IVF News

New research suggests that pregnancy via egg donation, in women with Turner's syndrome, carries an increased  risk for both mother and child.

Turner's syndrome is a condition, which affects around one in 2,500 women, where a woman is born with only one X chromosome, instead of the usual two. This can lead to a range of health problems, including short stature and an increased risk of heart disease. Women with this condition are often infertile, but may be able to have children using donor eggs.

The study followed the pregnancies of 93 mothers with Turner's syndrome who had undergone egg donation. Thirty-eight percent of the mothers had pregnancy-associated hypertensive, high blood pressure, disorders. These included four women who had severe eclampsia, a potentially life-threatening complication of pregnancy characterised by seizures.

In addition, 30 percent of the babies were found to have restricted growth pre-natally. Unfortunately, during the study two of the women died after giving birth, and another woman had a miscarriage following eclampsia. Overall only 40 percent of the pregnancies were defined as 'normal'.

Professor Patrick Fénichel from the University of Nice, who led the research, said: 'My group and the French oocyte donation research group will now concentrate on understanding if eclampsia is linked only to Turner’s syndrome or also to egg donation itself'.

'We will also look at ways in which better monitoring during pregnancy, delivery and the immediate post-partum period in an appropriate hospital centre might improve the outcomes of pregnancy in Turner’s mothers'.

The research was presented at the European Congress of Endocrinology, which was held in Rotterdam from 30 April to 4 May 2011.

Dear Colleagues,

Please find attached the program of the course that will take place in Valencia, Spain during 11^th- 15^th of July 2011. The course is entitled “New Tools for the Study of Gametes in Human Assisted Reproduction” and will be dictated in Spanish. It is an innovative ‘hands on’ course addressed to assisted reproduction laboratory specialists.

Participants will be able to apply new diagnostic tools in reproductive medicine, to analyze non fertilized oocytes, and sperm samples from infertile men. The student will learn different methods of immunocytochemistry and handling new technology to understand some underlying problems of gametes. Theoretical and practical classes will take place in small groups, so direct interaction with experts will take place.   

We are convinced that this course will be extremely useful for many professionals in the field of Assisted Reproduction. In this first year, the course will be held in Spanish but we plan an English version of it for future editions.

Contact information:  [email protected]

Fee: 1600€

Sincerely,

María Vila Marqués, MSc.

CREA

Embryology Director 

A British woman has agreed to donate her womb to her daughter if she's selected for experimental womb transplant surgery to be performed by doctors at the University of Gothenburg in Sweden.

Eva Ottosson, 56, told the BBC that this is the only chance for her daughter Sara, 25, who was born without a uterus and fully functioning reproductive organs, to have a child of her own barring surrogacy, which is prohibited in Sweden where Sarah lives.

Sara is one of around seven patients being evaluated by Dr Mats Brannstrom, who is leading the Swedish medical team, to establish patient suitability for the uterus transplant surgery which he wants to perform in five or six patients beginning early next year.

The surgery is high risk and has only been attempted once before in 2000 in a woman in Saudi Arabia using a womb from a 46-year-old donor transplanted into a 26-year-old. Complications due to blood clotting forced the uterus to be removed 99 days later.

In 2007, the Swedish team had some success in achieving a pregnancy in sheep, but others had fatal complications. Some scientists have criticised the procedure as too premature for human experimentation.

If the surgery goes ahead successfully, doctors will implant embryos created using her own eggs and her partner's sperm by IVF. Any birth will need to be by caesarean section. Provided all goes well, her mother's donated womb would have to be removed two to three years later to avoid future medical complications.

Dr Brannstrom admits that the procedure is much more technically demanding than a kidney, liver or heart transplant. 'The difficulty with it is avoiding haemorrhage and making sure you have long enough blood vessels to connect the womb', he told the Telegraph.

Ms Ottosson told the BBC that initially she thought it was a bit 'weird' for her daughter to use the same womb that she had developed in, but now they consider it to be equivalent to organ donation. She said they are focused on the risks of the surgery involved.

The procedure could bring hope to an estimated 15,000 women of childbearing age in the UK who are born without a uterus or have lost uterine function from damage or removal due to illnesses like cancer.

