Beta-amino acid transport in pig small intestine in vitro by a high-affinity, chloride-dependent carrier

AbstractThis study describes unidirectional influx of amino acids and d-glucose across the small intestinal brush-border membrane of fully weaned eight week old pigs. Influx is minimal in the duodenum and maximal in the distal and/or mid small intestine. Influx of β-alanine, taurine and N-ethyl-aminoisobutyric acid is chloride-dependent. The activation stoichiometry for taurine influx is 1.0 ± 0.2 chloride/2.4 ± 0.3 sodium/ 1 taurine. Influx of D-glucose, lysine, glycine and glutamate is chloride-independent. An ABC test demonstrates a common β-amino acid carrier: (a) the apparent affinity constant K12Taurine is 44 ± 13 μM (means ± S.D.) and the inhibitory constant (KiTaurine) against β-alanine influx is 41 ± 5 μM (means ± S.E.). (b) K12β-alanine is 97 ± 23 μM and Kiβ-alanine against taurine influx is 160 ± 22 μM. (c) KiHypotaunne against taurine and β-alanine influx is 43 ± 4 (n = 7) and 22 ± 5 μM (n = 7), respectively. In conclusion, a high affinity, low capacity, sodium- and chloride-dependent carrier of β-amino acids is present in pig small intestine

Preimplantation genetic testing legislation and accessibility in the Nordic countries

Abstract Introduction Assisted Reproduction Technologies are in rapid development and implementation of preimplantation genetic testing (PGT) has allowed patients with genetic disorders to initiate pregnancies while minimizing or eliminating the risk of transmitting these disorders to their offspring. Testing for numeric chromosomal anomalies has been proposed as a way to increase efficacy in assisted reproduction, however this remains disputed. Legislation is lagging behind the rapid developments in this field. Material and methods We conducted a structured online survey of legislation and accessibility to Preimplantation Genetic Testing in the Nordic countries to compare the regulation and uptake of this technique. The survey was designed and answered by the authors. Results Key elements in regulation of preimplantation testing for monogenic disorders and structural rearrangements are similar in the Nordic countries although accessibility varies since only Denmark, Finland and Sweden have national clinics offering treatment. In addition, Denmark and Finland have private clinics offering PGT. Regulation is most stringent in Norway where a national board evaluates all couples seeking treatment. Treatment volumes vary between the Nordic countries with Norway and Finland having lowest treatment numbers. Preimplantation genetic testing for aneuploidy in the embryo varies between the Nordic countries where Finland and Iceland are allowed to offer this form of treatment, Denmark and Sweden only in the form of a research protocol while this form of testing is not allowed at all in Norway. Therefore the number of treatment cycles involving testing for embryo aneuploidy are lower in the Nordic countries compared to other countries where this treatment option is more common. Conclusions Science needs to inform politics regarding the rapidly evolving field of reproductive medicine and we recommend harmonization of legislation and accessibility between the Nordic countries.Peer reviewe

Effect of women's age on embryo morphology, cleavage rate and competence:A multicenter cohort study

This multicenter cohort study on embryo assessment and outcome data from 11,744 IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of women's age on oocyte, zygote, embryo morphology and cleavage parameters, as well as cycle outcome measures corrected for confounding factors as center, partner's age and referral diagnosis. Cycle outcome data confirmed the well-known effect of women's age. Oocyte nuclear maturation and proportion of 2 pro-nuclear (2PN) zygotes were not affected by age, while a significant increase in 3PN zygotes was observed in both IVF and ICSI (p<0.0001) with increasing age. Maternal age had no effect on cleavage parameters or on the morphology of the embryo day 2 post insemination. Interestingly, initial hCG value after single embryo transfer followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and ICSI (p = 0.001) cycles. For the first time, we show that a woman's age does impose a significant footprint on early embryo morphological development (3PN). In addition, the developmentally competent embryos were associated with increased initial hCG values as the age of the women increased. Further studies are needed to elucidate, if this increase in initial hCG value with advancing maternal age is connected to the embryo or the uterus

Is paternal age associated with transfer day, developmental stage, morphology, and initial hCG-rise of the competent blastocyst leading to live birth?:A multicenter cohort study

In this study we investigated whether age of men undergoing assisted reproductive technology (ART) treatment was associated with day of transfer, stage, morphology, and initial hCG-rise of the competent blastocyst leading to a live birth? The design was a multicenter historical cohort study based on exposure (age) and outcome data (blastocyst stage and morphology and initial hCG-rise) from men whose partner underwent single blastocyst transfer resulting in singleton pregnancy/birth. The ART treatments were carried out at sixteen private and university-based public fertility clinics. We included 7246 men and women, who between 2014 and 2018 underwent controlled ovarian stimulation (COS) or Frozen-thawed Embryo Transfer (FET) with a single blastocyst transfer resulting in singleton pregnancy were identified. 4842 men with a partner giving birth were included, by linking data to the Danish Medical Birth Registry. We showed that the adjusted association between paternal age and transfer day in COS treatments was OR 1.06, 95% CI (1.00;1.13). Meaning that for every increase of one year, men had a 6% increased probability that the competent blastocyst was transferred on day 6 compared to day 5. Further we showed that the mean difference in hCG values when comparing paternal age group 30–34, 35–39 and 40–45 with the age group 25–29 in those receiving COS treatment, all showed significantly lower adjusted values for older men. In conclusion we hypothesize that the later transfer (day 6) in female partners of older men may be due to longer time spent by the oocyte to repair fragmented DNA of the sperm cells, which should be a focus of future research in men

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Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans. [Abstract copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe

STUDY QUESTION: How did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? SUMMARY ANSWER: MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. WHAT IS KNOWN ALREADY: With the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. STUDY DESIGN, SIZE, DURATION: A structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. PARTICIPANTS/MATERIALS, SETTING, METHODS: The information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. MAIN RESULTS AND THE ROLE OF CHANCE: By aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. WIDER IMPLICATIONS OF THE FINDINGS: The current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations.peer-reviewe