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.
Of all NK cells present in endometrium are
comprise of CD 56, CD 16 but in periphery it is CD 15 that potentiates the actions
of CD 56.
One has to remind that 90 & of endometrial u-N cells are comprise
of CD 56, CD 16. As mentioned earlier presence of high no of u-NKcells may
initiate aborting again. HLA-G & amount of interferon-¥ plays a significant role in the development process of spiral
arteries as occurs in preg.
Dr Pal’s long list: - My policy & what I
do:-My policy is to draw blood one time and to minimise the visits to pathology
Lab by the couple. It has been concluded
that psycho-immunology is an important factor. The members may rightly asked
list are quite costly and even if a deficiency is identified one is very certain whether such cause is playing
the role of abortion or else if a drug is available . For instance if Cong
Protein-C deficiency or Protein S deficiency will treatment be effective? Who
will supervise the following preg if treatment is implemented?
What are routine list of
investigations that have to be asked as a protocol of Lab assessment as
preconception medical fitness? Complete Heamogram, H [LC,
Group, & typing, Serology for STD –HIV, TPHA in particular, Viral
screening, Thyroid screening, PRL, Hepatitis serology, Rubella screening, Glycaemic
profile, LFT. Renal profile (at least
Creatinine), Routine Pelvic USG. Urine RE
& in myoma: - Antigen screening mechanism by T cells
Immunity
is of two types. .
A)
B-cell immunity: - or humoral (antibodies mediated
like –immunoglobulin’s of varying types) –noncellular i.e.
Serum immunity.
B)
T cell immunity: - this is a Cell mediated immunity
and is expressed by Macrophages, Lymphocytes, Lymph nodes and & effector T Cells. Unlike B cell immunity T cells are
not only restricted in blood stream and present in fair number in tissues as
well. In control of diseases both B and T cell immunity are required. Cell
culture technique can now differentiate detail functioning / dynamics of T cell
immunity mechanism.
C) CLASSIFICATION OF T CELLS
Mechanisms:-
D) Cytotoxic T cells
a) Cytotoxic T cells: - These are also called effector T cells, Carrying CD 8 markeràlysing the host cells which was
invaded by the pathogenic organism/ foreign antigens. B) T helper Cell this carry CD 4
marker):-: This type of cells in conjunction with
Macrophages /phagocytes destroy the invading enemy by releasing chemical
agents called CYTOKINES. Therefore in short T cells can destroy foreign
antigens either by lysis (cytotoxic CD8 cells) or can destroy by production id
cytokines (by CD4 Cells).
What are cytokines?
Therefore chemical agents are (cytokines are secreted by B-Helper cells
to release
Such bioactive substances.
T (Cellular) & B (humoral) cell
Dysfunction
Disorders of Immune dynamics can cause lot of diseases and even may be
prime cause extinction of human race in the centuries to come. It is for this
system we are still alive and their help is most needed in all most all
diseases including natural reproduction.
Types of B cell Dysfunction: - a) Over reaction b) Immunodeficiency
(reduced defense reaction) c) Autoimmunity-incorrect / inappropriate
response/reaction.
MHC:
MHC:- Major Histocompatibility Complex:- These are one type of friendly receptors present on the
surface of T cells-by which it recognize its own inherent antigens and do not response from reacting or
producing cytokines. But when foreign antigens present to the T cell surface
then T cell start producing antibodies.
.T cell response is of two types: - a) Cytotoxic response b) Helper
function:
CD8+ T cells (have power to recognize MHC class I antigens) but CD4+ T
cells have power to recognize MHC class II antigens.
Antigen screening mechanism by T
cells is an
inborn power whether to act or not to react. To whom to attack, when to attack,
how to attack the offending invader (in this case may be paternal
antigen/antigens) buy with some dignity so that endometrium itself is not
damaged or menorrhagia/Metrorrhagia do
not ensue as continued effect of sperm antigens/ placental antigens/antigen.
Memory cells.
Are capable of producing messenger cytokines after recognize fresh entry
of foreign antigens. Memory cells. Are capable of producing messenger cytokine
molecules. This can in turn attract and promote production of effector T cells.
:The issue of efficacy of progesterone in
idiopathic Rec abortion:-However , Efficacy of progesterone in apparently idiopathic Rec abortion as raised: May I
inform my dear members that there is am
trial going on "PROMISE"-WWW,medscinet.net/promise at UK &
Netherland. This is also applicable in cases of Sub chorionic haematoma.
