The association of antithyroid antibodies in euthyroid nonpregnant women with recurrent first trimester abortions in the next pregnancy.

OBJECTIVE: To evaluate the prognostic value of antithyroid antibodies in euthyroid women with a history of recurrent first trimester abortions on future pregnancy loss. DESIGN: The sera of 42 euthyroid women with a history of three or more consecutive first trimester abortions were evaluated for the presence of antibodies to thyroglobulin and thyroid peroxidase before pregnancy and again as soon as the diagnosis of pregnancy was made. SETTING: Medical school-affiliated private infertility center. PATIENTS: Forty-two women with a history of three or more consecutive first trimester abortions who were planning to conceive again. MAIN OUTCOME MEASURE: The presence of antithyroid antibodies in the nonpregnant state and their association with pregnancy loss in the next gestation. RESULTS: Thirteen of 42 women (31%) were positive for the presence of antithyroid antibodies at the initial screening before pregnancy. All 13 maintained positivity by the time their next pregnancy was diagnosed. Only 12 of those 42 women (29%) experienced a first trimester abortion. Eight of these 12 women (67%) were positive for one or more antithyroid antibody. In contrast, among 30 nonaborting women, only 5 of 30 (17%) exhibited thyroid antibody positivity. The detection of thyroid antibodies before conception carried an increased risk of pregnancy loss in the next pregnancy (8 of 13, 62% versus 4 of 29, 14%). CONCLUSION: The presence of antithyroid antibodies in nonpregnant women with a history of recurrent abortion identifies a subgroup of women at significantly increased risk for yet another pregnancy loss in their next gestation. Because organ-specific autoantibodies thus demonstrate similar prognostic significance to nonorgan-specific autoantibodies, it is tempting to conclude that peripheral autoantibody abnormalities seen in habitual aborters only reflect an underlying T-lymphocyte defect, which may be the actual cause of pregnancy loss.

Clinical significance of beta 2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: correlation with conventional antiphospholipid antibody detection systems.

OBJECTIVE: Our purpose was to determine whether beta 2-glycoprotein I-dependent anticardiolipin antibodies may represent a superior marker of reproductive risk than do conventional antiphospholipid antibodies. STUDY DESIGN: The incidence of beta 2-glycoprotein I-dependent and beta 2-glycoprotein I-independent anticardiolipin antibodies and of six conventional antiphospholipid antibodies was statistically compared between study groups with and without autoantibody-associated features of reproductive failure. Sera from 356 women were randomly selected from the frozen sera bank at the Center for Human Reproduction, Chicago. They included sera from 259 patients with autoantibody-associated features of reproductive failure such as unexplained infertility, endometriosis, and repeated pregnancy loss and 97 infertile controls. Autoantibody levels by a modified enzyme-linked immunosorbent assay for beta 2-glycoprotein I-dependent and beta 2-glycoprotein I-independent anticardiolipin antibodies and a standard enzyme-linked immunosorbent assay for anticardiolipin antibody and five other antiphospholipid antibodies were then compared. RESULTS: Patients demonstrated a significantly higher incidence of beta 2-glycoprotein I-dependent anticardiolipin antibodies (5.4%) than did controls (0%) in a modified enzyme-linked immunosorbent assay (p = 0.01). No such difference was, however, noted for beta 2-glycoprotein I-independent anticardiolipin antibodies or any one of six antiphospholipid antibodies. Two or more among six antiphospholipid antibodies, especially if involving anticardiolipin antibodies, antiphosphatidylserine and antiphosphatidylinositol, as assayed by standard enzyme-linked immunosorbent assay, were significantly more often (p = 0.02) positive in the patients (5.0%) than in the controls (0%). Moreover, positivity in two of those three antiphospholipid antibodies correlated in 59% of cases to positivity in the beta 2-glycoprotein I-dependent anticardiolipin antibody. CONCLUSIONS: As a single test beta 2-glycoprotein I-dependent anticardiolipin antibody appears to be superior to cofactor-independent anticardiolipin antibody or any other single conventional antiphospholipid antibody for the detection of autoantibody-associated conditions of reproductive failure. A broadly based panel of conventional antiphospholipid antibodies, especially if inclusive of anticardiolipid antibody, antiphosphatidylserine, and antiphosphatidylinositol, may, however, achieve similar results.

Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.

OBJECTIVES: The purpose of our study was to evaluate the incidence of antithyroid antibodies and non-organ-specific antibodies in women who have had three or more recurrent spontaneous abortions. STUDY DESIGN: Sera from 45 women for the presence of antithyroid antibodies to thyroglobulin and thyroid peroxide and for the non-organ-specific autoantibodies to 6 phospholipids, 5 histones, and 4 polynucleotides were analyzed. Sera from 100 apparently health blood donors served as controls. RESULTS: The test results of 14 (31%) of 45 study subjects were positive for one or both antithyroid antibodies compared with 19 (19%) of controls. Five (11%) of 45 patients had positive test results for one or more non-organ-specific antibodies, and 4 (8%) of 45 had positive test results for the lupus anticoagulant by either activated partial thromboplastin, tissue thromboplastin time, or both. Only 3 (21%) of 14 subjects whose test results were positive for thyroid antibodies also demonstrated non-organ-specific autoantibodies. COMMENTS: The incidence of antithyroid antibodies in women who have had recurrent abortions appears not to be significantly increased compared with a normal random control population. Antithyroid antibodies do occur, however, with significantly greater frequencies in women with recurrent spontaneous abortions than non-organ-specific autoantibodies (p = 0.02). Organ-specific and non-organ-specific autoantibodies may serve as independent markers of risk for repeated pregnancy loss in patient populations where pregnancy loss is associated with abnormal autoimmune function.

Autoantibody profiles and immunoglobulin levels as predictors of in vitro fertilization success.

OBJECTIVE: Our aim was to determine the predictive value of autoantibody and immunoglobulin determinations as indicators of the success of in vitro fertilization. STUDY DESIGN: This was a blinded study in which laboratory evaluations were performed on coded samples obtained from another institution. Codes were broken and data were analyzed after results of all laboratory tests had been reported out. One hundred five infertility patients who had undergone in vitro fertilization were randomly chosen. Among those, 46 were considered low responders (six or fewer oocytes were retrieved) and 59 as high responders (13 to 30 oocytes were retrieved). Total immunoglobulin G, M, and A levels and 15 autoantibody levels (6 antiphospholipids, 5 antihistones, and 4 antipolynucleotides) were determined separately for immunoglobulin G, immunoglobulin M, and immunoglobulin A isotypes. RESULTS: High and low responders demonstrated an unusual incidence of autoantibody (25% and 30%, respectively) and immunoglobulin (46% and 48%, respectively) abnormalities. They did not differ from each other, however, in either immunoglobulin or autoantibody parameters. Autoantibody and immunoglobulin abnormalities alone or in combination did not predict pregnancy success (24% vs 16%), incidence of chemical pregnancies (15% vs 24%), or clinical pregnancy loss (9% vs 11%) when such women were compared with those without either abnormality. However, the occurrence of hypergammaglobulinemias, in contrast to hypogammaglobulinemias, was associated with a significant decrease in the clinical pregnancy rate (6% vs 24%, p = 0.05). CONCLUSIONS: Neither autoantibody abnormalities nor total immunoglobulin abnormalities allow differentiation between high and low responders in in vitro fertilization cycles. The presence of autoantibody and total immunoglobulin abnormalities also does not predict low clinical pregnancy rates. Within a group of women with immunoglobulin abnormalities, those with hypergammaglobulinemias appear, however, at significant risk for low pregnancy rates with in vitro fertilization. This observation suggests that high total immunoglobulin levels may serve as a marker for an as yet to be determined immunologic factor that adversely affects the chance of conception. The evaluation of total immunoglobulin levels may be indicated as part of a routine infertility workup.