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Purpose of Review: The process of implantation involves the interaction of the human blastocyst and the uterine epithelium. Several autoimmune factors have been implicated to have an influence on implantation failure., Recent Findings: Recent studies have investigated the role of autoimmune factors in implantation in women undergoing in-vitro fertilization. Antiphospholipid antibodies are identified more frequently in women undergoing in-vitro fertilization, but their presence does not appear to influence the outcome of pregnancy, miscarriage, or live birth rates. Antithyroid antibodies are commonly found in women of reproductive age, but implantation rates and miscarriage rates are not altered when women have normal thyroid function. Antinuclear antibodies may be a marker for underlying autoimmune disease when coupled with certain signs and symptoms, but low-titer antibodies do not influence in-vitro fertilization outcome. Antisperm antibodies are more often associated with fertilization failure when found in high titers in seminal plasma, in sperm, or in the mucosal immune system of women. Antisperm antibodies are uncommon but most often associated with ovarian hypofunction., Summary: Implantation is characterized by the interaction of two immunologically and genetically distinct tissues. During implantation, local and systemic immune factors, cytokines, and growth factors may interact with adhesion molecules and other matrix-associated proteins, glycoproteins, and peptides.

The purpose of this study was to determine the association of antibodies to thyroglobulin and thyroid peroxidase and pregnancy outcome in women undergoing assisted reproductive techniques. The study included three centres and retrospectively evaluated patient sera for antithyroid antibodies, then related the results to pregnancy outcome. Enzyme-linked immunosorbant assays for thyroglobulin and thyroid peroxidase antibodies were performed using two different commercially available kits. Controls included 200 healthy women of reproductive age. Women (n = 873) who were undergoing assisted reproductive techniques for pelvic adhesions, endometriosis, ovarian dysfunction, or unexplained/other were included. All women utilized a standard regimen of gonadotrophin releasing hormone agonist down-regulation followed by ovulation induction. Embryos were cultured for 3 days, at which time embryo transfer occurred. Statistical analysis utilized the two-tailed Fisher's exact test. Antithyroid antibodies were positive in 143 of 873 (16.4%) women undergoing assisted reproductive techniques while 29 of 200 (14.5%) normal controls were positive (not significant). Deliveries were achieved in 396 of 730 (54.2%) of women who had no thyroid antibodies versus 78 of 143 (54.5%) of women who had thyroid antibodies (not significant). No difference in biochemical pregnancies (not significant) or clinical pregnancy losses (not significant) were detected. Antithyroid antibodies were found no more frequently in women undergoing assisted reproductive techniques than in normal controls. There were no differences in pregnancy outcome based on antithyroid antibody positivity in women undergoing assisted reproductive techniques. These data do not support the testing or treatment for antithyroid antibodies of women undergoing assisted reproductive techniques.

Objective: To assess the prevalence of antibodies to thyroglobulin and thyroid peroxidase (or microsomal) in women with recurrent pregnancy loss and women undergoing assisted reproductive techniques (ART) compared with healthy controls., Design: Retrospective, two-centered study., Setting: University-affiliated private patient centers., Patient(s): Included were 700 women with a history of two or more consecutive pregnancy losses, 688 women with a history of infertility who were undergoing ART, and 200 healthy, reproductive-aged female controls., Intervention(s): Blood was collected before ART cycles, frozen, and assayed., Main Outcome Measure(s): Standardized ELISAs were used to measure antithyroid antibodies and TSH levels. Statistical analysis was performed with use of the two-tailed Fisher's exact test., Result(s): Antithyroid antibodies were identified in 29 of 200 (14.5%) of controls and 158 of 700 (22.5%) of women with recurrent pregnancy loss and 132 of 688 (19.2%) of women undergoing ART. Less than 20% of the women with antithyroid antibodies were clinically hypothyroid., Conclusion(s): Antithyroid antibodies are identified more frequently in women with recurrent pregnancy loss than in controls but not in women undergoing ART. These autoantibodies may be markers of autoimmune activation and have been associated with an increased risk of pregnancy loss and postpartum thyroid disease.

