Understanding Thrombophilia and Recurrent Pregnancy Loss

Recurrent Pregnancy Loss: A Comprehensive Overview

Recurrent pregnancy loss is characterized by the loss of three or more consecutive pregnancies prior to the 20th week of gestation (Ford, 2009), excluding ectopic, molar, and biochemical pregnancies. This condition affects approximately 1-2% of women of reproductive age and remains a significant clinical challenge (Stephenson, 1996).

Nevertheless, when recurrent pregnancy loss is defined as the loss of two or more consecutive pregnancies (ACOG, 2013), the incidence rises to 5%. The risk of subsequent pregnancy loss increases to 24% after two miscarriages, 30% after three miscarriages, and up to 40% after four consecutive miscarriages (Regan, 1989).

Etiologies of recurrent pregnancy loss included:

• Anatomical uterine abnormalities, infections
• Endocrine and immunological disorders
• Thrombophilia
• Genetic abnormalities
• Environmental factors and causes unknown

Thrombophilia, a heterogeneous group of inherited or acquired thrombophilic disorders, has emerged as a significant risk factor for recurrent pregnancy loss.

Classification of Thrombophilia

Thrombophilia is a heterogeneous group of disorders characterized by an increased tendency of blood to clot. Both inherited and acquired thrombophilic states are prevalent. Approximately 15% of the Caucasian population carries a genetic mutation associated with a hypercoagulable state.

Classification of thrombophilia includes:

Inherited thrombophilia: Characterized by genetic mutations such as Factor V Leiden (FVL), prothrombin factor II G20210A gene mutation  (FII), methylenetetrahydrofolate reductase mutation (MTHFR) leading to hyperhomocysteinemia, and plasminogen activator inhibitor-1 (PAI-1) gene mutations.

Acquired thrombophilia: Including antiphospholipid syndrome (APS), protein S deficiency, and protein C deficiency.

Combined thrombophilia: A combination of inherited and acquired thrombophilic states, such as methylenetetrahydrofolate reductase gene (MTHFR) mutation in conjunction with folate and vitamin B12 deficiency.

Thrombophilia and Recurrent Pregnancy Loss

Recent research has focused on systematic reviews investigating the association between inherited thrombophilia and recurrent pregnancy loss, the role of thrombophilic gene polymorphisms, the efficacy of low-molecular-weight heparin, and the specific contributions of prothrombin G20210A mutation, Factor V Leiden mutation, and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms to recurrent miscarriage.

Women with a history of recurrent pregnancy loss should undergo a comprehensive preconception evaluation 3-5 months prior to attempting conception. This evaluation should include a thorough medical history, physical examination, and appropriate laboratory investigations to identify and address underlying factors contributing to infertility or recurrent pregnancy loss.

Thrombophilia Testing at GENTIS

Sample required: 2ml of whole blood 

Method: Genetic sequencing 

Turnaround time: 5 days 

Sensitivity: 100% 

Specificity: 100%

Sources: hosrem.org.vn, vinmec.com

REFERENCES

1. ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy. Obstetrics & Gynecology. 2018; 132(1): e18-e34. 
2. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012; 98 (5): 1103-1111. 
3. Ford HB & Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Reviews in obstetrics & gynecology. 2009; 2(2): 76–83. 
4. No, Green-top Guideline. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage, April 2011. 
5. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012; 120(6): 1514-1521. 
6. Rey E et al. Thrombophilic disorders and fetal loss: a meta-analysis, Lancet. 2003; 361(9361): 901-908. 
7. The ESHRE Guideline Group on RPL. ESHRE guideline: recurrent pregnancy loss, Human Reproduction Open. 2018; (2).