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Frozen IVF embryos produce healthier children, researchers claim: Times on Line

Author(s):Mark Henderson, Science Editor, in San Francisco

IVF produces healthier children when embryos are frozen and thawed before being transferred to the womb, according to new research. Babies born from frozen IVF embryos are less likely to be born prematurely or underweight than are those conceived during fresh treatment cycles, three independent teams of scientists have found. One of the studies also recorded lower rates of stillbirth and early death among frozen-embryo babies. The results, from researchers based in the United States, Australia and Finland, suggest that far from being riskier than conventional IVF, as is generally thought, cycles using frozen embryos may actually be safer. The research is particularly significant because separate teams from three countries have reached the same conclusion, each using large samples including thousands of IVF cycles.

A fourth team, from Denmark, also reported similar findings earlier in the year. Scientists said the work would be important because women are increasingly encouraged to use just one fresh embryo during IVF, to guard against damaging twin and triplet births, and to freeze any that are left over for later use. It will dispel doubts about whether this policy trades the risks of multiple births for hazards associated with frozen embryos.

Allan Pacey, secretary of the British Fertility Society, said: “This all works to the advantage of single embryo transfer. It suggests it might be better from the point of view of a healthy child to go for frozen embryos, which is an integral part of the strategy. People shouldn’t be scared of frozen embryos.” The studies, presented at the American Society for Reproductive Medicine conference in San Francisco, do not explain why babies born from frozen embryos seem to do better, but there are several hypotheses.When fresh embryos are used in treatment, women may still be under the influence of powerful hormonal drugs used to stimulate their ovaries into producing extra eggs, or the anaesthetics used during egg collection.

Either of these may interfere with the endometrial lining of the womb, and thus with the formation of the placenta. Another possibility is that as some frozen embryos generally fail to survive thawing, this effectively “weeds out” those that are of poor quality. A third possibility is that women who produce lots of good quality embryos are more likely to have frozen cycles, and also have a lower risk of complicated pregnancies. “These findings are really quite interesting,” Dr Pacey said. “It kind of defies logic to a certain extent. It seems to be an issue with the formation of the placenta, but how it has an effect isn’t known. “This may be a bit of biology that has escaped most people. The assumption has always been that if the endometrium [the womb lining] is thick, it’s functional. In an IVF cycle, the endometrium looks normal on ultrasound, but perhaps there is something subtle going on.”

Despite their apparent health benefits, however, frozen IVF cycles are unlikely to supplant fresh ones as the routine option because they have a lower success rate. In Britain, 24.4 per cent of fresh cycles lead to a live birth, compared to 17.4 per cent of frozen cycles. There were 33,916 fresh cycles performed in 2006, and 7,911 frozen cycles.

(Image - Lennart Nilsson/Reuters)

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The world’s first’ ice baby’ grows up

It is twenty five years ago that the first baby from a frozen embryo came into the world. Zoe Leyland was born at the Queen Victoria Medical Centre in Melbourne, Australia on 28 March 1984, helped on her way by Dr Alan Trounson and Dr Carl Wood who made medical history. The decision to try 'test tube' fertilization and embryo freezing was taken by them and Zoe's parents – mother a 33 year old New Zealander and father a 38 year old British born Australian resident. Her mother had hormonal stimulation and produced eleven eggs which were frozen using a then new type of controlled rate freezer made by London company Planer plc. One of those frozen embryos became Zoe - who weighed in at about 5 lbs or 2.5 kilos. Zoe and Professor Trounson set a bit of a trend and since then, of the three million or so babies born via assisted reproduction IVF techniques, some 20% or about 600,000 have been created from frozen embryos.

