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

Last updated: 20 January 2020


1. Basic Cell Biology

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

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

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

1.4 Basic gene regulation

2. Genetics

2.1 Basic genetics principles
Genotype and phenotype
Basic Mendelian inheritance patterns
Monogenic diseases
Mutations, copy number variation (CNV), de novo mutations
Chromosomal abnormalities: numerical, structural
Interpretation of an inheritance / family tree / pedigree

2.2 Genetic analysis and diagnosis
How and why is it performed
Diagnostic methods: cytogenetics (e.g. karyotyping, FISH), molecular genetics (e.g. PCR, array CGH, NGS)

3. Developmental Biology

3.1 Embryonic stem cells
Origins, definitions, characteristics

3.2 The fetal ovary
Factors regulating development
Primordial germ cells
Cell migration
Time scale (days / week)

3.3 The fetal testis
Factors regulating development
Primordial germ cells
Cell migration
Time scale (days / week)

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

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

3.6 Implantation
Hatching, adhesion, invasion, endometrium

3.7 Post-implantation embryology
Sex differentiation

3.8 Early pregnancy
hCG production, biochemical and ongoing pregnancy
Implantation, ultrasound (sacs, heartbeat)
Extra uterine pregnancies
Spontaneous abortions
Embryo factors vs. uterine factors in implantation/implantation failure

4. Female Reproduction

4.1 Anatomy and function of the female reproductive system
Role of accessory systems
Function of the organs

4.2 Oogenesis
Regulating factors
Hypothalamus, pituitary, gonad axis
Endocrine regulation
Theca & granulosa cells
Maturation biochemistry and metabolism of the oocyte
Oocyte morphology/structure
Function of each structure

4.3 The oocyte: markers of competence
Nuclear maturity
Polar bodies
Zona pellucida
Cumulus cells

4.4 Clinical workout
Evaluation of (in)fertility: aetiology, medical/physical aspects, genetic diagnosis, hormonal evaluation, treatment options, etc.
Definitions, primary infertility, secondary infertility
Serological screening for patients and/or donors
Effects of treatment
Oocyte donation

4.5 Ovarian hyperstimulation
Basic principles
Types of medication
Stimulation regimes (types, rationales)
Complications of treatment

5. Male Reproduction

5.1 Anatomy and function of the male reproductive system
Role of accessory systems
Function of the organs

5.2 Spermatogenesis
Regulating factors
Hypothalamus, pituitary, gonad axis
Endocrine regulation
Leydig & Sertoli cells
Differentiation and maturation
Biochemistry and metabolism of the sperm cell
Sperm morphology/structure
Function of each structure

5.3 Diagnosis of male infertility
Semen analysis (functional analysis, microscopic analysis)
WHO & ESHRE guidelines
CASA systems

5.4 Clinical workout
Evaluation of (in)fertility: aetiology, medical aspects, genetic diagnosis, hormonal evaluation, physical aspects, treatment options, etc.
Definitions, primary/secondary infertility
Serological screening for patients and/or donors
Sperm donation

6. ART Laboratory Procedures

6.1 Strategies for choosing fertilization procedures
IUI, IVF or ICSI, criteria
Donor sperm in relation to serological tests (different handling and storage)

6.2 The sperm sample: preparation methods
Gradient centrifugation, swim-up, swim-out, etc
Advanced diagnostic tests (evaluation of DNA damage, chromatin condensation, etc)
When to use what, why, differences

6.3 ART techniques
Practicalities for IUI, IVF and ICSI (timing, preparation procedures, materials, etc)
Pick-up, oocyte handling
IVF insemination
Denudation prior to ICSI
ICSI procedure

6.4 Embryo scoring, Day 1 - 6
PN scoring
Morphology criteria
Kinetics, genetics, physiology (e.g. amino acids, oxygen metabolism)
Destination of embryos: selection criteria for transfer, cryopreservation, biopsy, etc

6.5 Embryo transfer
Identity check
Selection and criteria for number of embryos to be transferred
Catheter loading and transfer procedure
Assisted hatching: pros-cons, evidence

6.6 PGT
Timing of biopsy
Tubing techniques
Zona opening (pros and cons)
Different biopsy types, number of cells to evaluate
Techniques used for evaluation of the cells biopsied
Results and recommendations upon transferring embryos after PGT

6.7 Culture conditions
Type of culture systems
Requirements for consumables
Physiochemical parameters (temperature, pH, osmolality)
Stage specific requirements

6.8 Non-routine methods:
Examples of non-routine methods, e.g. in vitro maturation, polar body evaluation, assisted hatching, etc

7. Cryopreservation

7.1 Principles of cryopreservation
Basic cryobiology
Cryoprotectants, additives
Slow freezing
Advantages/disadvantages with different methods
Fertility preservation in oncology cases

7.2 Cryopreservation of sperm
Theory and practice

7.3 Cryopreservation of oocytes
Theory and practice

7.4 Cryopreservation of embryos
Theory and practice

7.5 Cryopreservation of ovarian tissue
Theory and practice

7.6 Cryopreservation of testicular tissue
Theory and practice

7.7 Equipment
Contamination risk from storage medium
Minimal safety requirements

7.8 The cryopreservation-thawed/warmed embryo treatment cycle
Monitoring and timing of the thawing/warming cycle
Controlled and natural cycles

8. Laboratory and Quality Management

8.1 Patient data
Identity check
Keeping records
Safety, storage of data
Single European Code

8.2 Type and treatment choices
Hormone stimulation
Insemination IVF / ICSI
Use of fresh or frozen gametes
Gamete and embryo donation

8.3 Treatment outcome
The health of the children
Risk factors
Maternal factors
Paternal factors
Multiple pregnancies
Chromosomal factors

8.4 Quality assurance
Identification procedures
Laboratory and clinical KPIs
Standard operating procedures
Traceability of samples/material
Validation procedures
Risk analysis
Introducing new methods

8.5 Equipment and facilities
Validation, monitoring, logbooks, maintenance and control
Principals of optical system, calibrations, maintenance and control
Technical requirements in a ART lab facility

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

8.7 Legislation
ESHRE guidelines
Ethical considerations
Code of practice
European rules and regulations related to ART practice
EU Tissue and Cells Directives (EUTCDs)

8.8 Reducing risks/ dealing adverse events/ troubleshooting
Contaminated samples
Processing and storage of contaminated samples with contagious agents
Personal protective equipment (PPE)
Hygiene and disinfectants used at ART lab
Protective measures (alarm, sensors, etc)
Actions upon injury
Risk of mix-up of gametes, loss or damage during handling
Transfer of wrong embryos
Breakdown of equipment, back-up strategies