Curriculum

Last updated: 28 January 2025

Applicants will be expected to have a good knowledge of the following aspects of clinical embryology. Level of questions will depend on the type of exam (basic or advanced).

1. Cell Biology

1.1 Intracellular structures

Cell membrane; microvilli; cytoplasm; cytoskeleton; microtubules; actin and intermediate filaments ; centrioles, nucleus and chromosomes, mitochondria, endoplasmic reticulum, Golgi apparatus , cortical granules

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; replication, transcription, translation, secretion

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

1.5 Cell-cell interaction

Membrane receptors: function, type, regulation; signaling; junctions

1.6 Physiological processes

Movement of proteins, ions and vesicles; exocytosis, endocytosis, phagocytosis

1.7 Apoptosis and senescence

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

Mitotic and meiotic cell division; meiosis and recombination; meiotic and mitotic errors; mosaicism and chromosomal anomalies (numeric or structural anomalies); epigenetics

2.3 Monogenic diseases, chromosomal structural and numerical abnormalities

Mutations: inherited and de novo variants (SNPs, CNVs, deletions and insertions)

2.4 Genetic causes of infertility

Testing for infertility in males and 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, multiplex /real-time PCR) , Genetic testing methods for monogenic disease/structural rearrangements and numerical aberrations,: PGT -M/-SR/-A/ ( e.g array CGH, Next Generation Sequencing (NGS) WGS, SNP Array ).

3. Developmental Biology

3.1 Embryonic stem cells

Origins, definitions, characteristics

3.2 The fetal ovary and fetal testis

Factors regulating development; organogenesis; sex differentiation and sex determination; 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; extrauterine pregnancy; 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; pre- and post-puberty physiology, reproductive cycle in the females: preovulatory/menarche, menstrual cycle, menopause

4.2 Oogenesis

Regulating factors: hypothalamus – pituitary - gonad axis; endocrine regulation (hormones); FSH and LH receptors; theca & granulosa cells; maturation biochemistry and metabolism of the oocyte; completion of meiosis; oocyte’s morphology, structures, functions

4.3 Oocyte competence

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

4.4 Clinical workup and diagnosis of infertility

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 and cryo cycles including endometrium preparation (types, rationales: artificial vs natural cycles); complications of treatment (e.g. OHSS)

5. Male Reproduction

5.1 Anatomy and function of the male reproductive system

Function and regulation of the reproductive organs (HPG axis, Sertoli and Leydig cells); primary and secondary sexual characteristics; pre- and post-puberty physiology; regulation of the reproductive organs; role of accessory glands; ejaculatory disfunction.

5.2 Spermatogenesis

Regulating hormonal factors: hypothalamic, pituitary, gonadal axis; para- and endocrine regulation; Leydig & Sertoli cells; differentiation, maturation, biochemistry and metabolism of the spermatozoa; blood-testis barrier

5.3 Spermatozoa competence

Nuclear and cytoplasmic maturity; acrosome, neck and tail structures; morphology: particular dysmorphisms; fertilization capacity; capacitation, acrosome reaction and motility characteristics at fertilization

5.4 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)

5.5 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 Criteria and strategies for choosing fertilisation procedures

IUI, IVF or ICSI, criteria; PESA, TESA, TESE ,microTESE

6.2 The sperm sample: preparation methods

Density gradient centrifugation, swim-up, microfluidics, electrophoresis, MACS, 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; use of time-lapse technology in morphokinetics; embryo selection criteria for transfer, cryopreservation, biopsy; identity check before embryo transfer; catheter loading and transfer procedure ; the potential role of time lapse in embryo selection.

6.6 PGT (PGT-A, PGT-SR, PGT-M)

Timing of biopsy; different biopsy and tubing techniques; number of cells to evaluate; 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 postpuberal)

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); type of incubators; transportation dewar for frozen material

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 in males and females (pre- and postpuberal)

Theory and practice

8. Laboratory and Quality Management

8.1 Patient data

Identity check; confidentiality; keeping records; traceability; safety, risk 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 the 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 MAR labs; 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 European guidelines and legislation (see reading list)

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