Antibodies to Chlamydia trachomatis in sera of women with recurrent spontaneous abortions.

OBJECTIVE: The relationship between high-titer immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions was evaluated. STUDY DESIGN: Sera from the female partners of 258 couples with unexplained infertility, no history of chlamydial infection, and negative cervical cultures were diluted 1:128 and tested for immunoglobulin G antibodies to Chlamydia trachomatis. A subset of patients was also tested for antibodies to cytomegalovirus, cardiolipin, nuclear antigens, lactoferrin, and spermatozoa. RESULTS: Seven (41%) of 17 women with three abortions and 6 (60%) of 10 women with four abortions had chlamydial antibodies as opposed to 20 (13.5%) of 148 with no abortions, 6 (12.8%) of 47 with one abortion, and 4 (12.1%) of 33 with two abortions (p < 0.01). The incidence of > or = 3 spontaneous abortions was 31.8% among women with high-titer chlamydial antibodies and 7.5% among women who had seronegative results (p < 0.001). There was no relation between any of the other antibodies and > or = 3 abortions or antibodies to Chlamydia trachomatis. CONCLUSION: High-titer immunoglobulin G antibody to Chlamydia trachomatis was associated with recurrent spontaneous abortions. The mechanism may involve reactivation of a latent chlamydial infection, endometrial damage from a past chlamydial infection, or an immune response to an epitope shared by a chlamydial and a fetal antigen.     

A review on infection with Chlamydia trachomatis

Chlamydial infection affects young, sexually active patients. Multiple partners and not using condoms have been recognized as high risk factors. The diagnosis of PID is clinical and requires a high degree of suspicion and a low threshold for diagnosis. Patients with PID should have negative screening for sexually transmitted infections. Sexual partners of such patients still need to be treated for chlamydial infection. Nucleic acid amplification tests (NAAT) have the advantage of high performance and use of non-invasive specimens for diagnosis of chlamydial infection. Single-dose therapy with azithromycin 1 g stat is the treatment of choice for chlamydial infection.

• Diagnosis of chlamydial infection is best made by using nucleic acid amplification tests.

• Single-dose therapy improves drug adherence and success of chlamydial treatment.

• It is important to test and treat the partners of patients with chlamydial infection as soon as possible.

• A low threshold for diagnosis and treatment of pelvic inflammatory disease is recommended.

Thrombophilia and antithrombotic therapy in women with recurrent spontaneous abortions

OBJECTIVE: To investigate the association between thrombophilia and recurrent spontaneous abortions (RSAs) and to evaluate the efficacy of anticoagulant treatment. STUDY DESIGN: All couples with a history of RSAs were studied by immunologic tests and determination of coagulation factors. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy were used in 29 selected cases with acquired and inherited thrombophilia. The control group included 23 women with a history of RSAs and tests positive for thrombophilia who declined to receive medication during pregnancy. RESULTS: All couples with a history of RSAs were studied by immunologic tests and determination of coagulation factors. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy were used in 29 selected cases with acquired and inherited thrombophilia. The control group included 23 women with a history of RSAs and tests positive for thrombophilia who declined to receive medication during pregnancy. CONCLUSION: All couples with RSAs require screening for thrombophilia. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy appear to have a favorable effect on pregnancy outcome in selected women with RSAs and acquired or inherited thrombophilia.     

Combined thrombophilic factors among women with late recurrent spontaneous abortions

The aim of this study was to assess the role of combined thrombophilic factors carrier status for development of late recurrent pregnancy loss (RPL). The polymorphism 4G/5G (PL 4G/5G) - genotype 4G/4G in plasminogen activator inhibitor type 1 (PAI-1), Factor V Leiden (FVL) and prothrombin (FII) gene mutation 20210 G>A in 52 women with recurrent pregnancy loss between 10 and 20 weeks of gestation and in 125 healthy women with at least one uncomplicated full-term pregnancy was investigated. Combined carrier status for thrombophilic factors was more pronounce among women with RPL (7.7%) compared to control subjects (3.2%), (OR=2.52, 95% CI (0.5- 12.62), p-ns). The most common association was between FVL and PL 4G/5G (5.8% compared to 0.8% in patients and controls, OR=7.59, 95% CI (0.68 - 191.04), p-ns). Because of relatively small size of the study, the difference in carrier status between women with RPL and control subjects did not rich statistical significance. A weak association between double carrier status for inherited thrombophilic factors and RPL was established. The strong determination in larger studies of the relation between combined inherited thrombophilic status and RPL development could better specify anticoagulant prophylaxis in further pregnancy     

