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

NCT ID: NCT03209063

Last Updated: 2022-06-30

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 285 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2022-09-30

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.

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.

Conditions

Recurrent Miscarriage

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Group I

195 Patients having history of two or more miscarriages.

polymerase chain reaction

Intervention Type: DIAGNOSTIC_TEST

diagnostic test as Polymerase chain reaction for detection of Prothrombin gene and methylenetetrahydrofolate reductase gene polymorphisms

Group II

90 healthy controls less than 35 years with no history of miscarriage and at least one uncomplicated full-term pregnancy

polymerase chain reaction

Intervention Type: DIAGNOSTIC_TEST

diagnostic test as Polymerase chain reaction for detection of Prothrombin gene and methylenetetrahydrofolate reductase gene polymorphisms

Interventions

polymerase chain reaction

diagnostic test as Polymerase chain reaction for detection of Prothrombin gene and methylenetetrahydrofolate reductase gene polymorphisms

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

homocysteine assay

Eligibility 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) 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.

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Ghada Mahran

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ghada M Mahran, MD

Role: PRINCIPAL_INVESTIGATOR

Assiut University, Faculty of medicine

Central Contacts

Hanan G Abdelazim, prof.doctor

Role: CONTACT

hanangalal2000@yahoo.com

01227370520

References

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.

Reference Type: BACKGROUND

PMID: 26135458 (View on PubMed)

Ahmed Abd Elhameed Z, Shaaban OM, Abd Elazeem HG, Abouelfadle A, Farghaly T, Mahran G, Seddik MI. Role of Prothrombin and Methylenetetrahydrofolate Reductase Gene Polymorphisms as well as Thrombophilia Markers, as Risk Factors for Unexplained Recurrent Miscarriage: A Case-Control Study. Int J Fertil Steril. 2025 Jan 5;19(1):36-43. doi: 10.22074/ijfs.2023.1986225.1418.

Reference Type: DERIVED

PMID: 39827389 (View on PubMed)

Other Identifiers

TROPGP

Identifier Type: -

Identifier Source: org_study_id