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[The value of hysteroscopy in the diagnosis of infertility and habitual abortion].

Ninety cases of infertility and habitual abortion were analyzed by hysteroscopy from April 1983 to July 1990 in our hospital. Abnormal changes of the uterine cavity were seen in 75.6%. The result of hysterosalpingography was found to correspond to that of hysteroscopy in 62.5%, and the result of B-ultrasound corresponded to that of hysteroscopy in 52.5%. The diagnosis of adhesion and polyps of the uterine cavity was made accurately by hysteroscopy, and both could be operated under hysteroscopy. After operative removal of the adhesion, an IUD should be put into the uterine cavity for 3 months.

Abortion, Habitual↗

Antibodies to oxidized low-density lipoprotein and to cardiolipin in nonpregnant and pregnant women with habitual abortion.

OBJECTIVE: To determine the occurrence of antibodies to oxidized low-density lipoprotein (LDL) in women with a history of habitual abortion before and during pregnancy. DESIGN: Immunoglobulin G class antibodies to malondialdehyde modified LDL were determined by a solid-phase ELISA in 42 habitual aborters before pregnancy, in 39 patients during pregnancy, and in 23 comparable nonpregnant and 22 pregnant control women without a history of abortion. In addition, we assessed the presence of anticardiolipin antibodies by ELISA in the same sera. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Early pregnancy was accompanied by a decrease in the median levels of antibodies to oxidized LDL both in habitual aborters and in the control series. Only one patient exhibited a raised level of antibodies to oxidized LDL before pregnancy but, during pregnancy, nine patients (23%) had elevated levels of antibodies to oxidized LDL, similar to women with a favorable outcome of pregnancy (6/27, 22%) and in women whose current pregnancy also ended in abortion (3/12, 25%). Cardiolipin binding antibodies were detected in three habitual aborters before pregnancy (7%) and in nine women during pregnancy (23%), with a tendency to be more frequent in patients with miscarrying pregnancies than in those with continuing pregnancies (4/12, 33% and 5/27, 19%). Antibodies to oxidized LDL and cardiolipin were simultaneously present in three habitual aborters with continuing pregnancies. CONCLUSIONS: Increased levels of antibodies to oxidized LDL and cardiolipin may be associated with habitual abortion.

Abortion, Habitual↗

[Immunological disorders of coagulation in habitual abortion. Prospective study].

The physiopathological role of antithromboplastin-type circulating anticoagulants in habitual abortion may be envisaged since the presence of antithromboplastin has been reported in most studies on women at high risk of abortion. To avoid a possible statistical bias, we conducted a prospective study in a sufficiently large group of women with habitual abortion (n = 99) compared with a control group of women with normal fecundity (n = 50). In addition, all women were investigated for lupus symptoms. The circulating antibody was detected by the diluted thromboplastin time and activated cephalin time methods. The results were considered positive when the patient/control diluted thromboplastin time ratio was 1.2 and/or when the increase in activated cephalin time was not corrected by a control plasma. In the patients' group, 10 women (10%) had an anti-thromboplastin type circulating anticoagulant, whereas no circulating anticoagulant could be detected in the control group. Three women with circulating anticoagulant had signs of systemic lupus erythematosus. None of the patients presented with Soulier-Boffa syndrome. These data have established a significant correlation between habitual abortion and circulating anticoagulant whilst avoiding statistical bias. Our results suggest that women with idiopathic habitual abortion should be subjected to systematic immunological exploration and that a small number of them should be followed attentively.

Abortion, Habitual↗

Anti-PP1Pk (anti-Tja) and habitual abortion.

Blood group incompatibility as a cause of early or habitual abortion has been a matter of much debate. However, the abortion rate in such cases is much higher than that found in the general population. Two sisters having the rare genotype pp and anti-PP1Pk (anti-Tja) in their serum were reported as having habitual abortions; a third sister, with a normal P group, had a normal obstetric history. The relationship of anti-PP1Pk (anti-Tja) to the high rate of habitual abortion was discussed and added support was given to the existing evidence that certain maternal blood group antibodies can affect embryos early in uterine life.

Abortion, Habitual↗

Opinions on treatment of women with habitual abortion based on investigations for blocking antibody and autoantibodies.

