Physiology of Implantation | Jindal IVF Chandigarh
                     Physiology of 
Implantation
Umesh N Jindal
Jindal IVF Chandigarh
Embryo to Baby
• Embryo 
development
• Implantation
• Decidualization
• Placentation
• Pregnancy
• Parturition
Players in 
Implantation
• Free to move Blastocyst
• HCG
• Finds a place without 
MUC 1 and pinopods
• Surface Selectins to 
bind with surface 
selectin ligands on 
endometrium
• Express integrins, 
glycoproteins other 
adhesion molecules
Endometrium
• Typical menstrual Cycle • Differentiation during 
• Stratum basalis for luteal phase for a receptive 
regeneration and endometrium and 
hormone responsive implantation
functionalis for dynamic • Early Luteal,Mid Luteal 
remodelling • Late Luteal/Decidualization
The endometrium is 
hostile in pre-receptive 
and post-receptive phases 
and also in non favourable 
locations
Role of various cells
• Epithelial cells, Stromal cells, Immune cells, Endothelial cells
• expresses several genes during process of implantation
Epithelial to mesenchymal transition (EMT)
• Endometrial cell can exist 
in both epithelial and 
mesenchymal phenotypes
• Important for cellular traits 
necessary for implantation
• Loose apical polarity
• Loose tight junctions
• Acquire properties that 
promote invasion and 
migration
Mediators:The language of cross talk  
mediator source family actions
hCG embryo hormone •Luteotrophic
• Angiogenesis and vasodilatation in 
endometrium
• Immune modulation
•Uterine quiescence, A- SMA and Notch-1 
(decidualization)
LIF endometri Cytokine Pinopod development, 
um cell adhesion, invasion and placentation
Interleukin-6 both Cytokine Pro-inflammatory
(IL-6)
Interleukin-1 both Cytokine Cross talk, tissue remodelling and 
(IL-1) decidualization
Mediators: The language of cross talk
mediator source family actions
Integrins endometr Adhesion differentiation, apoptosis, motility and 
ium molecules attachment
(CAMs)
Cadherins cytotroph (CAMs) Restrain invasiveness in cytotrophoblast and 
oblast promotes in syncytiotrophoblast
Selectins embryo (CAMs) Crucial in adhesion
Mucin- endometr glycoprot Prevents adhesion, dissolves by signal from 
1(MUC-1) ium ein blastocyst, prevents adhesion at wrong site
MicroRNAs Both miRNA transcriptional and translational level 
contributing to the implantation process 
Controlled invasion
Steps in implantation for embryo
• We can add decidualization of endometrium and 
placentation for complete and successful pregnancy
Cross talk (apposition and adhesion)
Specific ICM 
orientation
• blastocyst expresses L-selectins and rolls freely to select site without 
MUC1
• L-selectins interact with the L-selectin ligands expressed on pinopodes
• Cytokines (LIF) andCAMs play important role in adhesion
Invasion and Decidualization
• Trophoblast cells develop invadopodia to penetrate loosened epithelium (EMT cells)
• Trophoblast differentiates into cyto and syncytio
• Stromal cells become decidualized
• Immune cells and uNK cells important for immune modulation
Decidualization
1. Reprogramming of endometrial stromal cells (elongated fibroblast-like cells), 
into a decidual cells (rounded epithelial-like cells) Under effect of Progesterone
2. Angiogenesis and  vascularized receptive tissue which increase vascular 
permeability with the purpose of initiating the development of the placenta 
and to coordinate an independent (embryo-mother), vascular system
3. Invasion of leukocytes and immune modifications 
Implantation and early Placentation
• Trophoectoderm differentiates into inner cytotrophoblast and outer 
syncyotiotrophoblast (syncytialization)
•Over time, the primary villi grow and branch into secondary and tertiary villi. 
This process is known as placentation 
Disruption of Embryo Implantation: RIF
More research is needed to investigate the immunologic, genetic, anatomic, 
hematologic, microbial, and endocrine factors that may be altered or optimized as 
we seek the elusive goal of 1 embryo equating to 1 live birth
Consequences of Defective Implantation: 
Clinical Relevance
Pregnancy complications
Implantation First Trim
25%
preclinical Clinical PIH
Failure 30% Miscarriage 15%
Placenta previa
Biochemical    preg Ectopic
30% Molar IUGR, LGA
Preterm

Impaired Expression Of Endometrial 
Factors Correlates With Reduced 
Implantation Chelsea Fox, Fertil Steril 2016
• Do Endometrial Receptivity Defects Exist? (Luteal 
Phase defect, Shift in WOI)
• Regulation of Endometrial Receptivity (Genes, 
receptors, P resistance)
• Disorders Associated with Implantation Failure 
(anatomical and inflammatory)
• Endometrial Factors as Biomarkers of Receptivity

THE EFFECT OF SYSTEMIC FACTORS ON
IMPLANTATION AFTER IVF
• Thyroid Dysfunction ( TSH>4.5, TSH between 
2.5-4.5, TPO antibodies)
• Vitamin D Deficiency (no Effect)
• Prolactin (no effect)
• Inflammatory Bowel Disease (no Effect)
• Obesity (negative effect)
• Cigarette Smoking (negative effect both active 
and passive) 
• Autoimmunity (mixed reports)
Thank You

Role of Heparin
Maternal vessel remodeling



Mediators
Mediators

Vascular remodelling