To what extent the
exhaustive investigations will help the couple? Idiopathic in about 40-50% cases of RSA !!!:-Clinicians feel sorry and
feel ashamed (at least I do feel guilty
& full of shyness prevail in my
face) :- if no cause is identified after exhaustive Lab tests & investigations spending
so much money for investigations:-In many studies
time and again , it has been firmly concluded, that in about 40-50% cases of
RSA-the etiology remain uncertain even in best centers including centers of western part of globe( unlike our
resource poor country) . What are routine list of investigations that have
to be asked as a protocol of Lab assessment as preconception medical fitness? Complete
Heamogram, H [LC, Group, & typing, Serology for STD –HIV, TPHA in
particular, Viral screening, Thyroid screening, PRL, Hepatitis serology,
Rubella screening, Glycaemic profile, LFT. Renal profile (at least Creatinine),
Routine Pelvic USG. Urine RE
What is the problem in
investigating cases of RPL who can afford? Multiple subtle ( for which no
marker is available till date –say genes/enzymatic deficiency at endometrial
level/Interleukins and Cytokines /Knell population/Factors which takes
overcharges from CL of preg to placental
factors for continuation pregnancy): taken together may eventually lead to RA.
Will detailed ,special &
costly investigations be helpful in treating subsequent pregnancies? Is it not
true that some minor other diseases or deficiencies will remain unnoticed
&unrecognized and she will any case abort as that diseases is not tretaed:
_Will investigation help the clinician? Is 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 guarantee about a Live birth: The inhibition of prescribing septic 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 o such defect
will materially help the distressed woman? What is meant by Int recommendations
as LEVEL of Evidence? Treat a How difficult 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”thogh
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) WHWTER 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
FUNCTIN 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 8weeks-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
preconceptionally tests are
1) Autoantibodies-ANA, Anti-ds-DNA
2) Tests for A-APL ab 3) Thrombophilia
screening3) 4) HSG /3-D usg/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 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 tat “Endometrial Leukocyte population –as separate from peripheral blood
CD 56+ cells activated by IL 15) have
three subtypes I end level .These age 1) u-NKcells 2) Normal macrophages and
third type of uterine leukocytes present are T calls, Of all NK cells present
in endometrium are comprise of CD 56, CD 16 but in periphery it is CD 15 that
potentiates tie cactions of CD 56.
One has to remind that
90& of endometrial u-N cells are comprise of CD 56, CD 16, AS mentined earlier
presence of high no of u-NKcells may initiate abortin again. HLA-G & amount
of interferon-¥ plays a significant role in the development process of spiral
arteries as occurs in preg.
Dr Pal’s long list: - My policy & what I
do:-My policy is to draw blood one time and to minimise the visits to pathology
Lab by the couple. 2 It has been concluded that psycho-immunology is an
important factor.
The members may rightly asked list are quite
costly and even if a deficiency is identified one is very certain whether such cause is playing
the role of abortion or else if a drug is available . For instance if Cong
Protein-C deficiency or Protein S deficiency will treatment be effective? Who
will supervise the following preg if TR is implemented?
What are routine list of
investigations that have to be asked as a protocol of Lab assessment as
preconception medical fitness? Complete Heamogram, H [LC,
Group, & typing, Serology for STD –HIV, TPHA in particular, Viral
screening, Thyroid screening, PRL, Hepatitis serology, Rubella screening,
Glycaemic profile, LFT. Renal profile (at least Creatinine), Routine Pelvic
USG. Urine RE
& in myoma: - Antigen screening mechanism by T cells
Immunity
is of two types. .
E)
B-cell immunity: - or humoral (antibodies mediated like
–immunoglobulin’s of varying types) –noncellular i.e. Serum immunity.
F)
T cell immunity: - this is a Cell mediated immunity
and is expressed by Macrophages, Lymphocytes, Lymph nodes and & effector T Cells. Unlike B cell
immunity T cells are not only restricted in blood stream and present in fair
number in tissues as well. In control of diseases both B and T cell immunity
are required. Cell culture technique can now differentiate detail functioning /
dynamics of T cell immunity mechanism.
