复发性流产与自身免疫性疾病

自身免疫性疾病（AID）是指机体产生高滴度自身抗体和（或）自身反应性淋巴细胞攻击相应的自身正常细胞和组织,导致组织器官损伤和功能障碍的综合征,是导致复发性流产（RSA）等妊娠并发症的重要原因。临床上常见的较易导致RSA的AID有：系统性红斑狼疮、抗磷脂综合征、干燥综合征、类风湿关节炎、系统性硬化症和未分化结缔组织病等。这些AID导致的RSA的治疗主要为小剂量免疫抑制剂联合抗凝治疗,且疗效肯定。     

复发性流产与自身免疫性疾病

自身免疫性疾病（AID）是指机体产生高滴度自身抗体和（或）自身反应性淋巴细胞攻击相应的自身正常细胞和组织,导致组织器官损伤和功能障碍的综合征,是导致复发性流产（RSA）等妊娠并发症的重要原因。临床上常见的较易导致RSA的AID有：系统性红斑狼疮、抗磷脂综合征、干燥综合征、类风湿关节炎、系统性硬化症和未分化结缔组织病等。这些AID导致的RSA的治疗主要为小剂量免疫抑制剂联合抗凝治疗,且疗效肯定。     

Histologic features of placentas and abortion specimens from women with antiphospholipid and antiphospholipid-like syndromes

OBJECTIVE: Antiphospholipid syndrome is characterized by recurrent pregnancy loss, thrombosis, and antiphospholipid antibodies. However, some women with clinical features of antiphospholipid syndrome test negative for antiphospholipid antibodies ("antiphospholipid-like syndrome"). Women with antiphospholipid and antiphospholipid-like syndromes have serum immunoglobulin G that harms murine pregnancy, suggesting that the mechanisms of fetal death may be similar in both groups. The objective of our study was to determine whether patients with antiphospholipid and antiphospholipid-like syndromes share pathophysiology by comparing the histology of gestational tissues from these groups. METHODS: Placenta and abortion specimens were obtained from 44 pregnancies in 26 women with antiphospholipid syndrome and 37 pregnancies in 21 women with antiphospholipid-like syndrome. Of these, 16 pregnancies with antiphospholipid syndrome and 8 with antiphospholipid-like syndrome were treated with a variety of medications intended to improve pregnancy outcome. Placentas from 31 elective pregnancy terminations and 40 pregnancies complicated by idiopathic preterm delivery served as an additional control group. Twenty histologic parameters were systematically assessed by a single investigator who was blinded to the clinical status of the specimens. Histopathologic findings were compared among groups using multivariate logistic regression analysis. RESULTS: Antiphospholipid syndrome pregnancies included 15 spontaneous abortions, 13 fetal deaths, and 16 live births. Pregnancies in the antiphospholipid-like syndrome group resulted in 5 spontaneous abortions, 30 fetal deaths, and one live birth. Gestational tissues from antiphospholipid and antiphospholipid-like syndrome pregnancies were similar for every histologic feature tested. Decidua from women with both antiphospholipid and antiphospholipid-like syndromes had more necrosis, acute and chronic inflammation, and vascular thrombus compared to controls. Placental tissue from antiphospholipid and antiphospholipid-like syndrome pregnancies showed more infarction, intravascular fibrin deposition, syncytial knot formation, and fibrosis than controls. Histologic features were variable within groups. There were no histologic differences in tissues from live births and pregnancy losses, or in treated and untreated pregnancies. CONCLUSIONS: Placental histopathology is similar in antiphospholipid and antiphospholipid-like syndrome pregnancies, suggesting that these disorders may share pathophysiology. Histologic findings in women with APS are non-specific and may not differentiate between women with APS and APS-like syndromes.     

