Effect of heparin on the outcome of IVF treatment: a systematic review and meta-analysis

Seshadri, Srividya; Sunkara, Sesh Kamal; Khalaf, Yakoub; El-Toukhy, Tarek; Hamoda, Haitham

doi:10.1016/j.rbmo.2012.08.007

Cited by 36 publications

(32 citation statements)

References 33 publications

(96 reference statements)

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“…Unfractionated heparin as well as LMWH is able to modulate the process of decidualization, potentially improving implantation success in ART conceived pregnancies, as well as, clinical pregnancy rates [14,15]. Regarding the effects of antithrombotic treatment in pregnancies conceived by ART, the majority of research to date has focused on three primary outcomes: implantation rate, clinical pregnancy rate, and live birth rate [16,17]. As a consequence, the body of research to date has not addressed the effect of antithrombotic treatment on specific aspects of perinatal outcomes, which are known factors associated with maternal, fetal and neonatal wellbeing.…”

Section: Discussionmentioning

confidence: 99%

Improved Outcomes in ART Pregnancies Complicated by Thrombophilia, Treated with Low Molecular Weight Heparin in Comparison to Spontaneously Conceived Low-Risk, Untreated Pregnancies: A Case Control Study

Àlex¹,

Kofinas²,

B??R??³

et al. 2018

OGIJ

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Objective: To compare severe pregnancy complications in ART singleton pregnancies treated with anticoagulation due to thrombophilia to low-risk, spontaneously conceived untreated pregnancies. Design: Retrospective case control.Setting: New York Presbyterian-Brooklyn Methodist Hospital, Brooklyn New York.Patients: 615 ART pregnancies compared with 391 low-risk, untreated pregnancies matched for age and time of delivery.Interventions: ART pregnancies were treated with LMWH and low dose aspirin daily and managed by MFM specialist during the entire pregnancy. Main Outcome Measures:Compared for intrauterine growth restriction (IUGR), preterm premature rupture of membranes (pPROM), thrombocytopenia, prematurity, preeclampsia, abruption, and fetal death. Results:The incidence of IUGR was significantly lower in the ART group (5.05% vs. 9.21%, p<0.01). Preeclampsia was significantly reduced in the ART group in comparison to the control, 1.14 % vs. 6.39 %, p<0.0001. PPROM was significantly reduced in the ART group in comparison to the control, 1.46 % vs. 7.67 %, p< 0.0001. Prematurity was reduced in the ART group, 3.43% vs. 9.72%, p<0.0001. Thrombocytopenia incidence was similar, 2.28 % vs. 2.05 %, p > 0.8. Abruption was similar in the two groups, ART 1.3 % vs. 1.02 %, p >0.68. There were more fetal deaths in the control group but due to the small numbers in both groups, statistical comparison was not possible. Conclusion:Use of antithrombotics in ART conceived singleton gestations complicated by thrombophilia under MFM specialty care resulted in significantly decreased prevalence of most major obstetrical complications when compared to low-risk unselected untreated pregnancies.

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Section: Discussionmentioning

confidence: 99%

Improved Outcomes in ART Pregnancies Complicated by Thrombophilia, Treated with Low Molecular Weight Heparin in Comparison to Spontaneously Conceived Low-Risk, Untreated Pregnancies: A Case Control Study

Àlex¹,

Kofinas²,

B??R??³

et al. 2018

OGIJ

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“…Different studies have shown that there is no evidence regarding the efficacy of heparin either in women with two or more consecutive previous pregnancy losses [30] or in those with unexplained recurrent miscarriage [31] or in women with inherited thrombophilia (TanWK). Also Seshadri et al [32] in their meta-analysis including 10 relevant studies (five observational and five randomized) did not observe any difference analysing only randomized studies with regard to clinical pregnancy rate (RR 1.23, 95% CI 0.97-1.57), live birth rate (RR 1.27, 95% CI 0.89-1.81) implantation rate (RR 1.39, 95% CI 0.96-2.01) and miscarriage rate (RR 0.77, 95% CI 0.24-2.42) between women receiving heparin compared to placebo during IVF treatment. On the contrary, a systematic review and a meta-analysis including two RCTs and one quasi-randomized trial showed a significant improvement in the LBR (risk ratio (RR) ¼ 1.79, 95% confidence interval (CI) ¼ 1.10-2.90, P ¼ 0.02) and a reduction in the miscarriage rate (RR ¼ 0.22, 95% CI ¼ 0.06-0.78, P ¼ 0.02) with LMWH compared with controls.…”

