Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilisation

2012 ◽  
Vol 108 (12) ◽  
pp. 1192-1197 ◽  
Author(s):  
Shlomo Berliner ◽  
David Steinberg ◽  
David Zeltser ◽  
David Levran ◽  
Orit Shimron ◽  
...  
Keyword(s):  
Success Rate ◽  
Embryo Implantation ◽  
Factor V Leiden ◽  
In Vitro Fertilisation ◽  
Healthcare Organisation ◽  
Factor V ◽  
History Of ◽  
Lower Fertility ◽  
The Mean

SummaryAssisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilias have been suggested by some investigators to play a role in abnormal embryo implantation and placentation. The objective of this study was to assess the role of common thrombophilias in women with unexplained infertility undergoing <i>in vitro</i>fertilisation (IVF). We retrospectively analysed 594 women from a large healthcare maintenance organisation going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organisation with no history of venous thromboembolism. The mean age of the women at the first cycle of IVF was 30.9 years (SD: 4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0%). None of the common thrombophilias tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and /or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.3% and 12.6%, respectively) in comparison to women who were tested negative (9.0% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure.

Prevalence of Common Thrombophilia and Antiphospholipid Antibodies in Unexplained Infertility Women Undergoing in Vitro Fertilization (IVF)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 628-628
Author(s):  
Arie Steinvil ◽  
Raanan Raz ◽  
Shlomo A. Berliner ◽  
David M Steinberg ◽  
David Zeltser ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Success Rate ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Unexplained Infertility ◽  
Factor V ◽  
Vitro Fertilization ◽  
History Of ◽  
The Mean

Abstract Abstract 628 Assisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilia have been suggested by some investigators to play a role in abnormal embryos implantation and placentation. The objective of this study was to assess the role of common thrombophilia in women with unexplained infertility undergoing in vitro fertilization (IVF). We enrolled five hundred ninety-four women from a large healthcare maintenance organization going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organization with no history of venous thromboembolisms. The mean age of the women at the first cycle of IVF was 30.9 years (SD: ±4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0). None of the common thrombophilia tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and/or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.25% and 12.64%, respectively) in comparison to women who were tested negative (8.98% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Successful pregnancy for primary amenorrhea and recurrent implantation failure and the role of hysteroscopic adhesiolysis: a case report

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Zakwan Khrait
Keyword(s):  
Uterine Cavity ◽  
Factor V Leiden ◽  
Estradiol Valerate ◽  
Primary Amenorrhea ◽  
Factor V ◽  
Reproductive Techniques ◽  
History Of ◽  
The Right

Abstract Background Infertility continues to be an enigmatic and emerging problem. Although in vitro fertilization has proved to be revolutionary and immensely beneficial to many people, it is far from perfect, and many women experience recurrent in vitro fertilization failures. There can be a multitude of factors involved in recurrent in vitro fertilization failures. The aim of this report was to explore the role of hysteroscopy in determining potential causes of in vitro fertilization failure and how the relevant hysteroscopic findings can address the issue of infertility in terms of a subsequent successful in vitro fertilization. Case presentation A 37-year-old white Arab woman with a history of eight in vitro fertilization failures and one curettage performed for a blighted ovum presented to our hospital because of inability to conceive. Her past medical history was significant for hypothyroidism and positive factor V Leiden. She underwent hystero contrast sonography, which revealed a normal uterine cavity with irregular fillings in the right corner. To explore this further, hysteroscopy was performed, which showed dense adhesions in the right upper corner and first-degree adhesions in the lower half of the uterus. After undergoing adhesiolysis and a cycle of estradiol valerate and progesterone, the patient successfully conceived twins. Conclusions Hysteroscopy may play an important role before or in conjunction with assisted reproductive techniques to help infertile women and couples achieve their goals of pregnancy and live birth of a child.

P–362 The effect of nolasiban on uterine contractility at the time of embryo transfer in in vitro fertilisation patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Rees ◽  
Y Huang ◽  
M Akhtar ◽  
M Mischi ◽  
A Humberstone ◽  
...  
Keyword(s):  
Uterine Contraction ◽  
Embryo Implantation ◽  
Group Versus ◽  
In Vitro Fertilisation ◽  
Measurement Tool ◽  
Uterine Contractility ◽  
Contraction Frequency ◽  
Uterine Contractions ◽  
The Mean

