Relationship between circulating antisperm antibodies in women and autoantibodies on the ejaculated sperm of their partners

The relationship between antibodies on the surface of ejaculated sperm and circulating antibodies in female partners was evaluated. Of 616 couples examined by the immunobead binding test, there was a 12.4% incidence of sperm-surface antibodies in men whose wives had antisperm antibodies in their sera, but only a 6.5% incidence in partners of women who lacked these antibodies (p less than 0.025). Sperm-bound immunoglobulin G and immunoglobulin A both occurred at a significantly higher frequency (p less than 0.05) in partners of women with serum antisperm antibodies. Increased incidence of both immunoglobulin G (p less than 0.01) and immunoglobulin M (p less than 0.005) circulating antisperm antibodies in females were observed when the male partners had antibody-bound sperm. Antibody-coated sperm may activate lymphocytes in the female partners after coitus, thus leading to the production of antisperm antibodies. This may be an additional mechanism that leads to female isoimmunity to sperm and infertility.     

Circulating antisperm antibodies in recurrently aborting women

One hundred seventy-three women with a history of three or more recurrent consecutive abortions were analyzed for circulating antisperm antibodies with a radiolabeled antiglobulin assay (RAA), a modified enzyme-linked immunosorbent assay (ELISA), a tray agglutination test (TAT), and a sperm immobilization test (SIT). No pregnancies were subsequently gestated to term in women who were antisperm antibody-positive unless they were inoculated with their husband's leukocytes as treatment for an immune basis (not related to antisperm antibodies) for their recurrent abortions. In women with an immune basis for their recurrent abortions, immunization with leukocytes from their male partners increased the ability of these women previously aborting their fetuses to carry their fetuses to term, even if they had positive results in the ELISA, TAT, and SIT; women with positive results in the RAA continued to abort subsequent pregnancies, despite leukocyte immunization. Immunization of antisperm antibody-positive women with their partner's leukocytes did not incite or increase the antisperm antibody titer, with any of the assay techniques.     

ELISA for antisperm antibodies in unexplained infertile women

It is commonly believed that autoimmune or isoimmune responses to human sperm antigens are associated with human infertility. We examined an enzyme linked immunosorbent assay (ELISA) kit used in the detection of antisperm antibodies in the sera of women with unexplained infertility. 1) For the ELISA assay, an absorbance at 405nm greater than 0.300 was considered positive. Of the 83 sera of infertile women studied, 20(24.1%) were positive. This value was significantly higher than that of the control group: 10% of pregnant women, 11.1% of unmarried women and 10% of healthy men (p less than 0.05). 2) The results obtained with ELISA were compared with those of the sperm immobilization test. Comparison of the results of ELISA with those of the sperm immobilization test indicated that these methods detect a different, though often overlapping, spectrum of antibody activity. 3) The results obtained with ELISA did not always correlate with those of the Huhner test. However the ELISA method may be useful in the clinical screening of antisperm antibodies because of its simplicity and rapidity.     

Clinical characteristics of subfertile men with antisperm antibodies

This study investigated the clinical features which could serve as markers to identify subfertile men with antisperm antibodies including age, duration of infertility, history of abdominal or perineal surgery and previous genital trauma. Of the 162 men studied, 43 had a positive test for antisperm antibodies. A significantly greater number of these patients had a history of genital trauma and appendicectomy. Whereas the aetiological role of genital trauma in spermatozoal autoimmunity is readily explicable, that of appendicectomy is not. It can only be postulated that inflammation of the appendix may sometimes affect the vas deferens or that there is some inadvertent injury to the vas deferens during appendicectomy.     

Clinical characteristics of subfertile men with antisperm antibodies

Summary. This study investigated the clinical features which could serve as markers to identify subfertile men with antisperm antibodies including age, duration of infertility, history of abdominal or perineal surgery and previous genital trauma. Of the 162 men studied, 43 had a positive test for antisperm antibodies. A significantly greater number of these patients had a history of genital trauma and appendicectomy. Whereas the aetiological role of genital trauma in spcrmatozoal autoimmunity is readily explicable, that of appendicectomy is not. It can only be postulated that inflammation of the appendix may sometimes affect the vas deferens or that there is some inadvertent injury to the vas deferens during appendicectomy.     

