Treatment outcome in women suffering from recurrent miscarriages and antiphospholipid syndrome

OBJECTIVE: To evaluate the outcomes of treatment in patients suffering from recurrent spontaneous abortion and antiphospholipid syndrome. MATERIALS AND METHODS: 148 observed women suffering from recurrent abortion with presence of lupus anticoagulant antibodies (LA) and/or high moderate concentration of anticardiolipin antibodies (ACA) have been divided randomly into followed three treated groups: I--56 patients treated by low-dose of acetylsalicylic acid (LDA, 75 mg daily); II--39 patients treated by low molecular weight heparin (applied in dose of 20 g daily); III--53 patients treated by LDA and low molecular weight heparin simultaneously. RESULTS: It has been affirmed that coincidental application of low-dose of acetylsalicylic acid and low molecular weight heparin statistically more often increase the percentage of successful pregnancy in comparison with application of low molecular weight heparin or acetylsalicylic acid alone. In the group where only low-dose of acetylsalicylic acid was applied the success of pregnancy equaled 89.3%, in the group where only low molecular weight heparin was applied the successful pregnancy equaled 81.1% and in the group with acetylsalicylic acid and low molecular weight heparin being applied together the successful pregnancy equaled 92.5%. In has simultaneously been affirmed that the percentage of pregnancy loss is statistically higher in the women suffering from isolated occurrence of lupus anticoagulant antibodies (21.2%) in comparison with the women suffering from occurrence of anticardiolipin antibodies (6.7%) and anticardiolipin antibodies with lupus anticoagulant antibodies simultaneously. CONCLUSION: 1. Simultaneous application of low-doses of acetylsalicylic acid and low molecular weight heparin seems to be the best solution in patients suffering from recurrent spontaneous abortion and antiphospholipid syndrome. 2. The occurrence of anticardiolipin antibodies in the serum of blood in patients suffering from antiphospholipid syndrome is a better foretelling factor for the future pregnancy outcome than the occurrence of lupus anticoagulant antibodies.     

Antiphospholipid antibodies in early repeated abortions: a case-controlled study

The relation among lupus anticoagulant (LAC), anticardiolipin antibodies (ACA), and repeated abortions was evaluated in a case-controlled study of 49 women with two or more unexplained spontaneous abortions (cases) compared with 141 control subjects, who had had one or more normal pregnancies and no previous spontaneous abortion. The women were admitted to the same hospital where the cases had been identified for acute conditions other than immunologic neoplastic, gynecologic or cardiovascular. LAC was detected in 7 out of 49 cases (14%, 95% confidence limits 8% to 26%) but in none of the 141 controls. Similarly, ACA were detected in four cases (8%, 95% confidence limits 0.3% to 30%) but no controls. These differences in frequency were statistically significant. These findings confirm that LAC and ACA are associated with a history of repeated abortions in clinically asymptomatic patients for immunologic conditions.     

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.     

Detection of interleukin-6 in human follicular fluid.

OBJECTIVE: To determine if interleukin-6 (IL-6) is a normal constituent of human follicular fluid (FF) after ovarian hyperstimulation and to assess whether IL-6 levels differ in conditions associated with immunological causes of infertility. DESIGN: After ovarian hyperstimulation for an in vitro fertilization (IVF) treatment cycle, FF samples were obtained at the time of oocyte retrieval. SETTING: Referral center at a tertiary care hospital. PATIENTS: Thirty women referred for IVF, including 10 patients with significant titers (greater than 40%) of antisperm antibodies and 10 with pelvic endometriosis. Ten patients with tubal infertility without antisperm antibodies or endometriosis served as controls. MAIN OUTCOME MEASURES: Analysis of FF levels for IL-6 using both bioassay and immunoassay. RESULTS: Bioactive (range 0.32 to 32.2 U/mL) and immunoreactive (range 0.34 to 13.6 ng/mL) IL-6 levels were detected in FF of all subjects after ovarian hyperstimulation. Follicular fluid IL-6 levels were substantially higher (3 to 30-fold) than that reported in serum. There was no difference in the mean concentrations of IL-6 levels between patients with antisperm antibodies, endometriosis, or tubal infertility. CONCLUSIONS: Bioactive and immunoreactive IL-6 are present in human FF after ovarian hyperstimulation, supporting a potential autocrine or paracrine role within the follicular microenvironment.     

