There are about 40 known tests in a case of RPL albeit most are of theoretical
benefit as in many such diseases there is no known therapy. As such, there are many experienced clinicians who stratify
cases according the time of abortion, if at all such miscarriages occur at
almost similar periods of gestations and try to limit the number of tests. There are equally another group of clinicians
who assume one or two types of cause based on his/ her clinical experience and
initially try to exclude only those particular diseases, This type of clinical thought
is often termed by the clinicians as “etilogy-oriented investigations”. There are yet another group of clinicians who don’t like to miss any
diagnosis and they (clinicians) refer the couple concerned to a reputed Lab asking
for “Recurrent Abortion Panel” and also to seek advise hematologist for any Thrombophilic
or other hematologic diosrder including hypercoagulable starts which we
gynaecologist don’t understand so well. That is not unfair and I should say
that if affordable is a good practice patter.
However, the following tests are very commonly performed in most cases
in nonpreg cases even after one pregnancy loss .Admittedly , these are
often routine tests and most are unrelated to preg loss . These are 1) Haemoglobin nature by HPLC, 2) Blood
Group, & typing, Indirect Coombs tests 3) Serology for STD –HIV, TPHA in particular,
4) Viral screening including hepatitis serology 5) Thyroid screening (Thyroid
profile) , 6) PRL*, Serum Progesterone & Day: 3 LH* , 7) Rubella screening,
8) serum tests PP Sugar & PP insulin to exclude insulin resistance , OGTT i.e. Glycemic
profile, 9) LFT.10) Renal profile (at
least creatinine), 11) Routine Pelvic USG-any myoma, endometriosis,
adenomyosis, 12) Urine RE , 13) USG:-AFC
& other imaging information as
available 14) HSG 15) Diag
lap-Hysteroscopy .16) AMH :: However those
marked with * are for cases of vary
early abortions . Of note in most of such disease some form tr can be
offered to improve fertility potential .Therefore these are first line
investigations (modifiable factors). Readers may add or subtract any of tests
depending on his/her belief and accumulated experience, as above mentioned list
is from my experience and not approved by any academic bodies.
Part II
1)
Thrombophilia screening. 2) Tests
for SLE like a) anti cardiolipin an GPL U/ml & Lupus anticoagulant ab like
divvy (LA 1) & APTT (PTT-LA) 3) Tests
four cong hypercoagulable diseases like deficient if protein C, S & Anti
thrombin III
4) Ant-do DNA ab, 5) Anti smooth ms ab, 6) Anti thymoglobulin ab, 7)
ANA, 8) anti-microsomal ab, 9) ANCA(anti neurtrophil cytoplasmic ab, 10) Karyotypes 11) Hysteroscopy/ HSG, 12) ,
Chlamydia, 13) Brucella screening , 14) Cervical swab & culture,. 15) Mycoplasma, 16)
HSV, 17) 3-D USG, 18) Homocysteine*, 19)
Polyspermia,
What is the problem in
investigating cases of RPL who can afford? Ans: If no therapy is available then
there is little benefit of testing. . There are multiple subtle diseases/ deficiencies
( known / as yet unknown) for which no marker is available till date
–say genes/enzymatic deficiency at endometrial level. Similarly abnormalities
of different interleukins and cytokines
/Knell population/Factors which takes over charges from CL of preg to placenta for continuation of smooth progress of pregnancy)
are difficult to diagnose but some agents are used like antioxidants, I V immunoglobulins.: Taken
together the lack of beneficial or blastocyst friendly growth factors may
eventually lead to RA. Empirical Tr are 1) antioxidants 2) life style changes
3) empirical tr with antibiotics for presumed / established reproductive tract
infections . 4) I V immunoglobulins :-Ivy has been successful in the treatment of recurrent miscarriage and recurrent implantation
failure among women with elevated APA and/or NK cell activity 5) Intralipid is
effective in the treatment of women experiencing reproductive failure who
display elevated NK cell activity. For immunological factors, other than APA
arguably, there is no clear-cut benefit of any intervention.AS such question
aeries
should we routinely sample
endo for uNK cells (uterine natural killer cells ) during hysteroscopy? If so will it be beneficial to concerned woman , and if so to
what extent? What does excessive u-u-NKcells population in endometrium
signify??