Antiphospholipid antibodies and recurrent abortion

We examined the association between anticardiolipin antibodies, lupus anticoagulant, and the risk of recurrent spontaneous abortion in a case-control study conducted in a network of general and teaching hospitals in northern Italy. Subjects consisted of 220 women with two or more unexplained consecutive spontaneous abortions and 193 controls admitted for acute conditions other than immunologic, infective, gynecologic, or cardiovascular. Lupus anticoagulant was detected in 16 of 220 cases (7%, 95% confidence interval 4-11%) but in none of the 193 controls (Fisher exact test, P less than .001). Increased anticardiolipin antibody levels were demonstrated in 19 of 99 cases (19%, 95% confidence interval 12-31%) (seven immunoglobulin (Ig) G, eight IgM, and four IgG and IgM) and in four (all IgG) of 157 controls (3%) for whom data were available. These results offer quantitative evidence on the association between antiphospholipid antibodies and recurrent abortion.     

Antizona and antisperm antibodies in women with endometriosis and/or infertility

OBJECTIVE: To measure the levels of antigamete antibodies in serum and peritoneal fluid of women with endometriosis and/or infertility. DESIGN: Antibody activity against human sperm and porcine oocytes was analyzed in selected subgroups of women. SETTING: Clinic of reproduction. PATIENT(S): Women with endometriosis and/or infertility. INTERVENTION(S): No treatment was implemented before peritoneal fluid and blood sample collection. MAIN OUTCOME MEASURE(S): Quantitative ELISA. RESULT(S): Four groups of women (n = 98) were analyzed for the presence of antizona and antisperm antibodies: infertile with endometriosis (n = 30), idiopathic infertility (n = 28), fertile with endometriosis (n = 20), and healthy fertile controls (n = 20). Antibodies were analyzed simultaneously in serum and peritoneal fluid. No statistically significant differences in antibody levels were detected in serum samples among the analyzed groups. The median values for antizona and antisperm antibodies in peritoneal fluid were significantly higher in women with idiopathic infertility than in the control group. In women with unexplained infertility, a high degree of correlation (Spearman) was found between the presence of antizona antibodies in peritoneal fluid and serum (r = 0.579). A positive predictive value of 80% was calculated for the presence of antizona antibodies (>5 ng/oocyte) in the peritoneal fluid of patients with infertility. CONCLUSION(S): Antizona antibodies locally produced in the peritoneal fluid have diagnostic value for infertility status; however, they cannot be treated as a marker or prognostic factor for minimal endometriosis and/or its treatment.     

甲状腺自身抗体与复发性流产关系的初步探讨

目的 研究抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体与复发性流产（RSA）之间的关系。方法 2004-08—2005—10选取山东省立医院妇产科门诊100例有复发性流产史非妊娠妇女为研究组，其中原发性RSA62例（原发性RSA组），继发性RSA38例（继发性RSA组），100例有正常妊娠史非孕健康妇女为对照组，化学发光免疫法测两组血清中的抗甲状腺抗体。结果 研究组血清中抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体的阳性率分别为：24％和28％，明显高于对照组的4％和6％（P〈0、05）。原发性与继发性RSA患者血清中抗体阳性率差异无显著性（P〉0、05）。结论 在复发性流产患者中，甲状腺自身抗体的阳性率增高，需进一步研究治疗后对妊娠结局的影响。     

