Effect of dalteparin sodium administration on IVF outcome in non-thrombophilic young women: a pilot study

Noci, Ivo; Milanini, Maria Novella; Ruggiero, María; Papini, Francesca; Fuzzi, Beatrice; Artini, Paolo Giovanni

doi:10.1016/j.rbmo.2011.03.016

Cited by 26 publications

(41 citation statements)

References 21 publications

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“…Heparin group showed a relative increase by 30 % in LBR, however statistical significance was not reached due to the low statistical power and the small sample size of the study [57]. However, a similar randomized control study of 172 women under 40 years of age failed to show also any clinical improvement in the LMWH group (IR, CPR, LBR in the LMWH group compared to controls were respectively 15% vs 12%, 26% vs 20%, 21% vs 16%) [58]. The same data was replicated in a larger single-center study on 219 women with no coagulation disorders who received LMWH at oocyte retrieval and showed that CPR, LBR, and IR were higher in the LMWH group (35.4%, 31.2%, 21.1%) compared to control group (27.9%, 23.2%, 15.8%) but failed to show a significant difference in outcomes.…”

Section: ) Inherited Thrombophiliamentioning

confidence: 88%

“…A systematic review and meta-analysis by Dentali, included 3 RCTs comparing LMWH with placebo in 305 women with [15] and without known thrombophilia undergoing ICSI and the effect of heparin on CPR and LBR was investigated [57] [58]. It showed a higher CPR (RR 1.38, 95% CI 1.02 -1.87) and LBR (RR 1.54, 95% CI 1.05 -2.26) among patients who used LMWH.…”

Section: ) Inherited Thrombophiliamentioning

confidence: 99%

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Recurrent Implantation Failure and Low Molecular Weight Heparin

Khalife¹,

Ghazeeri²

2018

OJOG

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Implantation of the embryo into the endometrium is the first step in the establishment of pregnancy. This process is complex, and depends on many factors. Recurrent implantation failure is a source of distress to patients and specialists. It is defined as failure to achieve a viable pregnancy, following ">3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers". Thrombophilic conditions that contribute to recurrent implantation failure are the main concern in this review. The mechanism of implantation failure is believed to be due to decreased blood flow to the endometrium and placenta which can hinder normal endometrial receptivity leading to miscarriage. Defects in early placentation resulting in pregnancy failure, have focused attention on the therapeutic potential of low molecular weight heparin in the implantation process. Heparin has a role at all stages of implantation to improve pregnancy outcomes. There are controversies in literature regarding the association between thrombophilia and recurrent implantation failure and available literature regarding this issue is very heterogeneous. Various investigators, have shown that women with RIF are more likely to have a thrombophilia disorder, yet a clear cause cannot be acknowledged from these studies. Heparin treatment has been evaluated in several studies, showing conflicting evidence. However, several studies have pointed out that it may play a role in a subset of patients who presents a thrombophilia mutation, thus the group of patients that might benefit is needed to be identified. This review is dedicated to evaluate the published literature about the role of low molecular weight heparin in case of recurrent implantation failure with or without the presence of thrombophilia.

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Section: ) Inherited Thrombophiliamentioning

confidence: 88%

Section: ) Inherited Thrombophiliamentioning

confidence: 99%

Recurrent Implantation Failure and Low Molecular Weight Heparin

Khalife¹,

Ghazeeri²

2018

OJOG

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“…1,6 Two meta-analyses included 3 randomized trials involving 386 women. 1,15,[22][23][24] Peri-implantation LMWH administration was associated with improvement in live birth rate compared with placebo or no LMWH; however, the results were sensitive to the statistical methods used. 1,22 When a random-effects model, rather than a fixed-effects model, was used; the results were no longer statistically significant.…”

Section: Antithrombotic Therapy To Enhance the Likelihood Of Success mentioning

confidence: 98%

“…49 conclusions about safety and efficacy. 15,17,[23][24][25]46 Whether bleeding risks are increased in this population with antithrombotic prophylaxis is uncertain. 47 There have been no randomized trials demonstrating that prophylactic anticoagulation prevents VTE in patients with severe ovarian hyperstimulation syndrome.…”

