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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Miscarriage
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 285

Contacts and Locations

• Study Contact: Name: Hanan G Abdelazim, prof.doctor; Phone Number: 01227370520; Email: hanangalal2000@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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

Description

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) 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 and anticoagulant drugs.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group I; 195 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 Names: homocysteine assay
Group II; 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 Names: homocysteine assay

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Ghada M Mahran, MD, Assiut University, Faculty of Medicine

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: July 1, 2017
• First Submitted That Met QC Criteria: July 3, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 25, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pregnancy Complications; Recurrence; Abortion, Spontaneous; Abortion, Habitual
• Other Study ID Numbers: TROPGP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No