Are we missing something in
the investigation panel ?? Will detailed special & costly investigations be
helpful in treating subsequent pregnancies? Is it not true that some minor
other diseases or deficiencies for which no tests are available will remain unnoticed & unrecognized.
In such situations and she will any case abort as such subtle diseases /
syndromes were never suspected and therefore possibility of such diseases will
remain untreated
Will investigation help the
clinician? If yes, to what extent? Multiple subtle factors
taken together may eventually lead to RA. Such researches and many senior
clinicians have also pointed out that multiple subtle factors taken together
may eventually lead to RA. They (researches) have stressed that a number of factors
may be operating in many cases and to make the matter more worse for the clinician’s investigators have opined that
in different pregnancies different factors may be may be operatoionable. That is their belief. That is why possibly
TLC has a major role in the management of such syndrome/ disease
To treat or not to treat if
a defect is observed in Lab tests –Will that Tr be effective at all?? It is couples & doctor’s
choice as there is no guarantee that Tr is going to offer about a live birth:
The inhibition of prescribing such drugs stems from Int recommendations as Level
of evidence!! Doctors are hesitant if level of evidence is 4!! :-Should we
regard/disregard a Lab report and whether Tr of such defect will materially
help the distressed woman? What is meant by Int recommendations as LEVEL of
Evidence? Now we can understand how
difficult is for us (clinicians) to lay importance on a particular disease as the prime cause of
abortion if Lab report so suggest: - Recommendations issued by different
International Agencies have be to be followed by us, Many agencies have stratified the efficacy
of different diseases as a causative factor RSA
as level of evidence in the format of evidence level-+1 ,2 ++, 3, 4 as in many other diseases. It is more
relevant so far as RCOG guidelines are followed. If recommendation is like
“evidence level 3 or say 4-then one is hesitant to prescribe drug for such
presumed diseases in cases of RPL as evidence is, say to say, lacking firmly.
Stratification of
etilogy-oriented investigations, thereby to cut short list of investigations
& revise the plan the list of investigations (to cut short long list of
investigations as per gest age of RSA):
What was the gest age when previous 2-3 abortions occurred-stratification
of etilogy-oriented investigations, The
very philosophy of stratification of etilogy-oriented investigations”- If one
believes in this proposition :-Then what special tests to be followed though as a clinician, most of us perform following
tests for Rec spont abortion cases ,particularly where there have been more
than 3 abortions and couple and their relatives are prepared to pay any amount of money before planning for
third pregnancy
Different attitudes of different clinicians about list of investigates :-Many clinicians have
different attitudes about list of
investigates and some astute clinicians stratify the list according to
gestational age of abortions –a) whether the previous losses were Early
Looses( then they strongly considers :- a) endocrine factor &
b)chromosomal/ c) genetic causes d) uterine natural killer cells-uNK cell
population—a very common cause of idiopathic early abortion .possibly more than
genetic or chromosomal disorders) ANF, tests for aPL ab
. But if Losses occurred
later after 10 week the possibility of following abnormalities be cone
stronger. e g. 1) Structural
malformations of uterus,-best by hysteroscopy) & at the same time Lap to
exclude minimal endometriosis which cannot be picked by USG or say asymptomatic
but continue to release oocyte toxic materials which eventually affect “ovum
pick up mechanism”. This release of toxic materials and gameto-toxic cytokines
is however also true for latent Kochs which can be occasionally be picked by
peritoneal sampling.
Hypercoagulability
disorders-acqd or congenital, /
platelate count by diff methods, platelate
function if possible, PT, PTTK Hhcy, environmental diseases, smoking, addiction, stress and possibly immunological
& above all psychological as the “week of previous risk” approaches,
Hystero-Laparoscopy,
If previous abortions
occurred after say 8 weeks-it is presumable that though
many clinicians don’t accept this stratification of etilogy-oriented
investigations, Instead they(clinicians) refer the couple concerned asking for
“Recurrent Abortion Panel”:. I don’ know whether such practice is appropriate
or not. What are the member’s advice & their practice pattern??
.