A man who froze his sperm at a fertility clinic over ten years ago has spoken of his distress after finding out his ex-wife had tricked the clinic into using the sperm, resulting in the birth of two children. He was then ordered by a court to pay £100,000 towards their upbringing.

The 57-year-old man, who cannot be named for legal reasons, stored his sperm at the Bourn Hall fertility clinic in Cambridge in 1999 while undergoing treatment for arthritis which could have left him infertile.

The couple divorced in June 2000 but the woman allegedly approached the clinic and forged his signature, allowing doctors to create embryos using his sperm. After giving birth to a girl in 2001, she reportedly returned to the clinic in 2003 and then gave birth to a boy.

The man, who has since remarried and has two other children, said he found out after receiving a text message from his ex-wife saying the girl wanted to see her father.

'I was stunned when I found out she had withdrawn my sperm without my consent because at the time we had split up and were going through a divorce', he said. 'It was a deliberate act to bring two children into this world without a father to look after them. I was never at the clinic and I never signed the documents'.

A court in 2007 ordered him to pay £100,000 to his ex-wife since the initial divorce settlement did not take the children into consideration. He says he has spent over £200,000 in legal fees battling with his ex-wife.

'I love the children and spend money on taking them out and buying them clothes, but it is an expense I shouldn't really have. The cost of this has been huge', he said. 'It is scary to think how little control I had over it all. I just can't understand how they believed her. The stress of it all has turned my life upside down'.

The man said when the children asked their mother where they came from she told them, 'the freezer'. His daughter asked to see her father and the man is permitted regular home visits.

His ex-wife said: 'I don’t believe I have done anything wrong. It was getting later and later for me and I wanted to have a child. If I had not done it then I would not be blessed with my children. I have no regrets'.

Stockholm, Sweden: Swedish researchers have, for the first time, developed a reliable way of deciding whether one or two embryos should be transferred during fertility treatment; the method simultaneously maintains a high chance of women giving birth to a live baby, while reducing the risk of twins.

Dr Jan Holte told the annual meeting of the European Society for Human Reproduction and Embryology, that if this model were to be applied in all fertility clinics, it had the potential to reduce the twin rates to the level of just under two percent seen in the normal population. Already, another four clinics have started to use the model.

Sweden leads the world in attempts to reduce multiple pregnancies by transferring only one embryo to a woman’s womb during fertility treatment whenever possible. In 2007 (the most recent year for which data are available*), 69.9% of embryo transfers were single embryos, 30.1% were double embryo transfers, and only 5.3% of deliveries after fertility treatment were multiple deliveries – the lowest multiple delivery rate in the world.

“However, until now, evidence-based strategies have been lacking for guidance on when to perform single embryo transfer in order to achieve the best possible balance between maintaining a high level of live birth rates, but reducing twin implantation rates,” said Dr Holte, who is medical director, a senior consultant and responsible for research at the Carl Von Linnéklinikken, Uppsala Science Park (Uppsala, Sweden).

Over a four-year period between 1999-2002 Dr Holte and his colleagues analysed a series of 3223 embryo transfers and recorded 80 different factors that played a role in the success of fertility treatment. They found that four variables were significant in predicting pregnancy outcome: the quality of the embryo, the age of the woman, ovarian responsiveness (the number of eggs retrieved in relation to the dose of ovarian stimulating hormones), and information about whether the woman had had previous IVF attempts with either fresh or frozen-thawed embryos, how many, and whether or not they resulted in a pregnancy.

Using these four variables, they constructed a mathematical model that predicted the chances of pregnancy after the transfer of one or two embryos and of the risk of twins. Over a subsequent four-year period between 2004-2007, they applied the model in the clinic for 3410 embryo transfers. They aimed to achieve a risk of twins of no more than 15% and any women that had a higher risk had only one embryo transferred in one cycle. Transfers of embryos that had been frozen, stored and then thawed before implantation followed the same model.

