Training and competency assessment of Clinical Embryologists and licensing of the profession in European countries.

STUDY QUESTION: How is the acquisition and testing of theoretical and practical knowledge in Clinical Embryology and the licensing of ART laboratory personnel carried out in European countries? SUMMARY ANSWER: Twelve out of 31 European countries have established some kind of verification of laboratory competency and skills in ART: in 7 countries, this was related to licensing, but where organized education for Clinical Embryologists existed, there were vast differences in the way these processes were undertaken. WHAT IS KNOWN ALREADY: In 2015, a report by the ESHRE Embryology Certification Committee concluded that regardless of the large number of people working in IVF laboratories, Clinical Embryology was only recognized as an official profession in 3 out of 27 European national health systems. In most countries, Clinical Embryologists needed to be officially registered under an alternative profession and there were limited opportunities for organized education in this specialist field. Five years after this report, the ESHRE Working Group on Embryologist Training Analysis conducted a survey to collect detailed information about how Clinical Embryologists from different European countries are acquiring their theoretical knowledge and practical skills in ART, and how their level of education and competence in Clinical Embryology is verified. STUDY DESIGN SIZE DURATION: Two questionnaires about the possibilities for acquiring the education and training needed to work in ART and verification of this knowledge were prepared by the ESHRE Working Group on Embryologist Training Analysis. The first was sent in 2020 to a panel of invited lead European Embryologists who attended an Expert Meeting held in Rome, Italy. In order to have a more comprehensive and updated picture, in 2021 the same survey was also sent to the ESHRE Committee of National Representatives (CNRs). At the end of 2021, the second survey with specific questions, more focused on Clinical Embryologists' training and licencing, was sent to the CNRs who reported on verification of education in Clinical Embryology. PARTICIPANTS/MATERIALS SETTING METHODS: The first survey consisted of 17 questions. It was initially submitted to 14 lead Embryologists and then resubmitted to the 34 ESHRE CNRs. Representatives from 31 countries responded. A second survey with 23 questions was sent to the 12 ESHRE CNRs who reported an established national system of verification of education in Clinical Embryology, with specific questions focused on the training of Clinical Embryologists. All 12 CNRs responded. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis showed that European national education programmes in Clinical Embryology could be split into 4 categories: non-existent (13 countries), recommended (5 countries), simple compulsory (9 countries), and complex compulsory (4 countries). A national document stating the minimum education requirements for staff to work in an IVF laboratory was reported by 19 respondents. The requirement to follow a prescribed theoretical and laboratory training programme in ART was compulsory in 9 and 10 countries, respectively. Some form of verification of laboratory skills, theoretical knowledge in ART, and continuing professional development was required in 12, 10, and 9 countries, respectively. A national trainee's logbook format was reported by seven respondents and a national tutorial system was available in six countries. Only seven countries had official licensing of ART laboratory staff. The title of Clinical Embryologist was not recognized in 13 countries and in 6 countries, it was used only by professional bodies, while in 12 countries the profession was at least cited in governmental regulations. The ESHRE Clinical Embryologist Certificate was officially recognized in eight countries. LIMITATIONS REASONS FOR CAUTION: The survey took place in two steps and the results were then combined to provide a representative picture for most of the European countries sampled. The vast majority, but not all, of the CNRs answered the request to participate in the survey. WIDER IMPLICATIONS OF THE FINDINGS: The professional recognition of Clinical Embryology within Europe is steadily evolving. However, it remains a concern that many countries continue to not recognize Clinical Embryology as a profession, with a vast difference in the reported organization of educational and training programmes and verification of skills. It is recommended that a training programme for Clinical Embryology and ART in Europe should be standardized and relevant issues should be addressed by competent authorities and European Union institutions. ESHRE is best placed to take a leading role in this educational process. STUDY FUNDING/COMPETING INTERESTS: The Working Group members who are the authors of this article did not receive payments for the completion of this study. The authors have no conflicts of interest to declare.

ESHRE Clinical Embryologist certification: the first 10 years.

