSA)
10000 IU of hCG (Choriomon5000 IU; IBSA) given intramuscularly
Triptorelin 0.2 mg (Decapeptyl 0.1 mg; Ferring)
GnRH agonist triptorelin 0.2 mg (Decapeptyl 0.1 mg; Ferring) subcutaneously.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Body mass index (BMI) \< 35.
3. Age less than 45.
4. Anti-Mullerian Hormone (AMH) ≤ 1.1 ng/ ml
5. Antral Follicle Count (AFC) ≤ 7 follicles
Exclusion Criteria
2. Surgically retrieved sperms.
3. Communicating hydrosalpinx.
19 Years
45 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Alexandria University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
Ding N, Liu X, Jian Q, Liang Z, Wang F. Dual trigger of final oocyte maturation with a combination of GnRH agonist and hCG versus a hCG alone trigger in GnRH antagonist cycle for in vitro fertilization: A Systematic Review and Meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:92-98. doi: 10.1016/j.ejogrb.2017.09.004. Epub 2017 Sep 14.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DT193
Identifier Type: -
Identifier Source: org_study_id