Mechanism of recurrent spontaneous abortions in women with mosaicism of X-chromosome aneuploidies

OBJECTIVE: To investigate the mechanism of recurrent miscarriages in women with mosaicism of X-chromosome aneuploidies. DESIGN: Prospective case-control study. SETTING: University-based reproductive clinic housed in a medical center with genetic laboratories. PATIENT(S): Eighteen women who experienced recurrent miscarriages and had mosaicism of X-chromosome aneuploidies; two control groups, one with a balanced structural autosomal rearrangement and the other without chromosomal abnormalities. INTERVENTION(S): Criteria were established for the diagnosis of low-grade X-chromosome mosaicism by using peripheral blood lymphocytes. Patients were evaluated for the pathogenesis of recurrent miscarriages. Their abortion rate was assessed, and each abortus was karyotyped. MAIN OUTCOME MEASURE(S): Abortion rate and karyotype of the abortus. RESULT(S): In comparison with patients with X-chromosome mosaicism with a balanced structural autosomal rearrangement, patients with X-chromosome mosaicism without a balanced autosomal structural rearrangement had a significantly higher incidence of diminished ovarian reserve (DOR) and had a somewhat higher prevalence of uterine anomalies. In comparison with controls without chromosomal abnormalities, the patients with a balanced autosomal structural rearrangement also had higher incidence of both conditions, but the differences were not statistically significant. At least two factors are implicated in recurrent miscarriages in women with X-chromosome mosaicism. Among them, DOR is the most prevalent (occurring in 44.4% of cases), followed by uterine anomalies (16.7% of cases). Cases with DOR had a higher abortion rate than did those without (68.6% vs. 44.1%). Cases with DOR also had a slightly higher rate of abnormal karyotypes in the abortus than did those without (73.7% vs. 42.9%). CONCLUSION(S): The oocytes of women with X-chromosome mosaicism are in a suboptimal state of development and are prone to embryonic lethality.     

Adenosine deaminase activity and its isoenzyme pattern in women with recurrent spontaneous abortions

Normal pregnancy is characterized by suppressed cell-mediated immunity. Adenosine deaminase (ADA) is a purine metabolic enzyme enriched in trophoblast cells of the placenta. It is an early marker of trophoblast cell differentiation. Also, the activation of ADA gene expression in the placenta is crucial and essential for proper fetal development. The activity of ADA shows changes in diseases characterized by the alteration of cell-mediated immunity. The purpose of this study was to assess the possible role of the alteration of cell-mediated immunity in women with recurrent spontaneous abortions (RSA) as a cause of changes in tADA activity, and also to evaluate the extent of the contribution of ADA1 and ADA2 to changes of tADA activity in serum and peripheral blood lymphocytes (PBLs). We measured in serum and in PBLs activities of tADA, ADA1 and ADA2 of 25 married women with RSA (group A) and of 28 healthy non-pregnant women (group B). According to our results in women with RSA, mean serum tADA, ADA1 and ADA2 activities were significantly higher than those of non-pregnant women (p < 0.001, p < 0.05 and p < 0.05 respectively). In women with RSA, mean PBLs tADA, ADA1 and ADA2 activities were significantly higher than those of non-pregnant women (p < 0.001, p < 0.05 and p < 0.05 respectively). The findings of this study show a marked increase of serum and PBLs ADA activities, which is derived from an increase of ADA2 and ADA1 activity in women with RSA. These changes reflect cell-mediated immunological changes.     

Survey of 1120 Japanese women with a history of recurrent spontaneous abortions.

