Mini Review
Volume 3 Issue 2 - 2016
Implantation: A Multifactorial Process that Affects IVF Success Rates
Klonos Eleftherios, Pados George* and Tarlatzis Basil
Department of Obstetrics and Gynaecology, Aristotle University, School of Medicine, “Papageorgiou” General hospital, Greece
Corresponding Author: Pados George, Associate Professor Department of Obstetrics and Gynaecology, Aristotle University, School of Medicine, “Papageorgiou” General hospital, Thessaloniki 54623, Mitropoleos 40, Greece.
Received: May 09, 2016; Published: July 12, 2016
Citation: Pados George., et al. “Implantation: A Multifactorial Process that Affects IVF Success Rates”. EC Gynaecology 3.2 (2016): 259-261.
The success rate after treatment by in vitro fertilization (IVF) is greatly depended upon cooperation of a suitably primed endometrium and the fertilized oocyte, which is at the blastocyst stage. Low pregnancy rates after in vitro fertilization are attributed to a failed implantation procedure. In this review article the various parameters which play a fundamental role in implantation are described.
Keywords: Implantation; Blastocyst; Endometrium
The embryo implantation stage is a complex process that requires the mutual interaction of a suitably primed endometrium and the penetration of the blastocyst. Low pregnancy rates after in vitro fertilization are attributed to a failed implantation procedure. On the contrary, the implantation is called successful when the blastocyst arrives at the suitable time frame implantation window when the endometrium is properly adapted and developed to become receptive to the blastocyst developmental processes [1]. The assessment of endometrial function in terms of receptivity in vitro Fertilization (IVF) cycles is, however, a highly controversial issue as to date no explicit marker of receptivity has been defined. This review depicts the cellular and molecular events that coordinate this complex process and highlight recent advances in this area of reproductive medicine.
Process of Implantation
Regarding the implantation stage in particular, steroid hormones play an important role in the coordination of the blastocyst and the endometrium. A necessary requirement for the implantation is the increased secretion of estradiol before ovulation, as at the given time the high concentration thereof contributes to the division and differentiation of the epithelial cells of the uterus. At the same time, the constantly increasing progesterone promotes the division and differentiation of stromal cells whose results in the transition of the endometrium to secretory and therefore able to achieve implantation [2].
The implantation process in humans can be presented as a gradual progress including the phase of apposition, attachment and finally of guided interaction between trophoblast and epithelial endometrial cells. Implantation can be divided in distinct stages related to the development of the hatching embryo and its interaction with the endometrial cells. In the human species, the embryo enters the endometrial cavity 72-96 hours after fertilization. The escape from the transparent zone is performed on the fifth day (approximately 110-120 hours after ovulation). The apposition, as well as, the attachment process is followed by the epithelial penetration process, thus signalling the beginning of stage 5 of implantation. Even though the mechanism of blastocyst penetration to the surface of the epithelium has not been fully investigated, it is certain that the determinant factor is the presence of endometrial receptors, as well as of necessary enzymes, cytokines, chemokines, other gene products and the presence of adhesion molecules [3,4].
The acquisition of special proteins on the endometrial surface and the embryonic epithelium is of vital importance for the promotion of the placentation process. The nature of the specific bio-indicators of endometrial receptivity proves that the processes of appositionattachment are promoted through the interaction between attachment molecules and the components of the extracellular matrix (ECM). As soon as the embryo acquires an expanded trophoblast layer, the cells of the syncytiotrophoblast penetrate through the basic membrane in the lower layer and continue to multiply. As soon as the process of attachment and penetration of the embryo are achieved, access to the endometrial vascular system is the first priority [5].
By the time, the increase in size and metabolism of syncytiotrophoblast require increased quantities of oxygen and nutrients in relation to a better management of cell waste, thus achieving a longer term survival. Finally, the cells of syncytiotrophoblast begin their penetration to the vascular system of the woman so achieving their integration to the vascular system wall, while at the same time they ensure access to the endometrial feeding sources.