Lupus anticoagulant and antibodies to beta 2-glycoprotein I, annexin V, and cardiolipin as a cause of recurrent spontaneous abortion

The prevalence of lupus anticoagulant (LAC), anticardiolipin (ACA), anti-beta(2) glycoprotein I (beta(2)GPI), and antiannexin V antibodies were determined in 200 recurrent spontaneous abortion (RSA) patients and 200 age-matched control women. ACA IgG was associated with early, while antiannexin V IgG and LAC were associated with late, and ACA IgG, antiannexin V IgG, and LAC were associated with combined early + late RSA, thereby recommending inclusion of their screening in RSA workout.     

Autoreactivity in women with endometriosis

Serum samples from 71 patients with laparoscopically staged endometriosis and from 109 age-matched non-pregnant control women were tested for antibodies to nuclear, phospholipid, smooth muscle and sperm antigens. Immunoglobulin G, M and A and complement components C3 and C4 were measured. Prevalence of the following autoantibodies was statistically significantly greater in women with endometriosis than in the control group: antinuclear antibodies, antibodies to ribonucleoproteins, smooth muscle antibodies, lupus anticoagulant and anticardiolipin antibody. Forty-one women with endometriosis (58%) had some type of autoantibody compared with 13 controls (12%). More women in the endometriosis group had IgG and IgM levels above the normal range. This was statistically significant for IgG in women with grade 3 and for IgM in those with grade 4 endometriosis, IgG levels were significantly higher in antibody-positive women with endometriosis than in the control group. Immunoglobulin and complement component levels tended to have a positive correlation with stage of disease.     

Failure to demonstrate significant antisperm antibodies in peritoneal fluid of patients with endometriosis

Endometriosis, even in mild cases, decreases monthly fecundity. Immunologic disorders have been suggested as the mechanism. In light of possible increases in serum autoimmune antibodies, increased peritoneal macrophages, and increased sperm phagocytosis associated with this disease, we postulated that peritoneal fluid antisperm antibodies would be increased and might be the cause of increased sperm phagocytosis and its associated infertility. Peritoneal fluid, from 18 patients with endometriosis and 10 infertile controls, was tested with the antisperm antibody immunobead test validated for peritoneal fluid. One of 18 patients with endometriosis and none of 10 controls had antisperm antibodies present. Therefore, increased sperm phagocytosis is unlikely a result of peritoneal antisperm antibodies in endometriosis patients.     

不孕症患者的自身免疫抗体分析

目的：探讨不孕症与患者自身免疫抗体的相关性。方法：采用酶联免疫吸附实验（ELISA）检测516例不孕症患者的血清抗精子抗体（ASAb）、抗卵巢抗体（AOAb）、抗子宫内膜抗体（EMAb）、抗绒毛膜促性腺激素抗体（hCGAb）及抗心磷脂抗体（ACAb）。选择125例正常妊娠妇女作为对照组．比较不孕症组与对照组5项抗体的阳性率。结果：不孕症组ASAb,AOAb,EMAb,hCGAb和ACAb的阳性率分别为26．7％,24．8％,25．2％,21．7％和21．3％。明显高于正常对照组4．8％,2．4％,1．6％,3．2％和1．6％（P均〈0．001）;5种抗体联合检测阳性率为38．2％,与分别单独检测这5项抗体的阳性率相比,差异均有统计学意义（P均〈0．05）。结论：ASAb,AOAb,EMAb,hCGAb和ACAb与不孕症有密切相关性,是引起不孕的重要原因。检测这5项抗体可作为不孕症病因诊断的一项指标。     

Autoreactivity in women with endometriosis

Summary. Serum samples from 71 patients with laparoscopically staged endometriosis and from 109 age-matched non-pregnant control women were tested for antibodies to nuclear, phospholipid, smooth muscle and sperm antigens. Immunoglobulin G, M and A and complement components C₃ and C₄ were measured. Prevalence of the following autoantibodies was statistically significantly greater in women with endometriosis than in the control group: antinuclear antibodies, antibodies to ribonucleoproteins, smooth muscle antibodies, lupus anticoagulant and anticardiolipin antibody. Forty-one women with endometriosis (58%) had some type of autoantibody compared with 13 controls (12%). More women in the endometriosis group had IgG and IgM levels above the normal range. This was statistically significant for IgG in women with grade 3 and for IgM in those with grade 4 endometriosis, IgG levels were significantly higher in antibody-positive women with endometriosis than in the control group. Immunoglobulin and complement component levels tended to have a positive correlation with stage of disease.     