Abstract Study question What is the effect of nolasiban on the uterine contractility of in-vitro fertilisation (IVF) patients prior to embryo transfer (ET) ? Summary answer A single oral dose of nolasiban 900 mg administered 4 h before ET significantly decreased contraction frequency and increased coordination compared to placebo. What is known already Nolasiban is an investigational oral oxytocin receptor antagonist (OTRa) being developed to improve the chance of pregnancy following ET. Increased uterine contraction frequency can influence embryo implantation, and the coordination of these uterine contractions is equally important. OTRa have been shown to decrease uterine contractions and increase endometrial perfusion. Recently, an automated and quantitative measurement tool using transvaginal ultrasound (TVUS) to better characterise uterine contractility has been developed which can be used to quantify the effect of nolasiban on uterine contractility. Study design, size, duration This study is part of a completed multi-centre randomised placebo-controlled trial (IMPLANT 1 – NCT02310802) in IVF patients (n = 247) carried out in 2015. Our study retrospectively assessed a sub-set of patients with good quality TVUS recordings to evaluate their mechanical uterine motion that were randomised to receive either nolasiban 900mg (n = 39) or placebo (n = 42). Participants/materials, setting, methods Subjects were &lt; 37 years, undergoing ET on Day 3 following IVF/ICSI and with evidence of uterine contractions 4 h before ET. Nolasiban was administered 4 h before ET. Patients underwent TVUS immediately before drug administration and again immediately before ET. Uterine contraction frequency, amplitude, power and coordination were measured by applying dedicated speckle tracking and strain analysis. The Shapiro–Wilk test, followed by the Wilcoxon rank-sum test were applied to compare features between treatment groups. Main results and the role of chance The mean (SD) frequency of uterine contractions was 1.54 (0.25) in the nolasiban group versus 1.57 (0.12) in the placebo group (p = 0.016). The mean (SD) coordination was 0.10 (0.17) in the nolasiban group versus 0.02 (0.16) in the placebo group (p = 0.034). The coordination feature was measured by assessing the presence of simultaneous movements of the anterior and posterior uterine walls, a higher value reflects increased coordination. There was no difference in contraction amplitude or power. Limitations, reasons for caution This was a retrospective analysis of TVUS videos. The small sample size limits the generalisability of the findings. Furthermore, our initial results do not show how the changes in uterine motion may affect pregnancy rate after ET, meaning that the clinical relevance of our results remains to be proven. Wider implications of the findings: Our results show that in patients taking one 900mg dose of nolasiban prior to ET, beneficial uterine contractions are seen, which could be promising for embryo implantation and pregnancy in IVF patients. Our quantitative TVUS measurement tool can be applied to different patient populations to accurately quantify uterine motion. Trial registration number NCT02310802

Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

1997 ◽  
Vol 77 (05) ◽  
pp. 0822-0824 ◽  
Author(s):  
Elvira Grandone ◽  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Marina d'Addedda ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Protein C ◽  
Strong Association ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Significant Difference ◽  
History Of ◽  
Fv Leiden ◽  
Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns

2006 ◽  
Vol 95 (03) ◽  
pp. 434-440 ◽  
Author(s):  
Satu Hyytiäinen ◽  
Ulla Wartiovaara-Kautto ◽  
Veli-Matti Ulander ◽  
Risto Kaaja ◽  
Markku Heikinheimo ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Factor V Leiden ◽  
Factor V ◽  
Cord Plasma ◽  
Adult Plasma ◽  
Thrombin Formation

SummaryThrombin regulation in newborns remains incompletely understood.We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor VLeiden (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1+2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was ∼60% of that in adult plasma, while thrombin formation started ∼55% and ∼40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5nM APC decreased ETP by 17.4±3.5% (mean±SEM) compared with only 3.5±3.8% in FVL-positive cord plasma (p=0.01). FVL-positive newborns showed similar levels of F1+2 but significantly decreased levels of factor V compared with FVL negative newborns both in cord plasma (FV 0.82±0.07 U/ml vs. 0.98±0.05 U/ml, p=0.03) and at the age of two weeks (FV 1.15±0.04 U/ml vs. 1.32±0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance and a procoagulant effect in newborn plasma. Lack of elevated F1+2 levels in FVL-positive infants, however, suggested the existence of balancing mechanisms; one could be the observed lower level of factor V in FVL heterozygous newborns.

scholarly journals A Giant Right Heart Thrombus-in-Transit: The Challenge of Anticoagulation in Factor V Leiden Thrombophilia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Andrew Chu ◽  
Thu Thu Aung ◽  
Minni Shreya Arumugam ◽  
Mauricio Danckers ◽  
Mohi Mitiek ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Single Point ◽  
Factor V Leiden ◽  
Single Point Mutation ◽  
Homozygous Mutation ◽  
Factor V ◽  
Right Heart ◽  
Blood Clots ◽  
History Of ◽  
In Transit

Factor V Leiden (FVL) is an autosomal dominant condition resulting in thrombophilia. Factor V normally acts as a cofactor for prothrombinase, helping cleave prothrombin to thrombin. A single point mutation in it disrupts factor V, making it unreceptive to protein C and increasing the risk of thrombosis. FVL mutation associated with right heart thrombus is a rare entity. Right heart thrombus or right heart thrombus-in-transit is associated with high mortality. We present a 51-year-old male with a past medical history of FVL homozygous mutation and recurrent blood clots, who has failed multiple different oral anticoagulants. He presented to the hospital with symptoms of shortness of breath and subsequently found to have a giant right heart thrombus. He was treated with surgical embolectomy. This case underscores the challenges faced by patients with FVL and recurrent blood clots.

