Unexplained IUFD / Recurrent Preg loss -How to investigate?

What tests that has to be done in a case of RPL / unexplained & unpredicted IUFD near term. Tests which are worth doing are: as follows:

Type I tests : Extrauterine factors  causing IUFD are more in number than intrauterine factors, which are like synechiae, septal disorders, submucous Myoma-3D USG.

Part I: common tets for  Extrauterine disorders causing IUFD/ RPL?  –To enquire detailed of medieval diseases & family history, consanguinity, operation. Work place toxicity, Complete haemogram, Thalassaemia screening, HBA1c, OGTT, Viral Serology (like CMV,. IgG rubella) , hepatitis serology , Pap smear . Thyroid, Rubella profile, Tests for N gonorrhoea (urethral dishrag) , Chlamydia screening,

1)     Screening for acquired antiphospholipid antibodies (Thrombophilic screening) ,. Protein C, S and or antithrombin III Deficincy. There is an entity called seronegative APLA. SLE causes thrombosis of small placental vessels causing RPL/ IUFD . We have to remember that naturally circulating anticoagulants are 1) Protein C, 2) Protein S  & 3) Anti thrombin III. If there is  genetic defect of production of Protein C, or S or Antithrobin III then there  will be minimal natural anticoagulants in body. Tendency of hypercoagulable state. Such an procoagulant state may be accentuated by following 8 added factors like 1) age > 35 yrs 2)  Migraine   3) Past H/O VTE of causes unreeled to APLA   4) Hyper triglyceridaemia 5) , HHcst         6) DM with partly vascular damage
2.)  Peripheral blood karyotyping: of foetus if possible , In about  5% of all RPL are due to balanced Translocation particularly 22q11.2 ( long arm of Chr 22 locus
3.)  Screening for inherited Thrombophilia, (one should remember that APLA panel include following parameters e.g. A)   B2 glycoprotein-divvy, B)  dry Vat Lupus anticoagulant ( apt, DRW screen ) ,C) ACA ( Anti cardiolipin ab)  Cardiolipin antibody,=IgM ab (ACA):- may also cause IUFD, ,Unexplained subfertility, ) (Ig &IgM ab)-Negative means the IgG GPL units /illegal is < 10 GPL units /ml , But if persistently high( that is the label is high to 40 GPL) that has a real significance.

4. Other autoimmune screening y ( ANF, anti-dse DNA ab, Anti-mitochondrial ab & Anti Neurtophil cytoplasmic ab(ANCA) , Anti smooth ms ab . Serum Homocysteine 5<   (normal range is 6-14micro mol/Liter. 6, Vit B 12 , Serum Folate, 
4. Referral to a clinical geneticist, about 5% of RPL are due to translocations.
5. Cytogenetic analysis of the products of conception, Foetal/POC chromosome   & Paternal chromosome--any translocations??  6) Tests for APL ,One may ask what step to be adopted if  only DRVTT positive? Ans:- I feel that under such circumstances one should be prescribe  LMWH and (LDA).  May proceed for tests for secondary APLA or other autoimmune probality ( ANF, anti-dse DNA ab,  or inherited thrombophilia unless u work up completely u all not know or 80 percent of times v may get negative results . Simplest trial is preconception folic wad b 12 n ecosprin n wad UPT positive itself start heparin may b diff in such cases to reach ideal time to start heparin . Class 3 tests (contd):-Not evidence based tests for RPL but people quite often in insist on such, possibly meaningless, clinically irrelevant tests? Therefore such tests are optional :- 1) serum homocysteine (normal level is 6-14 µmol/Lit, , Serum Vit D & B12 level, 2)

3) To relentlessly search for Chr. Nonspecific infn of uterus –Chlamydial screening, Mycoplasma culture,, Brucellosis, CMV screening, 4) Sperm-for Polyspermia( per sperm less DNA share à resulting into  Post implantation disorders), 5) Class 3 tests (contd):-Not evidence based tests for RPL but people quite often in insist on such,  Tests for Hypercoagulability-like less Protein C,(normal range of Pro C is 70-130 %of normal biological range- and Pro C is a cofactor for proteins, But this  range will be altered while someone is on Heparin  Ry ) :Protein-S deficiency (these two proteins C & S - are natural anticoagulants) –Normal value of Protein S is 55-122%of biological value   & raised ANTITHROMBIN III, 5) Class 3 tests (contd):-Not evidence based tests for RPL but people quite often in insist on such,  T Hysteroscopy for synechiae, anatomical defects of ut e.g. - small septum, polyp, slight duplications of ut, unicornate ut. Hysteroscopy also help us to rule out Koch's 6) Any subtle Endocrinopathy: - –autoimmune thyroiditis, PCOS women with androgen excess milieu, Poor Ov reserve (AFC, AMH), ERA tests-poor endometrial receptivity etc.

C)  What are the treatment modalities which are not agreed upon by most Int authorities?? Such Treatments which, as I mentioned are   less evidence based though, admittedly many advocate such procedures (not talking if tests):- cervical cerclage may be associated with a high risk of minor morbidity but no serious morbidity.
• Heparin can be associated with maternal complications including bleeding, hypersensitivity reactions, and heparin-induced thrombocytopenia and, when used long term, osteopenia and vertebral fractures. Two prospective studies have shown that the loss of bone mineral density at the lumbar spine associated with low-dose long-term heparin therapy is similar to that which occurs physiologically during normal.