Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study

Fawzy, Muhammad; Shokeir, Tarek; El-Tatongy, Mohamed; Warda, Osama; El-Refaiey, Abdel-Aziz A.; Mosbah, Alaa

doi:10.1007/s00404-007-0527-x

Cited by 125 publications

(93 citation statements)

References 22 publications

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“…Application of this sequential data to clinical practice could aid the early prediction of pregnancy outcome, and appropriate and timely counseling of patients. Particularly, earlier prediction of pregnancy outcome could provide appropriate reference to health care providers to establish a treatment plan for recurrent pregnancy losses or implantation failures [43][44][45], initiate earlier management of high risk pregnancies, and precise follow-up of abnormal pregnancies. Therefore, early pregnancy biomarkers such as POD 12 hCG-β level and its fold change based on embryonic age could provide a predictive and appropriate reference to both health care providers and patients and assist earlier management and precise follow-up of women with abnormal or high risk pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Sung

Kwak‐Kim

Koo

et al. 2016

J Assist Reprod Genet

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Purpose To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. Methods A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. Results POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/ mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/ mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-β level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-β level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-β was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-β level and fold increase of hCG-β significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. Conclusions Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of Capsule Early prediction of pregnancy outcome...

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Section: Discussionmentioning

confidence: 99%

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Sung

Kwak‐Kim

Koo

et al. 2016

J Assist Reprod Genet

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“…[15][16][17][18][19][20][21][22] Only one trial was placebo-controlled (the ALIFE study), a randomized trial among all-comer women (;85% had a negative thrombophilia workup), which resulted in a turning point: the lack of any beneficial effect of aspirin was clearly demonstrated. In addition, the use of openlabel LMWH combined with aspirin in a third intervention arm did not show any improvement in live-birth rates vs oral placebo.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, in a randomized single-blinded trial with some methodologic limitations, live-birth rates were significantly higher among women assigned to receive enoxaparin than among those assigned to receive a not-well-characterized oral placebo (81% vs 48%); all had a negative hereditary thrombophilia workup. 16 Thus, conclusive data were still lacking concerning the effect of LMWH alone in improving the outcome of pregnancy in women with unexplained recurrent miscarriage. This is supported by the last meta-analysis 23 in which the authors state that only the data of 6 patients 22 could be The women included in the per-protocol analysis were treated at least 7 days until loss or beyond 12 weeks' gestation, and the injections were started before 6 weeks' gestation or at least 1 week before the most advanced term reached before during previous pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial

Pasquier

Martin

Bohec

et al. 2015

Blood

104

102

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Key Points• The use of low-molecularweight heparin did not improve live-birth rates in nonthrombophilic women with consecutive recurrent miscarriage.• Prophylactic doses of lowmolecular-weight heparin should no longer be prescribed in this clinical setting.It is common practice in many centers to offer antithrombotic medications to women with unexplained recurrent miscarriage, in the presence or absence of inherited thrombophilia. Although no benefit of aspirin vs placebo has been clearly demonstrated, a doubleblind placebo-controlled trial on the effect of low-molecular-weight heparin is lacking. We enrolled 258 pregnant women with a history of unexplained recurrent miscarriage ( ‡2 consecutive miscarriages before 15 weeks' gestation) and a negative thrombophilia workup. They were randomly assigned to receive one daily subcutaneous injection of enoxaparin 40 mg or placebo until 35 weeks' gestation. We included 256 women (mean age 32 years, ‡3 miscarriages: 72%; mean gestational age 39 days of amenorrhea) in the intention-to-treat analysis; 66.6% of 138 who received enoxaparin had a live birth vs 72.9% of 118 who received placebo. The absolute difference was 26% (95% CI, 217.1 to 5.1), excluding a 10% increase in the rate of live-birth on enoxaparin (P 5 .34). In this first randomized, double-blind, placebo-controlled trial, enoxaparin (40 mg once daily) did not improve the chance of a live birth in nonthrombophilic women with unexplained recurrent miscarriage. This trial is registered at www.ClinicalTrials.gov as #NCT00740545 and the French