The world's first 'fresh’ test tube baby was Louise Brown born in England in 1978, but Zoe came from an embryo that had been frozen for a time before being thawed and implanted. To allow cells to survive liquid nitrogen temperatures (-196°C) the embryos had to be treated with cryo-protectant, then frozen down in the Planer freezer with extreme precision using different temperature ramps, before they could be stored in liquid nitrogen. This controlled rate freezing procedure was a breakthrough in 1984 but is now common and most IVF laboratories worldwide have rate freezers. Freezing an embryo allows physicians to replace one embryo at a time and store others or spares for later use; it may also help in allowing a patient to 'recover hormonal equilibrium' by delaying implantation to allow the IVF drugs to clear her body. Controlled rate frozen embryos appear to develop into equally healthy children compared with ‘fresh’ IVF ones. Recent studies from Denmark, Australia, the USA and Finland have indicated they may be even healthier. The freezing of embryos is becoming particularly important because of the interest in SET - selective embryo transfer - to help avoid multiple births and so a successful embryo freezing programme is essential for an IVF clinic.

The controlled rate freezing technique, originally suggested over thirty years ago by British Scientist Professor David Pegg, enabled Planer plc to pioneer this equipment. Many thousands of units are in constant use all over the world in IVF labs, hospitals and research institutions. Controlled rate freezing is needed before storing many cells in liquid nitrogen – in areas such as cord blood banking, bone marrow transplants, botanical matter, semen, oocytes, botanical seeds, skin, ovarian tissue, heart valves and blood vessels.

Professor Alan Trounson and inset the Planer freezerProfessor Alan Trounson, currently president of the California Institute of Regenerative Medicine, became a world authority on assisted reproduction and went on to pioneer work in the stem cell field. Alan Trounson is now based in San Francisco and has had a highly distinguished career in assisted reproduction, stem cell and gynaecological research in academic institutions after Monash University in Melbourne.

Recently Louise Brown, the first IVF baby, had her own child naturally – Zoe has no such plans yet and having finished her degree is working in Melbourne.

Background Information: Alan Trounson is President of the California Institute for Regenerative Medicine in San Francisco, California. Prior to joining CIRM in January 2008, Trounson was Professor of Stem Cell Sciences and Director of the Monash Immunology and Stem Cell Laboratories at Monash University, where he retains the title of Emeritus Professor. Dr. Trounson founded the National Biotechnology Centre of Excellence – ‘Australian Stem Cell Centre’. He held various positions at Monash University beginning in 1977 and was appointed Director of the Centre for Early Human Development in 1985. He was awarded a Personal Chair in Obstetrics and Gynaecology/Paediatrics in 1991, and in 2003 was awarded a Personal Chair as Professor of Stem Cell Sciences. A Fellow of the Royal College of Obstetricians and Gynaecologists and an Honorary Fellow of the Australian and New Zealand College of Obstetricians and Gynaecologists, Trounson was awarded an honorary doctorate by the faculty of medicine at the University of Brussels. He has been a pioneer of human in vitro fertilisation (IVF) and associated reproductive technologies; the diagnosis of inherited genetic disease in pre-implantation embryos; the discovery and production of human embryonic stem cells and of their ability to be directed into neurones, prostate tissue and respiratory tissue. http://www.cirm.ca.gov

Planer plc specialises in the measurement and control of physical parameters related to cell preservation and safety in hospitals, laboratories and universities. Based near London’s Heathrow airport the company has sold over ten thousand state of the art electronic, electromechanical and software products world-wide, via its network of fifty sales and service distributors, since 1973. Having pioneered the development and use of products for controlled rate freezing, the company received the Queen's Award for Technology and awards from the British DTI for Innovation and Good Practice in Micro-electronics. Customers who depend on the viability of their stored samples use Planer products, which include programmable freezers, incubators, monitoring equipment and software for the viable storage and preservation of medical and biological specimens - cells, cord blood, bone marrow, embryos, botanical matter, semen, oocytes, botanical seeds, skin, ovarian tissue, heart valves, blood vessels and more. http://www.planer.co.uk Mr. Jamie Bennet, Sales Director This email address is being protected from spambots. You need JavaScript enabled to view it. Mr. Paul Lakra, Managing Director This email address is being protected from spambots. You need JavaScript enabled to view it. Mr. Geoffrey Planer, Chair This email address is being protected from spambots. You need JavaScript enabled to view it. 44 1 (0) 9327 55000

