Association of HY-restricting HLA Class II Alleles, Sex of Firstborn Child, and Pregnancy Outcome in RPL Patients

NCT05342948 | Completed

• 1 other identifier: 2018-5
• Study Type: observational
• Target: 583
• Locations: 1 country
• Sites: 1

Brief Summary

This cross-sectional and prospective cohort study will investigate if sRPL patients with a first born boy who carry ≥1 HY-restricting (HY-r) HLA class II alleles are associated with a lower chance for a succesful reproductive outcome in first pregnancy after admission compared to sRPL patients with a first born girl carrying ≥1 HY-r HLA class II alleles and women with no HY-r HLA class II alleles and a firstborn boy. Also, the study will compare sRPL patients with a firstborn boy who do not carry a HY-r HLA class II allele with sRPL patients having a firstborn girl and carrying no such alleles. We hypothesize that sRPL patients with a first born boy compared to sRPL patients with a firstborn girl who carry ≥1 HY-r HLA class II alleles is associated with a negative prognosis, while no association between sex of firstborn child and pregnancy outcome is expected in sRPL carrying no HY-r HLA class II alleles. Neither do we expect an association between pregnancy outcome and carriage of HY-r HLA class II alleles in pRPL patients.

Conditions

Recurrent Pregnancy Loss

Keywords

Maternal immune system; HLA Class II alleles; Habitual Abortion; Immunogenetics; Recurrent Pregnancy Loss

Outcome Measures

Primary Outcomes (2)

• Live birth or prolonged pregnancy in patients with ≥1 HY restricted HLA class II allele

  The number of patients with a live birth or prolonged pregnancy (\>12 weeks) in first pregnancy after referral with 1-2 HY.-restricted HLA class II allele

  Through study completion, i.e. up to 5 years

• Live birth or prolonged pregnancy in patients with 0 HY-restricted HLA class II allele

  The number of patients with a live birth or prolonged pregnancy (\>12 weeks) in first pregnancy after referral in patients with no HY-restricted HLA class II allele

  Through study completion, i.e. up to 5 years

Secondary Outcomes (8)

• Maternal prevalence of 0 HY-restricted HLA Class II alleles

  Measured on the date of study entry and assessed within 2 weeks for each individual during study completion period, i.e. up to 5 years

• Maternal prevalence of ≥1 HY-restricted HLA Class II alleles

  Measured on the date of study entry and assessed within 2 weeks for each individual during study completion period, i.e. up to 5 years

• Maternal prevalence of HLA DRB1*15

  Measured on the date of study entry and assessed within 2 weeks for each individual during study completion period, i.e. up to 5 years

• Maternal prevalence of HLA DRB1*01 or HLA DRB1*10

  Measured on the date of study entry and assessed within 2 weeks for each individual during study completion period, i.e. up to 5 years

• Maternal prevalence of HLA DRB1*07

  Measured on the date of study entry and assessed within 2 weeks for each individual during study completion period, i.e. up to 5 years

Study Arms (3)

pRPL

Primary RPL patients: no prior birth ≥22 weeks

sRPL with a first born boy

Secondary RPL patients: ≥ 1prior birth ≥22 weeks of only boy(s)

sRPL with a first born girl

Secondary RPL patients: ≥ 1prior birth ≥22 weeks of only girl(s)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Among all patients admitted to The Center for Recurrent Pregnancy Loss of Western Denmark from 2016 to 2021 the patients fulfilling study criteria were included and follow up was done continuously until the estimated sample size was reached. The majority of patients were caucasians. Approximately 1/3 of patients were trying to conceive with IVF/ICSI/FER after referral while the remaining 2/3 tried to conceive naturally. About 45% of patients are sPRL patients.

You may qualify if:

• ≥ 3 consecutive pregnancy losses before admission

You may not qualify if:

• Significant uterine malformation
• Chromosomal abnormalities

Sponsors & Collaborators

• Aalborg University Hospital: lead

Study Sites (1)

The Centre for Recurrent Pregnancy Loss of Western Denmark, Department of Obstetrics and Gynaecology, Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Related Publications (2)

• Kolte AM, Steffensen R, Christiansen OB, Nielsen HS. Maternal HY-restricting HLA class II alleles are associated with poor long-term outcome in recurrent pregnancy loss after a boy. Am J Reprod Immunol. 2016 Nov;76(5):400-405. doi: 10.1111/aji.12561. Epub 2016 Sep 7.

  PMID: 27600856 BACKGROUND

• Nielsen HS, Steffensen R, Varming K, Van Halteren AG, Spierings E, Ryder LP, Goulmy E, Christiansen OB. Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy. Hum Mol Genet. 2009 May 1;18(9):1684-91. doi: 10.1093/hmg/ddp077. Epub 2009 Feb 17.

  PMID: 19223392 BACKGROUND

MeSH Terms

Conditions

Abortion, Habitual

Condition Hierarchy (Ancestors)

Abortion, Spontaneous; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Caroline Nørgaard-Pedersen, MD

  Aalborg University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 25, 2022
• Study Start: January 1, 2016
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 15, 2023

Record last verified: 2023-03

Locations

DK (1)