1. Inherited thrombophilia Screening
Dr. Z. Heidar
Associated Prof.
SBMU

2. Indication of screening
Common causes include : Factor V ,protrombin gen mutation , deficienies in pr C , pr S and antithrombin
Screening in asymptomatic family member with thrombophilia only if there is a strong family HX. Of VTE ( multiple first degree relatives with thrombotic event prior 50 )

3. ACOG
Weak association between inherited thrombophilias and adverse pregnancy outcomes.
Candidate for evaluation: a personal history of VTE with or without a recurrent risk factor
A first degree relative with history of high risk inherited thrombophilia
Not recommendedin women with hx of fetal loss or adverse pregnancy outcomes include abruption, preeclampsia ,IUGR,
Screening is usefull only when results will affect management decisions and not useful in situation that treatment is indicated for other risk factors.

4. What lab. test Factor V Prothrombin G20210A Antithrombin Pr S Pr C
Lab test is done 6WK after thrombotic event while the patient is not pregnant and not taking anticoagulant or hormonal therapy

5. Inherited deficiencies of anticoagulant proteins, e. g
Inherited deficiencies of anticoagulant proteins, e.g. protein C, protein S and Antithrombin are less common, but more strongly associated with venous thromboembolism than factor V Leiden and the prothrombin mutation. In a review, they reported no strong or significant association between deficiencies in these proteins and RPL

6. Treatment candidate
Decision to use anticoagulant in women with thrombophilia is influenced by :
Personal hx of VTE
Severity of thrombophilia
F.H of VTE
Additional risk factor such as c/s ,obesity ,prolonged immobility

7. Eshre guideline for RPL 2017
General recommendation:
Pregnancy loss is lowest in women 20-35
Stress , smoking , obesity , BMI are risk factor

8. investigation Hx
Genetic analysis of pregnancy tissue by array-CGH but not routinly
Parental karyotyping not routinly
For women with RPL, we suggest not to screen for hereditary thrombophilia unless in the context of research, or in women with additional risk factors for thrombophilia
screening for APA recommended after 2 abortions

9. HLA determination ,cytokin testing , NK testing ,antibody against HLA Ag,LPD testing , not recommended
TSH & anti TPO and assesment of uterine anatomy is recommended
In some situation : ANA . PRL , ovarian reserve ,sperm DNA fragmentation test

10. Hreditory thrombophilia & rif
ASRM :2012
Thrombophilia may be associated with risk for RIF. Once detected treatment with LMWH seems to improve IVF outcome.
OHSS

11. Reproductive biomedicine online :2014
Do not have a significant role in RIF.
Overall it remains to be determined whether thrombophilic conditions are a cause of RIF.

12. Assis reprod genet : 2016
Association between congenital and aquired thrombophilia and ART outcome is dubious.current evidence dose not support routinely testing or treatment for thrombophilia in the setting of ART nor in couples with implantation failour.A carefull personal and family history should be obtained and risk assesment for VTE should be made in every women undergoing COH and if positive, testing for thrombophilia is warranted.
FVL mutation → 3 fold increased risk of IVF failour

13. Eshre Recommendation 2017
If additional risk factors for hereditary thrombophilia are present (for instance family members with hereditary thrombophilia, or previous VTE), screening can be considered.

14. PLoS One. 2017 Oct 26;12(10):e0186022. doi: 10. 1371/journal. pone
PLoS One Oct 26;12(10):e doi: /journal.pone eCollection 2017.
The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population.
In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.