OBJECTIVE: The goal of this study was to modify and optimize the screening and diagnostic procedures of unexplained recurrent abortion. Antithyroid antibodies, parvovirus B19 (B19V) and cytomegalovirus (CMV) infections, which were usually overlooked in clinical practice of handling cases of recurrent abortion, were studied to evaluate their role in the pathogenesis of recurrent first trimester abortion. Also , we tried to elucidate the importance of detection of these agents and whether it should be routine prenatal investigations of women with unexplained recurrent abortion. STUDY DESIGN: sixty women with unexplained recurrent first trimester abortion were the study group and thirty term healthy pregnant women, were selected as a control. Placental and fetal tissues were analyzed for B19V and CMV deoxyribonucleic acids using nested polymerase chain reaction (PCR) assay. Also sera were analyzed for T3, T4 and TSH levels, the presence of antithyroid antibodies (thyroglobulin and thyroid peroxidase), CMV specific IgM antibodies and parvovirus B19-DNA by dot blot hybridization assay. RESULTS: Parvovirus B19-DNA was demonstrated in nearly one third of the aborted products (19/60 - 31.67 %) and 6.67% of the placentas of the control group, that represent highly significant difference (P <0.001). Whereas, serum samples of the two groups were negative for parvovirus B19 viral DNA by dot blot hybridization. Cytomegalovirus – DNA was demonstrated in 7/60 aborted tissues (11.67 %) and one placenta of the controls (3.33 %), that represent non significant changes (P > 0.05). In contrast, only 5 aborting women (8.33 %) and a woman of the control group (3.33%) were CMV-IgM seropositive, that also represent non significant changes (P > 0.05). Antithyroglobulin antibody levels were significantly higher in aborting women (7/60) than control (P < 0.05), whereas there was no significant changes in antithyroid peroxidase antibody levels between the two groups. Nine aborting women (15%) were seropositive for one or both of the thyroid autoantibodies compared with two (6.67%) of the control group, that represent non significant changes (P>0.05). We did not find any significant relation between thyroid autoimmunity and viral infections (B19V & CMV) in women with unexplained recurrent first trimester miscarriage. CONCLUSION: Parvovirus B19 infection was found to be an important pathogenic agent in recurrent first trimester abortion. It is essential to investigate for B19Vinfection among pregnant women with recurrent abortion. This significant finding demonstrates the usefulness of a sensitive molecular tool, PCR assay of viral DNA to aid in the diagnosis. However, testing for cytomegalovirus infection and antithyroid antibodies are not essential as routine prenatal investigations and should be restricted to certain patients with unexplained recurrent pregnancy loss.