Ignite Creation Date:
2024-05-06 @ 5:40 PM
Last Modification Date:
2024-10-26 @ 2:33 PM
Study NCT ID:
NCT05397795
Status:
UNKNOWN
Last Update Posted:
2022-05-31
First Post:
2022-05-26
Brief Title:
COMPARING TWO PROTOCOLS FOR FINAL OOCYTE MATURATION IN POOR RESPONDERS UNDERGOING GnRH-ANTAGONIST ICSI CYCLES
Sponsor:
Alexandria University
Organization:
Alexandria University
Study Overview
Official Title:
COMPARING TWO PROTOCOLS FOR FINAL OOCYTE MATURATION IN POOR RESPONDERS UNDERGOING GnRH-ANTAGONIST ICSI CYCLES
Status:
UNKNOWN
Status Verified Date:
2022-05
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Poor ovarian responders POR include a significant proportion of women referred for IVF treatments ranging from 9 to 24 most of whom are in late reproductive age
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 qualityAttempts 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 fertilizationintracytoplasmic sperm injection IVF-ICSI cycles using a GnRH-antagonist protocol
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 qualityAttempts 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 fertilizationintracytoplasmic sperm injection IVF-ICSI cycles using a GnRH-antagonist protocol
Detailed Description:
Poor ovarian responders POR include a significant proportion of women referred for IVF treatments ranging from 9 to 24 most of whom are in late reproductive age12 According to the Bologna criteria patients are classified as POR based on three conditions if two or more of the following features are present 1 advanced maternal age 40 years 2 a previous poor ovarian response cycles cancelled or 3 oocytes with a conventional protocol 3an abnormal ovarian reserve test antral follicle count 5-7 follicles or anti-Mullerian hormone 05-11 ng ml Two of these criteria are required for a POR diagnosis In addition two cycles with POR after maximal stimulation are sufficient to classify a patient as a poor responder even in the absence of other criteria mentioned 3
In fact the live birth rate in the entire POR category is poor about 6 per cycle45 however patients 40 years have a significantly better prognosis compared to older patients mainly due to better oocyte quality6 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 elusive7
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 surge9
Until now administering 5000 IU to 10000 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 LH10
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 LH11 With a shorter mean duration of LH surge of about 34 hours it is similar to the natural cycle duration of 48 hours12 effectively reducing the incidence of Ovarian Hyperstimulation Syndrome OHSS in high responders1314 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 surge15 in addition increased early pregnancy loss and decreased rates of ongoing pregnancy were noted by multiple studies1617 As such the idea of a dual trigger was developed18 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 271 of a study population19 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 HormoneFSH 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 cycle20-22 indicating the possible role of these hormones in regulation of endometrial receptivity2023 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 invasion2425 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 responders1626 including an improvement in total number of retrieved oocytes MII oocytes rates of embryo implantation clinical pregnancy and live birth rates27 Evidence from available meta-analysis in 2018 involving four studies including 527 patients found a significantly improved clinical pregnancy rate following dual trigger28 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 2930
In fact the live birth rate in the entire POR category is poor about 6 per cycle45 however patients 40 years have a significantly better prognosis compared to older patients mainly due to better oocyte quality6 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 elusive7
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 surge9
Until now administering 5000 IU to 10000 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 LH10
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 LH11 With a shorter mean duration of LH surge of about 34 hours it is similar to the natural cycle duration of 48 hours12 effectively reducing the incidence of Ovarian Hyperstimulation Syndrome OHSS in high responders1314 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 surge15 in addition increased early pregnancy loss and decreased rates of ongoing pregnancy were noted by multiple studies1617 As such the idea of a dual trigger was developed18 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 271 of a study population19 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 HormoneFSH 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 cycle20-22 indicating the possible role of these hormones in regulation of endometrial receptivity2023 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 invasion2425 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 responders1626 including an improvement in total number of retrieved oocytes MII oocytes rates of embryo implantation clinical pregnancy and live birth rates27 Evidence from available meta-analysis in 2018 involving four studies including 527 patients found a significantly improved clinical pregnancy rate following dual trigger28 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 2930
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None