20 June 2016
ESHRE supports opposition to proposed ART changes in Poland
ESHRE has expressed its full support to the Polish Gynecological Society and Polish Society for Reproductive Medicine and Embryology in their opposition to legislative changes proposed in the treatment of infertility. As proposed, the changes would in effect reverse legislation introduced by the former coalition government and apply restrictions likely to limit access to fertility treatments and limit the practice of ART. Among the proposed changes are a limit of one on the number of occytes for fertilisation and a ban on embryo freezing.
In 2013 the Polish Ministry of Health introduced a three-year IVF reimbursement programme. This so far has involved around 17,000 couples and seen the birth of 5200 children, a delivery rate of 34%. Now, however, following parliamentary elections in 2015 and the formation of a new conservative government, the IVF reimbursement programme has already been discontinued and proposals put in place for a new round of restrictive legislation.
If approved, such legislation would consign Poland to its former status, when it stood alone as the only major European country without any statutory support for ART. When similar restrictive legislation was introduced in Italy in 2004, it was seen as a denial of family rights and challenged - successfully - in the constitutional courts. Indeed, all the restrictive components of Italy's Law 40 have now been dismantled by the Italian courts.
At the time ESHRE expressed its full and continuing commitment to the wide application of safe fertility treatments in Italy, and does so now in Poland. ESHRE has given its support to the Polish societies in their efforts to maintain good practice in the treatment of infertility in Poland, and remains opposed to any statutory developments which limit both family rights and access to services.
* Former ESHRE chairmen Juha Tapanainen and Luca Gianaroli spoke at a press conference at the Polish Parliament in June in protest at the proposals, which can be seen at http://www.sejm.gov.pl/sejm8.nsf/transmisje_arch.xsp?unid=519E35970C2E3F40C1257FCD00290F73
20 June 2016
Record impact factor for Human Reproduction Update
ESHRE's review journal Human Reproduction Update, for many years the leading title in the citation categories of Reproductive Biology and O&G, has seen its impact factor rise from 10.165 to 11.194 in the latest journal analysis released in June. This is the highest recorded impact factor ever in these two categories.
Both of ESHRE’s other two titles also increased their
impact factor from last year. Molecular Human Reproduction rose from 3.747 to 3.943, and ESHRE's flagship title Human Reproduction confirmed its high-ranking status with a rise from 4.569 to 4.621.
"This is another important step towards an impact factor of 5 for Human Reproduction," said editor-in-chief Hans Evers. "For a journal with almost exclusively original scientific articles, this is indeed a proud achievement."
All three ESHRE journals now rank in the top ten titles in O&G, with two titles, Human Reproduction and Update, securely placed within the top four. Fertility & Sterility, with an impact factor of 4.426, fell back slightly from its score of 4.59 last year.
According to Thomson Reuters, owners of the Journal Citation Reports, the impact factor is a measure of the frequency with which the "average article" in a journal has been cited in a specified period. It is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years. The latest impact factors, for 2015, thus relate to all citable papers published in 2013-14. Despite emerging alternative metrics, impact factors remain the most reliable measure of journal quality.
Some of the highly cited papers contributing to the growing success of all three ESHRE journals can be read here.
9 May 2016
In vitro embryo development through the early post implantation stages
A new technique allowing embryos to develop in vitro beyond the implantation stage has been reported simultaneously by two research groups - from Cambridge, UK, and Harvard, USA.(1,2) The technique, which for the first time will allow analysis of key stages of human embryo development up to the agreed 14-day post-fertilisation limit, demonstrates the remarkable self-organising capacity of human blastocysts, which so far has been quite unseen and unknown. However, this same reorganisation of the embryo, which normally takes place during the early post-implantation phase, has now been achieved in the laboratory and thus presents a unique opportunity to better understand human development during these early crucial stages.
Both groups working in parallel established a system for the in vitro culture of human embryos and, using this technique, followed the development of the embryos up to day 13 - to a point just before the 14-day internationally (and legally) agreed limit for embryo research. Immediately following "implantation", the three cell types that comprise the blastocyst are seen to reorganise into a new configuration.