STUDY QUESTION: What has the ESHRE programme 'ESHRE Certification for Clinical Embryologists' achieved after 10 years? SUMMARY ANSWER: The post-exam analysis showed a pass rate of 60% for Clinical and 50% for Senior Clinical Embryologists and a high level of internal consistency of all exams, leading to a total of 773 certified Clinical and 493 Senior Clinical Embryologists over the decade. WHAT IS KNOWN ALREADY: In an ESHRE survey on the educational and professional status of Clinical Embryology in Europe, it was found that education of laboratory personnel working in the field of assisted reproduction is highly variable between countries. In 2008, ESHRE introduced a programme, curriculum and certification in the field of Clinical Embryology. Knowledge gained by postgraduate study of recommended literature, following a clear curriculum, is verified by a written two-level exam for obtaining a certificate for Clinical (basic) or Senior Clinical (advanced) Embryologists. With a total of 1266 certificates awarded over a period of 10 years and recognition by the Union Européenne des Médecins Spécialistes and their Council for European Specialists Medical Assessment, the ESHRE Clinical Embryology exams have become an internationally recognized educational standard in the field of Clinical Embryology. STUDY DESIGN SIZE DURATION: A retrospective analysis of all applications for ESHRE Clinical (2009-2018) and Senior Clinical Embryologist Certification (2008-2018) and exam results of the first decade was carried out by the Steering Committee for Clinical Embryologist Certification. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 2894 applications for ESHRE Certification for Clinical Embryologists and the results of 10 exams for the Clinical (1478 candidates) and 11 exams for Senior Clinical (987 candidates) levels were analysed. A detailed post-exam retrospective analysis was performed regarding difficulty, discrimination and reliability levels of 1600 multiple-choice questions (MCQs) with a single best answer among four options, from eight different curriculum topics (Basic cell biology, Genetics, Developmental biology, Female reproduction, Male reproduction, IVF laboratory, Cryopreservation and Laboratory management), representing the core theoretical knowledge of Clinical Embryology. Difficulty levels of the MCQs were subsequently compared regarding each topic and each yearly exam. The participation and success rates in the ESHRE Clinical Embryology exams were also assessed in terms of the educational and geographic backgrounds of candidates. MAIN RESULTS AND THE ROLE OF CHANCE: Over the 10 years studied, the mean pass rate for the Clinical Embryologist exam was 60% (range 41-86%), and for the Senior Clinical Embryologist exam was 50% (range 34-81%). On average, 63% European candidates and 35% non-European candidates passed the Clinical Embryologist exam, while 52% European candidates and 31% non-European candidates passed the Senior Clinical Embryologist exam. The candidates' educational level impacted on the success of the Clinical Embryologist exam but not of the Senior Clinical Embryologist exam. The mean difficulty indices by study topic showed that in the period of 10 years, there were no statistically significant differences between topics, for either the Clinical or Senior Clinical Embryologist exams. However, the overall exam difficulty varied between years. Reassuringly, the exam MCQ discrimination and reliability indices always showed a high level of internal consistency in all exams. LIMITATIONS REASONS FOR CAUTION: Some data from the initial ESHRE certification programme were not obtained electronically, in particular data for education, implying tables and figures reflect the specified valid data periods. Several countries exhibit different study profiles for those working in ART laboratories, such that laboratory technicians/technologists predominate in some countries, while in others only biologists and medical doctors are allowed to work with human embryos. Such differences could consequently affect the exam performance of candidates from specific countries. WIDER IMPLICATIONS OF THE FINDINGS: The ESHRE exams on Clinical Embryology are the most widely, internationally accepted tests of knowledge in the rapidly growing area of human reproduction. Clinical Embryology is increasingly recognized as a specific discipline for scientific staff who are collaborating closely with clinicians in managing human infertility through medically assisted reproduction. The analysis of the first 10 years of application of a two-level exam for Clinical Embryology shows a consistent high quality and reliability of the exam and MCQs used. These results represent an important follow-up of the quality of the ESHRE Certification programme for Clinical Embryologists, and convincingly position Clinical Embryology in the wider group of health disciplines that are harmonized through professional bodies such as ESHRE and European Board & College of Obstetrics and Gynaecology. The exams provide a clear step towards the increasing professional recognition and establishment of Clinical Embryology within health systems at both European and international level. STUDY FUNDING/COMPETING INTERESTS: No competing interest. All costs of the Steering Committee meetings were covered by ESHRE.

Association between early embryo morphokinetics plus transcript levels of sperm apoptotic genes and clinical outcomes in IMSI and ICSI cycles of male factor patients.