Studies on Health of cryopreserved embryos using controlled rate freezers (i)Dr Pinborg et al(Copenhagen University Hospital Rigshospitalet, Denmark) looked at all 1,278 children born from frozen embryos in Denmark between 1995 and 2006 showing that it appeared better to use frozen rather than fresh embryos in IVF treatment (reported ESHRE 2008). (ii) H. W. G. Baker et al: of Melbourne Hospital, Australia, Fertility and Sterility September 2008 (Vol. 90, Page S29) http://www.asrm.org/Professionals/Meetings/sanfrancisco2008/Abstracts2008.pdf (iii) S. Kansal Kalra et al University of Pennsylvania, Abstract at S.205 http://www.asrm.org/Professionals/Meetings/sanfrancisco2008/Abstracts2008.pdf (iv) S. Pelkonen et al Oulu& Helsinki University Hospitals, Finland In conclusion singletons born after IVF, ICSI or FET treatments seem to be more often premature and have more often low birth weight than singletons after spontaneous pregnancy. FET-singletons have better outcome compared with singletons born after fresh embryo transfer when examining birth weight or gestational age at birth. Abstract at S.65 http://www.asrm.org/Professionals/Meetings/sanfrancisco2008/Abstracts2008.pdf (v)http://www.ivf.net/ivf/slow_frozen_embryos_seem_to_produce_healthier_babies_in_ivf_correction-o3845.html

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Worse health for IVF twins but no harm in embryo freezing

Author(s):Reported by Benjamin Jones, Progress Educational Trust, London

Two studies have provided an insight into the health implications of using assisted reproductive technologies (ARTs). The first finds that twins conceived by ART are more likely to be born preterm, be of low birthweight and to be 60 per cent more likely to be admitted into neonatal intensive care. The second finds that embryos frozen shortly after cell division had begun are no more likely to lead to premature or underweight birth than fresh embryos.

The first study was conducted by a research group at the University of Western Australia. Its findings match those for singletons with the paper referencing numerous studies that document earlier birth, lower birthweight and a higher risk of physical malformation in ART pregnancies when compared with spontaneously conceived pregnancies.

The finding suggests that the increased problems surrounding ART twin birth are not solely a result of difficulties inherent to multiple births but are also associated with assisted reproduction. The finding provides further support to the argument that only single embryos should be implanted in IVF or ICSI procedures. It does not, however, demonstrate whether it is the technique itself or the reproductive abnormalities of the recipients that are the cause.

A spokesperson for the UK's Human Fertilisation and Embryology Authority (HFEA), commenting on the new research, told the BBC that 'clinicians have a duty of care to ensure that patients fully understand what IVF treatment involves and what the risks are, for both themselves and their babies', adding: 'This study is another piece of the jigsaw that women and their doctors need to consider before treatment'.

The second study involved a meta-analysis of 21 studies comparing ART with embryos that had been cryo-preserved and those that had not. The conclusion drawn from the pooled data was that there is no significant detrimental effect of the freezing of embryos on health outcomes.

Dr Allan Pacey, secretary of the British Fertility Society, commenting on the two studies, said that 'it is reassuring news about the embryo freezing'. However, he added that 'the issue of IVF twins is concerning, which is why we are trying to move towards single embryo transfer in as many women as possible to give these children the best start in life'.

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ICSI or IVF: Babies born from frozen embryos do just as well

Author(s):Queenie Neri, The Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University , New York

A recent study on babies born after freeze-thawing embryos found that births from frozen progressed just as well whether created by ICSI or standard IVF. Researchersat Cornell University examined around two thousand births of which some 1200 were from ICSI and frozen. Analysis found reassuring evidence that babies born from frozen embryos (all from Planer machines) and fertilised via ICSI do just as well as those born from frozen embryos fertilised via standard IVF treatment.

Amsterdam, The Netherlands:Analysis of the longest running ICSI programme in the United States has found reassuring evidence that babies born from frozen embryos fertilised via ICSI (intracytoplasmic sperm injection) do just as well as those born from frozen embryos fertilised via standard IVF treatment.