Our recent 7-year clinical survey showed that among the 1120 women with repeated spontaneous abortions registered in this clinic, 2898 out of a total of 3216 pregnancies (90.1%) had terminated in spontaneous abortion. Among these wastages, 84.2% occurred before 12 weeks of gestation, and 11.1 percent occurred between 12 and 15 weeks. Through routine examination of reproductive wastage, 82 (9.9%) of the 825 Japanese couples examined were shown to have either a chromosomal abnormality or normal variants in the wife and/or husband, thus demonstrating no racial difference in the incidence of chromosomal abnormalities in infertile patients in comparison with studies performed in other countries. One hundred and forty-seven congenital uterine anomalies (14.7%) were found in 1000 hysterosalpingographies, and 12 of 148 examined females were positive for anti-cardiolipin antibody. 393 other females with no major abnormalities likely to induce spontaneous abortions were indicated for immunotherapy. Ample time spent on genetic counseling prevented further reproductive wastage, and ideal metroplasty resulted in a successful post-operative pregnancy course in more than 85% of cases. Immunosuppressant and anticoagulant therapy decreased the serum titer of anti-cardiolipin antibody, enabling pregnancies to be maintained to term. Immunotherapy utilizing the husband's lymphocytes also brought more than 80% of pregnancies to successful completion, with 200 deliveries achieved with this therapy. In contrast, 64.1% of pregnancies again terminated spontaneously in patients who were indicated for immunotherapy but did not receive treatment. The findings of the present study suggest that the causes of reproductive wastage, especially the etiology of early recurrent spontaneous abortion, are complex.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Hormonal treatment of recurrent spontaneous abortions

A retrospective study with 79 pregnant women was conducted. All of them were diagnosed as spontaneous abortion. The patients were separated in two group and the women have been treated in two schemes--51%--Utrogestan and 49%--Utrogestan and Profasi. The medication was applied only into the first trimester of the pregnancy. The duration of the therapy was 15.0 +/- 12.34 days. The mean gestational age in this study was 7.6 +/- 3.0 gestational weeks. Women with a first pregnancy and spontaneous abortion were excluded from the study. The number of this hormonal treated pregnancy was 2.84 +/- 1.13. 10.2% of the followed women had 3 and more than 3 miscarriages. The followed group of women was historically and clinically heterogenic. For that reason we think that many other factors could play a role in the optimum outcome of this pregnancy. The criteria for positive result we accepted the vital embryo/fetus on the time of dehospitalization. From these pregnancy only 3 terminated with miscarriage--3.79%. The rest of 96.2% went at home with intact pregnancy. The authors try to find a theoretical support for use of micronized progesterone Utrogestan--there could be some changes in the cellular and humoral immunity at repeated abortions, related to the change of the cytokine production. It could be find an ability to realize a readjustment of the endocrine system of the mother and to control the immune reaction in the fetoplacental unit.     

Prospective study of anticardiolipin antibodies in immunized and untreated women with recurrent spontaneous abortions.

OBJECTIVE: To investigate whether active leukocyte immunization increases levels of anticardiolipin antibodies in women with recurrent spontaneous abortions. To assess the impact of anticardiolipin antibodies on pregnancy outcome in these women. DESIGN: Patients who had received various treatments in an ongoing randomized trial were studied prospectively. SETTING: A department of clinical immunology investigating women with recurrent spontaneous abortions from all over Denmark. PATIENTS: Eighty-nine patients with unexplained recurrent spontaneous abortions whose pregnancies had been completed during the course of the trial. INTERVENTIONS: After randomization, 44 patients were actively immunized with husband's or third party leukocytes, and 27 patients received placebo. Eighteen patients received anticoagulation therapy in pregnancy. MAIN OUTCOME MEASURES: Changes in levels of immunoglobulin (Ig)M class and IgG class anticardiolipin antibodies after active immunization. Frequency of new miscarriages in patients who were positive or negative for anticardiolipin antibodies. RESULTS: Neither IgM nor IgG anticardiolipin antibodies changed significantly after active immunization (P greater than 0.2). The interim results of the immunization trial showed a success rate of 68% in the treated group versus 56% in the placebo group (not significantly different). Relative risk of miscarriage in anticardiolipin antibody-positive patients compared with anticardiolipin antibody-negative patients was 1.3 (95% confidence interval 0.7 to 2.2; P = 0.4) in the combined study groups. CONCLUSIONS: Patients eligible for active immunization did not exhibit significant changes in anticardiolipin antibody levels subsequent to the treatment. The treatment did not seem to provide any overall benefit with respect to pregnancy outcome. Prospectively, the risk of miscarriage in patients positive for anticardiolipin antibodies was not significantly increased.     

Chromosome abnormalities in 118 couples with recurrent spontaneous abortions

Cytogenetic studies were carried out on 118 couples with recurrent spontaneous abortions. Four major chromosomal abnormalities were found including two 13/14 Robertsonian translocations, one t(7;12) and one t(1;10) reciprocal translocation. The incidence of chromosomal abnormalities in this study was 3.39%, which is lower than the mean value of the published data. The clinical significance of balanced translocations in recurrent reproductive loss is discussed.     