Three hundred and thirty-seven women with habitual abortion of unknown etiology were studied for cellular reactivity and blocking antibody in one-way mixed lymphocyte culture. Their sera were investigated for anti-cardiolipin antibodies, antinuclear antibodies, and antibodies against DNA, and the activated partial thromboplastin time (APTT) and complement levels of their plasma were determined. Increased anti-cardiolipin antibody levels were demonstrated in 77 (22%) of the 337 women, all of whom were considered healthy and had no signs of autoimmune disease. Most patients with high anti-cardiolipin antibody levels displayed lowered values of complement factor C4. According to our experiences, the mere occurrence of anti-cardiolipin antibody in women with habitual abortion is no absolute cause for treatment with prednisolone, not even in cases with greatly elevated anti-cardiolipin values. Therapy with prednisolone and acethylsalicylic acid (ASA) during pregnancy should be given to those women who have high levels of anti-cardiolipin antibodies concomitant with high APTT values, low values of complement C4, and strong blocking antibody. Anti-cardiolipin antibody has been investigated during pregnancy in 136 normal pregnant women, 11 of whom (8%) were positive at any sampling occasion, but only one of whom (1%) had high levels. Evidently the development of anti-cardiolipin antibody is no normal feature of pregnancy among Swedish women and thus the high frequency found among healthy Swedish women with habitual abortion remains unexplained. We have introduced an immunization program of leukocyte transfusions in habitual abortion. The development of previously absent blocking antibody seems to be a valuable prognostic sign of possible success for immunization therapy against habitual abortion.

Abortion, Habitual↗

Selection of patients with habitual abortion for paternal leucocyte immunization.

After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

Abortion, Habitual↗

Antibodies to beta 2-glycoprotein I and prothrombin in habitual abortion.

OBJECTIVE: To determine the occurrence of antibodies to beta 2-glycoprotein I (beta 2-GP-I) and prothrombin in women with histories of habitual abortions when pregnant and nonpregnant. DESIGN: Antibodies to beta 2-GP-I and prothrombin were measured by ELISA using irradiated polystyrene plates in 43 women with habitual abortions and 22 healthy controls. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki. PATIENT(S): Twenty-two women of the habitual abortion patients had never delivered (primary aborters) and 21 had delivered at least one living child before miscarriage (secondary aborters). INTERVENTION(S): Venous blood samples were collected before and during pregnancy. MAIN OUTCOME MEASURE(S): Immunoglobulin G class antibodies to beta 2-GP-I and prothrombin. RESULT(S): The secondary aborters showed higher levels of antibodies to prothrombin than the primary aborters when both pregnant and nonpregnant and also showed higher levels of antiprothrombin antibodies than the controls when pregnant. No such differences were found in levels of antibodies to beta 2-GP-I. The habitual abortion patients showed a tendency toward higher levels of these autoantibodies when pregnant than when nonpregnant. Gestational diabetes was more common among the antibody-positive habitual abortion patients than among the antibody-negative patients. CONCLUSION(S): Increased levels of antiprothrombin antibodies were associated with secondary abortions. Elevated levels of antibodies to beta 2-GP-I and prothrombin often were found in habitual abortion patients with gestational diabetes.

Abortion, Habitual↗

[Study on human leucocyte antigen-DQ region gene polymorphism in cases of habitual abortion with anticardiolipin antibody].

OBJECTIVE: To investigate the relationship between human leucocyte antigen(HLA)-DQ region gene polymorphism and habitual abortion with anticardiolipin antibody(ACL). METHODS: Polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) was used to type HLA-DQA1 and HLA-DQB1 alleles in 30 cases of habitual abortion with anticardiolipin antibody and 90 women with normal pregnancy history. RESULTS: The frequency of DQB1 * 0303 was found to be significantly higher in ACL(+) habitual abortion group (33.3%) than those in normal control group (P < 0.05). Whereas, there was no significant difference found not only in frequency of other DQB1 alleles, but also in frequency of DQA1 alleles and DQA1-DQB1 haplotypes between two groups. CONCLUSION: The results show an association between ACL(+) habitual abortion and HLA-DQB1 * 0303, which suggest DQB1 * 0303 may be susceptible gene to ACL(+) habitual abortion.

Abortion, Habitual↗

The outcome of in vitro fertilization in unexplained habitual aborters concurrent with secondary infertility.