Management of thrombosis in women with antiphospholipid syndrome

1) Antiphospholipid antibody syndrome may be associated with unusual sites of thrombosis. 2) Laboratory evaluation involves testing for antiphospholipid antibodies: lupus anticoagulant and anticardiolipin antibodies. 3) Acute management of thrombosis involves immediate anticoagulation. Low-molecular-weight heparins are as safe and effective as unfractionated heparin in this setting. Arterial events may require emergent thrombolytic therapy. Monitoring of the APTT with unfractionated heparin in the presence of a lupus anticoagulant is ineffective; these patients require monitoring of antifactor Xa levels or the use of LMWH, which does not require monitoring. 4) The pharmacokinetics of LMWH change in pregnancy, resulting in a shorter plasma half-life and larger volume of distribution. Monitoring of antifactor Xa levels is necessary. 5) Chronic anticoagulation is best achieved with warfarin, with significantly decreased rates of recurrent events when the INR is > or = 3.0. Long-term, if not life-long, anticoagulation is often necessary. Warfarin is teratogenic, and individuals desiring pregnancy will need to convert to therapeutic, not prophylactic, doses of either unfractionated heparin or LMWH. 6) As part of optimal management of thrombosis in APS, additional risk factors for thrombosis should be eliminated or reduced. These include comorbid illnesses such as hypertension and hyperlipidemia, as well as smoking. 7) Tamoxifen, raloxifene, oral contraceptives, and hormone replacement therapy are all associated with an increased risk of DVT in the general population. In APS patients receiving therapeutic anticoagulation, the addition of these drugs should not increase thrombosis risk. In APS patients not receiving anticoagulant therapy, these hormonal therapies may increase the thrombosis risk.     

Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death

OBJECTIVE: Studies in rheumatologic populations suggest that immunoglobulin A antiphospholipid antibodies are strongly associated with the clinical manifestations of antiphospholipid syndrome. However, the association between immunoglobulin A antiphospholipid antibodies and pregnancy loss is uncertain. We determined whether immunoglobulin A antiphospholipid antibodies, specifically anti-beta(2)-glycoprotein I and anticardiolipin, are associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 133 women who experienced unexplained recurrent spontaneous abortion, (2) 48 women who experienced unexplained fetal death, (3) 145 healthy fertile control subjects, and (4) 67 women with well-characterized antiphospholipid syndrome. Serum immunoglobulin A, immunoglobulin G, and immunoglobulin M anti-beta(2)-glycoprotein I and anticardiolipin antibodies were determined by enzyme-linked immunoassay. RESULTS: Groups of women who experienced unexplained recurrent spontaneous abortion and unexplained fetal death had a higher proportion of women who had positive test results for immunoglobulin A anti-beta(2)-glycoprotein I antibodies than fertile control subjects (P < .01, chi-square test); these subjects also had higher levels of autoantibody (P = .001, Kruskal-Wallis). Women who experienced recurrent spontaneous abortion had a higher proportion of women with positive test results for immunoglobulin A anticardiolipin antibodies compared to fertile control subjects (P < .05, chi-square test); this group also had higher levels of autoantibody (P = .0065, Kruskal-Wallis test). Linear regression analysis showed significant correlation between anti-beta(2)-glycoprotein I immunoglobulin A and anti-beta(2)-glycoprotein I immunoglobulin G (R = .609; P =.0001) and less correlation between anticardiolipin immunoglobulin A and anticardiolipin immunoglobulin G (R = .093; P = .065). CONCLUSION: Immunoglobulin A anti-beta(2)-glycoprotein I antibodies are more common in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death whose initial test results are negative for lupus anticoagulant and immunoglobulin G anticardiolipin antibodies compared to fertile control subjects. Therefore, these antibodies may identify additional women with clinical features of antiphospholipid syndrome who are not identified through traditional testing. It is unclear whether these antibodies are directly pathogenic, a result of the pregnancy losses, or markers for an underlying, yet uncharacterized autoimmune disorder.     

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.     

Anti-beta2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome.

OBJECTIVE: Studies in rheumatologic and hematologic populations suggest that anti-beta(2)-glycoprotein I antibodies are more specific for the clinical manifestations of antiphospholipid syndrome than anticardiolipin antibodies. However, the association between anti-beta(2)-glycoprotein I and pregnancy loss remains uncertain. We sought to determine whether anti-beta(2)-glycoprotein I is associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 152 healthy fertile control subjects, (2) 141 subjects with unexplained recurrent spontaneous abortions, (3) 58 subjects with unexplained fetal deaths, and (4) 73 subjects with well-characterized antiphospholipid syndrome. Serum anticardiolipin and anti-beta(2)-glycoprotein I levels were determined by enzyme-linked immunoassay. RESULTS: Patients with antiphospholipid syndrome had significantly higher levels of immunoglobulin G and immunoglobulin M anticardiolipin and anti-beta(2)-glycoprotein I than the other 3 groups (P <.0001). However, women in the recurrent spontaneous abortion, fetal death, and fertile control groups had similar levels of each antibody. Similarly, there were no differences in the proportion of women with positive test results for each autoantibody in these 3 groups. Linear regression analysis showed significant correlation between anticardiolipin immunoglobulin G and beta(2)-glycoprotein I immunoglobulin G (R (2) = 0.544786, P =.0001) and anticardiolipin immunoglobulin M and beta(2)-glycoprotein I immunoglobulin M (R (2) = 0.525048, P =.0001). CONCLUSION: Both anticardiolipin and anti-beta(2)-glycoprotein I are associated with antiphospholipid syndrome. However, testing for anti-beta(2)-glycoprotein I does not identify additional patients with either recurrent spontaneous abortions or unexplained fetal deaths who initially have negative test responses for anticardiolipin. This is likely because of the strong correlation between the 2 autoantibodies. Our data do not support routine testing for anti-beta(2)-glycoprotein I in addition to testing for antiphospholipid antibodies in women with recurrent pregnancy loss and unexplained fetal death.     

