Curriculum

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 Chromosomes

Concept of a gene.

Mutations

Epigenetics

1.4 Basic gene regulation

Translation.

Transcription.

Expression

Imprinting

1.5 Basic genetics

Genotype. Phenotype.

Basic Mendelian inheritance patterns

Monogenic diseases

Chromosomal abnormalities: numerical, structural

Interpretation of a pedigree

1.6 Genetic analysis

How and Why

Basic methods: Cytogenetics (karyotyping, FISH,..), Molecular genetics (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, T, 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

Microscopical analysis

WHO guidelines

CASA systems etc

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, E, 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, PN:s, 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 etc

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 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. AA:s, oxygen metabolism)

Consequences (freeze, transfer)

6.6 Culture conditions

Media

culture systems

requirements for consumables

physiochemical parameters (Temp, 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 (pro’s and con’s)

Different biopsy types, number of cells

Block 7 The cryopreservation programme

7.1 Principles for freezing and thawing of cells

Basic cryobiology

cryoprotectants, additives

slow freezing

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 FER treatment cycle

Monitoring and timing of the FER-cycle

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

SOP’s

traceability

validations

monitoring, 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- Directive

Examples of what the directive covers

Implementation in own country

8.6 Non-routine methods

IVM

PGS

AHA

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 measurements (gloves, masks etc)

Actions upon injury

9.3 Adverse events, back-up strategies

How to avoid, what to do?

e.g. Mix-up of gametes, loss or damage during handling

Transfer of wrong embryos

Breakdown of equipment, back-up strategies

9.4 Trouble shooting