"The stem cells in the epiblast that will form the future body have the remarkable ability to self-organise themselves and create a cavity that represent the basic structure of the early post-implantation human embryo," Professor Zernicka-Goetz, leader of the Cambridge group and an author on both papers. said in a press release. "Without this cavity, it would be impossible for the embryo to develop further as it is the basis for its future development. It is also a mechanism that we can study using human embryonic stem cells."
Comment on the study has not only raised the prospect of a better understanding of implantation in IVF, but also the applicability of the 14-day rule for embryo research. A commentary in the journal Nature, in which one of the reports appeared, forecast that such studies of human development in vitro "are on a collision course with an international policy that limits embryo research to the first two weeks of development".(3) At ESHRE's Annual Meeting in 2015, Dutch bioethicist Guido De Wert, a former co-ordinator of ESHRE's Task Force Ethics & Law, argued that it was now time to reconsider the 14-day time limit for embryo research, arguing that the "existing consensus reflects the will of policy-makers to draw a line somewhere rather than a shared understanding of why this should be at 14 days instead of another developmental stage".(4)
1. Deglincerti A, Croft GF, Pietila LN, et al. Self-organization of the in vitro attached human embryo. Nature 2016; doi: 10.1038/nature17948.
2. Shahbazi MN, Jedrusik A, Vuoristo S, et al. Self-organisation of the human embryo in the absence of maternal tissues. Nature Cell Biology 2016; DOI: 10.1038/ncb3347
3. Hyun I, Wilkerson A, Johnston J. Revisit the 14-day rule. Nature 2016; 583: 169-171.
4. De Wert G, Dondorp WJ. Time to reconsider the time limit for human embryo research? ESHRE Annual Meeting 2015; O-246.
1 March 2016
Functional gametes in vitro
In what appears to be a major step forward in the production of stem-cell derived gametes, scientists in China have reported the successful meiosis of primordial germ cells in the mouse to functional male gametes in vitro.(1) The scientists, from Nanjing Medical University, China, describe a process of complete in vitro meiosis, from primordial germ cell-like cells (derived from pluripotent embryonic stem cells) to the formation of male spermatid-like cells capable of producing viable fertile offspring via ICSI. So far, they write, the recapitulation of meiosis completely in vitro, a process unique to germ cells, "has remained a major obstacle" toward the production of functional stem-cell derived gametes.
The in vitro meiosis described was fully compliant with the gold standards of meiosis established in 2014, which included the correct erasure of imprints, synapsis, and recombination. According to reports, all other attempts to adequately control all the key stages of sex cell division according to these criteria had failed. In this case, the resulting embryos went on to full embryonic development and, following ICSI, produced fertile offspring that gave birth to the next generation.
"This unequivocally demonstrates the recapitulation of meiosis in a culture environment and proves the functionality of spermatids generated from pluripotent stem cells in vitro," the investigators reported. "Our findings could facilitate the generation of haploid human spermatids in vitro with the prospect of treating male infertility."
The achievements implicit in the report were universally greeted with excitement by scientists, although many lay press reports forecast the imminent redundancy of men. Chris Barratt, editor of ESHRE's Molecular Human Reproduction journal, said: "There have been numerous attempts and false dawns to developing a robust system for in vitro meiosis. A number of studies have been published that have subsequently been difficult to repeat, so this latest is a landmark study in that it has satisfied internationally agreed standards.”
1. Zhou Q, Wang M, Yuan Y, et al. Complete meiosis from embryonic stem cell-derived germ cells in vitro. cell Stem Cell 2016: DOI: http://dx.doi.org/10.1016/j.stem.2016.01.017
24 February 2016
HROpen: a fourth journal for ESHRE
Siladitya Bhattacharya, Professor of Reproductive Medicine at the University of Aberdeen, UK, will be the first Editor-in-Chief of ESHRE's new journal HROpen. His appointment, which was confirmed by ESHRE's Executive Committee following interviews in February, will be for a three-year term with opportunity for extension for a further three years.
While the primary aim of HROpen is to broaden the editorial range of the ESHRE journals and provide a publication of high quality research beyond the traditional focus of infertility, it was also apparent that a truly modern journal should meet two criteria: open access and online publication. HROpen will fulfil both these requirements - and indeed will be the first open access journal in reproductive medicine. More and more funding organisations, as well as academic institutions, require open access publication, and hopes are that HROpen will offer a rapid and inexpensive means of publication to research groups throughout the world, with a wider scope than ESHRE's present titles.