Hysteroscopic findings in 344 women with recurrent spontaneous abortion

STUDY OBJECTIVE: To evaluate the prevalence of different anatomic factors in women with recurrent spontaneous abortion (RSA). DESIGN: Retrospective analysis over 9 years (Canadian Task Force classification II-2). SETTING: University hospital-affiliated endoscopic unit. PATIENTS: Three hundred forty-four consecutive patients with RSA and 922 controls referred for abnormal uterine bleeding. INTERVENTION: Diagnostic hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Major and minor uterine mullerian abnormalities (septate, unicornuate uteri) were found significantly more often in women with RSA than in controls (32% vs 6%, p <0.001). The frequency of acquired uterine anomalies (submucous myomas, polyps) was significantly higher in controls (32% vs 9%, p <0.001). No significant differences were observed between groups in frequency of adhesions (4% vs 2%). CONCLUSION: Major mullerian uterine abnormalities are associated with RSA, and minor uterine anomalies may be correlated with an increased risk of recurrent miscarriage.     

A prospective study on the lack of development of antisperm antibodies in women undergoing intrauterine insemination

To test the hypothesis that intrauterine insemination with washed spermatozoa induces antisperm antibody formation, we measured serum antisperm antibody levels by the Immunobead technique in a population of women receiving exogenous gonadotropins. Antibody levels were measured before therapy (baseline) and then serially during subsequent stimulation cycles, for a maximum of six cycles. Twenty-eight patients underwent intrauterine insemination; each patient served as her own control. An additional 25 patients were treated with exogenous gonadotropins but did not undergo intrauterine insemination; they served as external controls. Antisperm antibody levels in women who underwent concomitant intrauterine insemination were compared with levels in those who did not. Of the 53 enrolled patients, 18 completed six treatment cycles, and 35 achieved pregnancy before six cycles. Forty-five patients (85%) had less than 10% Immunobead binding, six (11%) had binding between 10% and 25% (mean 16%, range 14% to 20%), and two had binding greater than 25% (28% and 42%, respectively). Mean binding was similar (less than 10%) in the intrauterine insemination and external control groups. Eighteen patients conceived in the intrauterine insemination group and seventeen in the control group. Of patients who conceived, all but one had less than 10% Immunobead binding at the time of conception (mean 1.6 months). In patients who did not conceive, there was no difference in Immunobead binding between control and intrauterine insemination groups after 6 months of therapy. Our data do not support the hypothesis that serum antisperm antibody levels, as detected by Immunobead binding, will increase in menotropin-stimulated women undergoing intrauterine insemination over a prolonged treatment period.     

Association between recurrent spontaneous abortions and circulating IgG antibodies to sperm tails in women

The isotype and regional specificity of antisperm antibodies in the circulation of women with recurrent spontaneous abortions was examined. There was a statistically significant association (P less than 0.005) between the presence of IgG tail-directed antisperm antibodies and a history of unexplained recurrent spontaneous abortion. These antibodies were detected in 36.4% of 44 women with recurrent abortions and 14.6% of 616 female partners of infertile marriages. In contrast, no differences in IgG sperm head-directed antibodies or in IgA and IgM antisperm antibodies were observed between the two groups. Husbands of women in the miscarriage or infertile groups had similar semen evaluations. Antisperm antibodies may be a marker for defective immunosuppression in women with recurrent miscarriages. Alternatively, exposure of sperm-sensitized pregnant women to sperm may activate the maternal immune system to respond to paternal antigens present on the embryo.     

Intrauterine insemination as a treatment of infertility in women with antisperm antibodies.

Twenty-four women with infertility caused by antisperm antibodies were treated by homologous intrauterine insemination. Initially, all the women had timed intrauterine insemination by washed spermatozoa for three cycles. The pregnancy rate per couple was 4.20%. The remaining 23 patients received a combined treatment of chlomiphene citrate and intrauterine insemination for three cycles, which did not increase the pregnancy rate per couple and per cycle (4.3% and 1.4% respectively). Thereafter, the remaining 22 patients received a combined treatment of hMG and intrauterine insemination for another three cycles which resulted in a pregnancy rate per cycle (6.1%) and per couple (18.20%) that was significantly greater (P less than 0.01). We conclude that infertile women with antisperm antibodies can benefit after a trial of induction of multiple follicular development with hMG in combination with intrauterine insemination.     