The cooperation between the activated blastocyst with the now receptive endometrium depends on many factors. To begin with, catechol estrogens (4-hydroxyestadial-17B) as well as the increasing secretion of chorionic gonadotropin play an important role in the production of steroid hormones thus maintaining the secretion of progesterone and facilitating the penetration of the blastocyst. Plateletactivating factor (PAF), heparin binding EGF - like growth factor (HB-EGF) and HSPG heparin sulfate proteoglycan (HSPG) are of great importance, since through their connection to the EGF promote the division and maturation of the blastocyst [6].
The production of prostaglandins is a necessary requirement for a successful implantation. More specifically, the COX enzyme is responsible for the transformation of the arachidonic acid to prostaglandins and it appears in two forms COX-1 and COX-2. The latter is directly related to the implantation process as well as to the presence of blastocyst. The genes of this enzyme, which is so necessary for the implantation are promoted through interleukin-1, while metalloproteinase-9 holds an assisting part as well. With the penetration of the blastocyst, the attachment receptors significantly decrease, while the receptors of the vascular cells increase, so facilitating the contact of embryonic cells with those of the mother and transformation of these cells to vascular with the higher aim of penetrating the uterus [6].
Finally, proteinases, catapsinases B and C integrins and growth factors IGF-1, IGF-2, play a determinant role, while the most important metalloproteinase-3 contributes mostly to diminish negative issues such as hemorrhage and placental abruption, as it promotes and postpones at the same time the penetration of the blastocyst, thus indicating the proper position in the endometrium and deterring the aforementioned negative results [6].
A further vital factor for the success of the implantation is the immunological factor. In particular, the fertilized oocyte constitutes a foreign body due to the genetic differentiation by half from the woman. The crucial point for the smooth outcome of the implantation is that the embryo when implanted is not identified by the mother’s immunological mechanisms and therefore is not rejected.
The main cause for this condition is the trophoblast, which contributes to the deactivation of immunological mechanisms, due to the direct contact with the uterine tissue and the uterine immune system. This deactivation is achieved because of the expression of the HLAG molecules, which protect the trophoblast cells from the dissolution that the uterine NK (natural killer) cells would cause under different conditions.
A second possible explanation is the lack of immunological elaboration by the anatomic part of the decidua of the uterus. This is the result of the presence of the NK CD56+ lymphocytes. These lymphocytes are characterized by decreased cytotoxicity compared to those of the peripheral blood. The suspended cytotoxicity is the result of the action of cytokines (produced by the blastocyst) as well as of the steroid hormones and progesterone. Finally, the corticotropin releasing hormone (CRH), which is expressed by the epithelial and stromal cells of the endometrium plays an important role and participates in the suspension of immunological processes so as to achieve a successful implantation stage [5,6].
Synchronization between blastocyst development and the acquisition of endometrial receptivity is a prerequisite for the success of IVF. Human embryo implantation should be considered a three-stage process, which includes apposition, adhesion and invasion. Although the recent discovery of molecules crucial for successful embryo implantation has offered new insights into this issue, focus on functional rather than the morphological characteristics of endometrial receptivity may give the answer for a successful embryo implantation, thus improving the ability of specialists to treat infertility.
  1. Wang X., et al. “Embryonic signals direct the formation of tight junctional permeability barrier in the decidualizing stroma durong embryo implantation”. Journal of Cell Science 117.1 (2004): 53-62.
  2. Edwards R., et al. “Factors influencing the success of in vitro fertilization for alleviating human infertility”. Journal of In Vitro Fertilization and Embryo Transfer 1.1 (1984): 3-23.
  3. Sharkey A and Smith SK. “The endometrium as a cause of implantation failure”. Best Practice & Research Clinical Obstetrics & Gynaecology 17.2 (2003): 289-294.
  4. Smith SK. “Angiogenesis and implantation”. Human Reproduction 15. Suppl 6 (2000): 18-23.
  5. Allen V., et al. “Pregnancy outcomes after assisted reproductive technology”. Journal of Obstetrics and Gynaecology Canada 28.3 (2006): 220-225.
  6. Lessey B. “Adhesion molecules and implantation”. Journal of Reproductive Immunology 55.1-2 (2002): 101-104.
Copyright: © 2016 Pados George., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

August Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the August issue of respective journals and can be viewed in the current issue pages.

Submission Deadline for September Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the September issue of respective journals. Submissions are accepted on/before August 15, 2020.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to