Infertility is a serious reproductive health problem that affects 8%-10% of couples worldwide (Boivin et al., 2007). It is predicted that around 9% couples are expected to be infertile in India (Katole and Saoji., 2019). Embryonic or maternal factors can contribute to both Recurrent Implantation Failure (RIF) and Recurrent Pregnancy Loss (RPL). Absence of clinical pregnancy following the transfer of high-quality embryos in at least three consecutive IVF cycles is considered as RIF. (Simon and Laufer, 2012, Comins Boo et al., 2016). RPL is explained as two or more clinically recognized pregnancy losses prior to 20 weeks of gestation and affects 1–2% of women. Established risk factors in both the scenarios includes infections, genetics, endocrine, uterine anatomical defects, and immunological factors (Ford and Schust, 2009). The failure to develop immunological tolerance to the fetus and immune system imbalances have both been suggested as potential causes of idiopathic RPL (Triggianese et al., 2014, Ali et al., 2017). Women who experience RPL are known to have significantly less peripheral blood T helper 1 (Th-1) cells when compared to normal fertile women (Hong Liu et al., 202). Increased proinflammatory cytokines and an up-regulated thrombophilic tendency appears to play a significant role in RPL (wak-Kim, 2003, Kumar Pandey et al., 2004).

The pathogenesis of the RPL in majority of cases is unknown. The maternal-fetal interaction has been hypothesized to involve the human leucocyte antigen (HLA). It has been suggested that excessive HLA antigen sharing between spouses is a mechanism causing maternal hyporesponsiveness to paternal antigens encountered during pregnancy and thus leading to a miscarriage (Jauniaux, 2006, Beer et al., 1981). In couples with increased HLA sharing and RPL often demonstrate lack of anti-paternal cytotoxic antibodies (APCA), mixed lymphocyte reaction blocking antibodies (MLR-Bf) and anti-idiotypic antibodies (Ab2). (Pandey MK, 2003).

HLA class I genes (HLA-A, -B and C) play important roles in transplantation immunology. HLA-C binds to killer immunoglobulin like receptors (KIRs) and facilitates trophoblast invasion. HLA-C has highest proportion of polymorphisms when compared to other HLAs which are expressed on the trophoblast (Christiansen, 2013). Some of these polymorphisms negatively impact trophoblast proliferation by inhibiting NK cells, resulting in RPL (Christiansen, 2013, Hiby et al., 2010, Nielsen et al., 2010, Moffett et al., 2015). Nonclassical class I HLA-G and -E molecules are expressed in extravillous cytotrophoblasts prior to implantation, (Le Bouteiller et al., 1999) while HLA-C antigens are minimally expressed (Onno et al., 1994). One of the potential roles of these antigens is the protection of trophoblasts from cytotoxicity. In the HLA class II system, the DQB1 allele polymorphism is relatively common and has been demonstrated to be strongly related with RPL (Arjmand et al., 2016).

According to a study, specific HLA alleles and the related ancestral haplotypes are key in the emergence of recurrent miscarriages (RM) in the Indian population (Shankarkumar et al., 2008). A Taiwanese study observed RPL in couples who share more than two pairs of HLA loci. The similarity of HLA sharing, expression of paternal HLA-DR allele and maternal HLA-B13 alleles may play a role in RPL (Tsun-Wen Hsiao et al., 2022).

When looking at the frequency of sharing 0, 1, or 2 alleles in multiple loci between women with RPL and their husbands, Meuleman et al. found that HLA-B and HLA-DR allele sharing was significantly higher in RPL couples. Reduced immunological allorecognition of paternal antigens in the fetus due to HLA allele matching between women with RPL and their foetuses results in increasing the risk for miscarriages (Meuleman et al., 2015).

The purpose of this study was to examine the role of HLA sharing between couples, as well as their allelic and haplotype frequency of HLA class I and class II molecules in couples with RIF and RPL in the south Indian population.