Curriculum

Applicants will be expected to have a good knowledge of the following aspects of clinical embryology.


Block 1. Basic concepts: cell biology, molecular biology and genetics

1.1 The cell
Internal organization
Cell cycle control, checkpoints
Mitosis and meiosis
The reproductive cells: spermatozoa and oocytes

1.2 Cell-cell interaction
Membrane receptors: function, type, regulation
Signalling
Junctions

1.3 Basic genetics of the cell
DNA chromatin and chromosomes
Concept of a gene
Mutations
Epigenetics

1.4 Basic gene regulation
Translation
Transcription
Expression
Imprinting

1.5 Basic genetics
Genotype and phenotype
Basic Mendelian inheritance patterns
Monogenic diseases
Chromosomal abnormalities: numerical, structural
Interpretation of a inheritance / family tree / pedigree

1.6 Genetic analysis
How and why is it performed
Basic methods: cytogenetics (e.g. karyotyping, FISH), molecular genetics (e.g. PCR)

1.7 Embryonic stem cells
Origins, definitions, characteristics


Block 2. Male Reproduction

2.1 The foetal testis
Factors regulating development
Primordial cells
Cell migration
Time scale (days / week)

2.2 Anatomy and function of the male reproductive system
Including accessory systems
Including function of the organs

2.3 Spermatogenesis
Regulating factors
CNS, pituitary
FSH, LH, testosterone, endocrine feedback
Leydig & Sertoli cells
Maturation
Biochemistry and metabolism of the sperm cell
Sperm morphology/structure
Function of each structure

2.4 The sperm sample – assessment
Functional analysis
Microscopic analysis
WHO & ESHRE guidelines
CASA systems


Block 3 Female reproduction

3.1 The foetal ovary
Factors regulating development
Primordial cells
Cell migration
Time scale (days / week)


3.2 Anatomy and function of the female reproductive system
Including accessory systems
Including function of the organs

3.3 Oogenesis
Regulating factors
CNS, pituitary
FSH, LH, Estrogen, feedback
Theca & granulosa cells
Maturation biochemistry and metabolism of the oocyte
Oocyte morphology/structure
Function of each structure

3.4 The oocyte - markers of competence
Nuclear maturity
Cytoplasm
Polar bodies
Zona pellucida
Cumulus cells


Block 4 Embryo development and early pregnancy

4.1 Gamete interaction – until 1st cleavage
Fertilization
Acrosome reaction
Sperm- oocyte signalling
Sperm decondensation
Oocyte activation
Meiosis II, pronuclei and spindle formation

4.2 Embryo development - from first cleavage to implantation
Metabolism, cell positions, embryonic axis
Kinetics, timing, regulation
Apoptosis

4.3 Implantation
Hatching, adhesion, invasion, endometrium

4.4 Post-implantation embryology
Gastrulation
Organogenesis
Sex differentiation

4.5 IVF outcome
hCG production, pregnancy test
Implantation rate, ultrasound (sacs, heartbeat)

4.6 Early pregnancy failures
Extra uterine pregnancies,
Spontaneous abortions
Embryo factors vs. uterine factors


Block 5 Infertility reasons, work-up and treatment

5.1 The infertile couple
Reasons, medical, genetic, hormonal, physical
Causes and effects
Definitions, primary infertility, secondary infertility, female vs. male

5.2 Patient screening
Physical / Serological
What tests are used? What to look for?
Screening of donors

5.3 Type and choice of treatment
Surgical
Hormone stimulation
Insemination IVF / ICSI
Sperm donation
Egg donation

5.4 Ovarian hyperstimulation
Basic principles
Types of medication
Stimulation regimes (types, rationales)
OHSS

5.5 Outcome
The health of the children
Risk factors
Maternal factors
Paternal factors
Multiple pregnancies
Chromosomal factors
Malformations
Imprinting


Block 6 Laboratory procedures - practical – from oocyte pick-up to transfer

WHY are we doing things in a certain manner / certain order?

6.1 Strategies for choosing fertilisation procedures
IVF or ICSI, criteria
IVM
PESA, TESA, TESE,
Donor sperm in relation to serological tests (different handling and storage)

6.2 The sperm sample – preparation methods
Centrifugation, swim-up, ”swim-out”, etc
Functional
When to use what, why, differences

6.3 IVF
Practicalities for IVF and ICSI
Pick-up, oocyte handling, insemination

6.4 ICSI
Denudation
Injection procedure

6.5 Embryo scoring, Day 1 - 6
PN scoring,
Morphology criteria
Kinetics, genetics, physiology (e.g. amino acids, oxygen metabolism)
Consequences (freeze, transfer)

6.6 Culture conditions
Media
Culture systems
Requirements for consumables
Physiochemical parameters (temperature, pH, osmolality)
Stage specific requirements

6.7 Equipment
Calibrations
Validation, monitoring, logbooks, maintenance and control

6.8 Microscopes
Principals of optical system, calibrations, maintenance and control

6.9 Embryo transfer
Identity check
Number of embryos
Catheter loading and checking

6.10 Cell biopsy
Zona opening (pros and cons)
Different biopsy types, number of cells


Block 7 Cryopreservation

7.1 Principles for freezing and thawing of cells
Basic cryobiology
Cryoprotectants, additives
Slow freezing, timing
Vitrification, timing
Advantages/disadvantages with different methods

7.2 Sperm freezing /thawing
Theory and practice

7.3 Oocyte freezing/thawing
Theory and practice

7.4 Embryo freezing/thawing
Theory and practice

7.5 Ovarian freezing/thawing
Theory and practice

7.6 Testicular freezing/thawing
Theory and practice

7.7 Equipment
Machines
Straws/ampoules
Media, contamination from storage medium (what and why)
Minimal safety requirements
Security

7.8 The frozen-thawed embryo treatment cycle
Monitoring and timing of the thawing cycle
Controlled and natural cycles


Block 8 Quality assessment, statistics, handling data, ethics, legislation

8.1 Patient data
Identity check
Confidentiality
Keeping records
Safety
Coding

8.2 Quality assurance
Identification procedures
Monitoring of performance, index variables
Standard operating procedures
Traceability
Validation
Monitoring and use of key performance indicators
Logbooks
If/ how/when to bring in new methods

8.3 Statistical analysis
Sample size evaluation
Study design
Statistical variance
Interpretation of results

8.4 Legislation
National legislation (what is allowed in your country)
Ethical consideration
Code of practice

8.5 The EU Tissue and Cells Directives (EUTCDs)
Examples of what the EUTCDs cover
Implementation in own country

8.6 Non-routine methods
Examples of non-routine methods, e.g. in vitro maturation, pregenetic screening, assisted hatching


Block 9 Risks

9.1 Contaminated samples
Processing and storage of sample known/suspected to be contaminated with contagious agents

9.2 Staff protection
Hygiene
Rules and regulations
Protective measures (gloves, masks, etc.)
Actions upon injury

9.3 Adverse events, back-up strategies
How to avoid, what to do?
Risk of mix-up of gametes, loss or damage during handling
Transfer of wrong embryos
Breakdown of equipment, back-up strategies

9.4 Troubleshooting