Infertility Clinical Trial
Official title:
TNFα (Tumor Necrosis Factor Alpha) and MFG-E8 (Milk Fat Globule-Epidermal Growth Factor 8): Novel Biomarkers to Predict Implantation Failure
Question: Can implantation failure (IF) be predicted prior to in vitro fertilization (IVF)? A pilot, non-interventional, clinical study Prospective, controlled, cohort study
The investigators hypothesize that TNFα and MFG-E8 cooperatively maintain the integrity of
the normal endometrium, and that in patients with IF or with recurrent pregnancy loss (RPL)
of unexplained origin, excessive TNFα increases the maternal shedding of MFG-E8, disrupting
the normal protective effect of this protein, resulting in damage of the endometrial
epithelium and impairing trophoblast invasion. The investigators propose that these molecules
can be measured in local tissue (endometrium) as well as in serum as a reflection of
increased inflammation and can therefore be used as markers of implantation and its failure.
The investigators hypothesis is that TNFα is up-regulated in serum of women with implantation
defects (IF and RM of unexplained origin) and this causes perturbation of MFG-E8 secretion.
These results will provide first evidence demonstrating endometrial dysfunctions resulting
from over-expression of pro-inflammatory molecules. The release of significant quantities of
these molecules into serum broadens the maternal-fetal interface beyond the uterus and into
the maternal circulation. The characterization of these molecules is essential to better
understand, not only their biological effects, but also their potential as prognostic and
diagnostic biomarkers for detection of IF. More importantly, these molecules could be
potential therapeutic targets (perhaps intrauterine infusion of MFG-E8 for tissue repair,
and/or oral administration of TNFα antagonists) to improve implantation outcomes. Two recent
studies have reported the successful therapeutic use of recombinant human MFG-E8 (rhMFG-E8)
in animals: one was used to decrease intestinal injury after whole body radiation (Ajakaiye
et al, 2012), and the other was to mitigate inflammation and tissue injury after hemorrhagic
stroke (Wang et al, 2012). Also, TNFα inhibitors have been shown to significantly increase
IVF outcome in infertile patients (Winger et al, 2009 and 2008). In summary, these two
pivotal studies show promising clinical uses of rhMFG-E8 in tissue repair/remodeling by
decreasing apoptosis, and provide basis for their use as candidates for further clinical
development in reproductive health.
Objectives: Here, the investigators seek to delineate novel diagnostic methods with the
ultimate long term goal of designing directed therapies to improve embryo implantation
competence.
- The specific aim is to quantify and correlate MFG-E8 and TNFα in serum and in
endometrial biopsies of women in 3 groups: controls, IF and RM.
- The ultimate goal of this study is to provide data leading to a simple and quick test to
measure soluble serum markers of IF/RM in order to discriminate prospectively between
these groups of patients.
- To translate these findings into the use of modulators of these inflammatory molecules
to improve pregnancy rates in patients with predicted implantation defects. It is widely
known that "classic" markers of endometrial receptivity such as those provided by an
invasive endometrial biopsy (with Hematoxilin-Eosin staining, or immuhistochemistry, or
even with microarray technology) are not reliable to establish clear-cut diagnosis due
to cycle-to-cycle variations and overlap of results.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03607409 -
Role of Inhibin A as Biomarker for Ovarian Response for IVF Treatment
|
||
Recruiting |
NCT02312076 -
GnRHa for Luteal Phase Support in Long GnRHa Protocol Cycles
|
Phase 4 | |
Terminated |
NCT02161861 -
Improvement of IVF Fertilization Rates, by the Cyclic Tripeptide FEE - Prospective Randomized Study
|
N/A | |
Completed |
NCT03287479 -
Comparison of a Semi-automated Closed Vitrification System (Gavi®) With a Manual Open Vitrification Sytem (Cryotop®)
|
N/A | |
Terminated |
NCT03522350 -
Randomized Trial Comparing EmbryoScope With EmbryoScope+.
|
N/A | |
Completed |
NCT04496284 -
Embryo Transfer Outcomes After Vitrification With Slush Nitrogen Compared to Liquid Nitrogen
|
N/A | |
Completed |
NCT03623659 -
pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts
|
N/A | |
Completed |
NCT03895099 -
New Ovarian Stimulation With Random Start, Use of Progestin Protocol for Oocyte Donors
|
Phase 3 | |
Active, not recruiting |
NCT04142112 -
Randomized, Standard-Controlled, Study to Evaluate the Ohana IVF Sperm Preparation Kit, SPeRtility IVF Next Generation
|
N/A | |
Completed |
NCT03152643 -
Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer
|
N/A | |
Recruiting |
NCT03683771 -
Assessment of Endometrial Pattern and Sub-endometrial Vascularity in ICSI Outcome
|
||
Recruiting |
NCT03161119 -
Comparing Two Different Embryo Transfer Catheters
|
N/A | |
Completed |
NCT04108039 -
Micronized Progesterone vs Gonadotropin-releasing Hormone (GnRH) Antagonist in Freeze-all IVF Cycles.
|
N/A | |
Completed |
NCT03678558 -
Oocyte Vitrification Aided With Cytochalasin B
|
N/A | |
Completed |
NCT03677492 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Cytochalasin D ( ICSI-CD)
|
N/A | |
Completed |
NCT03678818 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin A (ICSI-LA)
|
N/A | |
Completed |
NCT03678584 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Chaetoglobosin A ( ICSI-CA)
|
N/A | |
Completed |
NCT03678571 -
Oocyte Vitrification Aided With Latrunculin A
|
N/A | |
Completed |
NCT03678597 -
Supplementing Intracytoplasmic Sperm Injection Handling Medium With Latrunculin B ( ICSI-LB)
|
N/A | |
Completed |
NCT03678610 -
Handling Medium for ICSI With Ionomycin and Latrunculin A
|
N/A |