Section: Thrombosis Prophylaxis In Assisted Reproductionmentioning

confidence: 99%

Anticoagulation and in vitro fertilization and ovarian stimulation

Bates

2014

Hematology

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Assisted reproductive technology is widely used to treat couples affected by infertility. Complications associated with assisted reproduction include venous thromboembolism, ovarian hyperstimulation syndrome, and recurrent implantation failure. It has also been proposed that thrombophilia may be associated with an increased likelihood of these events. Although data are limited, antithrombotic therapy is frequently used to enhance the likelihood of successful assisted reproduction. This chapter reviews the risks of venous and arterial thromboembolism associated with assisted reproduction, as well as available data regarding the impact of thrombophilia on the risks of thromboembolism and failure of implantation. The role of antithrombotic therapy in reducing the likelihood of these events, along with recommendations from various guidelines, are also discussed. Learning Objectives• To discuss the available data regarding the role of thrombophilia testing in women undergoing assisted reproduction • To describe the state of the evidence with respect to the use of antithrombotic therapy in women undergoing assisted reproduction

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“…The fixed effect forest plot for the three randomized controlled trials [3][4][5] showed no significant improvement in the live birth rate (Risk Ratio[RR] 1.11, 95% CI 0.82-1.51, P = 0.51, I 2 = 0%) and clinical pregnancy rate (RR 1.03, 95% CI 0.80-1.33, P = 0.80, I 2 = 14%).Second, the study by Lodigiani et al 5 did not meet the strict requirements of the screening criteria. There is currently insufficient research to elucidate the effects of heparin in assisted reproduction, making it difficult to obtain high-quality answers in this meta-analysis.…”

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confidence: 99%

Efficacy of low molecular weight heparin on the pregnancy outcomes of assisted reproduction

Guo

2018

Acta Obstet Gynecol Scand

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Sir, I read with interest the systematic review and meta-analysis by Yang et al 1 on the efficacy of low-molecular-weight heparin in assisted reproduction. There is currently insufficient research to elucidate the effects of heparin in assisted reproduction, making it difficult to obtain high-quality answers in this meta-analysis. In the analysis, only five studies were included, a fact that also highlights the lack of research in this field. After carefully analyzing the published literature, I present my concerns. First, the total number of studies is insufficient, and any such study may have a large impact on the conclusions or even change them. In the review, one study included was a quasi-randomized controlled trial. In another the participants were grouped according to their wishes, 2 violating the basic principles of randomization. Therefore, the study cannot be classified as a randomized controlled trial. These problems reduce the quality of the evidence. A meta-analysis of the live birth rate and clinical pregnancy rate was performed after removing these two studies. The fixed effect forest plot for the three randomized controlled trials [3][4][5] showed no significant improvement in the live birth rate (Risk Ratio[RR] 1.11, 95% CI 0.82-1.51, P = 0.51, I 2 = 0%) and clinical pregnancy rate (RR 1.03, 95% CI 0.80-1.33, P = 0.80, I 2 = 14%).Second, the study by Lodigiani et al. 5 did not meet the strict requirements of the screening criteria. This study included a subset of women with thrombophilia without listing the relevant data, similar to several other studies that were excluded. Therefore, it is not appropriate to include all the data of the study. If that study is excluded, a meta-analysis of the remaining two studies 3,4 is not statistically significant: live birth rate (fixed effect): (RR 1.29, 95% CI 0.87-1.91, P = 0.21, I 2 = 0%); clinical pregnancy rate (fixed effect): (RR 1.22, 95% CI 0.88-1.68, P = 0.23, I 2 = 0%); MR (fixed effect): (RR 0.71, 95% CI 0.34-1.49, P = 0.36, I 2 = 0%).In addition, if the study by Xiong et al 2 is included, another study from the China National Knowledge Infrastructure database 6 should also be included, as the grouping method in this study is the same as that of Xiong et al, 2 which is not a true randomized controlled trial. If the study is also included in the meta-analysis, the conclusion remains negative: six studies reported the clinical pregnancy rate (fixed effect): (RR 1.10, 95% CI 0.91-1.34, P = 0.32, I 2 = 0%); and four studies reported the miscarriage rate (fixed effect): (RR 0.63, 95% CI 0.34-1.17, P = 0.14, I 2 = 0%). Of course, if this study 6 is not suitable for inclusion it should appear in the excluded table, stating the reasons for exclusion.Overall, various analyses lead to the same conclusion: excluding the benefits of heparin in improving assisted reproductive outcomes (all figures are available from the author). Even if more evidence becomes available in future, it is necessary to avoid adverse effects and to assess carefully whether the benef...

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Effect of dalteparin sodium administration on IVF outcome in non-thrombophilic young women: a pilot study

Cited by 26 publications

References 21 publications

Recurrent Implantation Failure and Low Molecular Weight Heparin

Recurrent Implantation Failure and Low Molecular Weight Heparin

Anticoagulation and in vitro fertilization and ovarian stimulation

Efficacy of low molecular weight heparin on the pregnancy outcomes of assisted reproduction

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