"We believe we can reach out to a wider range of the scientific community this way," says ESHRE Chairman Kersti Lundin, "and that the format will open up new ways of communicating." Authors will incur no processing fees for the first three years of the journal's life, and expectations are that the first papers will be published online before the end of this year.
There were more than 20 eminent applicants for the post of Editor-in-Chief, a number of whom were short-listed and interviewed. Bhattacharya, who has earned an international reputation in health services research, randomised trials and the epidemiology of reproductive medicine, was a welcome appointment and ESHRE is confident that he will steer the new journal to a respected place alongside its three sister publications.
25 January 2016
Rapid developments in gene editing
A short report published on the ESHRE website in March last year noted calls for a moratorium on genome engineering in reproductive cells.(1) The calls were made in advance of studies on the modification of DNA in human embryos. One commentary urged: "In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations . . . Such research could be exploited for non-therapeutic modifications."(2)
Since then, the techniques of genome editing have moved on at remarkable speed, highlighted most recently with the application from a UK group for a research licence to use the gene editing system of CRISPR to identify and understand the single genes involved in early embryo development.(3) By using this technique the group (from the Francis Crick Institute in London) plans to knock out up to four genes in a fertilised oocyte while still at the single-cell stage to determine their role in early embryonic human development.
In December last year in Washington an international summit meeting on gene editing agreed that:(4)
* basic and preclinical research in the specific alteration of genetic sequences should proceed, subject to appropriate legal and ethical rules and oversight
* clinical use in somatic cells (in which the edited genomes will not be inherited by future generations) can be rigorously evaluated
* germline editing poses "many important issues" - such as the risks from inaccurate editing and implications for future generations - and thus "it would be irresponsible to proceed with any clinical use of germline editing unless and until the relevant safety and efficacy issues have been resolved
Genomic editing of human non-reproductive cells - using the same CRISPR technology - aims to repair or eliminate a mutation underlying a monogenic disease. The principle is that corrective changes to a number of cells carrying the mutation could provide a once-and-for-all curative treatment for patients with some types of genetic disease. In December US scientists reported that they had used CRISPR to remove part of a defective gene in mice with Duchenne muscular dystrophy, allowing the animals to make an essential muscle protein. The journal Science described this as "the first time CRISPR has been successfully delivered throughout the body to treat grown animals with a genetic disease".(5)
A recent policy forum in Science, which hailed the CRISPR technology as the scientific breakthrough of 2015, concluded that the socio-ethical and policy concerns surrounding gene editing remain "high, with countries, the scientific community and individuals divided on the issue".(6) The report analysed human embryo policies in 16 countries and found that some ban the practice outright, while others allow a degree of related basic research. In addition, there are countries such as the UK and China which permit research for reproductive purposes and where potential clinical applications are not explicitly outlawed. The report reiterates the Washington summit's conclusion that it would be irresponsible to proceed with the clinical application of germline editing until the relevant safety issues have been resolved.
A writing group including several members of ESHRE has evaluated the current status of genomic editing in the human germline and pluripotent stem cells. In a paper now submitted for publication the authors have identified numerous technical challenges and limitations associated with the CRISPR/Cas genomic editing system, which in the human germline will require more research. However, they conclude that these limitations should not lead to a generalised moratorium on the technique in human embryos, but rather encourage efforts to establish an international regulated framework making transparent research possible.
A discussion of the risks, advantages and possible applications of gene editing will be featured in an ESHRE workshop in September organised in Amsterdam by several of the Society's Special Interest Groups.(7)
1. See https://www.eshre.eu/Press-Room/ESHRE-News.aspx
2. Lanphier E, Urnov F, Haecker SE. Don't edit the human germ line. Nature 2015; 519: 410-411.
3. See http://www.sciencemag.org/news/2016/01/uk-researcher-details-proposal-crispr-editing-human-embryos
4. See http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a
5. See http://www.sciencemag.org/news/2015/12/crispr-helps-heal-mice-muscular-dystrophy
6. Isasi RM, Kielderman E, Knoppers BM. Editing policy to fit the genome? Science 2016; 351: 337-339