The researchers also compared babies born as a result of cycles in which the women had additional hormone medication with babies born as a result of unmedicated, natural cycles, and, although they found a slightly higher rate of malformations in babies born from medicated cycles, the difference was small – 2.2% versus 0.4%. Ms Queenie Neri, a research associate at Cornell University (New York, USA) and a member of the team headed by Professor Gianpiero Palermo who pioneered ICSI in 1992, told the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam today (Monday) that she and her colleagues had looked at all births from frozen embryos, conceived via ICSI or IVF, between 1993 and 2007. Ms Neri identified 720 IVF and 1231 ICSI frozen embryo transfers. The survival rate of the frozen embryos was 74% after IVF and 77.2% after ICSI. The clinical pregnancy rate was 42.8% after IVF and 39.4% after ICSI. These resulted in 84.1% IVF and 89.7% ICSI deliveries. There were 27.8% multiple IVF pregnancies and 21.1% multiple ICSI pregnancies. Outcomes at the time of birth for Apgar scores, gestational ages, birth weights and congenital malformations were similar for both IVF and ICSI singleton babies.

When she grouped the babies according to whether they came from medicated or unmedicated cycles, she found that the clinical pregnancy rate was 42.1% and 39.4% respectively; delivery rates were 86.7% (with 28.7% multiple births) and 87.5% (19.2% multiple births) respectively. Gestational ages and birth weights were similar between the two groups, but the malformation rate was 2.2% from the medicated cycles and 0.4% from the natural cycles. Ms Neri said: “Freezing embryos as part of fertility treatment has become a fundamental part of assisted reproduction technology. We found no differences in the ability of embryo generated by IVF or ICSI to implant, even after undergoing the stress of cryopreservation. We were unable to confirm a significant benefit of the unmedicated cycle on the neonatal outcome of the cryopreserved embryos; the difference in malformation rates was small.

“The original premise of the study was to identify a difference in neonatal outcome while in the presence or absence of infertility medication, with the assumption that the unmedicated cycles would generate better offspring outcomes. Interestingly, we did not see any clear difference in neonatal outcomes between the medicated and unmedicated groups. From our study, the combination of exposure to cryopreservation and medications or both did not significantly impair offspring outcome.”

Full story at http://www.bio-medicine.org/biology-news-1/ICSI-or-IVF-3A-Babies-born-from-frozen-embryos-do-just-as-well-9047-1/

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India's first frozen oocyte baby born in a Chennai hospital

This first for India was achieved when a 29 year old woman, whose identity was kept secret, gave birth to a 2.5 kg boy at the G. G. Hospital in Chennai, India on August 27th 2008. The delivery was by Caesarian section, the new born was moved to a nursery ward for observation and his condition later was stated as stable.

Doctors Priya Selvaraj and Kamala Selvaraj, renowned locally in the field of assisted reproductive technology, pioneered the first pregnancy in India resulting from a controlled rate frozen oocyte. The woman in question had a chromosomal abnormality, which rendered any pregnancy unstable but needed only a donor egg to realize her dream of having a baby.

The gynaecologists, who jointly performed the procedure, said that whilst many babies had been born from frozen embryos, '' … this was for the first time in India that a woman gave birth using a frozen oocyte.''

Dr Kamala added ''In this particular case, the mother had previously conceived an abnormal baby and also gone through a miscarriage earlier. We helped her have a baby with this new technology called oocyte Cryopreservation.'' In these cases eggs, rather than embryos, are frozen for the necessary period of time donated by other women who for those in need. ''Cryopreservation involves a slow freezing process using a cryofreezer and the eggs are then plunged into liquid nitrogen at minus 196 deg centigrade. As and when required, the eggs are brought back to normal temperature and the sperm is injected into the egg to form the embryo,'' Dr Priya Selvaraj said. The Selvarajs used a Planer Kryo 360-1.7 supplied by Indus Instruments.

Dr Kamala said this technology would benefit young women diagnosed with blood cancer and those who wish to postpone childbirth. ''Till this date it has been possible only to freeze sperm in the semen banks, but going a step ahead, the GG Hospitals is planning to set up an egg bank,'' she added.

From http://news.webindia123.com

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Second baby for former cancer patient after frozen tissue transplant

A former cancer patient has made medical history by giving birth to two daughters after her fertility was restored with ovarian tissue that had been frozen.