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.     

Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation

The antiphospholipid syndrome (APS) is a leading cause of miscarriage and maternal and fetal morbidity. APS is characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Conventional treatment for APS patients is sub-anticoagulant doses of heparin throughout pregnancy. Could heparin prevent pregnancy loss by inhibiting complement? In our experimental model of APS, heparin inhibits activation of complement on trophoblasts in vivo and in vitro, and anticoagulation in and of itself is not sufficient to prevent pregnancy complications. These studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and raise the importance of developing and testing targeted complement inhibitory therapy for patients with APS.     

抗磷脂综合征的围产期抗凝治疗

抗磷脂综合征(APS)是一组以弥漫性动静脉血栓形成、病理妊娠和持续性抗磷脂抗体阳性为特征的综合征。APS能增加复发性流产、早产、死产、子痫前期、胎儿生长受限等妊娠并发症的发生率。不利的妊娠结局和妊娠期血栓形成之间有关联。围产期APS的治疗主要是对症治疗、防止再次发生血栓和病理妊娠。低剂量阿司匹林和肝素能改善APS的妊娠结局。     

Contemporary issues for spontaneous abortion. Does recurrent abortion exist?

Most of the time, spontaneous abortion is a random event and represents the natural selection process. Although a recurrent factor may be present and may cause one or more abortions for a given couple, such instances are rare. Well-substantiated causes include parental chromosomal abnormalities (e.g., translocation), antiphospholipid syndrome, PCOD, and maternal age greater than 40 years. Müllerian duplication defects are most likely a cause of pregnancy loss for some women. A growing body of evidence refutes the role of corpus luteum defect as a common cause of recurrent abortion. Other causes are numerically infrequent in occurrence. It is likely that cigarette smoking and alcohol consumption contribute to pregnancy wastage. Although some therapies for the causes listed herein have been proven effective by randomized controlled trials, most have not. Given the excellent outcome demonstrated for most couples with unexplained recurrent abortion in the absence of treatment, it is difficult to recommend unproven therapies, especially if they are invasive and expensive. Instead of examining the environment in which pregnancy has occurred or been planned, clinicians have simply counted the number of spontaneous abortions among couples in an attempt to determine who should be evaluated. The former approach would seem most appropriate and proactive.     

Enoxaparin versus unfractionated heparin in the management of recurrent abortion secondary to antiphospholipid syndrome

Objective

To determine whether low molecular weight heparin (LMWH) plus low-dose aspirin (LDA) is comparable in efficacy and safety to unfractionated heparin (UFH) plus LDA in the management of pregnant women with a history of recurrent spontaneous abortion secondary to antiphospholipid syndrome (APS).

Methods

In a randomized prospective study, 60 women with a history of 3 or more consecutive spontaneous abortions and positive antiphospholipid antibodies were assigned in equal numbers to receive either UFH (5000 units, twice daily) plus LDA, or LMWH (enoxaparin 40 mg, once daily) plus LDA as soon as pregnancy was diagnosed.

Results

Twenty-four women in the LMWH group (80%) and 20 women in the UFH group (66.67%) delivered a viable infant (P = 0.243). There were no significant differences in pregnancy complications or neonatal morbidity between the 2 groups. There were no incidences of excessive bleeding, thrombocytopenia, or osteoporotic fractures in either group.

Conclusion

LMWH plus LDA was successfully used as an alternative to UFH plus LDA in the management of recurrent abortion secondary to APS. The results highlight the need for a larger randomized controlled trial to determine whether LMWH plus LDA should be the treatment of choice for recurrent abortion secondary to APS.Clinicaltrials.govNCT01051778.     

