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ERA Test in Patients With Recurrent Implantation Failure

Not Applicable
Conditions
Repetitive Implantation Failure
Interventions
Other: ERA (Endometrial Receptivity Array)
Other: Personalized Embryo Transfer
Other: Second ERA
Registration Number
NCT01668693
Lead Sponsor
Igenomix
Brief Summary

The purpose of this study is to demonstrate the clinical efficiency of the Endometrial Receptivity Array (ERA) diagnostic tool in patients with repetitive implantation failure (RIF), leading to the new concept of the personalized window of implantation (pWOI) as diagnostic and treatment of patients with RIF of endometrial origin.

Detailed Description

Intervention(s): Endometrial sampling, either at LH+7 in a natural cycle or after 5 days of progesterone in a hormonal replacement cycle (HRT) and personalized embryo transfer (pET) on the designated day guided by the ERA prediction.

Repeated implantation failure (RIF) is an unsolved not well characterized major cause of infertility in otherwise healthy women. Although various definitions of RIF exist, the clinical community agrees that after failure of three IVF cycles, in which one to two morphologically high-grade embryos have been transferred, special protocols must be enforced, although no hard data from RCTs demonstrates that any of the current approaches in RIF have a significant clinical value .

Based on the large amount of information generated about the regulation and deregulation of the genes implicated in the endometrial window of receptivity (WOR), our group has developed a molecular diagnostic tool based on the specific transcriptomic signature that identifies the receptive endometrium at LH+7 in a natural cycle or on day 5 of progesterone impregnation (P+5) after proper estradiol priming in a hormonal replacement therapy (HRT) cycle. The endometrial receptivity array (ERA) consists of a customized array containing 238 genes differentially expressed that is coupled to a computational predictor able to diagnose the personalized endometrial WOI of a given patient, regardless of its histological appearance. The accuracy of the diagnostic tool ERA has been demonstrated to be superior to endometrial histology and results are completely reproducible 29 to 40 months later.

Compelling evidence indicates the existence of an endometrial receptivity alteration in patients with RIF.

The aim of this study is to demonstrate the diagnostic efficiency of the ERA test in RIF patients by identifying putative alterations related to the displacement of their personalized window of receptivity, and the therapeutic implications through personalization of the day of embryo transfer (pET), following the diagnosis obtained by this molecular diagnostic tool. An endometrial biopsy on day LH+7 in a natural cycle or on day P+5 in an HRT cycle and ERA diagnosis of receptive or non-receptive is informed. In receptive cases, embryo transfer (ET) will be performed in subsequent cycles on the indicated day. In non-receptive ERA, the test is to be repeated on the dayindicated by the predictor, and personalized ET guided in subsequent cycles according to ERA diagnosis.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
150
Inclusion Criteria
  • Women ≤38 years old
  • Normal ovarian reserve
  • FSH <8mIU/mL
  • Cycle with ≥6 MII oocytes/oocyte retrieval
  • ≥3 implantation failures in previous IVF/ICSI cycles with transfer of atleast two good quality embryos in each cycle Inclusion Criteria for ovum donation recipients
  • ≥3 implantation failures with transfer of atleast two good quality embryos in each cycle
  • Endometrial thickness ≥ 6 mm
  • Trilaminar pattern after proper progesterone priming
Exclusion Criteria
  • Existance of hydrosalpinx
  • Atrophic endometrium < 6 mm
  • Previous ectopic or uterine miscarriages
  • Presence of myomas or polyps
  • Previous embryo transfer with high difficulty and/or bleeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
RIF ERA Receptive 1ERA (Endometrial Receptivity Array)With the "receptive" results from the first Endometrial Receptivity Array (ERA), the patients will undergo embryo transfer on Day 5 of Progesterone administration in the cycle following the ERA diagnosis.
RIF ERA Non ReceptiveERA (Endometrial Receptivity Array)The "Non Receptive" results of the ERA diagnotic tool will indicate how many more days of Progesterone are necesary in order to obtain the "Receptive" daignosis. A second ERA will take place to confirm receptivity and in the following cycle, the personalized embryo transfer will take place on the day predicted by this diagnostic tool.
RIF ERA Non ReceptivePersonalized Embryo TransferThe "Non Receptive" results of the ERA diagnotic tool will indicate how many more days of Progesterone are necesary in order to obtain the "Receptive" daignosis. A second ERA will take place to confirm receptivity and in the following cycle, the personalized embryo transfer will take place on the day predicted by this diagnostic tool.
RIF ERA Receptive 1Personalized Embryo TransferWith the "receptive" results from the first Endometrial Receptivity Array (ERA), the patients will undergo embryo transfer on Day 5 of Progesterone administration in the cycle following the ERA diagnosis.
RIF ERA Non ReceptiveSecond ERAThe "Non Receptive" results of the ERA diagnotic tool will indicate how many more days of Progesterone are necesary in order to obtain the "Receptive" daignosis. A second ERA will take place to confirm receptivity and in the following cycle, the personalized embryo transfer will take place on the day predicted by this diagnostic tool.
Primary Outcome Measures
NameTimeMethod
Detection of the Receptive or Non Receptive endometrial status according to the ERA test.1 months
Secondary Outcome Measures
NameTimeMethod
Implantation4 months
Pregnancy6 weeks

Trial Locations

Locations (1)

IVI

🇪🇸

Valencia, VAencia, Spain

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