During this period the proportion of single embryo transfers increased to 76.2% (compared to 11.1% in the previous period between 1999-2002), and the rate of twin deliveries was reduced from 26.1% to 1.9%. Live birth rates per fresh embryo transfer fell from 29.1% to 24.6%, but when transfers of frozen-thawed embryos were included the live birth rate was similar during the two periods: 31.1% in the earlier period and 30.7% in the later period.

Dr Holte also made adjustments to take account of the fact that women in the later period tended to be older and have a less favourable prognosis than those in the earlier period and, therefore, would have a lower predicted live birth rate. Once he had done this, the live birth rate (including frozen-thawed embryos) in the later period was higher at 36% versus 31.1% in the earlier period.

Just as significant as the dramatic drop in twin births were the outcomes for babies born between 2004-2007. Average birth weights increased from 3086g to 3412g; the frequencies of babies born prematurely (before week 33) and babies with birth weights below 2500g were reduced by two-thirds; the frequency of babies born small for gestational age was reduced by 26%; and deaths either just before, during or just after birth were reduced by 58%.

Dr Holte said: “These improved outcomes were entirely due to the lower rate of twins. There was no significant differences in outcomes between the two periods when comparing only babies born as a result of a single pregnancy.”

The researchers found that their model correctly predicted the pregnancy rates that occurred in all women, regardless of their chances of becoming pregnant. Dr Holte explained: “The predicted chance of pregnancy for an individual couple ranged between around 5% up to around 60% per attempt. When the treatments were grouped according to their predicted chances into ‘stratas’ or groups of 0-10%, 10-20%, 20-30%, 30-40%, 40-50% and >50%, the corresponding observed clinical pregnancy rates were shown to fit very accurately with the predicted results.

“To our knowledge, this is the first time that a model has been developed that successfully predicts pregnancy and the risk of twin implantation during fertility treatment. The results suggest that application of the model may reduce twin rates to the desired level, in our case to that of the normal Swedish population, while totally preserving pregnancy rates and markedly reducing risks for the offspring.”

Multiple pregnancies, where a woman becomes pregnant with two or more embryos, carry a high risk to both mothers and babies; complications can include miscarriage, premature birth, low birth weight, cerebral palsy and death. For this reason, fertility doctors increasingly try to find ways of avoiding them without jeopardising women’s chances of becoming pregnant.

The model has been validated by another, independent Swedish clinic, with similarly good results over a five-year period, and now three other clinics (two in Sweden and one in Italy) have started to use it. Dr Holte and his colleagues are continuing to refine and test the model further.

Stockholm, Sweden: Researchers are developing a new way to test a woman’s egg for chromosome abnormalities that avoids the need to manipulate and biopsy the egg itself. The research may also shed light on the crucial role played by certain genes in the development of chromosome abnormalities that are a major cause of miscarriages and conditions such as Down’s syndrome.

At present, when a woman undergoes preimplantation genetic screening (PGS) in a fertility clinic, doctors are trying to select an egg or an embryo that is healthy and doesn’t have a chromosome abnormality such as an extra copy of chromosome 21, which causes Down’s syndrome. In order to establish this, they either have to biopsy a part of the egg called the polar body or remove a cell from the embryo for screening. Both procedures are expensive, invasive and can damage the egg or embryo.

Dr Elpida Fragouli, a research scientist at the University of Oxford and director of cytogenetics at Reprogenetics UK, will tell the annual meeting of the European Society of Human Reproduction and Embryology today (Wednesday) that she and her colleagues have discovered that cells surrounding the egg can provide information about the genetic and chromosomal status of the egg.

She explained: “In the ovary, human eggs are surrounded by a cloud of tiny cells, known as cumulus cells. The egg and the cumulus cells are in constant communication and depend upon each other for continued viability. We wondered whether the presence of chromosome abnormalities, which are extremely common in human eggs and are incompatible with the formation of healthy embryos, would have an effect on the surrounding cumulus cells. This is important for two reasons. Firstly, an increase in the understanding of how chromosome abnormalities arise in eggs is desperately needed. For several decades we have been aware that chromosome problems are common in human eggs, that they are the major cause of miscarriage, and that they are responsible for conditions such as Down syndrome. Yet the origins of chromosome abnormalities remain poorly understood. A better understanding of the factors that lead to chromosome abnormality may help us think of ways to reduce their frequency.