The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism

2013 ◽  
Vol 109 (01) ◽  
pp. 79-84 ◽  
Author(s):  
Sylvia Reitter-Pfoertner ◽  
Thomas Waldhoer ◽  
Michaela Mayerhofer ◽  
Ernst Eigenbauer ◽  
Cihan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Multivariable Analysis ◽  
Factor V Leiden ◽  
Arterial Disease ◽  
Factor V ◽  
Term Survival ◽  
Long Term Survival ◽  
History Of

SummaryData on the long-term survival following venous thromboembolism (VTE) are rare,and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 outpatients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.

Circulating microparticles in carriers of factor V Leiden with and without a history of venous thrombosis

2012 ◽  
Vol 108 (10) ◽  
pp. 633-639 ◽  
Author(s):  
Elena Campello ◽  
Luca Spiezia ◽  
Claudia M. Radu ◽  
Maria Bon ◽  
Sabrina Gavasso ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Annexin V ◽  
Factor V ◽  
Thrombotic Risk ◽  
Study Results ◽  
Significant Difference ◽  
Circulating Microparticles ◽  
Venous Thromboembolic ◽  
The Mean ◽  
And Gender

SummaryAlthough factor V Leiden (FVL) is a major determinant of thrombotic risk, the reason why less than 10% of carriers eventually develop venous thromboembolic (VTE) events is unknown. Recent observations suggest that circulating levels of microparticles (MP) may contribute to the thrombogenic profile of FVL carriers. We measured the plasma level of annexin V-MP (AMP) platelet-MP (PMP), endothelial-MP (EMP), leukocyte-MP (LMP) and tissue factor-bearing MP (TF+MP), and the MP procoagulant activity (PPL) in 142 carriers of FVL (of these 30 homozygous and 49 with prior VTE), and in 142 age and gender-matched healthy individuals. The mean (± SD) level of AMP was 2,802 ± 853 MP/ μl in carriers and 1,682 ± 897 in controls (p<0.0001). A statistically significant difference between homozygous and heterozygous carriers of FVL was seen in the level of PMP, EMP and LMP, but not in that of the remaining parameters. When the analysis was confined to carriers with and without a VTE history, the mean level of AMP was 3,110 ± 791 MP/ μl in the former, and 2,615 ± 839 MP/μl in the latter (p<0.005). The mean level of all subtypes of circulating MP showed a similar pattern. The PPL clotting time was 39 ± 9 seconds (sec) in carriers, and 52 ± 15 sec in controls (p=0.003); and was 35 ± 8 sec in carriers with prior thrombosis, and 41 ± 10 sec in thrombosis-free carriers (p<0.005). Our study results suggest that circulating MP may contribute to the development of thrombosis in carriers of FVL mutation.

Abstract 6207: Derivation of a Novel Prediction Algorithm for Idiopathic Venous Thromboembolism in Women

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Brendan M Everett ◽  
Nina P Paynter ◽  
Julie E Buring ◽  
Robert J Glynn ◽  
Nancy R Cook ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Information Criterion ◽  
Apolipoprotein A1 ◽  
Prediction Algorithm ◽  
Factor V ◽  
Risk Reclassification ◽  
Best Fitting ◽  
The Mean ◽  
Caucasian Women

Background : Established risk factors for idiopathic venous thromboembolism (VTE) include age, prothrombotic mutations, and obesity. A risk prediction algorithm might allow clinicians to focus preventive efforts. Methods : We derived a prediction model for idiopathic VTE using 22 possible predictor variables and their interactions in 19,458 initially healthy Caucasian women who were followed for incident idiopathic VTE. Minimization of the Bayes Information Criterion (BIC) was used to help identify the best, most parsimonious model, and estimates of discrimination (C-index) and calibration (Hosmer-Lemeshow (H-L) statistic) comparing observed and predicted risk were computed and compared with a model including only age and weight. Results: The mean (SD) age was 54.1 (7.1) years, the mean (SD) weight 69.9 (14.1) kilograms, and 2.8% and 5.3% of participants carried the prothrombin and factor V Leiden mutations, respectively. After a median of 12.4 years of follow up, we observed 130 idiopathic cases of VTE. The best fitting model included log(age), log(weight), log(apolipoprotein A1), and the presence of the prothrombin or factor V Leiden mutations (C-index 0.704; H-L statistic 5.9). When compared to model including only log(age) and log(weight) (C-index 0.636; H-L statistic 3.9), the full model achieved higher discrimination at similar calibration and led to a net reclassification of 34.5 percent (6705) of participants, all correctly. Conculsion: In our population of middle-aged, initially healthy Caucasian women, a model that includes age, weight, apolipoprotein A1, and the prothrombin and factor V Leiden mutations predicts incident idiopathic VTE more accurately than one including age and weight alone. Table. Idiopathic venous thromboembolism risk reclassification - basic and best-fitting models

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