Stinne Bergholdt, a doctor from Odense, Denmark, is the first woman in the world to give birth twice after undergoing the procedure, though seven others have had one child.

Writing in the journal Human Reproduction, doctors said that the birth of Dr Bergholdt’s second child, Lucca, demonstrated the long-term success of the procedure. Dr Bergholdt, now 32, was given a diagnosis of Ewing’s sarcoma, a rare cancer that mainly affects the bones, in 2004. Before starting chemotherapy, which would have left her sterile, part of her right ovary was removed and frozen. In December 2005, after successful treatment, six strips of frozen ovarian tissue were thawed and transplanted on to what remained of her right ovary. After mild ovarian stimulation she became pregnant and gave birth to her first daughter, Aviaja, in February 2007.

The following year Dr Bergholdt returned to the clinic where the transplant took place for in vitro fertilisation for a second baby. The treatment was not necessary, however — a test revealed that she had conceived again naturally. Professor Claus Yding Andersen, from the University Hospital of Copenhagen, who has pioneered the technique and treated Dr Bergholdt, said: “As long as the tissue remains properly stored in liquid nitrogen, it could remain functional for 40 years.”

Dr Andersen, professor in human reproductive physiology, used a Planer Kryo 10 series 2 for this procedure – he has used Planer for the last ten years - and states that he is "very satisfied with this equipment."

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Distributors Meeting held in Rome, July 2010

Distributors Meeting in RomeSomething of a standard feature now, the Planer European Distributors dinner and meeting was held in Rome, Italy during the 2010 ESHRE meeting.

ESHRE, the European Society of Human Reproduction and Embryology grew out of suggestions from Professors Edwards, Cohen and others and now the meeting is held in a different country each year. The aim of the group is to stimulate study and research in reproductive medicine and science. The Society held its first Annual meeting in Bonn in 1985 with a small number of delegates, but this year in Rome some 6,000 people came.

Although European in name, delegates attend from all over the world and so with Planer. At the dinner, as well as a dozen different countries, China and Lebanon were represented.

Distributors Meeting in RomeIn the photos you can see: Pedro, Luis, Roula, Toni, Helmut, Edwin, Mikko, Miloje, Richard, Morten, Jamie, John, Guillaume, Cemal, Didem and Rosa

Also present - though not for some reason captured by our photographer were Petr, Philippe, Beatrice, HuiMin, and Paolo

The dinner was held in the famous old restaurant "Alfredo alla Scofa" located in Rome's picturesque Via della Scrofa - see http://www.alfredoallascrofa.com/

The place, established in 1907, is famous for its fantastic fettuccine and famous past guest have included Jimi Hendrix, Sophia Loren, Ringo Starr, Frank Sinatra and Audrey Hepburn. It is one of two places in Rome each claiming to have created fettuccine. Douglas Fairbanks and Mary Pickford liked this dish so much they presented a golden spoon and fork to the owners when they parted with the recipe. The ritual of the Golden Spoon - the story is recounted as the fettuccine is served with a Golden Spoon - and the background of the Portuguese football team putting on a great show in the World cup, were highlights of the evening!

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Internships at Planer PLC

InternsLucy and Julie have just finished an eight week Internship in the Planer Sales Department. They arrived from Paris a little apprehensively at the end of April 2010 and stayed through May to June. Julie and Lucy were doing a module for their exams, under SIEC, l'académie de Créteil-Paris-Versailles, for their International Trade studies section.

This required them to complete an eight week internship in a foreign company; this was needed to complete their first year course.

The course is a commercial one so they were required to find out about procedures, legal framework, production, sales and the general mechanics of shipping scientific equipment round the world. Also "to look for new customers in a new market".

Help with looking for new customers is always welcome here - however the second task was rather harder since we export to 90 countries.

However the girls soon settled in and rose to the challenge! And they didn't take the easy way out by trying to sell to France!

By the time they went back their English was much improved and hopefully they know some of the background to running a busy manufacturing company.

In the picture, left to right: Ravi, Lucy, Julie and Nick

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