Curriculum

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

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
• 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

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)

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

• Fertilisation
• 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
• Apoptosis

3.6 Implantation

• Hatching, adhesion, invasion, endometrium

3.7 Post-implantation embryology

• Gastrulation
• Organogenesis
• 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

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
• Cytoplasm
• 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

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

MAR Laboratory Procedures

6.1 Strategies for choosing fertilization procedures

• IUI, 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

• 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 MAR 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)
• Time-lapse
• 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

• Media
• 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

Cryopreservation

7.1 Principles of cryopreservation

• Basic cryobiology
• Cryoprotectants, additives
• Slow freezing
• Vitrification
• 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

• Machines
• Straws/ampoules
• Contamination risk from storage medium
• Minimal safety requirements
• Security

7.8 The cryopreservation-thawed/warmed embryo treatment cycle

• Monitoring and timing of the thawing/warming cycle
• Controlled and natural cycles

Laboratory and Quality Management

8.1 Patient data

• Identity check
• Confidentiality
• Keeping records
• Safety, storage of data
• Single European Code

8.2 Type and treatment choices

• Surgical
• 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
• Malformations
• Imprinting

8.4 Quality assurance

• Identification procedures
• Laboratory and clinical KPIs
• Standard operating procedures
• Traceability of samples/material
• Validation procedures
• Risk analysis
• Logbooks
• Introducing new methods

8.5 Equipment and facilities

• Calibrations
• Validation, monitoring, logbooks, maintenance and control
• Microscopes
• Principals of optical system, calibrations, maintenance and control
• Technical requirements in a MAR 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 MAR 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 MAR 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