“Secondly, if chromosome abnormalities in the egg result in changes in the surrounding cumulus cells, it is possible that this could lead to a new way of testing eggs, before they are fertilised, revealing those with the correct number of chromosomes as well as those that are abnormal. This could help patients undergoing IVF, by identifying the eggs most likely to make a baby without having to use an invasive and expensive procedure. Cumulus cells are routinely stripped off eggs during IVF treatments and are usually discarded, so it should be straightforward to obtain them for analysis.”

Dr Fragouli and her colleagues examined the polar bodies and cumulus cells from 26 eggs donated by women undergoing PGS. Polar bodies are by-products of egg formation. They contain the chromosomes discarded by the egg as it moves from having the same number of chromosomes as all the other cells of the body (46) to the number that eggs and sperm have (23). The unfertilised egg needs to discard half of its chromosomes in order to make way for those that will be delivered by the sperm. If things go wrong and a chromosome abnormality arises in the first polar body (e.g. an extra copy of chromosome 21), then the corresponding egg will have the reciprocal abnormality (e.g. a loss of chromosome 21). The researchers identified a total of 13 normal and 13 abnormal eggs by testing the polar bodies.

“We then looked to see how active individual genes were in the cumulus cells that had surrounded each egg. This was done using two different methods. First we used a microarray, a powerful genetic technology that allows the activity of thousands of genes to be simultaneously tested. We found that 729 genes were expressed differently in cumulus cells that had surrounded eggs that contained an incorrect number of chromosomes. In other words, these genes were either more or less active than we would usually expect. In particular, 14 genes appeared to have highly significant differences in activity when their corresponding egg was abnormal,” said Dr Fragouli.

“We then used a second technique to confirm the initial findings. For this purpose we focused on 95 of the 729 genes that had been originally identified, including the 14 very significant genes. The method we used is known as real-time polymerase chain reaction (PCR). Real-time PCR is considered to be the most accurate way of quantifying the activity of genes, but is difficult to apply to large numbers of genes, which is why we used the microarray for the initial round of screening. The real-time PCR confirmed that most of the genes highlighted by the microarray do indeed show altered activity in cumulus cells associated with abnormal eggs.

“We are still in the process of establishing the usefulness of these genes as non-invasive markers of egg chromosome status and quality. However, it is interesting that several of these genes are involved in vital cellular functions of the cumulus cells and egg they enclose, such as cell signalling and regulation, hormonal response and cell death, and so they may shed light on the genetic origins of chromosome abnormality.”

The researchers are running further tests to see how well results from the expression of genes in cumulus cells compare with the more established PGS method for identifying faulty eggs. If there is a good correlation, then they plan to run a clinical trial in about a year’s time.

“The general idea is that instead of manipulating and biopsying the oocyte, a test examining the corresponding cumulus cells, which are currently discarded during regular IVF treatment, is developed. At the moment, as we are still working on this, I would envisage that results would potentially be obtained between three and five hours after egg retrieval. Theoretically, it would be possible to avoid fertilisation of abnormal eggs, which might have some ethical advantages over the current invasive methods that generally take longer. In addition, current diagnostic methods available for preimplantation genetic screening only provide information on the chromosome status of an egg. While this is a very important aspect of egg quality, it is not the only factor influencing the ability of the egg to lead to a successful pregnancy. The extra genetic information that we may be able to derive from examining the cumulus cells may give us a more detailed evaluation of an egg’s potential to lead to a successful pregnancy and a healthy live birth,” concluded Dr Fragouli.

Some of the highlights from the 27th Annual Meeting of the European Society of Human Reproduction (ESHRE) in Stockholm include good news for sperm donation in the UK; advice about how to reduce the effects of tobacco on unborn children; a 'non invasive' screening technique for chromosomal abnormalities in embryos; and a mathematical model to help reduce multiple births in IVF procedures.

UK sperm crisis 'averted'

On Monday, the London Sperm Bank (LSB) presented encouraging results from its recent marketing campaign to recruit the 500 sperm donors necessary to meet the current need in the UK.