Evaluation of circulating antisperm antibodies and seminal immunosuppressive material in repeatedly aborting couples

Circulating antisperm antibodies (ASA) and immunosuppressive material in seminal plasma (SPIM) were determined by solid-phase enzyme staining method and anticomplement test respectively in 686 patients with abortion, including 285 couples. 241 fertile couples served as control. It revealed that the positive rate of ASA in repeatedly aborting patients was significantly higher than that in fertile controls (P less than 0.001). ASA was also more frequently detected in repeatedly aborting patients than in those having 1-2 abortion. Male partners whose wives aborted 2-6 times had significantly less SPIM than the controls with sperm count and sperm motility also markedly decreased. Meanwhile, the incidence of pyosemia was remarkably higher than that in the controls. It is suggested that ASA and SPIM play an important role in the development of recurrent abortions.     

Anticardiolipin antibodies and complement in ninety-nine women with habitual abortion

Immunologic investigations were performed on sera from 99 women with habitual abortion (three or more consecutive miscarriages). All were considered healthy and clinical investigations had not revealed any cause for the miscarriages. Sixty-eight were considered to have primary habitual abortion whereas 31 had secondary habitual abortion. Increased anticardiolipin antibody levels were found in 42 patients. None had a primary diagnosis of systemic lupus erythematosus, but at follow-up studies one of them fulfilled the diagnostic criteria of systemic lupus erythematosus. Ten sera, all from patients with primary habitual abortion, showed high anticardiolipin antibody values (greater than or equal to 10 units) concomitant with significantly lower levels of complement factor C4 than those found in sera with moderate or normal anticardiolipin antibody levels. There was no indication of genetic defects explaining the low C4 values, which could be explained at least in part by an activation of complement by the classical pathway.     

Hysteroscopic metroplasty improves gestational outcome in women with recurrent spontaneous abortion

STUDY OBJECTIVE: To compare the reproductive outcome in women with recurrent spontaneous abortion (RSA) associated with septate uterus after hysteroscopic metroplasty compared with patients who did not undergo surgery. DESIGN: Longitudinal evaluation (Canadian Task Force classification II-2). SETTING: University of Rome, Tor Vergata-affiliated endoscopic unit. PATIENTS: Forty-eight consecutive women with septate uterus and RSA were enrolled in the study. INTERVENTIONS: Hysteroscopic metroplasty. MEASUREMENTS AND MAIN RESULTS: Reproductive outcome in terms of term pregnancy was significantly improved after hysteroscopic metroplasty compared with controls (76% vs. 20%). No differences were found in the prevalence of preterm delivery between groups (4% vs. 5%). CONCLUSION: Our data suggest that hysteroscopic septum incision can improve pregnancy outcome in patients with RSA associated with septate uterus.     

Extremely skewed X-chromosome inactivation patterns in women with recurrent spontaneous abortion

BACKGROUND: The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of recurrent spontaneous abortion (RSA) but the results obtained were conflicting. AIMS: We therefore investigated the XCI patterns in peripheral blood DNA obtained from 80 patients who had RSA and 160 age-matched controls. METHODS: Pregnancy history, age, karyotype, and disease information was collected from all subjects. The methylation status of a highly polymorphic cytosine-adenine-guanine repeat in the androgen-receptor (AR) gene was determined by use of methylation-sensitive restriction enzyme HpaII and polymerase chain reaction. RESULTS: Skewed XCI (> 85% skewing) was observed in 13 of the 62 patients informative for the AR polymorphism (20.9%), and eight of the 124 informative controls (6.4%) (P = 0.0069; chi2 test). More importantly, extremely skewed XCI, defined as > 90% inactivation of one allele, was present in 11 (17.7%) patients, and in only two controls (P = 0.0002; chi2 test). CONCLUSIONS: These results support the interpretation that disturbances in XCI mosaicism may be involved in the pathogenesis of RSA.