Embryo implantation failure general topics discussed

1. Embryo Implantation failure
By
Dr.Pavithra.A

2. Fertilization
 Fertilization involves fusion of the female (oocyte) and male gametes (sperm).
 The sperm fertilizes the oocyte creating a single diploid cell, the zygote.
 After successful fertilization in the ampulla of the fallopian tube, the zygote
migrates towards the uterine cavity with the assistance of the ciliary motility of
fallopian tube epithelium .
 During this time, the zygote undergoes a sequence of cell divisions resulting in a
multicellular structure termed the blastocyst.
 The blastocyst possesses an inner cell mass, which will form the embryo and an
outer layer of cells called trophoblasts, which will develop into the placenta

3. Fertilization = Sperm+ Ovum
Zygote
Compaction of morula
Cleavage formation
Blastocyst
Implantation
HUMAN DEVELOPMENT PROCESS

4. CLEAVAGE
 DEFINITION : It is the repeated mitotic divisions of the Zygote, resulting into a
rapid increase in the number of cells that are called BLASTOMERES
 SITE : The uterine tube medial to the ampulla.
 2 cell stage - 30 hrs after fertilization
 4 cells stage – 40-50 hrs after fertilization
 12 cell stage – 72 hrs after fertilization
 16 cell stage - 96 hrs after fertilization

5. Occurs 30 hours
after fertilization
Zygote divides
longitudinally into two
blastomeres
One cell is larger than
other
Occurs in the upper
portion of Fallopian
tube
Occurs 30 hours
after 1stcleavage
Occurs longitudinally
but at right angle to
the 1st one.
4 cells are formed

6. Name 6
3rd cleavage
occurs about
three days after
fertilization
Embryo
gradually pushed
from Fallopian
tube towards
uterus
At the end of 4th day of
fertilization, solid ball of
16-32 cells looking like
mulberry is formed
This is called Morula
Till this Zona pellucida
is retained around
embryo
No change in overall
size from zygote to
morula

7. Time consumed in completing the cleavage

8. BLASTOCYST
 The morula reaches the uterine cavity by the 4th day after fertilization &
remains free for one or two days
 Fluid passes from uterine cavity to the morula through the zona pellucida
 Now the morula is called Blastocyst , its cavity is called blastocystic cavity, its
cells divided into Embryoblast &Trophoblast

9.  The Embryoblast projects into the blastocystic cavity ,while the trophoblast forms
the wall of the blastocyst .
 Zona pellucida degenerates &disappears by the 5th day to allows the blastocyst to
increase in size and penetrates the endometrium
 BY 6th day the blastocyst adheres to the endometrium
 By 7th day, Trophoblast differentiated into 2 layers
 CYTOTROPHBLAST ,inner layer ,mitotically active
 SYNCYTIOTROPHOBLAST (outer multinucleated mass, with indistinct cell
boundary
 By 8th day the blastocyst is superficially embedded in the compact layer of
endometrium

10. Difficulties in studying the process of
Implantation
Successful Implantation Requires
“Two way Interaction “
Blastocyst-Endometrium

11. DEFINTION :
 Penetration of the blastocyst into the superficial (compact)layer of the
endometrium.
 The endometrium after implantation is called Deciduas
SITE OF IMPLANTATION :
 Posterior wall of the uterine body in the functional layer of the
endometrium during the secretory phase of the cycle
TIME:
 Implantation occurs at the 6th day after fertilization and is completed
about the 11th day
IMPLANTATION

12. Window of Implantation(WOI)
 The implantation window is a short interval during the mid-secretory
phase, when the endometrium is most receptive to blastocyst implantation.
 It begins on days 20-22 of an ideal menstrual cycle and lasts less than
48hrs Integrins are the markers for WOI.
 During the WOI ,the endometrium which has been primed by estrogen
and progesterone is characterized by change that are collectively termed
Endometrial receptivity

13. Pinopods are bleb –like protrusions found on the apical surface of the endometrial
epithelium
 Appear only during implantation
Pinopods absorb the fluid from the uterine cavity forcing the fluid from the blastocyst to
be in contact with endometrial epithelium
They are the morphological markers for endometrial receptivity and implantation
PINOPODS

14. Decidualization
 Decidualization is a biological transformation by which the endometrial
stromal cells ( fibroblast –like ) differentiate into a highly specialized secretory
epithelioid cell type ,termed decidual cells
 Decidualization occurs during the last secretory phase (day 23-28) and is a
pre-requisite for successful blastocyst implantation
 FUNCTION OF DECIDUAL CELLS
Controlled Trophoblast Invasion : Deciduas forms a local micro
environment to promote trophoblast attachment &invasion as well as limit the
extent of aggressive invasion
Protection of concepts from maternal immune rejection :
Act as gate keeper that controls immune tolerance during pregnancy by
blocking T cells that would otherwise attack the developing conceptus

15. STAGES OF IMPLANTATION

16. APPOSITION
The blastocyst expresses L -selectins.
Presence of Mucin-1 (MUC-1) repels
the blastocyst and prevents it from
attaching outside of the window of
uterine receptivity.
L-selectins interact with the L-selectin
ligands, Which are expressed mainly on
the pinopodes during the implantation
window.
ADHESION PHASE
The blastocyst promotes the cleavage of
MUC-1 at the implantation site to
ensure successful attachment
Cytokines such as Leukemia inhibitory
factor (LIF), play an important
role during human implantation by supporting
the embryo-endometrial interactions.

17. INVASION/PENETRATION
The trophoblast cells from the
blastocyst penetrate the
endometrial epithelium into the
stroma.
The extra-villous trophoblast cells start
proliferating and differentiate into inner
cytotrophoblast and outer
syncytiotrophoblast
DECIDUALIZATION
Once implantation is initiated and the
embryo breaches the luminal epithelium,
the stromal cells surrounding the embryo
transform into decidualized cells .
Immune cells such as macrophages and
uterine natural killer (uNK) cells play an
important role during decidualization to
promote an environment that is conducive
to successful implantation

18. REGULATORY FACTORS IN EMBRYO IMPLANTATION

19. Embryo implantation is regulated by diverse factors.
(A)The ovarian steroid hormones progesterone and estrogen facilitate the
appropriate morphology, function, and development of the
endometrium during the implantation period.
(B) The cytokines leukemia inhibitory factor (LIF) and interleukin 6
(IL6) are involved in the regulation of endometrial receptivity via
expressing adhesion molecules, which play a crucial role in the
attachment of the trophoblast to the uterine epithelium.
(C) The growth factors transforming growth factor-β (TGF-β) and heparin
binding-epidermal growth factor (HB-EGF) are expressed in
endometrial stromal and epithelial cells to regulate endometrial cell
proliferation and decidual transformation.

20. A. Estrogen – Endometrium
proliferation
B. Progesterone – Endometrial
differentiation .
C. The blastocyst enters the uterus & rolls
freely over the endometrium under
signals by L- Selectin
D. (MUC-1) repels the blastocyst and
prevents its adhesion to endometrial
areas with poor chances of
implantation
E . Chemokines and cytokines attract the
blastocyst to the optimal implantation
spot.
F. Adhesion molecules (Integrins &
cadherins ) firmly attach the
blastocyst to pinopods for successful
implantation
ROLE OF MEDIATORS IN IMPLANTATION

21. FACTORS AFFECTING IMPLANTATION IN HUMANS