Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization

doi:10.1016/j.thromres.2018.05.006

Thrombosis Research

Volume 167, July 2018, Pages 26-31

https://doi.org/10.1016/j.thromres.2018.05.006 Get rights and content

Highlights

•
The presence of two or more thrombophilic defects was infrequent in women undergoing in-vitro fertilization.
•
The effects of multiple thrombophilic defects on outcomes of in-vitro fertilization remain unclear.
•
Live birth was lower with one or more thrombophilia, albeit differences were not significant.

Abstract

Introduction

The effects of multiple inherited and acquired thrombophilic defects on the outcome of in-vitro fertilization (IVF) remain unexplored. The aim of this study was to evaluate the association between multiple thrombophilia and clinical outcomes in a large prospective cohort of women undergoing IVF.

Materials and methods

Consecutive women scheduled for IVF were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, clinical pregnancy, and symptomatic venous thromboembolism.

Results

687 women with a mean age of 34.6 (±3.2) years were included. Overall, 22 women (3.2%) had two or more thrombophilic defects. The probability of live birth was not statistically significantly different between women with ≥2 thrombophilia (odds ratio [OR] 0.62; 95% confidence interval [CI], 0.18 to 2.11) or ≥1 thrombophilia (OR 0.67;95% CI, 0.41 to 1.09) and women without any thrombophilia. None of the individual inherited thrombophilia nor positivity to antiphospholipid antibodies or lupus anticoagulant were associated with live birth. Single positivity for lupus anticoagulant carried a more than threefold higher risk of abortion (OR 3.74; 95% CI, 1.30 to 10.75). There were no statistically significant associations between individual or multiple thrombophilic defects and clinical pregnancy or pregnancy test results. No woman had a history of venous thromboembolism and none developed a thrombotic event during the study.

Conclusions

In women undergoing IVF, the presence of two or more thrombophilic defects was rare and showed no statistically significant associations with IVF outcomes.

Introduction

The failure rate of assisted reproductive techniques such as in-vitro fertilization (IVF) remains as high as 60–70% causing intense emotional distress in women undergoing these procedures [1,2]. The pathophysiology behind the high failure rate is largely unexplained and likely multifactorial [3]. One of the potential mechanisms includes the abnormal coagulation activation at the maternal–fetal interface leading to thrombosis of the placental vessels and secondary implantation or placentation failures [4]. In a previous systematic review on the association between thrombophilia and outcomes of assisted reproduction techniques, we summarized the evidence from 33 studies involving 6092 patients and found that women with IVF failures tested more frequently positive for factor V Leiden and antiphospholipid antibodies [5]. However, these associations were only observed in case-control studies with a number of methodological limitations and were not confirmed in prospective cohorts. Since that meta-analysis, few other studies evaluated the potential influence of thrombophilia on the outcomes of IVF. In a large prospective cohort of 1717 women undergoing fresh non-donor IVF cycles, none of the eight inherited thrombophilia seemed to predict clinical pregnancy, live birth, or pregnancy loss [6]. In a retrospective analysis of 594 women with unexplained infertility initiating IVF treatment, none of the thrombophilia tested were significantly associated with the number of IVF cycles nor with lower fertility success rate [7]. Unexpectedly, carriers of factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.3% and 12.6%, respectively) in comparison to women who tested negative (9.0% and 9.7%, respectively). These and previous observations focused on inherited thrombophilia or separately evaluated individual thrombophilic defects without assessing the potential effects of multiple inherited and acquired thrombophilia that remain therefore unexplored.

The aim of this study was to evaluate the association between multiple inherited and acquired thrombophilia and clinical outcomes in a large prospective cohort of women undergoing IVF.

Section snippets

Study population

Consecutive women scheduled for IVF were eligible for this study. Exclusion criteria were an ongoing or indication for anticoagulant treatment, thrombophilia screening not available before IVF, age ≥40 years, embryo transfer not performed, lack of informed consent. The study was approved by the local institutional review board and all women signed a written informed consent before study procedures. The study is registered in clinicaltrial.gov with accession number NCT02407730.

Study outcomes

The primary study

Results

From March 2015 to July 2017, a total of 1008 eligible women were evaluated of whom 321 were excluded because of an ongoing anticoagulant treatment with low-molecular-weight heparin for ovarian hyperstimulation syndrome (n = 22), IVF cancelled or treatment discontinued for any reason (n = 75), no thrombophilia available before IVF or patients refused measuring any thrombophilia (n = 93), age ≥40 years (n = 125), or more than one of above reasons (n = 1, Fig. 1). Five additional patients moved

Discussion

In women undergoing IVF, the presence of two or more thrombophilic defects is rare. Our study did not detect statistically significant associations between multiple thrombophilia and live birth, abortion, clinical pregnancy, or positive pregnancy test.

A previous meta-analysis found an inconsistent association between thrombophilia and IVF outcomes [5]. While case-control studies suggested that infertile women tested more frequently positive for anti-phospholipid antibodies than fertile

Conclusion

The presence of two or more thrombophilic defects is uncommon in women undergoing IVF. Because of the imprecision in the estimates, the current study provides very weak evidence for an association between multiple thrombophilia and lower odds of live birth and higher risk of abortion. While larger studies may inform the debate about the effects of thrombophilia on IVF outcomes, the rarity of multiple thrombophilic defects questions their clinical relevance. Furthermore, the rare occurrence of

Conflict of interest

None of the authors have potential conflicts of interest to declare in relation to the current work.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' roles

Concept and design: MDN, GMT, EP. Interpretation of data, critical writing or revising the intellectual content, and final approval of the version to be published: MDN, AP, GMT, MDG, AWSR, EP.

Acknowledgments

None.

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Full Length ArticleEffects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization

Highlights

Abstract

Introduction

Materials and methods

Results

Conclusions

Introduction

Section snippets

Study population

Study outcomes

Results

Discussion

Conclusion

Conflict of interest

Funding

Authors' roles

Acknowledgments

Semin. Perinatol.

Blood

Chest

Fertil. Steril.

Lancet

J. Thromb. Haemost.

Lancet

Fertil. Steril.

Lancet

Am. J. Obstet. Gynecol.

J. Thromb. Haemost.

J. Thromb. Haemost.

J. Thromb. Haemost.

J. Thromb. Haemost.

European IVF-monitoring (EIM); consortium for the European society on human reproduction and embryology (ESHRE). Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE

Hum. Reprod.

Assisted reproductive technology in the United States: 2000 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry

Fertil. Steril.

Implantation and survival of early pregnancy

N. Engl. J. Med.

Full Length Article
Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization