Clinical trial NCT03209063: The Role of Prothrombin Gene and Methylenetetrahydrofolate Reductase(MTHFR) Gene Polymorphisms as Risk Factors for Recurrent Miscarriage
Official title: The Role of Prothrombin Gene and Methylenetetrahydrofolate Reductase(MTHFR) Gene Polymorphisms as Risk Factors for Recurrent Miscarriage
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Recurrent Miscarriage
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-07-06
Enrollment: 285
Sex: FEMALE
Minimum age (years): 17
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

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.

Primary outcomes:
measure: The study will compare the percentage of prothrombin gene and MTHFR gene polymorphisms in cases with recurrent miscarriage and healthy control group.
timeFrame: 2 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University, Faculty of medicine
name: Ghada M Mahran, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.