Clearance of antiphospholipid antibodies in pregnancies treated with heparin

OBJECTIVE: To describe the natural history of serum antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) in pregnant women treated with heparin, and to identify a possible association between changes in antibody status and outcomes of subsequent pregnancies. METHODS: Thirty-six women with antiphospholipid antibodies who had three or more repeated miscarriages were enrolled. Intravenous heparin was used for each of the first pregnancies after referral. Changes in antibody status were investigated with relation to outcomes of the index and subsequent pregnancies. RESULTS: Eighteen of 23 pregnancies in 36 antibody-positive women treated with heparin resulted in term or preterm deliveries with live-born infants, and five ended in abortions. Antibodies cleared in ten of 12 term pregnancies, in five of six preterm pregnancies, and in one of five abortions. There was a statistically significant difference between the term pregnancy and abortion groups (P <.05). Eleven second and third pregnancies in nine women in whom antibodies cleared resulted in term or preterm deliveries of live-born infants, without heparin therapy. The second and third pregnancies in one woman whose antibodies persisted ended in miscarriages despite repeated heparin administration. CONCLUSION: Antiphospholipid antibodies cleared spontaneously in some pregnant women treated with heparin. Subsequent pregnancies among women in whom antibodies cleared were managed successfully without medication, whereas pregnancies in women with persistent antibodies required treatment.     

Obstetric antiphospholipid syndrome: an update on pathophysiology and management

Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids, a group of inner and outer cell membrane antigens found in mammals. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Although obstetric APS was originally reported in association with slow progressive thrombosis and infarction in the placenta, it is most often associated with a poor obstetric outcome. In fact, obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss (RPL). Thus obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiological mechanisms of action of aPLs have been described. The most common histopathological finding in early pregnancy loss has been defective endovascular decidual trophoblastic invasion. Treatment with heparin and aspirin is emerging as the therapy of choice, with ～75% of treated women with RPL and aPLs having a successful delivery compared with <50% without treatment. This review highlights the diagnostic challenges of obstetric APS, the obstetric complications associated with APS, proposed pathophysiological mechanisms of APS during pregnancy, and the management of women during and after pregnancy.     

Ovulation induction in women with polycystic ovary syndrome: an update

Infertility is frequently caused by anovulation. The affected women present with irregular menstrual cycles and the most common diagnosis is polycystic ovary syndrome. Ovulation induction is commonly used to treat these women. Clomiphene citrate (a selective estrogen receptor modulator or SERM) remains the most used medication for treating this condition. Alternatives that have been used include other SERMs such as tamoxifen, aromatase inhibitors, insulin sensitizing agents, and ovarian drilling. Evidence for and against the effectiveness of these agents has fluctuated over the last decade. Controversies surrounding the use of ovulation induction such as development of functional cysts, high-order multiple births, and development of ovarian cancer have been further studied and some controversies have almost been laid to rest in the last decade.     

A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome

Objective:To study the outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome treated with the standard treatment regimes including intravenous immunoglobulin (IV Ig). Methods: Forty three patients with recurrent pregnancy loss associated with antiphospholipid syndrome diagnosed before pregnancy and subdivided into primary (18) and secondary (25) subgroups were closely monitored all through pregnancy with serial blood tests and ultrasonography until the pregnancy ended in miscarriage or delivery. The patients were treated with low-dose aspirin and heparin and or steroids and IV Ig given to some selected patients. The maternal and fetal outcomes were analysed. Results: The mean age of the patients in the primary sub group (24.60±4.30) years was significantly lower than the mean age of the secondary recurrent pregnancy loss group (31.50±4.50) years, (p<0.0001). 85.00% of all the previous miscarriages were in the first trimester. There was no significant difference in the incidence of live births in the primary (77.80%) and secondary (84.00%) groups, (p>0.05); the babies were of normal birth weight. The incidence of caesarean section in the primary and secondary groups, 22.23% and 12.00% respectively, were not significantly different (p>0.05). Intravenous immunoglobulin added to the standard therapy resulted in 100% live births. Maternal complications were negligible. Conclusions: The fetal and maternal outcome of pregnancies in patients with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome were virtually identical and quite satisfactory. Intravenous immunoglobulin added to the standard therapy resulted in excellent fetal and maternal outcome, although its definitive role will have to wait for the outcome of randomised trials. Received: 22 November 2000 / Accepted: 19 February 2001     

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.     

Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels

Our objective was to determine whether there is a relationship between low antiphospholipid (aPL) antibody levels and the obstetrical complications of antiphospholipid syndrome (APS) and to analyze the impact of conventional APS treatment in patients with low aPL levels. To this end, we retrospectively reviewed the files of all patients referred to our unit (2003-2010) for unexplained pregnancy morbidity, with an aPL test result. We compared patients with APS confirmed by Sapporo criteria (Group 1) with patients with APS-like obstetrical complications with an aPL titer below the intermediate titer (Group 2). Overall, 57 patients were included (25 in Group 1; 32 in Group 2). Obstetrical events were recurrent spontaneous abortion <10th week of gestation (n=9 patients in Group 1; n=13 patients in Group 2), fetal death (n=11 and 16, respectively), preeclampsia (n=5 in Group 1; n=6 in Group 2). The total number of obstetrical events per patient was very similar before APS treatment (3 [1-8] in Group 1; 3 [1-6] in Group 2) and decreased significantly after APS treatment to 0 [0-2] and 0 [0-2], respectively (p<0.05). The incidence of premature births and the characteristics of neonates were similar in the two groups. In this study, treatment of patients with low aPL levels and APS-like obstetrical events was associated with outcomes similar to those found in otherwise normal women with recurrent miscarriage or other adverse events. However, properly designed treatment trials would be required to prove the benefit of such treatments.     

Outcome of pregnancy in women with Marfan's syndrome

Objective To improve life expectancy and prevent premature mortality in women with Marfan's syndrome.
Methods During the development of a regional genetic register for Marfan's Syndrome the outcome of 91 pregnancies in 36 women with this condition was established retrospectively and the cardiovascular and obstetric complications documented.
Results No patient had a significant cardiovascular abnormality limiting function before her pregnancy. Of 36 women, four had an aortic dissection relating to pregnancy and two others required aortic surgery following delivery. Thirty women had uncomplicated gestational histories. The incidence of obstetric complications did not exceed expectation.
Conclusions Women with Marfan's syndrome are at significant risk of aortic dissection in pregnancy even in the absence of preconceptional cardiovascular abnormality. Aortic root dilatation may be a predictor of risk but dissection may occur without significant dilatation. Guidelines for obstetric care are suggested and preconceptional assessment recommended.     

Outcome of twin, triplet, and quadruplet in vitro fertilization pregnancies: the Norfolk experience.

OBJECTIVE: To review the maternal morbidity and neonatal morbidity and mortality associated with in vitro fertilization (IVF) multiple pregnancies. DESIGN: Retrospective analysis of data collected from office and hospital records and from questionnaires sent to patients, their obstetricians, and pediatricians. SETTING: Patients (all with private insurance carriers) enrolled in an academic IVF program (The Jones Institute for Reproductive Medicine). PATIENTS, PARTICIPANTS: All IVF pregnancies resulting in one or more gestational sacs on the initial ultrasound at 6 to 7 weeks were reviewed. MAIN OUTCOME MEASURES: The frequency and severity of obstetrical and neonatal complications and the perinatal mortality of IVF twins, triplets, and quadruplets were compared. These were also compared with non-IVF multiple pregnancies. RESULTS: From 1982 to 1990, 629 IVF pregnancies progressed beyond 20 weeks; 115 twins (18.3%), 15 triplets (2.4%), and 4 quadruplets (0.6%). There was a high incidence of antenatal complications such as abortions (30.3%, 42%, and 20%), premature labor (41.5%, 92.3%, and 75%), pregnancy-induced hypertension (17.0%, 38.6%, and 50%), and gestational diabetes mellitus (3.1%, 38.5%, and 25%) for twins, triplets, and quadruplets, respectively. The mean gestational age at delivery was 35.5 +/- 3.7, 31.8 +/- 2.7, and 31.0 +/- 1.7 weeks, respectively. There was also a proportionate progressive increase in neonatal complications. The mean weights were 2,473 +/- 745, 1,666 +/- 441 and 1,414 +/- 368 g, respectively. Twins (22.7%), 64.1% of triplets, and 75% of quadruplets needed admission to the neonatal intensive care unit and remained for an average of 12.0 +/- 2.3, 17.4 +/- 14.0, and 57.8 +/- 17.9 days, respectively. There was no difference in the mean Apgar scores or the incidence of congenital malformations in the three groups. The corrected perinatal mortality rates were 38.5, 0.0, and 0.0 per thousand live births, respectively. CONCLUSION: Triplet and quadruplet IVF pregnancies have increased obstetrical and neonatal complications compared with IVF twins. The perinatal mortality and the incidence of congenital malformations are, however, comparable in all three groups.     

未成熟卵母细胞体外成熟培养治疗多囊卵巢综合征不孕患者的妊娠结局

新生儿肺炎死亡,其余至今未发现明显畸形.10例早产,占21.3%(10/47),36例足月产,占76.6%(36/47),1例过期妊娠.新生儿平均出生体重2972 g,低体重儿17例,占26.2%(17/65).结论 多囊卵巢综合征不孕患者行未成熟卵母细胞IVM培养后,虽然获得了较高的临床妊娠率,而且早期流产率、异位妊娠率、妊娠并发症发生率、围产儿死亡及新生儿缺陷的发生率等不高,但多胎妊娠、早产、低出生体重儿发生率较高.     