Autoimmune antibodies and pregnancy outcome in women with false-positive syphilis test results. A retrospective controlled investigation of women from 5170 deliveries

Nine pregnant women with false-positive syphilis test results, and 13 matched controls, were screened for autoimmune antibodies to ascertain whether any relationship might exist between their presence and the occurrence of obstetric problems. Investigations included assays for anti-cardiolipin antibodies (ACA), lupus anticoagulant (LAC), anti-nuclear antibodies (ANA) (including antibodies against extractable nuclear antigen), anti-smooth muscle antibodies, anti-mitochondrial antibodies, anti-DNA antibodies, IgM-RF and complement factors. We found no significant difference in the incidence of obstetric problems between the two groups. Except that significantly more women were positive for ACA in the group with false-positive syphilis tests than in the control group, there were no differences between the groups with regard to the antibodies tested for. There was only one case of SLE, a patient positive for LAC, and who had had several miscarriages and no pregnancy resulting in a live birth. Our findings suggest that it would be unwarranted to devote resources to routine screening for these antibodies in healthy women with a false-positive syphilis test result, though the presence of LAC could possibly be used as an indicator of the risk of spontaneous abortion due to SLE.     

A retrospective study on IVF outcome in patients with anticardiolipin antibody: effects of methylprednisolone plus low-dose aspirin adjuvant treatment

Patients undergoing in vitro fertilization-embryo transfer have a high prevalence of anticardiolipin antibody (ACA). However, the relationship between ACA and IVF outcome is still controversial. The aim of the present study was to evaluate the potential effect of anticardiolipin antibody on IVF outcome and determine the role of adjuvant treatment in these ACA positive patients. The study included a total of 116 infertile women (116 IVF-ET cycles) positive for ACA, including 56 women pretreated with methylprednisolone plus low-dose aspirin before IVF (treated ACA+ group) and 60 patients without treatment (untreated ACA+ group). In addition, 518 infertile women (518 IVF-ET cycles) negative for ACA were enroled as controls (ACA- group). The results show that ACA+ patients who did not receive any adjuvant treatment showed a significantly lower fertilization rate, less high-quality embryos, as well as a markedly lower pregnancy rate and implantation rate than controls. Moreover, ACA+ patients who received methylprednisolone plus aspirin achieved significantly higher fertilization, pregnancy and implantation rates than untreated ACA+ patients (FR 69.0%, PR 46.4% and IR 25.4% vs. FR 60.0%, PR 33.3% and IR 17.9%, respectively). The overall IVF results in the treated ACA+ group were comparable to patients negative for ACA (PR 53.9% and IR 32.3%). Thus, while the presence of ACA exerts a detrimental effect on IVF outcome, ACA+ patients have a better outcome if given methylprednisolone for immunosuppression and low-dose aspirin as an anti-thrombotic agent.     

Immune abnormalities in endometriosis compromising fertility in IVF-ET patients.

OBJECTIVE: To evaluate the incidence of immune abnormalities in patients with endometriosis and primary or secondary infertility. STUDY DESIGN: This study analyzed the incidence of alloantibodies and autoantibodies in 100 women with endometriosis and 62 patients with unexplained infertility without endometriosis who enrolled in an assisted reproduction program at the Colombian Fertility and Sterility Center from January 1, 1996, to May 30, 1997. The alloimmune status of the women was determined by testing for the presence or absence of antileukocyte antibodies. The autoimmune studies included antinuclear antibodies, antiphospholipid antibodies and lupus anticoagulant antibody. RESULTS: Negative titers of IgG antipaternal antibodies were identified in 34% of patients with primary infertility and in 34% of women with secondary infertility and a history of pregnancy losses. Positive titers of antinuclear antibodies were found in 27% (27/100) of the group of patients with endometriosis; of them, 30% (15/50) had primary infertility and 24% (12/50), secondary infertility. The average titer was 1/80. Forty-eight percent of the infertile patients (48/100) showed titers of antiphospholipid antibodies for IgG and IgM; 46% of these patients had primary infertility (23/50) and 50% (25/50), secondary infertility. This was significantly higher than in controls (P < .05). Two patients were positive for lupus anticoagulant antibody. In the group of patients with unexplained infertility without endometriosis, the incidence of antinuclear antibodies was 17.7% and of antiphospholipid antibodies, 30.6%. CONCLUSION: For women with endometriosis, alloimmune and autoimmune evaluation is recommended prior to their undergoing assisted reproduction in order to provide appropriate therapy for each case.     

