The Role of Prothrombin Gene and Methylenetetrahydrofolate Reductase(MTHFR) Gene Polymorphisms as Risk Factors for Recurrent Miscarriage

• ClinicalTrials.gov Identifier: NCT03209063
• Recruitment Status: Unknown
• First Posted: July 6, 2017
• Last Update Posted: December 19, 2019
• Sponsor: Assiut University
• Information provided by (Responsible Party): Ghada Mahran, Assiut University

Study Description

Brief Summary:

Recurrent miscarriage is a pregnancy loss before 20 weeks of gestation. The recurrent pregnancy loss(RPL) usually occurring in the first trimester of gestation and its rate is quite high (15-20% even in full reproductive period) . In 2012, the American Society for Reproductive Medicine Practice Committee issued a statement that defined recurrent pregnancy loss as a disease distinct from infertility defined by two or more failed consecutive pregnancies.approximately 40% of couples will have an etiology identified that could be associated with their loss.

Condition or disease	Intervention/treatment
Recurrent Miscarriage	Diagnostic Test: polymerase chain reaction

Detailed Description:

Recurrent miscarriage is a pregnancy loss before 20 weeks of gestation. The recurrent pregnancy loss usually occurring in the first trimester of gestation and its rate is quite high (15-20% even in full reproductive period) . In 2012, the American Society for Reproductive Medicine Practice Committee issued a statement that defined recurrent pregnancy loss as a disease distinct from infertility defined by two or more failed consecutive pregnancies.approximately 40% of couples will have an etiology identified that could be associated with their loss.Thrombophilia is the tendency to develop thromboses due to inherited defects in the coagulation system.Thrombophilia was identified as a major cause of RPL,Because pregnancy is a hypercoagulable state, thromboembolism is the leading cause of antepartum and postpartum maternal mortality .The four most common genetic markers for thrombophilia are; prothrombin gene mutation(FII, G20210A), methylene tetra hydrofolate reductase mutations (MTHFR ,C677T and A1298C), factor V Leiden (FVL, G1691A) , and plasminogen activator inhibitor 1 (PAI-1) . Prothrombin G20210A refers to a human gene mutation that increases the risk of blood clots . Approximately 1 in 50 people in the white population in the United States and Europe has prothrombin thrombophilia. Study was conducted to evaluate the frequency of PT20210 among healthy Egyptians, (1.06%) had PT20210 G-A mutation.The variant causes elevated plasma prothrombin levels (hyperprothrombinemia), Prothrombin is the precursor to thrombin, which plays a key role in causing blood to clot (blood coagulation).Prothrombin G20210A can thus contribute to a state of hypercoagulability . Methylene tetra hydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the Methylene tetra hydrofolate reductase gene. It was thought that deficient Methylene tetra hydrofolate reductase, by causing elevated homocysteine levels, led to an increased risk of venous thrombosis, coronary heart disease, and recurrent pregnancy loss . Previous studies suggested that percentage of PT20210 in patients with unexplained RPL is ( 10.9%),however searching literatures didn't find any estimation of this percentage in Egyptian population.

Study Design

• Study Type: Observational
• Estimated Enrollment: 180 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: The Role of Prothrombin Gene and Methylenetetrahydrofolate Reductase(MTHFR) Gene Polymorphisms as Risk Factors for Recurrent Miscarriage
• Estimated Study Start Date: December 20, 2019
• Estimated Primary Completion Date: August 1, 2020
• Estimated Study Completion Date: December 30, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Group 1; 90 healthy controls less than 35 years with no history of miscarriage and at least one uncomplicated full-term pregnancy.	Diagnostic Test: polymerase chain reaction; diagnostic test as Polymerase chain reaction for detection of Prothrombin gene and methylenetetrahydrofolate reductase gene polymorphisms; Other Name: homocysteine assay
Group 2; 90 Patients having history of two or more miscarriages.	Diagnostic Test: polymerase chain reaction; diagnostic test as Polymerase chain reaction for detection of Prothrombin gene and methylenetetrahydrofolate reductase gene polymorphisms; Other Name: homocysteine assay

Outcome Measures

Primary Outcome Measures :

1. The study will compare the percentage of prothrombin gene and MTHFR gene polymorphisms in cases with recurrent miscarriage and healthy control group. [ Time Frame: 2 days ]
   using polymerase chain reaction Polymerase chain reaction

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The study will be conducted at Clinical Pathology Department,Women's Health Hospital ,Assiut University Hospital, Faculty of Medicine, Assiut University

Criteria

Inclusion Criteria

1. Age less than 35 years.
2. History of two or more spontaneous miscarriages

Exclusion Criteria:

1. Age more than 35 years.
2. . Women with elevated level of TSH above (2.5 mIU/ml) or prolactin above( 19.5 ng/mL)and uncontrolled DM.
3. Women with autoimmune disorder (antiphospholipid antibody syndrome)with LA1/LA2 ratio more than( 1.2).
4. Women receiving oral contraceptive pills.

Contacts and Locations

Contacts

Contact: Hanan G Abdelazim, prof.doctor; 01227370520; hanangalal2000@yahoo.com

Sponsors and Collaborators

Assiut University

Investigators

• Principal Investigator: Ghada M Mahran, MD; Assiut University, Faculty of medicine

More Information

Publications:

Farahmand K, Totonchi M, Hashemi M, Reyhani Sabet F, Kalantari H, Gourabi H, Mohseni Meybodi A. Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. J Matern Fetal Neonatal Med. 2016;29(8):1269-73. doi: 10.3109/14767058.2015.1044431. Epub 2015 Jul 2.

• Responsible Party: Ghada Mahran, principal investigator, Assiut University
• ClinicalTrials.gov Identifier: NCT03209063
• Other Study ID Numbers: TROPGP
• First Posted: July 6, 2017
• Last Update Posted: December 19, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Abortion, Spontaneous; Abortion, Habitual; Pregnancy Complications