PURPOSE: The aim was to assess the correlation of sperm apoptotic transcript levels with cleavage stage embryokinetic and pregnancy outcomes of intracytoplasmic morphologically selected sperm injection (IMSI) and ICSI methods in patients with male factor infertility. MATERIAL AND METHODS: Eighty male factor cases were divided into ICSI and IMSI groups. ICSI was done routinely, and for IMSI, sperm was selected at high magnification and injected. On day 3, time-lapse parameters were evaluated, and the best embryos were transferred and followed to delivery. In addition, sperm DNA fragmentation and apoptotic transcript levels were quantified using reverse transcription Q-PCR between the groups. RESULTS: IMSI selected spermatozoa had lower DNA fragmentation and apoptotic transcript levels compared with ICSI (p < 0.0001). Moreover, all cytokinetic variables and cleavage abnormalities were noticeably different between groups (p < 0.0001); the rates of clinical outcomes were higher in the IMSI group. The transcript levels of Caspase 3 showed a moderate negative correlation with s2 and s3 (rs = - 0.57, P = 0.008 and rs = - 0.51, p = 0.021, respectively) in the IMSI group. However, there was no relationship between sperm apoptotic transcript levels and clinical outcomes in two groups. CONCLUSIONS: Sperms selected at high magnification showed lower DNA fragmentation and apoptosis genes transcript. Also, better embryo kinetics and clinical outcomes were confirmed in IMSI than ICSI groups. Some time-lapse parameters may be associated with transcript levels of apoptosis genes. Therefore, these noninvasive techniques may be unique in assisting couples with male factor infertility. TRIAL REGISTRATION: This trial retrospectively registered on 4 July 2020 (IRCT20180130038561N1).

Time-lapse imaging of inner cell mass splitting with monochorionic triamniotic triplets after elective single embryo transfer: a case report.

RESEARCH QUESTION: Can detailed scrutiny of time-lapse imaging (TLI) of inner cell mass (ICM) splitting help to reduce the frequency of multiple pregnancies following elective single embryo transfer (eSET)? DESIGN: Retrospective analysis of time-lapse images of an embryo in vitro, which resulted in a monochorionic triamniotic pregnancy following eSET on Day 5 of development. RESULTS: A 37-year-old female patient underwent a frozen embryo transfer cycle whereby a single vitrified/warmed embryo was transferred at the hatching blastocyst stage. The subsequent pregnancy scan revealed a monochorionic triamniotic pregnancy. Because the blastocyst was cultured in an incubator incorporating TLI, retrospective scrutiny of the digital recordings demonstrated two distinct ICM structures splitting apart, which formed during the '8-shaped hatching'. CONCLUSIONS: Assisted reproductive techniques and in-vitro culture have been associated with an increased frequency of embryo splitting. This has been postulated to be linked to the in-vitro hatching method observed at the blastocyst stage of development. This case report highlights the need to objectively assess any splitting of the ICM, beyond standard grading of the quality of the ICM and the trophectoderm. Such assessments of ICM splitting should be routine practice in clinical embryology when selecting embryos for transfer.

Prevalence of blood borne viruses in IVF: an audit of a fertility Centre.

OBJECTIVE: The rate of infertility continues to be on the increase in the developing world. Similarly, the rates of blood-borne viral infections (BBVs) such as Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are also on this rise. In 2014, the World Health Organization (WHO) quoted prevalences of 1.5% (HIV), 15% (HBV) 1.3 - 8.4% (HCV) in the Ghanaian general population. It has been reported that BBVs can adversely affect male fertility, specifically sperm count and progressive motility. The aim of this study was to evaluate the prevalence of BBVs in people with infertility attending an IVF clinic and whether or not BBVs impacted on sperm parameters. METHODS: A retrospective cohort study at a private fertility center in Accra, Ghana. We had 229 recruited couples assayed for HBV, HCV and HIV. Sperm parameters of the male partners were also assessed. The analysis performed included student t-test and Fisher's exact test. RESULTS: We found prevalence rates of 1.7% (HIV), 7.9% (HBV) and 0.4% (HCV), which is similar to what has already been reported in the Ghanaian community. There was no significant difference between BBV positive and negative subjects for sperm count (13.6 million/ml vs. 17.7 million/ml, P = 0.0599), percentage of progressive motility (26% vs. 30%, P = 0.2129), percentage of normal forms (3% vs. 3%, P = 0.0617) and clinical pregnancy rates per embryo transfer (36.1% vs 34.9%, P = 0.5) between BBV positive and BBV negative subjects, respectively. CONCLUSION: There is a similar prevalence of BBVs in sub-fertile couples and the general Ghanaian population. However, no detrimental effect has been reported for sperm parameters on grounds of BBV infectivity of the male partner.

How strict should specimen acceptance or rejection criteria be for diagnostic semen analysis? An opinion.

