Background: Recurrent unexplained miscarriage is still an unsolved reproductive health 15 problem. Inherited thrombophilias have been accused as one of the causes. Secondary to an 16 increased tendency for venous thromboembolism because of a mutation in a gene encoding a 17 protein involved in the coagulation cascade. These include prothrombin gene (PT G20210A) and 18 methylenetetrahydrofolate reductase (MTHFR) mutations. The study aims to evaluate the 19 association between polymorphisms in the prothrombin gene and the MTHFR gene with 20 recurrent miscarriage (RM). We also evaluated the association between Protein C (PC), Protein S 21 (PS), Antithrombin III (ATIII), and homocystiene with recurrent miscarriage (RM). 22
Methods: We conducted a comparative study on women with a history of two or more 23 miscarriages and healthy controls with no history of miscarriage and who had at least completed 24 one full-term normal pregnancy. Genetic analysis of the participants was done using the 5' 25 Nuclease Assay (TaqMan) PCR technique and various other blood tests were performed to check 26 general health indicators and thrombophilia markers. 27
Results: In this study of 195 RM group (Group I) participants and 90 healthy controls (Group 28 II), we noted significant discrepancies in health conditions. PC deficiency occurred in 7.2% of 29 Group I, but only 1.1% of Group II. PS deficiency was found in 65.6% of Group I versus 7.8% 30 of Group II. ATIII deficiency was observed in 9.2% of Group I and 2.2% of Group II. 31 Hyperhomocysteinemia was noted in 10.8% of Group I, and 2.2% of Group II. For the 32 prothrombin gene G20210A, two Group I participants were A/G, with no A/G in Group II, and 33 no AA carriers in either group. G allele was in 99.5% of Group I and 100% of Group II, while 34 the A allele was in 0.5% of Group I only. MTHFR C677T gene showed C/T mutation in 33.3% 35 of Group I and 32.2% of Group II, and T/T mutation in 12.8% of Group I and 8.9% of Group II. 36 The C allele was found in 70.5% of Group I and 75% of Group II, with the T allele in 29.5% of 37 Group I and 25% of Group II (p=0.269). 38
Conclusion: Prothrombin gene G20210A and MTHFR C677T gene polymorphisms are not 39 correlated with RM in the Egyptian population. About 70% of women in upper Egypt have at 40 least one type of MTHFRC677T gene polymorphism. However, Egyptian women with RM are 41 strongly associated with hyperhomocysteinemia, PC, PS, and AT deficiencies. 42