妊娠合并抗磷脂综合征的诊治

抗磷脂综合征（antiphospholipid syndrome,APS）是一种由抗磷脂抗体引起的非炎症性自身免疫病。妊娠合并APS易发生早期反复自然流产,孕晚期胎死宫内,胎儿生长受限,血小板减少,子痫前期或子痫以及胎盘功能障碍等不良妊娠结局,严重危及母儿健康。临床上应充分重视妊娠合并APS的诊断和治疗。     

Acquired thrombophilias and pregnancy

Acquired thrombophilias are hypercoagulable states secondary to various aetiologies. In particular, during pregnancy the risks are exaggerated due to the underlying physiological changes. The commonest cause of acquired thrombophilia in pregnancy is antiphospholipid syndrome. Antiphospholipid syndrome (APS) is a complex multisystem disorder that has been associated with varied medical and obstetric complications. The pathogenesis of APS has been further elucidated in recent studies. The two most clinically significant antiphospholipid antibodies that are associated with recurrent pregnancy loss and thromboembolism are anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). The laboratory diagnosis is based on the presence of moderate to high positive aCL and/or LA antibodies. It is crucial that APS is not inappropriately diagnosed as this has implications for counselling and management with thromboprophylaxis during pregnancy. Over the last decade there have been significant changes in the laboratory and clinical criteria for the diagnosis of APS. National and international collaborations have made efforts to standardize the laboratory methods. There have been very few randomized placebo-controlled trials of drug therapy and so not all drug treatment strategies have a strong evidence base. With current management strategies, using low-molecular-weight heparin and aspirin, a greater than 70% live birth rate may be achieved in affected pregnancies. A multidisciplinary approach in the management of these women is vital.     

Antiphospholipid antibodies and recurrent abortions: possible pathogenetic role of annexin A5 investigated by confocal microscopy

AIM: It has been established that antiphospholipid antibodies (aPL) are associated with recurrent abortions, but the pathophysiologic mechanisms that characterize thrombosis and recurrent pregnancy losses are still not clear.However, it is known that they are associated with the presence of antibodies directed against anionic phospholipids and putative cofactors. In this study the pathogenetic role of annexin A5, a potent anticoagulant cofactor protein for its anticoagulant property in recurrent abortions, was investigated. METHODS: Endothelial cells of human umbilical veins 'EAHY2936 Line' in culture were used, incubated with antiphospholipid anticardiolipin (ACA) antibodies purified from plasma of patients with recurrent abortions. The expression of annexin A5 on the cells with ACA was investigated by immunofluorescence and by confocal microscope. The negative control was also carried out: EAHY cells in cultivation medium without ACA. RESULTS: Confocal analysis revealed a uniform distribution of annexin A5 on the cellular membranes in the negative control. Instead, in EAHY cells with ACA, the annexin A5 appears distributed in irregular manners on the cellular membranes (cytoplasmic and nuclear). CONCLUSION: The results of an irregular 'cluster' distribution of annexin A5 on the EAHY cells in presence of aPL, and in agreement with the literature, demonstrated that aPL, inhibiting annexin A5 ability to protect anionic phospholipid, promote the coagulation factors to diffuse laterally against phospholipids.     

Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology.

A group of 153 women with 3 or more recurrent spontaneous abortions (RSAs) with unknown etiology and 90 normal multigravida controls were evaluated for antibodies to phospholipids and nuclear antigens. We demonstrate that women with recurrent spontaneous abortions showed significantly higher incidence of antibodies to phospholipids than normal multigravida controls. In contrast, the incidence of antibodies to polynucleotides and histones was not different between these two groups. These findings suggest that antiphospholipid antibodies are either epiphenomena or causally related to recurrent spontaneous abortions.     

反复自然流产与抗活化的蛋白C的研究

目的了解抗活化的蛋白C(APCR)在反复自然流产(RSA)患者中的发生情况,并进一步探讨APCR引起胎盘血管微小血栓形成并进而引起RSA的发生机制。方法采用APC-KPTT法,ELISA法和PTT-LA法分别对32例RSA及20例正常对照(NC)进行APCR、抗心磷脂抗体(ACA)和狼疮抗凝物(LA)检测。结果32例RSA患者共17例抗磷脂抗体(APA)阳性,其中9例LA阳性,12例ACA阳性(4例LA、ACA同时阳性),阳性率(53.1％)明显高于NC组(0/20)(P＜0.005);其中LA阳性率为28.1％,明显高于NC组(P＜0.01),患者ACA-IgG(0.32±0.22)、IgM(0.51±0.25)、IgA(0.40±0.27)与NC组无显著性差异(P＞0.05)。患者APCR阳性率为37.5％,明显高于NC组(5.0％)(P＜0.001),而活性蛋白C敏感比值(APC-SR)低于NC组(P＜0.05)。相关分析显示LA阳性组中的APCR阳性率(66.7％)明显高于LA阴性组(26.1％)(P＜0.05);而ACA阳性组中的APCR阳性率(25.0％)与ACA阴性组(25.0％)无显著性差异(P＞0.05)。结论APCR在反复自然流产患者中有较高的发生率且与LA有明显相关性,提示APCR可能是引起胎盘微血栓形成并引起反复自然流产的另一重要因素。     

