Recurrent Pregancy Loss investigations

 

Causes & investigations and management of RPL :  

:Q.1:  What are the causes of RPL(Rec Preg Loss) and how to investigate?? -Cause can be ascertained at best only in just above 50% cases. After one loss second loss probability is about 25-28%.  But after two spont losses the third successive loss chances are 30-35%

 

Q,2: Definitions : Different committee opinions were made and later either withdrawn or modified regarding definition of RPL  

Q.3: Why treatement outcome is so poor?? Ans: Even with treatment successful outcome is possible in about 75% cases .Because because some cases are genetic, emotional, endocrinologic, anatomic, immunologic causes which cannot be modified in fair number of cases. .

Q.4: When to define? Ans:  After two spont abortions.

Q5: When to initiate detailed & costly work-up?

Ans: It is true that evaluation of a healthy woman after one loss is not recommended.  But after two/or three losses most physicians will strongly insists on detailed investigations. But debate is still there in poor countries primary for cost saving approach.

Q.6: Which tests are debatable??

 Paternal chromosome

Q.7:-Which tests are desirable?? Ans:-1) Foetal/POC chromosome 2) Tests for APL 3) Hysteroscopy/HSG 4)

 

Q.8: Omissions on the part of clinicians:-While we continue to debate we often forget to elicit history in details!!! 1) Emotional trauma/ Stress-Psych-neuro-endocrinology 3) smoking & substance abuse 4) genital Kochs 5) travel and heavy prolonged duty at office 6) Family H/O/ Abnormal baby? 7) Uterine surgery? 8) Routine drug intake which she usually does not want to disclose. 9) Tr for infertility elsewhere? Any record LPD?10) above all omission of TPO ab as mild auto-immune thyroiditis is the one of the chief immunologic cause of RPL

Q.9:-FLOW CHART after second abortion:

Perform embryonic / washed products-even in dead chorionic tissue will do àInsist on Microarray karyotypeà Unbalanced-à No further investigation to motheràconsider PGS in ART center, Or else  can go for donor gametes.

Q.10 Unbalanced chromosomal say translocation/ inversion disorders of foetusà Parenteral Karyotypeà PGD.

No aneuploidy of foetusà 

Q.11: But if   EUPLOID POC  (Microarray cGH)  à Recurrent Preg Loss works up.                                     -à1) Anatomic-HSG/Hysteroscopy 2) Endocrinology TSH, PRL, Glycaemic 3) Autoimmune –a)aPL b)  LAC   c) beta-2-GP-1 ;

 

Q.11: Treatment albeit empirical: Initiate aspirin, Calcium, Vit D, preconceptionally, to add Progesterone up to  14 weeks of preg.  4)   Life style-exercise, 5) TLC- emotional support, Avoiding excessive tea, Coffe,  alcohol smoking   . 

Q,. 12: What surgery for antomic defects is worthy? –septal resection, adhesiolysis, myomectomy.

Q,13:-What Tr for endocrinological  disorders?

A)   à a) immune Dysfunction abnormal T cell function -> Duphaston:: b) untreated mild auto-immune thyroiditis: about 10% of Indian women  cases of RPL this autoimmune diseases may be responsible . For definition of RPL the ideal TSH prior to conception should be as low as 1.0—2.5 IU /L or milii U/ml. There is no clinical evidence hypothyroidismà but antithyroid antibodies are almost always present. It is these antibodies cause pregancy loss  . In India Indian Thyroid Society recommend those with TSH level of 2.5 to 10 mili IU/mà One should mediate start thyroxine at the dosage of  50 mcg. And not 25 mcg,

   B)      LPD the story of progesterone Deficiency:- A day 21 serum P > 10 ng/ml suggest reasonably health endometrium. But if folliculogenesis is imperfect then progesterone receptors at endometrial level may be inadequate to respond. Therefore Cochrane Review evaluating 15 trials concluded that in all PRL cases Progesterone be supplemented in Luteal phase. Besides Progesterone comes in pulsatile fashion so serum level of    progesterone varies considerably. Vaginal Suppository - 50-100 mg BD from the day of LH surge and then   continuing upto at least 10-14 weeks. Some also administer Inj 50 / 100 mg (ART) IM on daily schedule.                     C)    Can hyperglycaemia or compensatory hyperinsulinaemia exhibit spont abortion? =Possibly yes. This state cause hyperandrogenism and impaired folliculogenesis. This is true in cases associated with obesity. This latent hyperandrogenism induced by hyperinsulinaemia there will be  

 poor follicle & LPD.

Therefore question arises should we routinely empirically supplement Metformin therapy particularly in SE Asia ??? In this context many trusts on HBa1C which is  a better guide than Fast Insulin / Glucose  ratio.    

d) Hyperprolactinaemia:-to supplement Bromocriptine.

e) Low AMH-< 0.5 on two separate Lab - DOR: Should we counsel for donor egg??

Immune Related: 1)aPL antibodies:- 15-20% of all RPL.

What are the other auto antibodies that may lead to RPL? Adv: Nuclear antibodies, Ab to serine phosphatidyl Serine, SLE related Ab.

I fact how does aPL Ab induce abortion??  The explanations are  1) Vascular thrombosis in placental bed 2) inhibits beta HCG production from  syncetiotrophoblasts 3) destroys tropho.