NLRP7 variants in spontaneous abortions with multilocus imprinting disturbances from women with recurrent pregnancy loss

Journal of Assisted Reproduction and Genetics - Comparative analysis of multilocus imprinting disturbances (MLIDs) in miscarriages from women with sporadic (SPL) and recurrent pregnancy loss (RPL)...     

A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy

OBJECTIVE: Our goal was to compare the efficacy of azithromycin with that of amoxicillin for the treatment of Chlamydia trachomatis infection during pregnancy. STUDY DESIGN: A randomized controlled trial of pregnant women with cervical C trachomatis infection receiving care at two inner-city, university-based prenatal clinics. Pregnant women were randomly assigned to receive either oral amoxicillin, 500 mg, three times daily for 7 days, or oral azithromycin, 1 g, in a single dose. Partners were referred for treatment. Tests of cure were scheduled 4 weeks after initiation of treatment. Statistical analysis was performed by using the Student t test and chi2 analysis. RESULTS: One hundred twenty-nine pregnant women were enrolled, and 110 (85%) completed the protocol. There was similar treatment efficacy between amoxicillin and azithromycin (58% vs 64%, respectively,P =.56). In the amoxicillin group 3 women (5.5%) were intolerant, compared with 6 (10.9%) in the azithromycin group (P =.31). CONCLUSION: Amoxicillin and azithromycin are equally efficacious in the treatment of cervical C trachomatis during pregnancy.     

Immunological analysis of women with repeated spontaneous abortions

The study deals with 9 women with recurrent abortions who do not possess the blocking factor which is present during normal pregnancy and which inhibits, nonspecifically, a cellular cytotoxicity reaction in vitro. Electrophoresis of the women's serum revealed an abnormal glycoprotein, migrating in the alpha-globulin zone, which gives a precipitate with an anti-gamma-globulin serum after mercaptoethanol treatment. These last two findings may indicate a possible abortion.     

Killer immunoglobulin-like receptor repertoire on uterine natural killer cell subsets in women with recurrent spontaneous abortions

Objective

The objective of this study is to investigate the distribution of inhibitory and activating killer immunoglobulin-like receptors (KIRs) on uterine natural killer (uNK) cells and the compatibility of KIR/HLA-C at the maternal–fetal interface in women with unexplained recurrent spontaneous abortion (RSA) in the Chinese population.

Study design

Sixteen patients with unexplained recurrent spontaneous abortion were enrolled in this study. The PCR sequence-specific primers (SSP) method was used to detect the inhibitory/activating KIRs in uterine NK cells and the HLA-C gene polymorphism expressed on the trophoblast.

Results

The frequencies of inhibitory KIR2DL2 in the RSA group were increased significantly compared with those of the controls. The other inhibitory KIR2DL families did not show significantly different frequencies in the RSA group. No difference in numbers of inhibitory KIR genes with statistical significance was observed between the RSA group and the controls. When analyzing activating KIRs, none of the KIR2DS1–5 family showed statistically different frequencies in the RSA group compared with the controls. Similarly, there was no statistically significant difference between the numbers of activating KIR genes in the RSA group and the controls. Finally, the matching of the inhibitory or activating KIRs/HLA combination at the maternal–fetal interface did not play a dominant role in the pathogenesis of pregnancy loss.

Conclusions

This study suggests that the imbalance of inhibitory and activating KIRs in uterine NKs might confer susceptibility to the occurrence of pregnancy loss. The maternal inhibitory/activating KIRs-HLA-C polymorphism expressed on trophoblast cells from decidual tissues seems to play a limited role in abortion.     

Progesterone profiles in luteal-phase defects associated with recurrent spontaneous abortions

Purpose: Histologically documented luteal-phase defects (LPD) have been detected in 20–40% of women with recurrent spontaneous abortions. In 28 patients with recurrent spontaneous abortions, luteal-phase serum progesterone (P) levels (days 19, 21, 23, 25) and endometrial biopsies were evaluated. Methods: On the basis of endometrial biopsy findings, the patients were separated into two groups: Group 1, recurrent spontaneous abortions with LPDs (n=18); and Group 2, recurrent spontaneous abortions with normal biopsies (n=7). The data are shown in the table below. Conclusions: This study demonstrated that the P values found in Group 1 were significantly lower than those in Group 2, almost throughout the luteal phase. The results also indicate a close relationship between the P profile in the luteal phase and endometrial biopsy.