OBJECTIVE: To compare the IVF-ET reproductive performance of unexplained habitual aborters with nonaborting women with similar characteristics also treated with IVF-ET. DESIGN: Controlled clinical study. SETTING: In Vitro Fertilization Unit, Assaf Harofeh Medical Center, Zerifin, Israel. PATIENT(S): Twenty patients with habitual abortions and secondary infertility were subjected to 42 IVF-ET cycles. Their reproductive performance in IVF-ET was compared with the performance of the next followed nonaborting patients, pulled from a database, based on similar age and IVF indications. INTERVENTION(S): Ovulation induction with IM Depo-triptorelin 3.75 mg and menotropins. Oocyte retrieval, embryo transfer, and luteal supplementation with hCG. MAIN OUTCOME MEASURE(S): Mean number of oocytes and fertilizations, mean number of embryos and their morphology. Pregnancy rates (PRs) and pregnancy outcome. RESULT(S): The mean number of oocytes, fertilizations, and embryos was higher in the aborters compared with the controls. Morphology of the transferred embryos was similar in both groups though in general better quality embryos developed in the aborters group. Pregnancy rates were similar in both groups (32% and 29% per cycle). Pregnancy outcome of the habitual aborting patients in IVF-ET remained unsuccessful, as before treatment: 50% abortions (7/14) compared with only an 8% abortion rate (1/12) in the controls. CONCLUSION(S): Habitual aborters' performance at early stages of IVF-ET is better compared with their controls. Despite similar PRs in IVF-ET cycles, their pregnancy outcome after IVF-ET is unsuccessful, as before IVF-ET.

Abortion, Habitual↗

[The study on human leucocyte antigen DQ region genes polymorphism in unexplained habitual abortion patients].

OBJECTIVE: To investigate whether human leucocyte antigen DQ (HLA-DQ) genes polymorphism are related to the susceptibility to unexplained habitual abortion. METHODS: HLA-DQA1 and HLA-DQB1 gene typings are performed by polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP) technique in 32 cases of unexplained habitual abortion and 54 women with normal pregnancy history. RESULTS: In unexplained habitual abortion group, the frequency of DQB1 * 0604, 0605 allele is increased significantly compared with that of controls(12.5% and 2.8%, P < 0.05) and the frequency of DQB1 * 0501, 0502 allele is decreased significantly (3.1% and 11.1%, P < 0.05). The frequency of DQA1 alleles do not differ significantly between two groups. Furthermore, the frequency of DQA1 * 01/DQB1 * 0604,0605 haplotype in patients is significantly increased than that of controls (12.5% and 2.8%, P < 0.05). CONCLUSION: The results suggest that DQB1 * 0604,0605 allele and DQA1 * 01/DQB1 * 0604,0605 haplotype may be a susceptible gene and haplotype of unexplained habitual abortion, while DQB1 * 0501,0502 allele may be a protective factor for habitual abortion.

Abortion, Habitual↗

[Investigation of viral pathogens contributing to habitual abortion].

OBJECTIVE: To investigate the association of Coxsackie B virus (CBV) with habitual abortion. METHODS: CBV IgM antibody, viral RNA and virions were detected in 86 women with habitual abortion and 40 with induced abortion by means of enzyme-linked immunosorbent assay (ELISA), RT-PCR and virus isolation, respectively. RESULTS: The positivity rate of CBV IgM were 87.2% and 35% in the two groups, respectively, and the detection rate of the viral RNA was 53.5% and 17.5% in blood lymphocytes, and 59.3% and 17.5% in the placentas. The virions were found in the placentas in 41.9% and 6.9% of the women, respectively. The positivity rates of CBV IgM, viral DNA and virions showed significant difference between the two groups (P<0. 01). CONCLUSION: CBV might be one of the causes responsible for habitual abortion.

Abortion, Habitual↗

Serodiagnosis of Toxoplasma gondii in habitually aborting women and other adults from North Jordan.

The prevalence of anti-Toxoplasma gondii antibodies in serum samples of 55 habitually aborting women, 46 women with normal pregnancies, 92 outpatient adults, and 150 University students from North Jordan was studied using the enzyme linked immunosorbent assay (ELISA). Sera from the habitually aborting group were also tested by the indirect immunofluorescent (IIF) test. No significant difference was found between the overall prevalence rates in University students, outpatient adults and women with normal pregnancies (25.3%, 22.8% and 26.1% respectively). The prevalence in habitually aborting women exceeded two times that in women with normal pregnancies or in outpatient females (58.2%, 26.1% and 25.0% respectively), and was approximately three times that in female University students (18.3%). The greatest difference in the prevalence rate between habitually aborting women and those with normal pregnancies or outpatient females was found in groups having the highest antibody level (greater than or equal to 100% of standard positive controls). A positive correlation between the results of the ELISA and those of the IIF test occurred at titres of greater than or equal to 1:40 of the latter test in habitually aborting women.