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“…A tromboprofilaxia tem sido associada a desfechos favoráveis em mulheres com perda fetal recorrente. Acredita-se que além de sua ação anticoagulante, a enoxaparina tenha um efeito anti-inflamatório, que pode neutralizar os mecanismos pró-inflamatórios e citocinas envolvidas nas perdas gestacionais 24,25 .…”

Section: Discussionunclassified

“…Verificou-se que ambas as opções de tratamento resultaram em taxas melhores de nascidos vivos em comparação ao placebo 25 .…”

Section: Discussionunclassified

Eficácia de intervenção com enoxaparina baseada em sistema de pontuação nos desfechos perinatais de gestantes com trombofilias

Figueiró-Filho¹,

Oliveira²,

Breda³

et al. 2012

Rev. Bras. Ginecol. Obstet.

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ResumoOBJETIVO: Avaliar se a intervenção com heparina de baixo peso molecular (HBPM) -enoxaparina sódica -foi eficaz na melhora dos desfechos perinatais de mulheres com trombofillias com base em sistema de pontuação. MÉTODOS: Estudo prospectivo, não randomizado, não controlado, realizado em um Ambulatório de Gestação de Alto Risco, durante o período de novembro de 2009 a novembro de 2011. Foram incluídas gestantes com diagnóstico e intervenção terapêutica para trombofilias adquiridas e/ou hereditárias na gestação atual. Os dados obstétricos e perinatais das gestantes anteriores à intervenção foram comparados com os desfechos subsequentes à intervenção, sendo analisados estatisticamente através do teste do χ 2 , com correção de Yates, considerando significativos quando p<0,05. A dosagem inicial de HBPM foi norteada por sistema de pontuação, baseado no histórico clínico e gestacional das pacientes, além de exames de rastreamento de trombofilias adquiridas e/ou hereditárias. RESULTADOS: Foram incluídas 84 mulheres grávidas com 175 gestações anteriores ao diagnóstico, das quais 20,0% resultaram em morte fetal ou perinatal, 40,0% resultaram em abortamento, 17,7% desenvolveram pré-eclâmpsia ou eclâmpsia, 10,3% foram partos a termo e 29,7% partos pré-termo. Nas 84 gestações após a intervenção, 6,0% resultaram em morte fetal ou perinatal, 1,2% em abortamento, 4,8% desenvolveram pré-eclâmpsia/eclâmpsia, 22,6% em parto prematuro e 70,2% parto a termo. Observou-se redução significativa na taxa de óbito fetal ou perinatal (p<0,05) e abortos (p<0,0001), e aumento significativo (p<0,05) no número de nascidos vivos após a intervenção. CONCLUSÃO: A intervenção baseada na enoxaparina utilizando um sistema de pontuação em gestantes com trombofilia mostrou-se eficaz na melhora do desfecho perinatal. Abstract PURPOSES:To assess whether an enoxaparin-based intervention using a score system was effective in improving perinatal outcome in women with thrombophilia. METHODS: Study Design: Prospective, not randomized, uncontrolled, performed at a Clinic of High-Risk Pregnancy from November 2009 to November 2011. We included women with a diagnosis and therapeutic intervention for thrombophilia acquired and/or inherited in the current pregnancy. The obstetric and perinatal outcomes of pregnant women before the intervention were compared with outcomes after the intervention, and statistically analyzed using the χ 2 test with Yates correction, considered significant when p<0.05. The initial dose of low-molecular-weight Heparin (LMWH) was guided by a scoring system based on the clinical and gestational history of the patients and screening tests for acquired and/or inherited thrombophilia. RESULTS: We included 84 pregnant women with 175 pregnancies before diagnosis, 20.0% of which resulted in fetal ou perinatal death, 40.0% resulted in abortion, 17.7% developed preeclampsia/eclampsia, 10.3% resulted in full-term births, and 29.7% in premature births. In the 84 pregnancies after intervention, 6.0% resulted in fetal ou perinatal death, 1.2% in ...

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Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study

Abstract: A combination treatment consisting of high-dose, low-duration prednisone, progesterone and aspirin might be an effective treatment as enoxaparin alone. Both regimens were associated with a good pregnancy outcome.

Cited by 125 publications

References 22 publications

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial

Eficácia de intervenção com enoxaparina baseada em sistema de pontuação nos desfechos perinatais de gestantes com trombofilias

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