Last updated: 6 October 2022

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

1. Cell Biology

1.1 Intracellular structures
Cell membrane; microvilli; cytoplasm; cytoskeleton; microtubules; microfilaments; centrioles, nucleus and chromosomes, mitochondria, endoplasmic reticulum, Golgi apparatus

1.2 Metabolism in the mammalian cell
Carbohydrates; fats and lipids; proteins, enzymes, cytokines; metabolic pathways; reactive oxygen species

1.3 Fundamental principles of molecular biology
DNA and RNA structure; cellular replication

1.4 Mitosis and meiosis, cell cycle, checkpoints, signals and controls

1.5 Cell-cell interaction
Membrane receptors: function, type, regulation; signalling; junctions

1.6 Physiological processes
Movement of proteins, ions and vesicles; exocytosis, endocytosis, phagocytosis

1.7 Apoptosis

2. Genetics

2.1 Basic genetics principles
Genes, genotype and phenotype; basic Mendelian inheritance patterns; Interpretation of an inheritance/family tree/pedigree; DNA chromatin and chromosomes; characteristics of the sex chromosomes: structures and specific genes

2.2 Genetic mechanisms
Mitosis and meiosis; meiotic cell division; meiosis and recombination; meiotic and mitotic errors; mosaicism and chromosomal anomalies (numeric or structural anomalies); epigenetics

2.3 Monogenic diseases and chromosomal abnormalities
Mutations: inherited and de novo variants (SNPs, CNVs, deletions and insertions)

2.4 Genetic causes of infertility
Testing for infertility in males (most common genetic anomalies: chromosomes or genes affected); testing for infertility in females (most common genetic anomalies: chromosomes or genes affected); genetic consequences for offspring in ageing males or females

2.5 Genetic analysis and diagnosis
Diagnostic methods: cytogenetics (e.g. karyotyping), molecular genetics (e.g. PCR, array CGH, Next Generation Sequencing: WES and WGS); techniques for PGT -A/SR/M

3. Developmental Biology

3.1 Embryonic stem cells
Origins, definitions, characteristics

3.2 Primordial Germ Cell migration
Organogenesis; Sex differentiation

3.3 The fetal ovary and fetal testis
Factors regulating development; primordial germ cells; germ cell migration; time scale (days/week)

3.4 Gamete interaction – until 1st cleavage
E.g. acrosome reaction; chromatin decondensation; fertilisation; oocyte activation; meiosis II, pronuclei and spindle formation; syngamy

3.5 Embryo development - from first cleavage to implantation
Cleavage embryos, morulas and blastocysts; metabolomics, cell allocation and differentiation, embryonic axis; morphokinetics, timing, regulation; cell differentiation; cleavage irregularities

3.6 Implantation and post-implantation embryology
Hatching, decidualization, window of implantation, apposition, adhesion, invasion, gastrulation

3.7 Early pregnancy
hCG production, biochemical and ongoing pregnancy; implantation, ultrasound (sacs, heartbeat), monozygotic twinning; 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
Function and regulation of the reproductive organs (HPG axis; ovaries and uterus); primary and secondary sexual characteristics; reproductive cycle in the females: pre ovulatory/menarche, menstrual cycle, menopause

4.2 Oogenesis
Regulating factors: hypothalamus – pituitary - gonad axis; endocrine regulation (hormones); theca & granulosa cells; maturation biochemistry and metabolism of the oocyte; oocyte: morphology, structures, function

4.3 Oocyte competence
Nuclear and cytoplasmic maturity; polar bodies; zona pellucida; cumulus cells; SER; dysmorphisms

4.4 Clinical workup
Evaluation of (in)fertility: aetiology, medical/physical aspects, genetic diagnosis, hormonal evaluation (incl. what days of cycle to test), ovarian reserve, treatment options, etc.; definitions, primary infertility, secondary infertility; oocyte and embryo donation (selection and workup); serological screening for patients and donors

4.5 Ovarian stimulation
Basic principles (use of agonists vs antagonists); ovulation induction; ovarian hyperstimulation; stimulation regimes in fresh or cryo cycles (types, rationales: artificial vs natural cycles); complications of treatment (eg OHSS)

5. Male Reproduction

5.1 Anatomy and function of the male reproductive system
Primary and secondary sexual characteristics of the males function; pre- and post- puberty; regulation of the reproductive organs; role of accessory glands

5.2 Spermatogenesis
Regulating hormonal factors: hypothalamus, pituitary, gonad axis; para- and endocrine regulation; Leydig & Sertoli cells; differentiation, maturation, biochemistry and metabolism of the spermatozoa; sperm morphology/structure; blood-testis barrier

