PREDICTIVE IMMUNOLOGICAL STUDY OF RECURRENT ABORTIONS AND IMPLANTATION FAILURE

Predictive Inmunological Study to Assess the Rate of Gestation, Abortion and Live Newborn in Patients With Recurrent Abortions and Recurrent Implantation Failure.

The involvement of the immune system in the process of implantation and its modulation as a therapeutic line in these alterations, failure of implantation and repetition abortion are controversial and make it necessary to conduct clinical studies properly led and with a study population chosen by strict criteria in order to better understand the involvement of the different innate and adaptive immune mechanisms in the field of reproductive medicine and especially in clinically expressed failures recurrent implantation failure and recurrent abortions.

Study Overview

• Status: Completed
• Conditions: Maternal-Fetal KIR-HLA-C Compatibility
• Intervention / Treatment: Diagnostic test: HLA-C and KIR determination for patients, couples, oocyte or semen donors, abortive tissue and newborn.

Detailed Description

A prospective pilot study is proposed in patients with recurrent implantation failure and recurrent abortions undergoing assisted reproductive techniques.

The main objective of this study is to determine the involvement of key effectors of innate immune response in the endometrium that induces a pro-inflammatory response, and to be able to know in particular what is the distribution of KIR receptors in the uNK and the HLA-C typing in patient-mother, egg/semen donors, male-father, abortive remains, live newborns.

To this end, the distribution of KIR and HLA-C receptors will be studied two arms/patient groups, divided from a population chosen according to inclusion/exclusion criteria:

• Group I: group recurrent abortions.
• Group II: group recurrent implementation failure. The study population will include subjects of older age (aged between 18 and 37 years) who will be divided into 2 total Study Arms N x 200 (n x 100 for each arm).

• Study Type: Observational
• Enrollment (Actual): 200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women with a history of recurrent abortion (more than 3 idiopathic involuntary abortions) or recurrent implantation failure (more than 3 failures of IVF cycles with good quality embryos or more 2 failures in cycles with donor eggs) that will undergo a cycle assisted reproduction

Description

Inclusion Criteria in recurrent implantation failure:

• Body mass index between 19 and 27 kg/m2
• Patients with 3 or more IVF failures following transfer of good quality embryos or with 2 or more failures following embryo transfer in egg donation cycles.
• At least one embryo transfer is required to have been made in a blastocyst state (embryo on day 5) and with the current partner/donor.
• Study of normal karitype..
• Normal thrombophilia study.
• Vaginal exudate (Chlamydia, ureaplasma) normal
• Normal immune study.
• No hormone treatment in the two months prior to inclusion in the study.

Inclusión criteria in recurrent abortion:

• Body mass index between 19 and 27 kg/m2
• Patients with 3 or more recurrent abortions, natural gestations or after transfer of good quality embryos (own or ovodonation)
• Study of normal karitype.
• Normal thrombophilia study.
• Vaginal exudate (Chlamydia, ureaplasma) normal
• Normal immune study.
• No hormone treatment in the two months prior to inclusion in the study.

Exclusion Criteria:

• Pregnant or lactating women.
• They cannot offer cooperation.
• Participation in a study or clinical trial during the 3 months prior to inclusion.
• Patients with fibromes.
• Patients with PCOS.
• Patients with some genetic alteration (altered karitype, cystic fibrosis, multiple sclerosis, rheumatoid arthritis...)
• Patients chronic infectious disease.
• Patients in maintenance treatment with immunosuppressants.
• Patients who have received systemic corticosteroids in the last 4 weeks.
• Patients diagnosed with chronic lymphoproliferative disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with recurrent abortion.; More than three idiopathic involuntary miscarriages.	Diagnostic test: HLA-C and KIR determination for patients, couples, oocyte or semen donors, abortive tissue and newborn.
Patients with implantation failure.; More than three IVF abortions with good quality embryos or more than two abortions in oocyte donation cycles.	Diagnostic test: HLA-C and KIR determination for patients, couples, oocyte or semen donors, abortive tissue and newborn.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal genetic compatibility profile fetal KIR-HLA-C	KIR AA, KIR AB, KIR BB	2 years

Collaborators and Investigators

• Sponsor: IVI Madrid
• Investigators: Principal Investigator: Diana Alecsandru, IVI Madrid

Publications and helpful links

General Publications

• Adams EJ, Parham P. Species-specific evolution of MHC class I genes in the higher primates. Immunol Rev. 2001 Oct;183:41-64. doi: 10.1034/j.1600-065x.2001.1830104.x.
• Apps R, Murphy SP, Fernando R, Gardner L, Ahad T, Moffett A. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies. Immunology. 2009 May;127(1):26-39. doi: 10.1111/j.1365-2567.2008.03019.x.
• Arck PC, Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med. 2013 May;19(5):548-56. doi: 10.1038/nm.3160. Epub 2013 May 7.
• Alecsandru D, Barrio A, Garrido N, Aparicio P, Pellicer A, Moffett A, Garcia-Velasco JA. Parental human leukocyte antigen-C allotypes are predictive of live birth rate and risk of poor placentation in assisted reproductive treatment. Fertil Steril. 2020 Oct;114(4):809-817. doi: 10.1016/j.fertnstert.2020.05.008. Epub 2020 Jul 31.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Abortion, Spontaneous; Abortion, Habitual
• Other Study ID Numbers: 1405-MAD-026-JG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No