It reports that between March and December 2010 potential donor enquiries numbered 3,062, and of the 397 men who attended an interview 34 percent went on to join the program. The research team says that the 2,410 donations now stored could theoretically provide over 2,000 treatment cycles, which is around half of the annual UK demand.

Dr Gulam Bahadur from the LSB believes its approach of promoting dedicated facilities with sympathetic surroundings; a humorous logo aimed at a wider audience; an advanced quality management system focused on listening, engaging and reacting to potential donors' needs; and an improved follow-up system will encourage the behavioural change needed to recruit more donors.

Quit smoking when you find out you're pregnant and your baby won't suffer

Stopping smoking when you find out you are pregnant is enough to avoid the adverse effects of tobacco on your baby, UK researchers reported on Wednesday.

Dr Nick Macklon and his team at the University of Southampton used data from more than 50,000 pregnancies to show that women who gave up smoking when they realised they were pregnant had babies with similar birth weights to women who had never smoked.

The results were adjusted for factors that are linked to birth outcomes, such as obesity, maternal age and socio-economic background. However, Dr Macklon did warn that smoking can adversely affect fertility, making it harder for couples to conceive. He said the message is that if you do fall pregnant while you are still smoking 'it's not too late to do something about it'.

'Non-invasive' chromosome test revealed

A new way of checking that embryos implanted during assisted reproductive therapies have the correct number of chromosomes was revealed on Wednesday.

The current methods of PGS involve taking a cell directly from the embryo to test it for conditions such as Down's syndrome, or biopsying a part of the woman's egg before it is fertilised. Both procedures risk the egg and embryo's survival.

However, research led by Dr Elpida Fragouli from the University of Oxford has found that the cells surrounding the egg can provide information about its genetic make-up.

'If chromosomal abnormalities in the egg result in changes in the surrounding cumulous cells, it is possible that this could lead to a new way of testing eggs, before they are fertilised', said Dr Fragouli. 'Cumulous cells are routinely stripped off eggs during IVF treatments and are usually discarded, so it should be straightforward to obtain them for analysis'.

The research team are currently comparing the standard methods of PGS with their new approach and, with good results, will undertake a clinical trial next year.

Mathematical model developed to reduce twins while maintaining good pregnancy chances

Swedish researchers have developed a mathematical model that can predict whether women should undergo single or double embryo transfer, thereby maximising the chances of pregnancy while reducing the risk of a multiple birth.

Dr Jan Holte from Carl von Linneklinikken in Uppsala, Sweden found that combining four factors – the quality of the embryo, the age of the woman, her ovarian responsiveness, and information about any previous IVF attempts, such as whether they involved fresh or frozen cycles – reduced the twin rate while maintaining live birth rates.

This model was used in his clinic between 2004 and 2007 for 3,410 embryo transfers, and compared to 1999-2002 the amount of single embryo transfers increased from 11.1 percent to 76.2 percent. The rate of twin deliveries dropped from 26.1 percent to just 1.9 percent, while live births remained at similar levels.

'The results suggest that application of the model may reduce twin rates to the desired level, in our case that of the normal Swedish population, while totally preserving pregnancy rates and markedly reducing risks for the offspring', he commented.

The fertilisation of aneuploid eggs is the major cause of infertility, recurrent miscarriages and genetic disorders such as Down syndrome. Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg’s progenitor cell. The basis for particularly error-prone chromosome segregation in human oocytes is not known. 

The pioneering study published in Science by the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, in collaboration with Bourn Hall Clinic, has revealed some of the reasons why this happens. 

Dr. Zuzana Holubcová and her colleagues established an experimental system for ex vivo high-resolution fluorescence microscopy of human oocytes that enabled them to observe the major stages of meiosis in the laboratory. Using high-end imaging techniques, the scientists studied more than 100 immature eggs as they developed in vitro. For the first time ever, they were able to watch in real time the step-by-step process that leads to the formation of fertilisable human eggs.

