Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score

Miscarriage, Recurrent Clinical Trial

— TiC-RPL  

Official title:

Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03336463
• Other study ID #: FerrerinCode
• Status: Completed
• Phase: N/A
• First received: October 23, 2017
• Last updated: November 3, 2017
• Start date: February 2015
• Est. completion date: January 2017

Study information

• Verified date: November 2017
• Source: Ferrer inCode, S.L.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recurrent pregnancy loss (RPL) is a clinical problem affecting 1-5% of couples of reproductive age. The contribution of thrombophilia to RPL is disputed. This controversy is partly due to low sensitivity of the genetic variants currently used to evaluate hereditary thrombophilia: the Leiden mutation (identified as rs6025) in the coagulation factor 5 (F5L) gene and mutation G20210A (identified as rs1799963) in the prothrombin (PT) gene.

Our objective was to determine whether a wider algorithm that includes clinic and genetic variants associated with thrombophilia could be more useful in the prediction for RPL than FVL and PT alone.

Description:

Recurrent pregnancy loss can affect up to 5% of women in child-bearing age and is considered one of the most common causes of female sterility. In recent years, the association between thrombophilia and pregnancy failure has been observed in a number of studies, varying according to the nature of the thrombophilia (for example the antiphospholipid syndrome as opposed to the hereditary forms) or the type of pregnancy loss (either isolated or recurrent, or early or late). It has therefore been accepted that thrombophilia is detected in a significant number of idiopathic pregnancy losses, reaching 66% of the cases in some series.

Since the 1990's, a number of studies have associated recurrent pregnancy loss with FVL mutations (most frequently) and G20210 PT. In a systematic review, it was confirmed that women with thrombophilia have a higher risk of developing thromboembolism and complications in pregnancy. Another recent meta-analysis of prospective cohort studies concluded that women who were carriers of FVL had a higher risk of late pregnancy loss, at 52%, as opposed to non-carriers (OR=1.52), though the differences in absolute risk were discreet (4.2% and 3.2%, respectively). However, the analysis of these 2 single nucleotide polymorphisms (SNPs) showed low discriminative capacity and diagnostic sensitivity.

This study hypothesize that the use of the Thrombo inCode® in the screening for hereditary thrombophilia in patients with recurrent pregnancy loss can improve the diagnostic sensitivity and predictive capacity of the routine genetic panel, based on FVL and G20210A PT. Thus, the Thrombo inCode® model can accurately identify more patients with clinical-genetic risk of thromboembolism and therefore establish the appropriate preventive measures.

A transversal observational case-control study will be carried out, with retrospective data analysis. The screening for hereditary thrombophilia will be performed through the Thrombo inCode® panel in cases and controls. The results produced from a single genetic analysis will allow comparison to the centres' routine protocol (FV Leiden and G20210A PT) with the complete Thrombo inCode® panel, that also includes the previously-mentioned classical variants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: January 2017
• Est. primary completion date: November 2016
• Gender: Female
• Age group: 18 Years to 37 Years

Eligibility

CONTROLS

Inclusion Criteria:

• Women >18 and < 38 years old at the time of the first pregnancy.

• Women with successful implantation and at least one full-term pregnancy

• No chronic pathology

Exclusion Criteria:

• Personal or family history of thrombosis

• Personal history of obstetric complications Miscarriage or foetal death Pre-eclampsia or eclampsia Intrauterine growth restriction Placental abruption

• Concomitant anticoagulant treatment and/or antiplatelet treatments during pregnancy

CASES

Inclusion Criteria:

• Repeated clinical miscarriages and/or foetal death (= 2 consecutive or = 3 non- consecutive) before the 20th weeks of pregnancy, from spontaneous or assisted pregnancies.

• Recurrent miscarriage with the same gametic origin.

Idiopathic origin:

Women < 38 years old Non-severe seminal factor (sperm concentration > 2 mill/ml) Normal karyotypes in both spouses (or in the male and the donor in the case of ovocyte donation) Antiphospholipid syndrome negative Normal or corrected thyroid function BMI < 30

Exclusion Criteria:

• Diabetes

• Chronic pathologies

• Hydrosalpinx

• Concomitant anticoagulant or antiplatelet treatment

Related Conditions & MeSH terms

• Abortion, Habitual
• Abortion, Spontaneous
• Miscarriage, Recurrent
• Thrombophilia

Locations

Country	Name	City	State
Spain	Institut d'Investigació Sant Pau	Barcelona
Spain	Gendiag.exe, S.L.	Esplugues de Llobregat	Select State
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Instituto Salud Carlos III	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Instituto de Investigaciones Sanitarias La Fe	Valencia
Spain	IVI-RMA Valencia	Valencia
United Kingdom	IVI-RMA-London	London

Sponsors (9)

Lead Sponsor	Collaborator
Ferrer inCode, S.L.	Clinica Universidad de Navarra, Universidad de Navarra, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Gendiag.exe, S.L., Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Instituto de Investigacion Sanitaria La Fe, Instituto de Salud Carlos III, Instituto Valenciano de Infertilidad, IVI VALENCIA, IVI-RMA London

Countries where clinical trial is conducted

Spain,  United Kingdom, 

References & Publications (1)

Soria JM, Morange PE, Vila J, Souto JC, Moyano M, Trégouët DA, Mateo J, Saut N, Salas E, Elosua R. Multilocus genetic risk scores for venous thromboembolism risk assessment. J Am Heart Assoc. 2014 Oct 23;3(5):e001060. doi: 10.1161/JAHA.114.001060. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrent Pregnancy Loss	Repeated clinical pregnancy loss and/or foetal death (= 2 consecutive or = 3 non-consecutive) before the 20th weeks of pregnancy	20 weeks
Primary	Pregnancy at term	Pregnancy with life-birth	20 weeks