Detailed List of
investigation:-Pros & Cons: - - To investigate at one time (one stop
Investigatios particularly who have more than three pregnancy losses excluding
those Lab tests which have already done earlier. Admittedly such list is long
(most of the members, I am sure will disagree with me about my philosophy of
getting all tests done) may cost Rs 25,000/- to Rs 35,000/- according to
quality and name & fame of Lab List is, though exhaustive but excludes
usual preconception ally tests are
1) Autoantibodies-ANA, Anti-do-DNA
2) Tests for A-APL ab 3) Thrombophilia
screening3) 4) HSG /3-D us/SIS choice /preference of Gynecologist
concerned.4) LPD as a precursor of early preg failure-by causing poor
endometrial development. ?? 5)Infection screening:-Chlamydial &
Gonococci screening if not done earlier, &Mycoplasma & Listerosis are
not available at Kolkata. 6) Homocysteine
Normal value of plasma is 6-14 µ.mol/L, Mostly, low Homo signify defective Vit B12 metabolism due
possibly to Foliate or other enzymatic disorders(inborn), Hyper level of Homo
causes much damage not only in the preg
outcome but abnormal accumulation of homocysteine in serum (-H.Hys ) is a
marker/ warning lab parameter of
thrombo-embolism including
Coronary thrombosis,7) Estimate AMH
& Gaunt AFC: _Low AMH, AFC & DOR:-as a cause of poor oocyte
qualityà failure to development of
onwards growth of embryo//foetus (disordered post zygotic events)-genetic error
by aged Oocyte .akin to trisomy in aged females.
8) Detailed & special
sperm function tests”
9) Parental karyotyping:
Scrum progesterone in day 22 of unstimulated
cycle in cases of early failures-admittedly questionable because most of us
suppl P after UPT is +ve, but if P value in luteal phase is suboptimal (if <
3-4 ng/ml)-but fortunately such P level is above 10 ng/ml in mid/late luteal
pages then there is possibly no indication for LPD support in the cycles when
they will be attempting for pregnancy. The date of drawing blood in irregular
unstimulated cycle may be done either as LH Urine test /FM .then we have to suppl
after,
- 6) Infection screening:-Chlamydial
& Gonococci screening if not done earlier, &Mycoplasma & Listerosis
are not available at Kolkata. &
8) Homocysteine
Normal value of plasma is 6-14 µ.mol/L, Mostly, low Homo signify defective Vit B12 metabolism due
possibly to Foliate or other enzymatic disorders(inborn), Hyper level of Homo
causes much damage not only in the preg
outcome but abnormal accumulation of homocysteine in serum (-H.Hys ) is a
marker/ warning lab parameter of
thrombo-embolism including Coronary thrombosis,
9) Estimate AMH & Gaunt AFC: _Low AMH,
AFC & DOR:-as a cause of poor oocyte qualityà failure to development of
onwards growth of embryo//foetus (disordered post zygotic events)-genetic error
by aged Oocyte .akin to trisomy in aged females.
10) Detailed & special
sperm function tests”
11) Parental karyotyping:
12) - Elevated
APAs are equally prevalent among women experiencing unexplained infertility,
recurrent implantation failure, and recurrent pregnancy loss. Heparin and
aspirin are successful in the treatment of elevated APA among women with
recurrent miscarriage but not with recurrent implantation failure.IVIg has been successful in the treatment of
recurrentmiscarriage and recurrent implantation failure among women with
elevated APA and/or NK cell activity Intralipid is
effective in the treatment of women experiencing reproductive failure who
display elevated NK cell activity. For immunological factors, other than
APA arguably, there is no clear-cut benefit of any intervention...
Should we routinely sample
endo for uNK cells during hysteroscopy? If so will such test be beneficial, and if so to what extent? What
does excessive u-u-NKcells population in endometrium signify?? Is it a danger
signal of again another recurrent abortion? Few points about u-NK cell
population as assayed by immunohistchemistry –sampling done at the time of
hysteroscopy along with Kochs diagnosis by stain, special culture, exclusion of synechiae, polyp or
septum s other commonly observes diseases in diagnosed at hysteroscopy? It is
said that endometrial NK cell act as traffic control- by preventing entry of
friendly classical T cells). We are already ware that “Endometrial Leukocyte population –as separate
from peripheral blood CD 56+ cells
activated by IL 15 , There are three subtypes
end level .These age 1) u-NKcells 2) Normal macrophages and third type
of 3) uterine leukocytes present are T calls.
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