Role of antiphospholipid antibodies in 147 patients with spontaneous abortions and stillbirths: a retrospective and prospective analysis

Antiphospholipid antibodies (aPL) are a family of autoantibodies including lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and ect. That appear to react with negatively charged phospholipids. These antibodies induce thrombosis and pregnancy complications including recurrent spontaneous abortions (RSA), recurrent stillbirth (SB), preeclampsia and intra-uterine growth retardation, although their exact pathogenic mechanisms remain poorly defined. The aim of this study was to investigate the frequency and the role of a aPL women with a history of RSA and SB due to positive aPL. The study included 147 women with a history of RSA and 48 women with a history of SB and to investigate the histological changes in the heams and stillborn fetuses in aCL positive women. We established that: 1, aCL were significantly increased in 62.2% (n = 92) in women with history of RSA and in 71% (n = 34) in women with history of SB; 2. aTr antibodies were positive in 22.7% (n = 5) in women with history of SB; 3. Tr activation status was increased in 77.3% (n = 17) in women with history of SB. CONCLUSION: The investigation of aPL in women with history of RSA and SB provides new insights into the disease and offers promise for prophylaxis and treatment in subsequent pregnancies.     

A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies.

OBJECTIVES: A prospective, controlled multicenter study was performed to estimate the obstetric risks of antiphospholipid antibodies (the lupus anticoagulant and anticardiolipin antibodies). In addition, the risks of prior thrombosis, obstetric history, systemic lupus erythematosus, and high-dose prednisone treatment were evaluated. STUDY DESIGN: After screening for antiphospholipid antibodies in patients with lupus erythematosus or women with prior fetal loss(es), 59 subsequent pregnancies with and 54 without these antibodies were followed. RESULTS: The presence of the lupus anticoagulant and a history of at least three spontaneous abortions could predict fetal loss (p = 0.032 and 0.001, respectively). In live born infants, a low birth weight could be predicted by the presence of anticardiolipin antibodies (p = 0.034), prior intrauterine fetal death (p = 0.025), and treatment with high-dose prednisone (p = 0.002). No relationships were seen between antiphospholipid antibodies and small-for-gestational-age newborns and pregnancy-induced hypertension or preeclampsia. The disappearance of antiphospholipid antibodies during pregnancy was not correlated with live birth. CONCLUSION: It is concluded that the presence of antiphospholipid antibodies is a risk factor for adverse pregnancy outcome.     

Autoimmunity and pregnancy loss

Clinicians have recognized for several decades that certain autoimmune conditions, such as systemic lupus erythematosus (SLE), are associated with pregnancy loss. During the 1980s, investigations focused attention on fetal wastage in women with antiphospholipid antibodies and the antiphospholipid antibody syndrome (APS) was characterized. Its defining features include fetal wastage in the presence of significant levels of anticardiolipin antibodies. Since that time, interest in other autoimmune diatheses and various specific autoantibodies as possible causes of pregnancy loss has increased. Investigators have attempted to establish an association between recurrent pregnancy loss and the presence of a specific autoantibody or patterns of autoantibodies. Thus far, only modest evidence supports the concept that other autoantibodies are linked to, much less cause, pregnancy loss. In this review, we will define pregnancy loss in its various forms and discuss pregnancy loss in well-characterized autoimmune diseases such as SLE and APS. We will focus on the diagnosis and management of these conditions in women attempting to achieve successful pregnancies. Later we discuss the evidence concerning the less well defined association of antiphospholipid antibodies other than the lupus anticoagulant and anticardiolipin antibodies to recurrent pregnancy loss. We then outline the significance of antinuclear antibodies and antithyroid antibodies pertaining to adverse pregnancy outcome and conclude by summarizing and making some suggestions for further study.