The paradox of the Italian clinical embryologist in the national public health system: hints towards harmonization of a postgraduate educational curriculum.

Clinical embryologists are highly trained laboratory professionals with multiple roles, including laboratory, clinical, biobanking and quality system management. In most European countries, clinical embryologists are trained to work in Medically Assisted Reproduction (MAR) centres without a specifically dedicated educational path. The criteria required for employment vary according to the educational structure and the public or private nature of the centre. We have herein described the educational profile required by Italian clinical embryologists to work in MAR centres of the National Health System (NHS). Public centres currently represent 36% of all the Italian MAR clinics. According to the Italian law, a future clinical embryologist must achieve a 3-4 year unpaid post-graduate specialization in a different field, choosing from Genetics, Microbiology, Clinical Pathology or Nutrition. Accesses to the above-mentioned post-graduate courses are themselves very limited. Clinical embryologists are basically trained by senior colleagues. This situation makes inevitably difficult to recruit laboratory staff in NHS centres. Moreover, it represents an emblematic example of the need for an equal training curriculum, possibly ensuring a comparable education quality, mobility of trainees and dissemination of skills for clinical embryologists all over Europe.

Inter-centre reliability in embryo grading across several IVF clinics is limited: implications for embryo selection.

RESEARCH QUESTION: What is the intra- and inter-centre reliability in embryo grading performed according to the Istanbul Consensus across several IVF clinics? DESIGN: Forty Day 3 embryos and 40 blastocysts were photographed on three focal planes. Senior and junior embryologists from 65 clinics were invited to grade them according to the Istanbul Consensus (Study Phase I). All participants then attended interactive training where a panel of experts graded the same embryos (Study Phase II). Finally, a second set of pictures was sent to both embryologists and experts for a blinded evaluation (Study Phase III). Intra-centre reliability was reported for Study Phase I as Cohen's kappa between senior and junior embryologists; inter-centre reliability was instead calculated between senior/junior embryologists and experts in Study Phase I versus III to outline improvements after training (i.e. upgrade of Cohen's kappa category according to Landis and Koch). RESULTS: Thirty-six embryologists from 18 centres participated (28% participation rate). The intra-centre reliability was (i) substantial (0.63) for blastomere symmetry (range -0.02 to 1.0), (ii) substantial (0.72) for fragmentation (range 0.29-1.0), (iii) substantial (0.66) for blastocyst expansion (range 0.19-1.0), (iv) moderate (0.59) for inner cell mass quality (range 0.07-0.92), (v) moderate (0.56) for trophectoderm quality (range 0.01-0.97). The inter-centre reliability showed an overall improvement from Study Phase I to III, from fair (0.21-0.4) to moderate (0.41-0.6) for all parameters under analysis, except for blastomere fragmentation among senior embryologists, which was already moderate before training. CONCLUSIONS: Intra-centre reliability was generally moderate/substantial, while inter-centre reliability was just fair. The interactive training improved it to moderate, hence this workflow was deemed helpful. The establishment of external quality assessment services (e.g. UK NEQAS) and the avant-garde of artificial intelligence might further improve the reliability of this key practice for embryo selection.

Production of sHLA-G molecules by in vitro matured cumulus-oocyte complex.

Oocyte selection with the highest competence is a major goal in IVF. Several studies demonstrated that non-classical HLA class I HLA-G molecule modulation creates a tolerogenic microenvironment at the feto-maternal interface and is implicated in embryo implantation. This study investigated if soluble HLA-G molecules producted by the cumulus-oocyte complex (COC) are markers of oocyte maturation. sHLA-G molecule levels were analyzed using Bio-Plex assay in 152 COC supernatants obtained from 42 women and maturated by an 'in vitro maturation procedure'. The presence of sHLA-G molecules was confirmed by Western blotting technique. The results demonstrate detectable amounts of sHLA-G molecules ranging from 300 to 800 pg/ml in 14/73 (19%) COCs that generated mature oocytes and complete absence of detectable sHLA-G antigens in the supernatants of COCs that corresponded to immature oocytes. The detection of sHLA-G molecules in the COC culture supernatants corresponding to matured oocytes is proposed to be a marker to identify gametes with higher functionality. This non-invasive marker could be used, in addition to morphological approaches, to reduce the number of fertilized oocytes and transferred embryos.