To the best of our knowledge, this is the first study that has examined the Androgen Receptor exon 1 CAG repeat variation in RSA. Our findings indicate that RSA women have a significantly greater frequency of longer AR CAG alleles (>19 repeats) and biallelic means (≥21 repeats) than fertile control women. The longer CAG repeat lengths were associated with increased odds of RSA. A number of earlier studies have focussed on the skewed X-Inactivation patterns among the RSA women yielding conflicting results, 
only 3 of the 7 studies reported association 
. In our case, the overall X-Inactivation pattern was not different between cases and controls, hence no perceptible epigenetic influence, which is in accordance to some of the previous studies where skewed XCI could not be associated with RSA 
. It is pertinent to note that earlier investigations on the X-Inactivation patterns primarily addressed the issue of identification of the X-linked recessive lethal traits with the underlying genetic hypothesis that carriers of the recessive lethal traits manifest the molecular phenotype of non-random (skewed) X chromosome inactivation. In addition to this, it was also proposed that a subset of these lethal traits may cause an increased frequency of spontaneous abortions in carriers if the hemizygous trait produces a clinically detectable pregnancy 
Given the inverse relationship between the CAG repeat length of the androgen receptor (AR) gene and the receptor activity, the alleles with longer CAG repeat length are expected to show a state of biochemical hyperandrogenism Infact previous studies have reported hyperandrogenism to be associated with RSA where they have demonstrated elevated levels of androgens among RSA women in contrast to the controls 
. Therefore, we tried to examine the X-Inactivation patterns vis-a-vis the CAG repeat polymorphism of the AR gene. Although we did not observe any significant epigenetic influence, we could establish strong genetic association of CAG repeat length (>19 in case of total alleles and ≥21 in case of biallelic mean) with RSA yielding highly significant odds ratio with adequate statistical power (~90%) conforming to our hypothesis. However, since the epigenetic influence was examined using peripheral blood samples in the present study and given that there are great variations in the degree of X-inactivation between ages and tissues 
, it thus becomes imperative to study the tissue specific XCI patterns in future (for eg. uterine cells, CVS) which might provide more unequivocal answers to the relative expression of CAG longer alleles and subsequent hyperandrogenic condition in RSA. Nevertheless, except in experimental situations including a couple of samples, it may not be feasible to obtain specific tissue samples especially in the Indian situation.
Individual analysis of the hospital-specific samples also yielded similar results to that of the pooled cohort, suggesting internal consistency in the data. Unfortunately, we could not obtain the serum androgen profiles of the cases in our study to verify if the biochemical hyperandrogenism is involved in the manifestation of RSA. Nevertheless, our study qualifies to provide the genetic evidence for possible biochemical hyperandrogenism 
as we could establish strong association of longer CAG repeat length with the RSA suggesting a possible endocrine aetiology of RSA. Further, while there was no significant difference in the CAG allele distribution patterns between the two abortion categories of our study, a highly significant difference was observed for CAG alleles with biallelic mean ≥21 repeats when these groups were separately compared with the controls. The higher abortion category exhibited a greater degree of difference with the controls which implies that longer CAG alleles may predispose women with a higher risk for spontaneous abortions.
In conclusion we may say that this maiden investigation of the CAG repeat polymorphism in RSA provides strong evidence of association of the longer CAG alleles with RSA, opening up the possibility of employing this as a meaningful prognostic genetic marker for identification of RSA cases. However, it is necessary to replicate and establish this association in other populations of the region before its prognostic value can be suggested with certainty. Further genetic and physiological (functional) studies are also required to ascertain the precise role of CAG polymorphism in the manifestation of this disorder, which may help in developing relevant endocrine therapeutic strategies for prevention of further miscarriages.