Human embryo research in Belgium: an overview.

OBJECTIVE: To present an overview of the numbers and types of human embryos used in research projects in Belgium from 2007 to 2015. DESIGN: Analysis of all research proposals approved by the Federal Commission for Medical and Scientific Research on Embryos In Vitro. SETTING: Not applicable. PATIENT(S): Not applicable. MAIN OUTCOME MEASURE(S): Number of embryos used for research, number of embryos created for research, and areas of embryo research. RESULT(S): Since 2007, 15,811 embryos were used for 36 research projects. In total, 10,492 (66%) fresh supernumerary embryos (unfit for transfer or freezing) were used, 4,083 (26%) frozen supernumerary embryos (donated by parents whose child wish was completed or abandoned), and 1,236 (8%) embryos created for research. Most projects focused on research into embryo development. Fresh supernumerary embryos were mainly used for human embryonic stem cell (hESC) research. Frozen supernumerary embryos were almost exclusively used for research into embryo development and for hESC research. Embryos created for research were used for research into embryo development, oocyte research, research into cryopreservation of oocytes, and hESC research. CONCLUSION(S): Having concrete data on embryo research is crucial for an informed debate. Moreover, these data are necessary to find out trends in research such as the numbers of embryos needed and the areas of research. Data collection requires a sufficiently clear definition of "research" and "embryo." These conceptual questions frequently reveal lack of clarity in legislation.

Reproductive hormones of ICSI-conceived young adult men: the first results.

STUDY QUESTION: Are reproductive hormone levels (FSH, LH, inhibin B and testosterone) in male offspring conceived by ICSI because of male infertility comparable with those from peers born after spontaneous conception? SUMMARY ANSWER: In this cohort of 54 young men conceived by ICSI because of male-factor infertility, mean and median reproductive hormone levels were found to be comparable with results from spontaneously conceived peers, but ICSI-conceived men were more likely to have low inhibin B (<10th percentile) and high FSH (>90th percentile) levels. WHAT IS KNOWN ALREADY: Since the worldwide oldest ICSI offspring have recently reached young adulthood, their reproductive health can now be investigated. This typically involves semen analysis and a hormonal profiling including the measurement of FSH, LH, inhibin B and testosterone. Circulating levels of FSH and inhibin B are generally known as markers of the exocrine function of the testis, i.e. spermatogenesis, while LH and testosterone reflect its endocrine function. We have previously observed a normal pubertal development and comparable levels of inhibin B and testosterone among pubertal ICSI boys when compared to spontaneously conceived peers. However, at present, information on the gonadal function of ICSI offspring in adulthood is still lacking. STUDY DESIGN, SIZE, DURATION: This study, conducted between March 2013 and April 2016 at the UZ Brussel, is part of a larger follow-up project focusing on reproductive and metabolic health of young adults between 18 and 22 years and conceived after ICSI because of male infertility. The ICSI men are part of a longitudinally followed cohort while the spontaneously conceived controls were recruited cross-sectionally. PARTICIPANTS/MATERIALS, SETTING, METHODS: Results of a single fasting blood sample from 54 young adult ICSI men were compared to that of 57 spontaneously conceived peers. Reproductive hormone analysis involved FSH, LH, testosterone and inhibin B measurement. Furthermore, the association between their reproductive hormones and their sperm parameters was examined. Data were analyzed by multiple linear and logistic regression adjusted for covariates. MAIN RESULTS AND THE ROLE OF CHANCE: ICSI men had comparable mean levels of FSH, LH, testosterone and inhibin B in comparison to spontaneously conceived counterparts, even after adjustment for confounders, such as age, BMI and season. Young ICSI-conceived men were more likely to have inhibin B levels below the 10th percentile (<125.2 ng/l; Adjusted Odds Ratio (AOR) 4.0; 95% CI: 0.9-18.4; P = 0.07) compared with spontaneously conceived peers and were more likely to have FSH levels above the 90th percentile (>5.5 IU/L; AOR 3.3; 95% CI: 0.9-11.9; P = 0.06) compared with spontaneously conceived peers, but neither difference reached statistical significance. FSH, LH and inhibin B, but not testosterone, levels were significantly associated with sperm concentration and total sperm count. LIMITATIONS, REASONS FOR CAUTION: The main limitation is the small study population. Furthermore, the results of this study should be interpreted according to the background of the participants: all subjects in our study group were conceived by ICSI because of severe male infertility and hence the results cannot be generalized to all ICSI offspring because the indications for performing ICSI have since been widened. WIDER IMPLICATIONS OF THE FINDINGS: These first results in a small group of ICSI men show reassuring reproductive hormonal levels. However, larger studies are required to confirm our results. Since inhibin B and FSH are consistently correlated with semen characteristics, we would suggest that the reproductive status of young adults conceived by ICSI is explored with a hormonal assessment given its easier acceptance compared to semen sampling. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). A grant from the Belgian Society for Pediatric Endocrinology and Diabetology was received for this project. All co-authors, except M.B. and H.T., declare no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough, Merck for establishing the database for follow-up research and organizing the data collection. The institution of HT receives research grants from the 'Research Fund of Flanders' (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility. TRIAL REGISTRATION NUMBER: N/A.

Progesterone rise on the day of human chorionic gonadotropin administration impairs pregnancy outcome in day 3 single-embryo transfer, while has no effect on day 5 single blastocyst transfer.

Four hundred eighty-two patients undergoing single ET with GnRH-antagonist/recFSH protocol were analyzed. The incidence of premature luteinization (P above 1.5 ng/mL on the day of hCG administration) was 18.2%. Even modest rises of P in the follicular phase have detrimental effect on the implantation potential of a good-quality cleavage stage embryo. On the contrary, premature luteinization in the blastocyst subgroup had no effect on the pregnancy outcome.