G) CLASSIFICATION OF T CELLS
Mechanisms:-
H) Cytotoxic T cells
a) Cytotoxic T cells: - These are also called effector T cells, Carrying CD 8 markeràlysing the host cells which was
invaded by the pathogenic organism/ foreign antigens. B) T helper Cell this carry CD 4
marker):-: This type of cells in conjunction with
Macrophages /phagocytes destroy the invading enemy by releasing chemical
agents called CYTOKINES. Therefore in short T cells can destroy foreign antigens
either by lysis (cytotoxic CD8 cells) or can destroy by production id cytokines
(by CD4 Cells).
What are cytokines?
Therefore chemical agents are (cytokines are secreted by B-Helper cells
to release
Such bioactive substances.
T (Cellular) & B (humoral) cell
Dysfunction
Disorders of Immune dynamics can cause lot of diseases and even may be
prime cause extinction of human race in the centuries to come. It is for this
system we are still alive and their help is most needed in all most all
diseases including natural reproduction.
Types of B cell Dysfunction: - a) Over reaction b) Immunodeficiency
(reduced defense reaction) c) Autoimmunity-incorrect / inappropriate
response/reaction.
MHC:
MHC:- Major Histocompatibility Complex:- These are one type of friendly receptors present on the
surface of T cells-by which it recognize its own inherent antigens and do not response from reacting or
producing cytokines. But when foreign antigens present to the T cell surface
then T cell start producing antibodies.
.T cell response is of two types: - a) Cytotoxic response b) Helper
function:
CD8+ T cells (have power to recognize MHC class I antigens) but CD4+ T
cells have power to recognize MHC class II antigens.
Antigen screening mechanism by T
cells is an
inborn power whether to act or not to react. To whom to attack, when to attack,
how to attack the offending invader (in this case may be paternal
antigen/antigens) buy with some dignity so that endometrium itself is not
damaged or menorrhagia/Metrorrhagia do not ensue as continued effect of sperm
antigens/ placental antigens/antigen.
Memory cells.
Are capable of producing messenger cytokines after recognize fresh entry
of foreign antigens. Memory cells. Are capable of producing messenger cytokine
molecules. This can in turn attract and promote production of effector T cells.
C/s.
C/s.
Kindly
give suggestions regarding Recurrent first trimester loss (blighted ovum,
missed abortion) evaluated found to have elevated homocystein
methylcobamin 1500 b.d ,folic acid,
Arginine
How
high is it? What is pts age? Any other factor for RPL
History:
- What about her nutrition, any F/H/O of Koch’s?, Explore family tree for
genetic diseases, Life style disease /habit of either partn
Common Tests”- In addition suggestions made by some forum members, may carry out
Complete haemogram, Thalassaemia screening, Viral screening, Metabolic screen
(HBA1C & PPBS) & endocrine screen( TSH, PRL, Total testosterone).
Thrombophilias Screening, A...
Uncommon
Tests:- AMA, ANA. Hystero-Laparoscopy-Minimal endometriosis & septal
diseases of uterus.I often perform this test. To me this operation should be in
the list of common tests, but many differ due to cost / invasiveness.
Psycho-immunology
in the treatment of RSA is an emerging subject. Support of the family members
& relatives/ friends .But in the days of consumers many doctors are
hesitant to assure the couple “All is well, Next time such unfortunate event
will not occur. I am with you. God is going to bless you this time.”.
Summary:-Above
all, uterine malformations, endocrine disorders and advanced age of any one
partner are the usual causes of RSA.
May
read RCOG green top guideline no. 17 (issued on April, 2011). In about 50%
cases the etiology remains unexplored. But in such situation, I do prescribe,
albeit imperially a course of antibiotics for pelvic . Infection like
doxycycline & Azithromycin.
One
of my close friends presented with similar history,
elevated
homocysteine with recurrent losses.
later
on on further evaluation due to affordability,
she
was found to have mutation in MTHR,
currently
on nutritional supplements,L-methyl folate the active form of frolic acid apart
from b12 etc.other
hereditary thrombophilia screen were
negative like factor V Leidin.. mutation in MTHR.
MTHFR
gene mutation is common in Asians and doesn't require treatment! That cannot be
cause for RPL
Thank u mam smile emoticon yeah her treating
RPL : Q What %
of conception proceed to live birch?? Ans: Human reproduction is remarkably inefficient; nearly
70% of human conceptions do not survive to live birth.
What
is the commonest cause of spont abortion??