Medical laboratory accreditation (previously by Clinical Pathology Accreditation UK Ltd and now by the United Kingdom Accreditation Service) has been integral to improving standards and service quality in the UK. With the recent introduction of the ISO15189 standard, all laboratories offering a clinical diagnostic service are required to demonstrate further improvement, with more emphasis on validation and assessment of the uncertainty levels associated with testing. This applies not only to 'bench testing', but also to the evidence-base for all pre-analytical and post-analytical procedures. To reduce the risk of external influences on andrology test results, semen sample rejection criteria were developed, including confirmation of patient identity, a strict time limit from sample production to testing, the use of toxicity-tested containers, a prescribed sexual abstinence and a need for complete sample collection. However, such criteria were originally developed by the World Health Organization in order to standardise analysis rather than reject testing outright, and should therefore be implemented with caution. Rejecting samples with normal semen parameters because they fail to meet some of the criteria as outlined above would be a waste of resources and adversely affect user (the person who requested or provided the sample) satisfaction. This document evaluates the evidence base underlying commonly used criteria for specimen rejection and suggests how they may be applied more pragmatically in order to improve efficiency and reduce the waste of resources.

Spindle position assessment prior to ICSI does not benefit fertilization or early embryo quality.

Intracytoplasmic sperm injection (ICSI) is traditionally performed with the first polar body at 6 or 12 o'clock, and the injection pipette inserted at 3 or 9 o'clock. This positioning aims to direct the path of the injection pipette at a distance from the presumed metaphase II spindle position. Since spindles can now be imaged directly in living oocytes using computer-assisted polarized light microscopy, the effectiveness of this positioning precaution was studied. Patients undergoing oocyte collection and ICSI had their oocytes non-invasively imaged for spindles prior to ICSI. The spindle position relative to the first polar body at 6 o'clock was assessed using an analogue clock face as an approximation. Fertilization and embryo quality were recorded blind to spindle position. Polar body displacement and spindle position at ICSI did not significantly affect fertilization or embryonic quality. The highest frequency of normally fertilized oocytes and good quality embryos developed from oocytes with spindles located in or near the plane of injection at ICSI (the 3, 4, 8 and 9 o'clock positions). This study questions the usefulness of spindle imaging and the relevance of positioning the first polar body at 6 o'clock during ICSI.

A comparison of headfirst and tailfirst microinjection of sperm at intracytoplasmic sperm injection.

OBJECTIVE: To investigate whether the direction of sperm loading and exit from the injection pipette during intracytoplasmic sperm injection (ICSI) had any bearing on ability to cause fertilization or affect subsequent embryonic development. DESIGN: Prospective randomized trial. SETTING: Hospital-based IVF center. PATIENT(S): Twenty-five couples participating in an intracytoplasmic sperm injection (ICSI) program. INTERVENTION(S): Sperm microinjection was randomly divided into either headfirst injection or tailfirst injection. MAIN OUTCOME MEASURE(S): Fertilization, embryo quality, and implantation rates. RESULT(S): There were no significant differences in the fertilization rates or the proportion of good-quality embryos, according to the direction of sperm injection. Of the embryos selected for transfer, 41.3% originated from headfirst sperm injection, and 58.7%, from tailfirst sperm injection. After transfer of either two or three embryos into 24 patients, 11 embryos implanted, with an equal probability that these embryos originated from either headfirst or tailfirst sperm injection. However, one dizygotic twin pregnancy was traced to the transfer of two embryos; one resulted from headfirst sperm injection, and one from tailfirst sperm injection. CONCLUSION(S): The direction of sperm microinjection at ICSI appears to have no effect on fertilization or subsequent development. The preliminary findings of this study have some interesting practical implications for the procedure of ICSI.

Lesbian intra-partner oocyte donation: a possible shake-up in the Garden of Eden?

Treatment of same-sex couples using infertility therapies has become more acceptable over the years, but remains controversial. In December 2005, two law changes came into force in the UK that impact same-sex couples. Firstly, the Civil Partnership Act 2004 acknowledged legal relationships between same-sex couples; and secondly, the Adoption and Children Act 2002 allowed same-sex couples to adopt. In view of these law changes, it is timely to consider procreation in same-sex couples and, particularly, the possibility of intra-partner oocyte donation within a lesbian relationship. Such treatment would require one female partner to provide the oocyte and the other female partner to act as embryo recipient. The embryo(s) could be created using IVF with registered anonymous donor sperm. The novelty of allowing a lesbian couple to cause a pregnancy in this way could allow the recipient to give birth to a baby that was genetically related to her partner. If society finds this acceptable, intra-partner oocyte donation using donor sperm for IVF could successfully provide a family for lesbian couples, offering an alternative to individual donor insemination. The ethical aspects of the treatment are discussed.