Scientists have found that unlike in other cell types, the cellular machinery - called a spindle - that eliminates half of the chromosomes, was assembled over an extremely long time period compared to other cells in the body. Human oocyte spindle assembly was controlled primarily by chromosomes and the small guanosine triphosphatase Ran and was independent of centrosomes or other microtubule organizing centres. This process took about 16 hours to complete, considerably longer than 30 minutes needed for spindle assembly in cells undergoing mitosis or the 3-5 hours required for mouse oocyte meiosis.

The unusually long spindle assembly period was marked by intrinsic spindle instability. This frequently led to an abnormal arrangement of chromosomes in the spindle and an uneven distribution of chromosomes during cell division. The research suggests that differences in the mechanism by which the spindle is assembled could explain why chromosome separation in human eggs is less reliable than in other cell types.

To improve fertility treatments it is essential to have a better understanding of meiosis and of the causes of chromosome segregation errors in human oocytes. This study reveals how fertilisable eggs are generated in humans. The imaging assays developed during this research will now allow studies of meiosis directly in live human oocytes and will provide the foundation to develop improved fertility treatments. 

The study published in Science  

(doi: 10.1126/science.aaa9529).

Holubcová et. al. Science 5 June, 2015: Vol. 348 no. 6239 pp. 1143-1147.

Images and Videos freely available on 

http://www.eurekalert.org/multimedia/pub/93112.php
http://www.eurekalert.org/multimedia/pub/93113.php
http://www.eurekalert.org/multimedia/pub/93114.php
http://www.eurekalert.org/multimedia/pub/93115.php

• The most important, human oocyte maturation 

http://www.eurekalert.org/multimedia/pub/93116.php
http://www.eurekalert.org/multimedia/pub/93117.php

Full paper, supplementary material and movies

https://www.dropbox.com/sh/w2an846xhb7lw0i/AAD1is_IUDi5L_AxyjkF9KEga?dl=0

Dec 3 – 15, 2012
Courtyard Marriott, Mumbai, India

www.embryologysummit.com

The technological advances in the field of ART are pushing the envelope by giving the reproductive laboratory professionals unsurpassed options to further improve the outcome of their patients. The very first International Embryology Summit organized by the Embryology Academy for Research and Training (EART) is conceived with the goal to disseminate the specialized know-how of the latest ART techniques and equipments used and available in the world. The Embryology Academybrings you extensive 12 days long comprehensive hands on teaching and learning with 2 workshops and 6 training modules. Each workshop module will be headed by 8 International Celebrity Embryologist (from Europe, United States and supported by 40 renowned Indian Embryologist), hand picked for their excellence and expertise in specific ART related technologies.

International Faculty:

Peter Nagy, Atlanta, USA – Scientific Chairman

Lodovico Parmegiani, Bologna, Italy

Inge Agerholm, Braedstrup, Denmark

Ronny Janssens, Brussels, Belgium

Alpesh Doshi, London, UK

Yona Barak, Tel Aviv, Israel

Botros Rizk, Mobile, USA

Ashok Agarwal, Cleveland, USA

Indian Faculty:

These Workshops will provide personalized learning environment with a) daily lectures on current and cutting edge issues in clinical embryology and ART, b) live demonstration and explanation of various ART related technologies, c) hands-on practice under expert supervision in an advanced ART facility equipped with the latest equipment and d) opportunity to clear your doubts during informal discussions with key opinion leaders in ART field.

Program Highlights:

·         Disseminate the latest know-how in the field of embryology/ART and human reproduction.

·         Interact and engage with key opinion leaders under informal setting.

·         Restricted number of participants and an adequate course faculty will offer ample time for in-depth discussion to clear one's doubts.

This meeting is organized by the Experts in Embryology and Reproductive Medicine for reproductive professionals everywhere (such as: gynecologists, embryologists, andrologists, veterinarians, biologists, research scientists and others) interested in learning the mind boggling advances in ART and Embryology fields. We assure you of an unsurpassed learning experience.

Come join us this December and learn from the leaders in Embryology!

To register, contact:

Embryology Academy for Research & Training

Mumbai, India.

Tel:  +91 22 2896 1768, 2897 6769, 2896 6770 | Mobile: +91 93219 92764

E-mail: [email protected] | [email protected]

Web site: www.ivftraining.com