Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss.
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ABSTRACT:
SUBMITTER: Hamulyak EN
PROVIDER: S-EPMC7195627 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objectives To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose aspirin. Preconception anticardiolipin (aCL) and anti-?2-glycoprotein-I (a-?2-I) were assessed in 1208 women with one or two prior pregnancy losses and no more than two prior live births. Comparison cohorts were defined by positive aPL (+aPL) or negative aPL (-aPL) status. All women were followed for six menstrual cycles while trying to conceive; if successful, they underwent an ultrasound at 6-7 weeks' gestation. EPL was defined as loss prior to 10 weeks' gestation; embryonic loss was loss after visualization of an embryo but prior to 10 weeks; clinical loss was any loss after visualization of an embryo (with or without fetal cardiac activity detected). Results In total, 14/1208 (1%) tested positive for +aPL. 786/1208 (65%) women had positive human chorionic gonadotropin during the study period, of which 9/786 (1%) had +aPL. Of the 786 pregnant women, 589 (75%) had live births and 24% had pregnancy losses. Women with +aPL experienced EPL at similar rates as women with -aPL, 44% vs 21% (aRR 2.4, 95% confidence interval (CI) 0.5-10.9). Embryonic loss was more common in women with +aCL IgM (aRR 4.8, 95% CI 1.0-23.0) and in women with two positive aPL. Clinical pregnancy loss was more common in women with positive a-?2-I IgM (50% vs 16.5%, aRR 3.7, 95% CI 1.3-10.8). Conclusion Positive levels of aPL are rare in women with one or two prior pregnancy losses and are not clearly associated with an increased rate of subsequent loss. Clinical trial registration The original source study was registered at ClinicalTrials.gov (#NCT00467363).
| S-EPMC6027606 | biostudies-literature
Project description:Aspirin and heparin are widely used to reduce the risk of recurrent pregnancy loss in women with antiphospholipid syndrome. This practice is based on only a few intervention studies, and uncertainty regarding benefits and risk remains. In this case-based review, we summarize the available evidence and address the questions that are most important for clinical practice. We performed a systematic review of randomized controlled trials assessing the effect of heparin (low molecular weight heparin [LMWH] or unfractionated heparin [UFH]), aspirin, or both on live birth rates in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Eleven trials including 1672 women met the inclusion criteria. Aspirin only did not increase live birth rate compared to placebo in one trial of 40 women (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.71-1.25). One trial of 141 women reported a higher live birth rate with LMWH only than with aspirin only (RR 1.20; 95% CI 1.00-1.43). Five trials totaling 1295 women compared heparin plus aspirin with aspirin only. The pooled RR for live birth was 1.27 (95% CI 1.09-1.49) in favor of heparin plus aspirin. There was significant heterogeneity between the subgroups of LMWH and UFH (RR for LWMH plus aspirin versus aspirin 1.20, 95% CI: 1.04-1.38; RR for UFH plus aspirin versus aspirin 1.74, 95% CI: 1.28-2.35; I2 78.9%, p = .03). Characteristics of participants and adverse events were not uniformly reported. Heparin (LMWH or UFH) plus aspirin may improve live birth rates in women with recurrent pregnancy loss and antiphospholipid antibodies, but evidence is of low certainty.
| S-EPMC8252114 | biostudies-literature
Project description:It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-β2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions ∼6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P = .09) in the 25.9% of patients with an APA on ≥1 occasions, 2.7 (95% CI, 1.1-.7; P = .03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P = .006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APA on the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00720915.
| S-EPMC6536697 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-09-16 | E-GEOD-65102 | biostudies-arrayexpress
Project description:Study questionWhat is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature?Summary answerThe guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized.What is known alreadyA previous guideline for the investigation and medical treatment of recurrent miscarriage was published in 2006 and is in need of an update.Study design size durationThe guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 31 March 2017 and written in English were included. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes.Participants/materials setting methodsBased on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.Main results and the role of chanceThe guideline provides 38 recommendations on risk factors, prevention and investigations in couples with RPL, and 39 recommendations on treatments. These include 60 evidence-based recommendations - of which 31 were formulated as strong recommendations and 29 as conditional - and 17 good practice points. The evidence supporting investigations and treatment of couples with RPL is limited and of moderate quality. Of the evidence-based recommendations, only 10 (16.3%) were supported by moderate quality evidence. The remaining recommendations were supported by low (35 recommendations: 57.4%), or very low quality evidence (16 recommendations: 26.2%). There were no recommendations based on high quality evidence. Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions investigations and treatments that should not be used for couples with RPL.Limitations reasons for cautionSeveral investigations and treatments are offered to couples with RPL, but most of them are not well studied. For most of these investigations and treatments, a recommendation against the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.Wider implications of the findingsThe guideline provides clinicians with clear advice on best practice in RPL, based on the best evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. One of the most important consequences of the limited evidence is the absence of evidence for a definition of RPL.Study funding/competing interestsThe guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. J.E. reports position funding from CARE Fertility. S.L. reports position funding from SpermComet Ltd. S.M. reports research grants, consulting and speaker's fees from GSK, BMS/Pfizer, Sanquin, Aspen, Bayer and Daiichi Sankyo. S.Q. reports speaker's fees from Ferring. The other authors report no conflicts of interest.ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.
| S-EPMC6276652 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-09-16 | GSE65102 | GEO
Project description:In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women. The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages. 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss.
2015-09-16 | E-GEOD-65099 | biostudies-arrayexpress
Project description:Decidual transformation of the human endometrium is not dependent on embryo implantation. Instead, this process is initiated during the mid-luteal phase of each cycle in response to the postovulatory rise in progesterone and increasing endometrial cAMP levels. Consequently, decidualization is a reiterative process directly linked to cyclic activation of mesenchymal stem cells (MSCs) and subsequent differentiation into mature stromal cells in regenerating endometrium. We reasoned that aberrant remodeling of the HESC epigenome would disrupt decidualization in RPL patients and account for the functional memory of HESCs in culture. To explore this possibility, we performed MeDIP-seq, which involves immunoprecipitation of DNA with a 5-methylcytosine antibody followed by deep sequencing, on primary HESC cultures established from four RPL patients and four control subjects. Eight samples were analyzed: derived from four control and four recurrent pregnancy loss (RPL) patient cultures.
2015-09-16 | E-GEOD-65100 | biostudies-arrayexpress
Project description:Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p?=?0.01), CXCL11 (p?<?0.001) and the Th17-associated chemokine CCL20 (p?=?0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Student's t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance.
| S-EPMC6707182 | biostudies-literature
Project description:Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal-fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.
| S-EPMC6862690 | biostudies-literature