Homocysteine levels in women with antiphospholipid syndrome and normal fertile controls

OBJECTIVE: Recent studies have identified hyperhomocysteinemia as a risk factor for both recurrent pregnancy loss and thrombosis. Antiphospholipid syndrome, an autoimmune disorder, is also characterized by recurrent pregnancy loss and thrombosis. Thus, our purpose was to determine if hyperhomocysteinemia is more common in patients with APS than normal fertile controls. METHODS: Plasma, sera and whole blood were obtained from two groups of women: (1) 22 with well-characterized antiphospholipid syndrome; and (2) 41 healthy fertile controls. Levels of fasting homocysteine, vitamin B16, vitamin B12, folate and the incidence of the C677/T mutation of the methylene tetrahydrofolate reductase genotype (C677T/MTHFR) were determined. RESULTS: The proportion of individuals with hyperhomocysteinemia and fasting plasma homocysteine levels were similar in women with APS and controls. Levels of vitamin B6, vitamin B12, folate and the incidence of C677/MTHFR were also similar in the two groups. CONCLUSION: Hyperhomocyteinemia and the C677T/MTHFR mutation are not common in women with antiphospholipid syndrome. Abnormal homocysteine metabolism is unlikely to play a major role in the pathogenesis of antiphospholipid syndrome.     

Outcome of pregnancies with an intrauterine devices and their management

The authors report a study of 157 cases of pregnancy occurring with an intrauterine device (IUD) in place. Particular attentions was paid to developments in patients who had accepted pregnancy (n : 67). The frequency of gravidic complications was much higher when the IUD was in place, and two septic abortions were seen between the fourth and sixth months of pregnancy. The authors put forward a new method of echo-guided removal of the device.     

Outcome of twin pregnancies with extreme weight discordancy.

The objective of this paper is to examine the outcome of pregnancies with extreme weight-discordant twins. Percentage of birth weight discordancy was defined as the birth weight difference between the twins divided by the larger twin's weight and multiplied by 100. Discordancy was calculated for all twin births in which both fetuses were live born. In 33 pairs, the discordancy was defined as extreme (>35%) and they constituted the study group. Thirty-three pairs of twin defined with mild weight discordancy (15-25%), and 33 pairs defined as concordant to birth weight (<15% difference) were matched to the study group patients based on gestational age at delivery (+/- 7 days) and on the mode of delivery, and constituted the control groups. The records of all the patients were reviewed for pregnancy complications and for major and minor neonatal outcome variables. Significantly more parturients in the study groups were primiparous undergoing in vitro fertilization treatments to conceive. Significantly more women in the study group had severe preeclampsia compared with women with mild discordancy or concordant twins (12.1 vs. 3.0% and 0%, respectively, p <0.025). No significant differences were encountered between the groups in neonatal mortality or morbidity factors except an increased rate of hyperbilirubinemia in the study group, p = 0.006. Using logistic regression analysis, discordancy was not defined as an efficient predictor for adverse neonatal outcome. Twin pregnancies with extreme discordancy have a favorable neonatal outcome in correlation with gestational age and not with the percentage of discordancy.     

Maternal and fetal outcome in women with antiphospholipid syndrome: a three-year observational study

Objectives: To assess prospectively the maternal and fetal outcome in women with primary antiphospholipid syndrome (APS) and to find out predictors of poor obstetric outcome.

Methods: A prospective observational study included 162 patients with primary APS who were divided into two groups, group 1 with previous thrombosis (n?=?74) and group 2 without previous thrombosis (n?=?88). Patients were followed from the start of pregnancy till delivery under standard treatment to detect maternal and fetal outcome.

Results: There was a significant difference between the two groups with higher rate of miscarriage (p?<?0.05), maternal venous thromboembolism (p?<?0.001), intrauterine fetal demise and neonatal death (p?<?0.05) in group 1. No significant difference between the two groups regarding the rate of preeclampsia, eclampsia, postpartum hemorrhage, prematurity and admission to neonatal intensive care unit (p?>?0.05). By univariate and multivariate analyzes in the whole study participants, previous thrombosis, triple positivity of APS antibodies, previous delivery before 34 weeks, the presence of antiβ2GP1 antibodies and maternal age above 30 years were independent predictors of pregnancy loss.

Conclusion: Poor obstetric outcome is higher in patients with previous thrombosis. The search for optimal prognostic markers and new therapeutic measures to prevent complications in APS patients is warranted.