Maternal KIR and Fetal HLA Influence Reproductive Success in ART-oocyte Donor.

NCT ID: NCT05606679

Last Updated: 2024-01-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-12-31

Brief Summary

The present project is an ambispective study designed to answer how HLA-F SNPs, as well as KIR-HLA-C compatibility, influence reproductive outcomes in oocyte donation cycles. On the one hand, healthy patients without history of RIF and RM and with indication of egg donation cycle as ART treatment will be genotype for KIR, HLA-C and HLA-F. HLA-C from male partners and egg donors will be also analyzed. No matching based on HLA-C genotypes would be performed and donors would be assigned to recipients following the routine clinical practices. After SET, patients will be followed up until delivery or until the end of treatment. On the other hand, access to data from patients who have equally undergone oocyte-donation cycles, who meet the inclusion criteria and who have been genotyped for KIR and HLA-C as a matter of routine practice, will be requested.

For this study, only the first SET of oocyte-donation that patients undergo will be considered. LBR will be the primary endpoint of the study. In addition, secondary endpoints such as embryo development, sustained implantation, progesterone levels, implantation failure, miscarriage rate and unwanted events (preeclampsia, fetal grow restriction, premature birth, low birth weight…) will also be evaluated.

Detailed Description

This is an ambispective study in which healthy patients without history of RIF and RM and with indication of egg donation cycle as ART treatment will be genotyped for KIR, HLA-C and HLA-F. Male partners and egg donors will also be studied for their HLA-C alleles. Patients would be assigned to donors, following routine clinical practice, without matching based on donor's HLA-C genotype. They would undergo SET and be followed up until delivery.

In addition to this prospective part, we will request access to data from patients who have equally undergone oocyte donation cycles at the clinic, who meet the inclusion criteria and who have been genotyped for KIR and HLA-C as a matter of routine practice.

Combinations of maternal KIR and HLA-C genotypes of the egg donor and fetus (based on the genotypes of the donor and male partner), as well as different HLA-F SNP genotypes of the recipients (form the prospective part of this proyect) will be correlated with reproductive outcomes. LBR will be the primary endpoint of the study. In addition, secondary endpoints such as embryo development, sustained implantation, progesterone leves, implantation failure and miscarriage rate will also be evaluated. Obstetrical complications such as preeclampsia, premature birth (<34 weeks) and low birth weight will also be evaluated.

Conditions

Reproductive Issues

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Study Groups

Patients undergoing ART with oocyte donation

Healthy patients with no history of RIF and RM which have undergone or are undergoing ART with oocyte donation and SET.

Analysis combinations of maternal KIR and HLA-C genotypes

Intervention Type: GENETIC

Analysis of combinations of maternal KIR and HLA-C genotypes of the egg donor and fetus (based on the genotypes of the donor and male partner), as well as different HLA-F SNP genotypes of the recipients

Interventions

Analysis combinations of maternal KIR and HLA-C genotypes

Analysis of combinations of maternal KIR and HLA-C genotypes of the egg donor and fetus (based on the genotypes of the donor and male partner), as well as different HLA-F SNP genotypes of the recipients

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Patients who have undergone or are undergoing their first egg donation cycle.
• Between 18 and 45 years of age.
• BMI between 19 and 25 kg/m2
• Signed written informed consent submitted.
• No history of RIF, defined as implantation failure after 4 consecutive blastocysts are transferred.
• No history of RM, defined as the presence of 2 or more clinical miscarriages.
• Normal blood pressure and viral serology.

Exclusion Criteria

• Male partner diagnosed with severe male factor
• Patients who test positive for thrombophilic disorders (factor V Leiden, prothrombinG20210A mutation, positive antiphospholipid antibodies)
• Participation in a different study or clinical trial with a research drug or device in the last three months prior to recruitment.
• Known abnormal karyotype of subject or of her partner
• Any known clinically significant systemic disease
• Known inherited or acquired thrombophilia disease.
• Any known endocrine or metabolic abnormalities with the exception of controlled thyroid function disease.
• Severe psychiatric conditions.
• Patients with uterine factor/abnormalities (eg. myomas, polyps, adenomyosis, etc), that determines an unsatisfactory ultrasound for their ART.
• Patients with PCOS.
• Patients diagnosed with autoimmune diseases (eg. Systemic Lupus erythematosus, multiple sclerosis, rheumatoid arthritis).
• Patients with recent diagnosis (6 months) of chronic infectious disease (HPV, HBV, HCV, HIV, TBC).
• Patients with current treatment of immunosuppressant (eg. corticosteroids, monoclonal antibodies…).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Diana Alecsandru

UNKNOWN

Sponsor Role: collaborator

IVI Madrid

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan Antonio Garcia Velasco, PhD

Role: PRINCIPAL_INVESTIGATOR

IVIRMA MADRID

Locations

Instituto Valenciano de Infertilidad

Madrid, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Diana Alecsandru, PhD

Role: CONTACT

Diana.Alecsandru@ivirma.com

+34 91 180 29 00

Juan Antonio Garcia Velasco, PhD

Role: CONTACT

juan.garcia.velasco@ivirma.com

+34 91 180 29 00

Facility Contacts

Juan A Garcia-Velasco, MD

Role: primary

341802900

Other Identifiers

2207-MAD-098-DA

Identifier Type: -

Identifier Source: org_study_id