ABC of
Endometrial Receptivity.
Basic aspects of
implantation & Placentation.
: Questions:
What are the different strategies to
improve ER?
a) Develop a protocol which does not impede
ER. a) Many centers, therefore, has
switched over to protocols other than CC. b) If at all CC is used, especially inn PCOS
women then think of adding EE -> idea is to improve ER.
b) Antagonists protocols –impedes HOXA10 gene expression in the stromal
cellsà so time has come when we should reconsider the use of antagonists.
Antagonists do some harm the ER in some cases. d)
c)
No Transfer in the same cycle: -- All Freeze –Subsequent transfer. (ER
Book-Duphaston-pp.125 Ed B N Chakravarty).
d) Improve uterine vascularization.
e) To treat the existing pelvic pathological
conditions:-
f)
High E2 levels –supraphysiological
levels of steroids-.This is interceptiveàAltered E2/P ratio.
Q.1. what agents can alter
receptivity of endometrium negatively? –
A) CC & possibly antagonists prevents
endometrial receptivity.
B) Moreover those cases where in ART cycles
elevated serum progesterones in late follicular phase à ER is poorà therefore cryopreservation of
embryosà transfer in next cycle is recommended.
C) In gonadotrophin cycles: where high
steroids are circulating – may itself bock/ disfavor the implantation process.
But in case of donor cycle –where recipient is not stimulated by
gonadotrophins-thereby no Supraphysiological steroidsà there per cycle implantation rate is
high.
Q.1. what are the different
Stages of fertilized Ova before implantation? - There are basically 3
stage of nidation. Firstly embryo when enters in ut cavity at 8-16 cell stage
morula. -->at cavity it becomes 32-64 cell stage, blastocyst. Then the
blastocyst àApposition, Stable attachment-adhesion, and
then local invasion-penetration of blastocyst inside the endometrium. Endometrium
becomes receptive += 6 days postovulatory.mm
Q.2.
what is meant by Window of implantation
(WOI) Process: - It is the time frame when the endometrium will allow
the blastocyst to get adheres and implant. It lasts for about 4-5 days about 6
days after ovulation .The receptivity persists for restricted time frame days
20-24 of cycle.
Q3.
What are the clinical conditions that
need to be addressed before ART is implanted and/or L Support is
mandatory?
Pelvic
disease like endometriosis, Myomas, intrauterine adhesions, endo polyp,
endometritis, ut septum, endometriosis, PID, Kochs, Hydrosalpinx. Adenomyosis,
PCOS, Autoimmune diseases.
Q8. How to improve ER? Endometrial
receptivity (thin Endometrium): can
be improved by 1) Low dose aspirin, 2) LMWH 3) Vaginal Sildenafil, 3)
L-Arginine, 4) Tocopherol, 5) Pentoxyphylline. 6) Chinese herbal medicines may
improve receptivity.
Q.9.
what are the agents in pipeline to improve the endometrial thickness and
Receptivity?:- IV-immunoglobulin’s, Intralipid, Allogenic Lymphocyte therapy,
Local injury, Traditional Chinese herbs and acupuncture NSAID-all can improve
Thin endometrium.
Q2. Prerequisites of Successful
implantation:-Competent blastocyst and receptive endometrium are essential.
So, Blastocyst competency and endometrial receptivity both are essential. The
ideal time implantation in a 28 days cycle is day 20-24 days of cycle-called
implantation window.
Query 6 :: what is the
prevalence of early pregnancy loss & incidence of failed implantation?
The
prevalence of early preg loss –is estimated to be 25-40%., of this 75% is due
to implantation failure.
Q8 Query 6. What agents prevent
implantation? CC & possibly antagonists prevents endometrial receptivity.
Q.4. Query 6 what are the
factors controlling implantation?
Various
endocrine, paracrine, autocrine, molecular, biochemical changes. The following
factors favour / promote implantation. Cytokines (IL-5, IL-11), growth factors.
(EGF, TGF-β, FGF, Transcription Factors (Hox), And lipid –all are modulated by
sex steroids mainly by Oestrogen and Progesterone.
Oestrogen
and progesterone have two types of receptor
namely ER -α ER-β and Progesterone A
& B receptors.
Progesterone is responsible for promotion of stromal
transformation or decidualization, glandular secretions and vascular remodeling
receptors are expressed by two different gens bit P –A & B receptors are
expressed by single gene—and these genes are
members of steroid
receptor superfamily.
Query 6 What is HOXA-10? : - This gene rises or
overexpressed dramatically during implantation. It indicates progesterone responsiveness
at stromal tissue.
1)
Adhesive Molecules:-
2)
Cytokines:-
3)
Extracellular matrix Proteins.-
4)
Vascular Endothelial Growth Factors VEGF-Fibroblast growth Factor
Family, an angioproteins.)
Query 6 What
are Immunomodulators? Natural Killer Cells: - Represent 70% of uterine lymphocytes at the
time of implantation. The word Killer is misnomer as it (uNK cells-- Uterine NK
cells) does not kill but help to preserve the preg.
Query 6 What is Immune Tolerance:-? In response to presence of embryo containg
paternal antigens –there is a local immune response occurs as is represented by
large population of T-cells in the area of implantation.
Q6. What is meant by
Immune Tolerance?
Half of the gene of embryo is foreign. Therefore
some immunomodulators are needed for successful implantation and prevention of
rejection.
Q6 Query 6.