The relationship between antisperm antibodies prevalence and genital chlamydia trachomatis infection in women with unexplained infertility

Chlamydia trachomatis infection is one of the most common sexually transmitted diseases and sperm-associated antibody could impair fertility through various mechanisms. Both factors could be correlated to affect the fertility status of women. A retrospective case-control study was performed enrolling ninety (n = 90) patients with primary or secondary infertility as the case group, in addition to another eighty (n = 80) healthy women attending the family planning clinic to investigate the correlation between C. trachomatis past and current infections and antisperm antibodies (ASA) in women with unexplained infertility. The PCR prevalence of C. trachomatis didn't differ significantly among both groups (2.4 versus 1.6%, P = 0.66). In contrast, significantly higher prevalence of anti-C. trachomatis specific IgG (39% versus 19%, P = 0.87) antibodies were found among infertile women. ASA prevalence was significantly higher in infertile group (20 % versus 5%, P = 0.04). The final study results have failed to find a positive correlation between current or past C. trachomatis infection and the level of antisperm antibodies level in women suffering of un-explained infertility. Anti-sperm antibodies were significantly higher in infertile women, but without a significant difference between the incidences of ASA in infertile women with past or current C. trachomatis current infection.     

Relation between antisperm antibodies and the rate of fertilization of human oocytes in vitro

To clarify further the role of antisperm antibodies in in vitro fertilization, the occurrence of antisperm antibodies on ejaculated sperm and in sera was determined by the immunobead binding assay in 67 couples after an unsuccessful in vitro fertilization cycle. Antisperm antibodies in maternal sera were associated with a failure of oocyte fertilization (P <0.02) or with fertilization of only 9–19% of the oocytes (P <0.01) in vitro. Antisperm antibodies were detected in sera from 13 of 24 women (54.2%) where no fertilization occurred, 9 of 14 women (64.3%) where less than 20% of the oocytes fertilized, and 3 of 19 women (15.8%) where greater than 40% of the oocytes fertilized. Antisperm antibodies in these sera were mostly IgG and directed against the sperm tail. Antibodies on the surface of ejaculated motile sperm were also associated with a low (9–19%) fertilization rate (P <0.01). Sperm-bound antibodies were detected in 2 of 24 men (8.3%) where no fertilization occurred, 5 of 14 men (35.7%) where less than 20% of the oocytes fertilized, and 0 of 19 men where fertilization was greater than 40%. Sperm-bound antibodies were mainly IgA and were tail-directed. Antisperm antibodies in sera of males were not related to the rate of fertilization. Antisperm antibodies were detected in female partners of 21 of 46 couples (45.7%) with unexplained infertility, 2 of 12 women (16.7%) with blocked tubes, 4 of 7 women (57.1%) with endometriosis, and 0 of 2 women with adrenal hyperplasia. There was no relation between the fertilization rate and the maternal age, number of oocytes harvested, or semen quality. We conclude that antisperm antibodies are present in sera from a high percentage of women with unexplained infertility and that antibodies reacting with sperm tails may directly interfere with fertilization in vitro or may be a surrogate marker for another factor that interferes with this event.     

Polycystic ovary syndrome and ovarian autoimmunity--assessment of ovarian antibodies by EIA

There are conflicting reports of an association of ovarian antibodies, detected by immunofluorescence, with polycystic ovary syndrome (PCOS). The objective of this study was to evaluate the association of ovarian autoimmunity with PCOS. A validated immunoassay for ovarian antibodies was used to assess serum from women with PCOS and with menopause and normal cycling women as controls. The frequency of ovarian antibodies was similar (25%) among the controls and PCOS. Thus, unlike the association of ovarian antibodies detected with this test in patients with unexplained infertility and premature menopause, the prevalence of ovarian antibody in patients with PCOS is not significantly different to controls.     

