Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis

Nisio, Marcello Di; Rutjes, Anne W S; Ferrante, Noemi; Tiboni, Gian Mario; Cuccurullo, Franco; Porreca, Ettore

doi:10.1182/blood-2011-03-340216

Cited by 83 publications

(61 citation statements)

References 54 publications

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“…While some studies have suggested that repeat IVF failure may be associated with an increased incidence of thrombophilia [37][38][39][40][41] others have negated such an association [42][43][44]. In a recent systemic review and metaanalysis, pooled data from patients in 8 case control studies showed an overall 3-fold increased risk of ART failure in association with factor V Leiden; while in the 3 cohort studies there was no difference in outcome between those with and those without factor V Leiden mutation [45]. Although our study was not targeted to examine the association between thrombophilia and repeat IVF failure, our findings do not support such an association.…”

Section: Discussionmentioning

confidence: 99%

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Younis

Ben‐Ami

Izhaki

et al. 2013

J Assist Reprod Genet

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Purpose In the last few years more robust evidence is emerging to point out at an increased rate of prematurity and low birth weight in singleton pregnancies following ART. Whether this increased rate is related to ART practice or to infertility per se, is still an open question. Our aim in this study was to explore this question by evaluating Protein C (ProC) Global assay in infertile women before ART treatment. Methods A cohort of 95 unselected and consecutive infertile women, eligible for ART, was prospectively recruited for the study. The control group included 77 matched healthy fertile women with a history of spontaneous conceptions. Pro C Global assay was evaluated in both groups. A full thrombophilic work-up was performed in the study group.Results ProC Global assay level was found to be significantly lower in the study as compared to the control group, corresponding to 0.78 ± 0.16 and 0.88 ± 0.16, respectively (P <0.01). As well, abnormal ProC Global assay level of ≤0.8 was significantly higher in the study as compared to control group corresponding to 53 % and 29 %, respectively. ProC Global assay level was significantly lower in women within the study group found to have APCR, factor V Leiden and high factor VIII level, any thrombophilia or combined thrombophilia when compared to women without these thrombophilic risk factors. Conclusions Reduced ProC Global assay level is encountered in infertile women prior to ART treatment. This finding may suggest a unique anticoagulation Protein C pathway in infertile as compared to fertile women. Further studies are encouraged to explore this finding.

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Section: Discussionmentioning

confidence: 99%

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Younis

Ben‐Ami

Izhaki

et al. 2013

J Assist Reprod Genet

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“…No significant differences were found in relation to other thrombophilia mutations. The results of this review were inconclusive, since the methodological quality of studies was poor, many were retrospective case-control, known to be limited by poor collection of data D. Khalife, G. Ghazeeri Open Journal of Obstetrics and Gynecology on potential confounders and recall bias [49]. Ricci has confirmed the absence of association of thrombophilia with adverse IVF outcome by conducting a prospective cohort study of 510 women to compare the prevalence of factor V leiden and prothrombin gene G20210A mutation in women undergoing IVF and showed no statistical significant difference in the reproductive outcomes (implantation rate (IR), clinical pregnancy rate (CPR), and livebirth rate (LBR)) compared to non-mutation carrier women [43].…”

Section: Thrombophilia and Ivfmentioning

confidence: 91%

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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“…Although the relationship between vascular thrombosis and obstetric complications was first recognized in women with Antiphospholipid Syndrome (APS), both inherited and acquired thrombophilia have been associated with recurrent pregnancy loss and pregnancy complications, such as severe pre-eclampsia, fetal growth restriction and stillbirth [41].…”

Section: Thrombosis and Rmmentioning

confidence: 99%

“…However, it is noteworthy that women with the presence of aPL and no evidence of placental thrombosis also experience pregnancy loss [41,54]. Thus, pathophysiology other than placental thrombosis may influence pregnancy outcome.…”

Section: Acquired Thrombophilic Conditionsmentioning

confidence: 99%

Recurrent Miscarriage: A Review

Barrenetxea¹

2017

RMGO

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pregnancy events [2]. Clinical miscarriages may be subdivided into early clinical pregnancy losses (before gestational week 12) and late clinical pregnancy losses (gestational weeks 12 to 21). The term miscarriage is preferred rather than abortion both by patients and physicians, although "spontaneous abortion" is still used in scientific literature [3,4].For more than 30 years, controversy has existed on the number of miscarriages required to define RM and when diagnostic testing is warranted [5] EpidemiologyEarly pregnancy loss is perhaps the most common obstetric complication, occurring in over two-thirds of human conceptions. Approximately 15 -20% of all clinically recognized pregnancies will end in a miscarriage [4,9,10]. However, prospective cohort studies using sensitive and specific daily urinary hCG assays in women trying to conceive have demonstrated that only around one-third of conceptions progress to a live birth. Most of the losses occur before the clinical recognition of pregnancy as implantation failures. An estimated 30% of human conceptions are lost prior to implantation and a further 30% following implantation but before the missed menstrual period, that is in the third or fourth week of gestation. These are often termed preclinical losses [11].The risk of sporadic miscarriage between 6 and 12 weeks of gestation in women less than 35 years of age is 9% to 12%. The risk increases with age. In women older than 40 years of age, the sporadic miscarriage rate approaches 50%. Late losses between 12 and 22 weeks occur less frequently and constitute around 4% of pregnancy outcomes [4,9].Compared to sporadic miscarriage the prevalence of RM is considerably lower irrespective of whether biochemical losses are included or not. Approximately 1% of all women trying to conceive have recurrent miscarriage, defined as three previous miscarriages; when recurrent miscarriage is defined as two previous miscarriages, the proportion rises to 3% [12,13]. EtiologyMultiple potential etiologies for RM have been described (Table 1). As a consequence, several recommendations have been published regarding the evaluation and management of RM [3].The potential etiologies of RM can be divided into embryologically driven causes (mainly due to an abnormal embryonic karyotype) and maternally driven causes which affect the endometrium and/or placental development [14,15]. Thus, studies that focus on RM have Barrenetxea G, et al., J Reprod Med Gynecol Obstet 2017 AbstractHuman reproduction is characterized by its inefficiency. The loss of pregnancy at any stage can be a devastating experience and particular sensitivity is required in assessing and counseling couples with Recurrent Miscarriage (RM). Recurrent Miscarriage (RM) represents a clinical challenge for physicians not only because there are multiple possible etiologies, but also because the diagnostic testing is costly and time consuming. Despite several well-known etiologic factors, the cause of RM cannot be determined in almost 50% of cases. Multiple potential etiolo...

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Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis

Cited by 83 publications

References 54 publications

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Recurrent Implantation Failure and Low Molecular Weight Heparin

Recurrent Miscarriage: A Review

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