Recurrent Spontaneous Abortions (RSA) is defined as repeated occurrence of 3 or more miscarriages before 24th
week of gestation 
. The modern definition, however, is the spontaneous loss of 2 or more consecutive pregnancies before 20 weeks of gestation 
. Implantation of the embryo is a critical event in pregnancy. In humans, peri-implantation pregnancy loss contributes to more than 20% of unexplained infertility. Deficient hormone levels result in aberrant growth and support of the uterine lining making it un-ideal for implantation.
Progesterone, a 21 carbon steroid hormone, mainly produced in the ovaries, placenta, brain and the adrenal glands, is required for the maintenance of pregnancy and treatment with progesterone supplementation was observed to prevent abortions. It is mainly involved in the female menstrual cycle, pregnancy and embryogenesis in most mammalian species. It stimulates and regulates various functions - i) helps in preparing the body for conception and pregnancy (implantation of the embryo, promoting uterine growth and suppressing myometrical contractility) 
ii) acts as an anti-inflammatory agent and regulates the immune response 
and iii) regulates estrogen levels and thus prevents endometrial cancer.
Progesterone receptor (PR) mediates the physiologic effects of progesterone. The PR gene uses separate promoters and translational start sites to produce 2 isoforms, PRA and PRB, the only difference between the two being an additional 165 amino acids present in the N terminus of PRB. The human progesterone receptor (hPR) gene was localized to 11q22–q23 
and spans over 90 kb containing eight exons 
. The open reading frame corresponds to a protein of 933 amino acids with a molecular weight of 98,868 Da 
Three linked single nucleotide polymorphisms (SNPs) (exon 1: G 1031 C; S344T, exon 4: G 1978 T; L660V and exon 5: C 2310 T; H770H) in the PR gene were found to be associated with RSA 
. The SNP in the exon 1 is reported to be apparently linked to the SNPs in exons 4 and 5 
, which are in turn in linkage disequilibrium (LD) with PROGINS, a 306 base pairs (bp) insertion of PV/HS-1 Alu
subfamily in intron G, between exons 7 and 8 in the codifying region of the hormone binding domain 
. However, contrary to the expectation, Kurz et al. 
suggest that PROGINS is not associated with idiopathic RSA. Thus, only two studies dealt directly with the association of PR mutations with RSA, one dealing with PROGINS insertion and other with the 3 SNPs. Polymorphic variants of hPR gene have been implicated in implantation failure 
. There were also studies which did not show association of PR mutations in implantation failure 
and preterm birth 
. To the best of our knowledge, most of the earlier studies on the role of the PR mutations in adverse reproductive outcomes were in isolation not in conjunction with the PROGINS insertion. Further, LD between the PROGINS and the SNPs has been assumed rather than empirically tested. Thus, the earlier studies concerning the role of hPR gene in RSA have been largely inconclusive.
Given that most studies hitherto undertaken were on the Caucasian populations, it is not known if ethnicity has any role in the observed pattern of association of PR polymorphisms with adverse pregnancy outcomes. There were no studies on the role of these polymorphisms vis-à-vis RSA in the Asian populations, especially from India, which is known for its unique population structure characterized by strictly endogamous castes and tribes. In view of this, we attempt to ascertain if the 3 linked SNPs of the hPR gene and the PROGINS insertion are associated with RSA in the relatively homogenous Indian sample. We also attempt to explore if we can find any novel SNPs in hPR gene that can be implicated in RSA.