O-312 Does infertility relate to Human Leucocyte Antigen similarity? – a genetic analysis based on 609 couples

Abstract

Abstract Study question Do infertile couples differ from the average population in Human Leukocyte Antigen (HLA) similarity? Summary answer Infertile couples share a significantly higher number of genes than expected by chance in four out of six HLA loci. What is known already HLA genes encode the peptides for the formation of the innate immune system and are highly polymorphic. To allow increased variability of the innate immune system for the offspring, it is necessary that the parental alleles of the HLA complex are dissimilar. In animal studies, such mechanisms have been shown to play a role in mate choice. While some large studies show that humans in Western cultures do not engage in HLA-based mate choice, it has also long been hypothesized that a couple's fertility and pregnancy outcome is influenced by the degree of HLA similarity. Study design, size, duration A multicenter study including a total number of 609 couples was performed between May 2020 and November 2021 at a private fertility center and a department of reproductive medicine of a university clinic. All couples were diagnosed with primary infertility prior to assisted reproductive techniques. Buccal swab samples were provided by both partners to determine HLA profiles. Participants/materials, setting, methods Primary infertile couples (mean age women: 34.35 years, men: 37.59 years) were recruited before undergoing IVF or ICSI therapy. Couples with former pregnancies, tubal factor, azoospermia or donor therapies were excluded. Six different HLA genes (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) were analysed using next-generation sequencing. Subsequently the number of HLA similarities was determined per couple. Comparison against chance level was performed using a random permutation approach with 100,000 repetitions. Main results and the role of chance Our analysis revealed a higher degree of HLA similarity in infertile couples, than expected by chance, for the loci HLA-C, -DPB1, -DRB1 and HLA-DQB1, but not for the loci HLA-A and HLA-B. A priori power analysis was performed to statistically ensure a small effect size at a � = 0.05 ������������ 1 − � = 0.95 and resulted in a number of 536 couples. Limitations, reasons for caution Conclusions are limited due to the inclusion of predominantly Caucasian couples. Wider implications of the findings This study adds new evidence to former publications with small study groups. HLA similarities may be a contributing factor to primary infertility. Further on, we will examine whether HLA similarities relate to success rates of infertility treatment and outcome of pregnancies. Trial registration number not applicable