Ans;- the most common cause for spontaneous loss, is fetal aneuploidy is particularly in the first
trimester of pregnancy. Although losses may be due to A) owing to de novo fetal
aneuploidy occur at similar frequencies among women with sporadic and
recurrent losses, B) Equal no have couples additional associated genetic factors
and C) The other causes of RSL /RPL are monogenetic etiologies.
Q, How useful is Genetic testing of the products of conception
from couples experiencing two or more losses?? Ans:-Genetic testing of
the products of conception from couples experiencing two or more losses may aid
in defining the underlying etiology and in counseling patients about prognosis
in a subsequent pregnancy.
How
important is Parental karyotyping of couples Ans:-Parental karyotyping of couples who have
experienced recurrent pregnancy loss (RPL) will detect some couples with an
increased likelihood of recurrent fetal aneuploidy; this may direct
interventions. Parental
karyotyping is better than on POCs, only because 70% SABs have chromosomal
abnormalities, but that does not change the outcome for future pregnancies. On
the other hand, if either of the parents are carriers of balanced translocation
[6% possibility], then the recurrence risk will depend on the specific
translocation
How important is PGS?? The utility of Perimplantation genetic analysis in couples
with RPL is unproven, but new approaches to this testing show great promise.
Haemoglobin nature by HPLC,
Blood Group, & typing, Serology for STD –HIV, TPHA in particular, Viral
screening, Thyroid screening (T .profiler) , PRL*, Hepatitis serology, Rubella
screening, Glycemic profile, LFT. Renal profile (at least Creatinine), Routine
Pelvic USG-any myoma, endometriosis, adenomyosis, Urine RE ,Karyotypes, Day 3LH*, .TPHA,
Thrombophilia screening . Homocysteine*, Ant-do DNA ab, Anti smooth ms ab, Anti
thymoglobulin ab, ANA, anti-microsomal ab, ANCA(anti neurtrophil cytoplasmic
ab, USG serum testis , Insulin to
exclude PCO, Hysteroscopy, HSG, GTT , Chlamydia, Brucella screening , Cervical
swab & culture,. Mycoplasma, HSV, 3-D USG, Polyspermia, Serum Progesterone
Tets for SLE (like a) anti cardiolipin an GPL U/ml & Lupus anticoagulant ab
like divvy (LA 1) & APTT (PTT-LA)
Tets four cong hypercoagulable diseases like deficient if protein C, S
& Ante thrombin III
What is the problem in
investigating cases of RPL who can afford? Multiple subtle ( for which no
marker is available till date –say genes/enzymatic deficiency at endometrial
level/Interleukins and Cytokines /Knell population/Factors which takes
overcharges from CL of preg to placental
factors for continuation pregnancy): taken together may eventually lead to RA.
Will detailed ,special &
costly investigations be helpful in treating subsequent pregnancies? Is it not
true that some minor other diseases or deficiencies will remain unnoticed
&unrecognized and she will any case abort as that diseases is not treated:
_Will investigation help the clinician? Is 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 guarantee about a Live birth: The inhibition of prescribing septic 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 o such defect
will materially help the distressed woman? What is meant by Int recommendations
as LEVEL of Evidence? Treat a How difficult 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”thogh 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) WHWTER 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
FUNCTIN 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 8weeks-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 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 tat “Endometrial Leukocyte population –as separate from peripheral blood
CD 56+ cells activated by IL 15) have
three subtypes I end level .These age 1) u-NKcells 2) Normal macrophages and
third type of uterine leukocytes present are T calls, Of all NK cells present
in endometrium are comprise of CD 56, CD 16 but in periphery it is CD 15 that
potentiates tie cactions of CD 56.
One has to remind that
90& of endometrial u-N cells are comprise of CD 56, CD 16, AS mentined earlier
presence of high no of u-NKcells may initiate abortin again. HLA-G & amount
of interferon-¥ plays a significant role in the development process of spiral
arteries as occurs in preg.
Dr Pal’s long list: - My policy & what I
do:-My policy is to draw blood one time and to minimise the visits to pathology
Lab by the couple. 2 It has been concluded that psycho-immunology is an
important factor.
The members may rightly asked list are quite
costly and even if a deficiency is identified one is very certain whether such cause is playing
the role of abortion or else if a drug is available . For instance if Cong
Protein-C deficiency or Protein S deficiency will treatment