Abortion, Habitual↗

Antineutrophil cytoplasmic antibodies and other immunologic abnormalities in patients with habitual abortion.

PROBLEM: The immunologic mechanisms of pregnancy loss in habitual aborters with antiphospholipid and antinuclear antibodies have not been fully clarified. The possible association of antineutrophil cytoplasmic antibodies (ANCAs) with recurrent miscarriage was examined. METHOD OF STUDY: In a prospective, controlled trial of 59 women with recurrent abortion, the prevalence of pANCA (antimyeloperoxidase), cANCA (antiproteinase-3), and immunoserologic abnormalities of systemic lupus erythematosus (SLE) anti double-stranded DNA, anti-SSA, anti-SSB, anti-U1RNP, anti-Sm, anticardiolipin and antinuclear antibodies, LE-cell, lupus anticoagulant, and complement-3 were investigated. RESULTS: pANCA occurred in 2, and cANCA in 6 of 59 case patients, but neither was observed in the controls (P = 0.09 for cANCA). cANCA levels were significantly higher in patients than in controls (P = 0.028). Six recurrent aborters were identified as having a group of immunoserologic abnormalities characteristic of SLE. CONCLUSIONS: Immunologic mechanisms detectable in SLE may operate in a subgroup of habitual aborters with suspected immunologic cause. ANCAs occur more frequently in patients with recurrent miscarriage than in controls.

Abortion, Habitual↗

Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion.

A diagnostic screening program was applied to 195 couples with a prior history of habitual abortion (i.e., three or more consecutive abortions). Abnormalities were identified in 110 (56%) of the couples. Such identification was significantly more frequent in couples with primary habitual abortion than in couples with secondary habitual abortion (p less than 0.001) and also more frequent in couples with second-trimester abortions than in those with first-trimester abortions (p approximately equal to 0.01). The abnormalities most commonly observed were anomalies of the uterine body (15%), endometrial infections (15%), and cervical incompetence (13%). Hormonal dysfunctions were detected in 5%, and there were chromosomal aberrations in 3% of the couples. The women in the group showing abnormalities were offered surgical or medical treatment, and 80% of those who subsequently conceived carried their pregnancies to term. Among the couples with no abnormal findings, women receiving specific antenatal counseling and psychological support had a pregnancy success rate of 86%, as compared to a success rate of 33% observed in women who were given no specific antenatal care (p less than 0.001).

Abortion, Habitual↗

Thromboxane dominance and prostacyclin deficiency in habitual abortion.

To evaluate the significance of vasoactive prostanoids in habitual abortion, we measured urinary excretion of prostacyclin metabolites (6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and of thromboxane A2 metabolites (TxB2 and 2,3-dinor-TxB2) during 25 pregnancies in 22 women with recurrent spontaneous abortion (RSA). The control group were 16 pregnant women with no history of abortion. Ultrasound examination at first follow-up appointment showed a living fetus in 23 pregnancies of women with RSA. 9 of these pregnancies ended in abortion; 14 continued to term as did all the pregnancies in the control group. Compared with controls, women with RSA had a lower (p less than 0.05) ratio of prostacyclin to thromboxane between weeks 4 and 7 of gestation and a lower (p less than 0.01) output of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11. Women whose pregnancies ended in abortion had higher (p less than 0.05) output of 2,3-dinor-TxB2 between weeks 4 and 7 of gestation and lower (p less than 0.01) excretion of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11 compared with women whose pregnancies proceeded to term. We conclude that deficiency of vasodilatory prostacyclin may be a factor in habitual abortion.

6-Ketoprostaglandin F1 alpha↗

[Causes, diagnosis and therapy of habitual abortions].

Recent knowledge concerning the etiology of habitual abortions is reviewed by the author. The anatomic, genetic, endocrine and immunologic causes furthermore the assumed role of maternal diseases and infections are summarised. Besides diagnostic procedures and therapeutic possibilities are discussed.

Abortion, Habitual↗