Laparoscopy for the treatment of unexplained infertility

Aim:  To determine the best treatment for unexplained infertility.
Methods:  A retrospective study was used to examine Japanese women with unexplained infertility that had undergone laparoscopy. The main outcome measure of the study was the rate of pregnancy after laparoscopy.
Results:  One hundred and thirty-eight women diagnosed with unexplained infertility received laparoscopy and as a result 55 women had their diagnosis of unexplained infertility confirmed. There were no statistically significant differences between the women who became pregnant after laparoscopy in terms of duration of infertility, duration of treatment or age. The pregnancy rate of women with unexplained infertility was 56.4%, with 90% of these pregnancies achieved within the first 6 months. There were 64 women with minor endometriosis considered to be suffering from unexplained infertility before laparoscopy. The characteristics of the patients in the unexplained infertility group and in the minor endometriosis group were similar, but patients with minor endometriosis were found to have a lower pregnancy rate compared to those with unexplained infertility (35.9% vs 56.4%; P  = 0.02).
Conclusions:  The effective period after laparoscopy appears to be 6 months. Assisted reproductive technology should be considered after that time. Pregnancy rates were low in women with minor endometriosis compared with unexplained infertility. It is important to clarify the cause of infertility using laparoscopy. (Reprod Med Biol 2006; 5 : 59–64)     

Women who are not exposed to spermatozoa and infertile women have similar rates of stage I endometriosis.

OBJECTIVE: To compare the prevalence of endometriosis and its different stages in infertile women and women not exposed to spermatozoa. DESIGN: Prospective study. SETTING: Artificial insemination donor program at a university hospital. PATIENT(S): One hundred fifty women unable to conceive because they had not been exposed to spermatozoa (134 with azoospermic partner, 10 with an HIV-positive partner, and 6 without a male partner). Controls were 750 women in infertile couples in which the male partner had normal sperm. INTERVENTION(S): Laparoscopy was systematically performed in a blinded manner in both groups as part of the infertility work-up. MAIN OUTCOME MEASURE(S): Diagnosis of endometriosis. RESULT(S): In unexposed women and controls, the prevalence of endometriosis was similar (32% and 34.5%). Rates of stage I disease were also similar in both groups (26% and 19.3%). There was a significant trend toward higher stages of endometriosis in infertile women (stage II disease, 3.3% vs. 5.7%; stage III disease, 1.3% vs. 3.1%; stage IV disease, 1.3% vs. 6.4%). Endometriosis was not associated with the few demographic characteristics that differed between groups. CONCLUSION(S): From an epidemiologic point of view, stage I endometriosis is not more common in infertile women than in unselected women. However, stage II to IV endometriosis was more frequent in infertile women. Whereas a relation between stage I endometriosis and infertility seems unlikely, the relation between stages II to IV endometriosis and infertility seems possible.     

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.     

Antisperm antibodies in women: variability in antibody levels in serum, mucus, and peritoneal fluid.

OBJECTIVE: To look for patterns of antisperm antibody expression in women by exploring the levels of antisperm antibodies in different body fluids. This was achieved by studying sequential serum samples from individual patients and by comparing the levels of antisperm antibodies in serum from a number of patients with the levels of antisperm antibodies in cervical mucus or peritoneal fluid (PF). DESIGN: Prospective studies were performed on sequential serum samples within a menstrual cycle. Retrospective studies were done to compare antisperm antibodies in serum and mucus or PF. The immunobead assay was used to measure antisperm antibodies in these fluids. SETTING: Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. PATIENTS: A random sample of patients undergoing evaluation for infertility. RESULTS: The levels of antisperm antibodies in sera drawn from patients at different points in a menstrual cycle stimulated by the presence of exogenous hormones did not change during the follicular phase of the menstrual cycle. Also, in many samples, the antisperm antibody level in serum did not correlate with the antisperm antibody levels in mucus or PF. CONCLUSIONS: The data suggest that measurement of antisperm antibodies at a single point in time or from a single fluid is not sufficient when evaluating a woman for immunological infertility. The data also suggest that numerous and complex factors contribute to the expression of antisperm antibodies in women.