Problem: Research studies in animal and human systems have demonstrated conclusively that antisperm antibodies can interfere with fertilization. In the male, autoantibodies to sperm can be detected both in the sera and seminal plasma., Method of Study: Ninety-seven men who were tested for antisperm antibodies as a part of an infertility evaluation were identified. Complete medical history was obtained, including information related to events suspected of being associated with antisperm antibodies. History of surgery (varicocele repair, hernia repair, and vas reversal) and infection (epididymitis, sexually transmitted disease, and orchitis) were compared with semen parameters (motility less than 60%, concentration less than 20 x 10(6), and volume less than 2 cc). These were compared to antisperm antibody results of mixed agglutination reaction (MAR) and direct immunobead binding test (IBT) for immunoglobulin G (IgG). Statistical analysis was performed using Fishers exact two-tailed test., Results: As expected, prior vas reversal was significantly associated with the presence of antisperm antibodies (P = 0.0002) by MAR or IBT with a fivefold increased relative risk (95% confidence interval, 1.97-12.38). Other surgeries manipulating the cord structures independent of vas reversal were not associated with antisperm antibodies (P = 0.09). Prior infections, independent of vas reversal, were significantly associated with antisperm antibodies by MAR (P = 0.04) with a 3.8-fold increased relative risk (95% confidence interval, 1.06-13.87) but not by IBT. Sperm concentration less than 20 x 10(6), motility less than 60%, and a volume less than 2 cc were not associated with antisperm antibodies by MAR or IBT., Conclusion: These findings suggest that manipulation of the cord structures excluding the vas were not associated with antisperm antibodies; however, vas reversal and prior infection are significant risk factors for the development of antisperm antibodies.

Several laboratories currently offer panels of serum autoantibody assays to screen women with unexplained infertility and those undergoing in vitro fertilization (IVF). Offering these tests implies that they have predictive value for the outcome of proposed infertility treatments such that the results of the testing would alter clinical management. Because screening for antiphospholipid antibodies adds expense to already costly procedures, it is an appropriate time to review the justification for the use of these panels.

Problem: (1) To determine the IgA subclass distribution of antibodies in the serum and on the sperm of infertile male patients. (2) To determine the effect of an IgA1 protease on the binding of IgA antisperm antibodies (ASA)., Method: Fifteen infertile males with ASA in serum (10) or on sperm (5) were recruited for this study. Duration of infertility was at least one year. Monoclonal antibodies to human IgA1 and IgA2 were conjugated to immunobeads. The distribution of IgA1 and IgA2 subclass ASA was determined for positive serum and sperm samples. The effects of an IgA1 protease (isolated from Neisseria meningitidis strain HF13) on sperm-bound antibodies was evaluated by immunobead binding., Results: In serum, the IgA1 subclass ASA was predominate (91%) when compared with IgA2 (9%) subclass. Direct sperm-bound antibodies displayed a distribution more characteristic of the secretory immune system with IgA1 accounting for 63% and IgA2 accounting for 37% of the total IgA ASA. Enzyme treatment dramatically reduced the amount of serum IgA antibodies bound to sperm (P < 0.05). Similarly, a significant reduction in direct sperm-bound antibodies was observed after enzymatic treatment with no loss in sperm motility., Conclusions: (1) Although IgA1 direct sperm-bound antibodies were dominant, when compared with serum there was a higher proportion of IgA2 subclass, which suggests a local production of IgA. (2) Specific IgA1 protease treatment is capable of reducing the amount of immunobead-detectable IgA on sperm. Hamster oocyte sperm-penetration assays are ongoing to determine if this treatment might improve sperm penetration rates.

Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain immunoglobulins with antitumor activity. Autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions react with cell-surface antigens on different human ovarian cell lines, surgical specimens of human ovarian adenocarcinoma, and human ovarian tumors grown in athymic Balb/c mice. The antibodies do not react with tissue preparations from normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that these antibodies are capable of complement-mediated lysis of human ovarian tumor cell lines in vitro. Preliminary characterization of the autologous ovarian tumor-associated antigen(s) indicates that it may be composed of three large-molecular-weight proteins of 182,000, 164,000, and 122,000 d.

Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain large amounts of soluble immunoglobulins without detectable antibody activity against human ovarian tumor cell lines by indirect immunofluorescence. Membrane fragments were prepared from 56 human ovarian effusions, and the presence of membrane-bound IgG, IgA, and IgM was demonstrated. The predominant membrane-bound immunoglobulin class was IgG, which ranged from 18 to 4275 ng/ml on samples tested, whereas IgA was present in the range of 5 to 52 ng/ml. The autologous membrane-bound antibodies strongly recognized cell-surface antigens on four human ovarian cell lines and four surgical specimens of human ovarian adenocarcinoma but did not react with normal human ovaries, non-ovarian normal and neoplastic tissues, or non-ovarian human cell lines by indirect immunofluorescence assay. These studies indicate that patients with ovarian cancer have the capability of recognizing and forming antibodies against autologous ovarian tumor-associated antigens.