Section: Heparinmentioning

confidence: 97%

Adjuvants Therapies for Women Undergoing IVF: Is There Any Evidence of their Safety and Efficacy? An Updated Mini-Review

Fabozzi¹

2017

OGIJ

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In the last two decades a series of adjuvant therapies have been proposed to improve the success of IVF and most of them are currently prescribed even though the quality of scientific evidence supporting their efficacy in improving live birth rates after IVF is weak. The aim of this paper is to describe some of the therapies mostly used by women undergoing IVF such as dehydroepiandrosterone, testosterone, low-dose aspirin, low-molecular-weight heparin (LMWH), corticosteroids and endometrial scratching, and to assess the current evidence about their safety and efficacy. (Relative Risk (RR) 2.13; 95% CI 1.12-4.08). Similar results were obtained in subgroup analyses including randomized controlled trials and case-control studies (RR 2.57; 95% CI 1.43-4.63) and self-controlled studies (RR 3.95;). However, the effects of DHEA on oocyte retrieval, implantation, and abortion were not significant. The Cochrane review conducted in 2015 showed higher ongoing pregnancy rates or live birth rates following the pre-treatment with DHEA. Nevertheless, no benefit was observed when studies with high risk of bias were excluded [14,15]. Finally, a third meta-analysis analysing the effect of DHEA in women with DOR including a total of nine studies, four RCTs, four retrospective and one prospective concluded that clinical pregnancy rates were increased significantly in DOR patients who were pre-treated with DHEA (OR = 1.47, 95% CI: 1.09-1.99), whereas no differences were observed in the number of oocytes retrieved, the cancellation rate of IVF cycles and them is carriage rate between the cases and controls (WMD= −0.69, 95% CI: −2.18-0.81; OR = 0.74,95% CI: 0.51-1.08; OR = 0.34, 95% CI: 0.10-1.24). However, restricting the analysis to only RCTs, a non-significant difference in the clinical pregnancy rate was observed(OR = 1.08, 95% CI: 0.67-1.73) [15]. Keywords: Conclusive statementAlthough the effect of DHEA on improving ovarian response seems to be promising, there is insufficient evidence to recommend DHEA supplementation at this time. Furthermore, the long-term risk of DHEA administration remain unknown. More RCTs with large sample size are needed to obtain good quality evidence on its safety and efficacy. Testosterone (TT)Testosterone is a downstream molecule in the steroidal pathway from DHEA. It can be administered either trans-dermally or orally. Different RCTs report a beneficial effect of TT pre-treatment [16,17] and the meta-analysis from Bosdou et al. [18] analyzing both trials conducted by Massin et al. [16] and Kim et al. [17] reported that pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy (risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%) and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. A second meta-analysis conducted by also reported that testosterone-treated women achieved a significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy ra...

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“…After pooling the results, randomized studies showed no difference in the CPR (RR 1.23, 95% CI 0.97 -1.57), LBR (RR 1.27, 95% CI 0.89 -1.81) and IR (RR 1.39, 95% CI 0.96 -2.01) and abortion rate (RR 0.77, 95% CI 0.24 -2.42). However, this review was highly susceptible to publication bias secondary to the high methodological heterogeneity between the trials in which heparin's effect was assessed irrespective of the failed cycles, small numbers of women included with considerable difference in the administered formulations, dosing, timing of onset and duration of therapy [61].…”

Section: ) Inherited Thrombophiliamentioning

confidence: 99%

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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Effect of heparin on the outcome of IVF treatment: a systematic review and meta-analysis

Cited by 36 publications

References 33 publications

Improved Outcomes in ART Pregnancies Complicated by Thrombophilia, Treated with Low Molecular Weight Heparin in Comparison to Spontaneously Conceived Low-Risk, Untreated Pregnancies: A Case Control Study

Improved Outcomes in ART Pregnancies Complicated by Thrombophilia, Treated with Low Molecular Weight Heparin in Comparison to Spontaneously Conceived Low-Risk, Untreated Pregnancies: A Case Control Study

Adjuvants Therapies for Women Undergoing IVF: Is There Any Evidence of their Safety and Efficacy? An Updated Mini-Review

Recurrent Implantation Failure and Low Molecular Weight Heparin

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