5.3 Diagnosis of male infertility
Semen analysis (basic and functional); diagnosis of azoospermia: obstructive vs non-obstructive (preparation and procedures); globozoospermia and other genetically related diagnosis; CASA systems; advanced diagnostic tests (evaluation of DNA damage, chromatin condensation, etc)

5.4 Clinical workup
Evaluation of (in)fertility: aetiology, medical aspects, genetic diagnosis, hormonal evaluation, physical aspects, treatment options, etc.; definitions, primary/secondary infertility; sperm donation (selection and workup); serological screening for patients and donors

6. MAR Laboratory Procedures

6.1 Strategies for choosing fertilisation procedures
IUI, IVF or ICSI, criteria; PESA, TESA, TESE

6.2 The sperm sample: preparation methods
Gradient centrifugation, swim-up, microfluidics, etc; when to use what, why, differences

6.3 ART/MAR techniques
Practicalities for IUI, IVF and ICSI (timing, preparation procedures, materials, etc); pick-up, oocyte handling; IVF insemination; oocyte denudation; ICSI; troubleshooting ART procedures (what can go wrong in the lab?)

6.4 Culture conditions
Media composition; stage-specific requirements; type of culture systems and incubators; quality requirements for consumables (CE marking, in vitro diagnostic vs in vitro medical devices); quality control testing (embryo toxicity tests, endotoxin test); sterilisation methods; physicochemical parameters (temperature, pH, osmolality)

6.5 Oocyte to blastocyst grading and embryo transfer
Oocyte; zygote; cleavage-stage; morula; blastocyst; stage-specific morphology criteria; morphokinetics; atypical embryo cleavage features observed with time-lapse technology; embryo selection criteria for transfer, cryopreservation, biopsy; identity check before embryo transfer; catheter loading and transfer procedure

Timing of biopsy; different biopsy and tubing techniques; number of cells to evaluate; tests for genetic evaluation of the cells biopsied; interpretation of results and recommendations for transferring embryos after PGT ; quality control for PGT (contamination risk)

6.7 Awareness of add-on techniques and non-routine methods
e.g. in vitro maturation; IMSI, PICSI; assisted hatching; artificial oocyte/sperm activation

6.8 Donation of oocytes/sperm/embryos
Donor selection, testing and handling donor samples

7. Cryopreservation

7.1 Principles of cryopreservation
Basic cryobiology; cryoprotectants; slow freezing; vitrification; lyophilization (freeze-drying); advantages/disadvantages of different methods

7.2 Cryopreservation of gametes, zygotes and embryos
Theory and practice

7.3 Cryopreservation of ovarian and testicular tissue (pre- and post-puberal)
Theory and practice

7.4 Equipment
Consumables and devices; open and closed systems; contamination risks; cryostorage (liquid and vapour phase); safety requirements (personal protective equipment, oxygen/nitrogen alarms)

7.5 Embryo warming/thawing cycle
Monitoring and timing; transfer in controlled and natural cycles; cryo survival assessment; theory and practice

7.6 Fertility preservation (pre- and post-puberal)
Theory and practice

8. Laboratory and Quality Management

8.1 Patient data
Identity check; confidentiality; keeping records; traceability; safety, management, storage and protection of data; Single European Code

8.2 Quality assurance
Identification procedures; standard operating procedures (SOPs); traceability (e.g. sample, material, operator, equipment, timing); validation procedures; quality control and risk management; KPI evaluation (clinical and laboratory); operator logbooks; training and competence assessment; introducing new methods

8.3 Quality management of equipment and facilities
Qualification, validation, calibration, monitoring; records (logbooks for equipment, data and material); maintenance and control; principals of optical systems; technical requirements in an MAR lab facility (premises, air quality and air pressure, lab hygiene); decontamination of equipment

8.4 Statistical analysis
Sample size evaluation; study design (RCT, meta-analysis, prospective vs retrospective); descriptive statistics ; statistical variance; interpretation of results (statistical significance)

8.5 Reducing risks, troubleshooting and biovigilance
Processing and storage of contaminated samples and in patients with a viral infection or disease; 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; identification and management of serious adverse events and reactions (according to EU Tissue and Cells Directives)

8.6 Treatment outcomes
The health of the children; risk factors; maternal factors; paternal factors; multiple pregnancies; genetic factors; malformations; imprinting

8.7 Guidelines and legislation
ESHRE guidelines; ISO standards; European rules and regulations related to MAR practice; EU Tissue and Cells Directives (EUTCDs); cross-border treatment and transportation of human material; distribution; export/import