What are the molecules that favour
nidation? These molecules help
immune acceptance: - The list of products that are favoures immune acceptance
to pregnancy: - These molecules are 1) some A) human Leukocyte associated antigens Dr-α, and Fas Fas Ligand
system. Near the trophoblast one can see
too much HLA-C, HLA-E, and HLA-G. These are beneficial, But those HLA which
promotes embryo rejection are HLA-A
and HLA-B which induce allograft rejection. This -HLA-C, HLA-E, HLA-G.
2) Interleukins specially IL-1, 15. 3)
Fas. It is the Fas ligand system is known to be important for immune acceptance
of pregnancy.
B) Fas
ligand (Fas or CD95L) belongs to TNF family. This Fas-L protein
induces death/ apoptosis of T cells. So
Fas ligand promotes apoptosis of activated lymphocytes.
C) Natural
Killer Cells:-
D)
Homeobox Genes: - The expression of Hoax 10 and HoxA 11 rise during secretory
phase .These are in fact transcriptor factors belong to multigene family. These
genes control both embryonic developments as well as help I implantation.
People are trying to discover gene Ry for this gene.
E
prostaglandins: - Phospho-lipase,
Cyclo-Oxygenase and prostaglandin synthase are the enzymes that form PG:-
F) Matrix
Metalloproteinase:-MMP-9- Matrix
Metalloproteinase-9 helps in remodeling stroma favorably and tissue inhibitors
of MNP (TMNP)-help in matrix degeneration favoring implantation.
Query14.
How to pharmacologically reduce T cell population:
A reduction
in level of tryptophan à inhibits T cell proliferation in uterine wall. Uterine tryptophan
has to be increased.
Query14.. What changes
occur in endometrial bed?
There are
epithelial,-both surface and glandular, Stromal cells –mesenchymal cells are involved
in diff kind of changes glandular and Thickness of endo at the beginning of
prolif phase is about 2 mm. -->at midluteal phase it is about 10-14 mm.
Query15. What is Progesterone induced Blocking Factor?
What are asymmetric antibodies? These
antibodies protect the foetus from rejection. PIBF produce Th2, NK cells,
.These protect the foetus from rejection.
What are symmetric antibodies? These
are Th1 cells
Query 16. What are the different stages of embryo: - After fertilization the embryoà 8 cell stage on day 3-4 postfertlizationà then undergoes a stage called compactionà 8-16 cell morula, no increase in size of embryo though no. of DNA&
nuclei enlarges.-à Compact embryo(Morula)à Blastocyst 32-64 cells(at 4-5 days post ovulatory)à,
Query 16. How and why -àMorula to Blastocyst Transition:- Some genes are responsible for
Nanog & Oct4 genes are responsible for segregation and of Trophoectodrm and
ICM inner cell Mass).a CAVITY APPEARS
INSIDE THE BLASTOCYST AND TWO DISTIBCT CELL TYPE ARE FORMED E.G.
Tropho-ectoderm(outer cell mass)& Inner cell Mass.
To conclude the drama for
tonight:-Query 17:: How we came to world and now ready to vote in Lok Sabha in April-May, 2019:_Steps of : FERTILIZATION
AND IMPLANTATION
( VERY EARLY PREGNANCY Embryonic
genome Activation:- Next process is embryonic gene
expression: - Reprogramming is imposed by epigenetic modifications. This must
happen and sadly over this a prospective mother has no say, including in
IVF settings. Otherwise drama will
fall & menstruation will resume.
. Thank God all members were born and
are now reading all these rubbish.compiled by Dr S K Pal. At the end , let me
thank & offer my my sincere thanks
to she (a respected member of this group) who intiated me about use of Bharglobe in Rec Impl
failure. She ignited me to write all these nonsense of
science. We Obstetricians beter understand CS/Lap Hyst.
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)
Do You Understand Your Body? How
does a Embryo Establish Contact with it's Mother?
What Is Implantation ?
PREGNANCY BEGINS
An updated version of this web page is available here
Unfortunately the latest versions of Internet
Explorer have a compatibility problem with Java Script and the new pages
menus might not display properly. If that is
how the egg cell is fertilized and how the early
pregnancy attaches itself to the womb. A link between the new life(embryo)
and its mother will be formed. Implantation is the establishment of this link
between the mother and the embryo.
discuss the phenomena known as implantation
bleeding.
The egg cell is released by one of the ovaries and
than sucked into a fallopian tube. The lining on the inside of the fallopian
tube is also a highly specialized mucus membrane. The cells on the surface of
this mucus membrane contain specialized hair like protrusions which is
constantly moving in such a way that there is a constant movement of fluid from
the ovary towards the opening of tubes and from there toward the cavity in
the womb. This movement causes a suction effect. Anything in the vicinity of
the ovaries ( like the egg cell) will be sucked into the womb. Refer to Normal
Ovary .
An interesting fact is that fertilization does not
occur in the womb , but at the opening of the tube near the ovary. That
sperms swim all the way from the vagina, through the womb and upstream
through the fallopian tubes.
After fertilization the fertilized egg cell is
slowly sucked through the fallopian tubes into the cavity of the womb. It
only arrives in the womb about five days after conception. The egg than
attaches itself to the endometrium (the lining on the inside of the womb.).
The drawings in the next section (further down) will
illustrate the whole process.
We will also discuss implantation bleeding.
Implantation bleeding should not be confused with bleeding during pregnancy.
We regard real implantation bleeding as a bleeding episode that occurs two
weeks after conception (four weeks after the previous menstruation), but more
about it near the end of this page.
The discussion continues slightly further down the
page.
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