'Nursemaid' cells reveal the best IVF eggs

Genetic clues contained in the cells that nurse and nurture developing eggs could help identify which ones to choose for IVF.

There is currently little that can be done to predict which eggs are most likely to generate healthy embryos. After an egg has been fertilized, doctors can take biopsies from early embryos or examine their shape to predict which are most likely to implant and produce healthy children. Despite this, around 8 out of 10 embryos conceived through IVF fail to implant when transferred to the womb.

While an egg is developing it is nurtured by specialized cells called cumulus cells, which provide it with the nutrients it needs to grow. "The final state of the egg depends on the relationship with the cumulus cells," says Samir Hamamah at the Montpellier University Hospital in France. So he and his colleagues wondered whether there are genetic markers in these cells that could predict the quality of the resulting embryos and the likelihood of a successful pregnancy.

To investigate further, the team retrieved eggs and their associated cumulus cells from 30 women undergoing IVF. After extracting and freezing the cumulus cells, they fertilized the eggs by intra-cytoplasmic sperm injection (ICSI) and inspected the resulting embryos for quality. They then looked at the gene expression profiles of the cumulus cells corresponding to the eggs that produced good and bad embryos, as well as those that failed to fertilize.


This analysis showed that the levels of expression of three genes, called BCL2L11, PCK1 and NFIB, were strongly associated with embryo quality (Molecular Human Reproduction, DOI: 10.1093/molehr/gan067). BCL2L11 is involved in triggering cell death in response to abnormalities, PCK1 is associated with energy production, and NFIB regulates some of the earliest processes in embryo development.

Hamamah's finding opens up the possibility that doctors might be able to check the level of expression of these cumulus cell genes to predict the viability of the egg. "This is a novel concept, offering a new potential strategy for competent embryo selection," he told a meeting of the Preimplantation Genetics Diagnosis International Society in Miami, Florida, last week.Fertility doctors might be able to check the level of gene expression to predict the viability of an egg

He plans to confirm that this strategy works by using the three genetic markers to select eggs to fertilize and implant, and then see how many of these result in healthy pregnancies compared with those from unscreened eggs.

"Trying to establish the importance of particular gene products in assessing embryo viability is very important," says Simon Fishel, managing director of the Care fertility clinic in Sheffield, UK. "Whether it will become a valuable clinical [tool] remains to be seen. Our understanding of genes in relation to embryo viability is still crude."

Lab Grown Eggs

A major breakthrough by British scientists could bring new hope for women facing the heartbreak of infertility. For the first time a team has managed to grow hundreds of eggs in the laboratory using a new technique which could help cancer patients whose treatment can leave them infertile. It would also allow thousands more women to wait until middle age to have children.
The scientists from Edinburgh University have shown that immature eggs can be frozen, grown and matured in the lab. The process could lead to women having pieces of ovary containing the immature eggs removed and stored. Much later on, they could be thawed, fertilised and finally implanted into the womb. Some say it is morally wrong for a woman to do so and have them fertilised years later in order to delay having children while she pursues a career. However, scientists hope the new process will revolutionise fertility preservation for women because it will allow them to store many more eggs than they can under traditional IVF techniques. And, because immature eggs survive the freezing process much better than the mature ones used in IVF, it is much more likely that older women will be able to conceive using them. It brings forward the prospect that thousands of women will use the technique to side-step the menopause, delaying motherhood for the sake of their careers.
The process, which could be available in five years, also provides hope for cancer sufferers who at the moment are often left infertile following chemotherapy and radiotherapy. Powerful anti-cancer drugs can destroy follicles in the ovaries, wiping out any possibility of women having children. At the moment, these women have a piece of ovary removed, frozen and then re-transplanted after their cancer treatment. But there is always the danger that the cancer could be reintroduced by the implant.
The new technique means women's immature eggs contained in the patch of ovary could be grown in the lab and then screened for cancer before being used in IVF treatment.

There are also hopes it will provide a rich source of eggs for scientists to study for clues on ways to treat a range of diseases.
There is a shortage of human eggs for medical research, and if the technique works it would bypass the controversy over the use of animal-human 'hybrid' embryos. The research, carried out by an Edinburgh University team led by Dr Evelyn Telfer,has been published in the journal Human Reproduction. "This is a significant step in developing immature eggs to maturity outside the body," said Dr Telfer. "Women who face infertility as a result of chemotherapy, or who want to put their biological clock on hold, could benefit from this system. "However, there is a lot more research to be carried out before this technique could be safely applied within a clinical setting."

Last year, Canadian scientists announced the first birth of a child created from a human egg matured in the laboratory. However, they did not use the same "primordial follicles" studied by the researchers from Edinburgh. These are the tiny egg-bearing pockets within the ovaries that are present in their millions at birth, but gradually die off over the course of a woman's life. They represent a woman's fertility "battery" which once depleted cannot be recharged. Many remain dormant, but some go on to mature and eventually release their eggs in preparation for fertilisation. For the first time, the team led by Dr Telfer has succeeded in growing primordial follicles to a late stage of maturation in the lab. They took pieces of ovary containing the follicles from six volunteer women who were giving birth by caesarean section. These were then exposed to a chemical that promotes growth, similar to the one that functions in the ovaries. Around a third of them survived and went on to reach the advanced 'antral' stage of development. At this stage, the follicles are filled with fluid and contain eggs almost ready to be fertilised. It means that it could soon be possible to grow hundreds of eggs in the laboratory.

The Canadian team which managed to create a child from immature eggs was working with only around a dozen. Another advantage is that the follicles mature much more quickly in the lab than they do in the ovary. The scientists do not yet know whether eggs - or oocytes, to give them their technical name - matured in this way are completely normal and suitable for in-vitro fertilisation. But animal studies suggest they are. The next step is to use hormones and other substances to try to nudge the 'antral' eggs on to the next stage of maturation, and then test the technique on humans. "We believe there's good evidence that we can get normal oocytes, but of course you would never apply this technique clinically until you are sure," said Dr Telfer.
"We're seeking funding for further research to bridge that gap. It might take five to ten years from now before we get to the stage of a clinical trial." Dr Jane Stewart, consultant in reproductive medicine at the Newcastle Fertility Centre, said:
"This work increases our understanding of the maturation of human eggs in the lab and takes us a step nearer the goal of strong immature eggs for fertility preservation for women."

Egg Quality

A common cause of infertility in women is poor egg quality. Poor egg quality does not have to be the end of your chances for pregnancy – a variety of unique fertility treatments are available to help you achieve your pregnancy. All women have a finite number of eggs in their body which, when released during ovulation, can be fertilized to produce a child. Most people believe that all that matters when you are trying to get pregnant is the number of eggs you have – as long as you have a lot of eggs, you’ll get pregnant. Unfortunately, this is not the case. True, the number of eggs that you have does matter, but so does the quality of those eggs. Together, the number and quality of your eggs are referred to as your ovarian reserve. Egg quality refers to how prepared your eggs are to develop into embryos once they are fertilized. In order to be healthy enough to develop, an egg needs to have the proper chromosomes and the ability to combine those chromosomes with sperm. Some eggs in your body just don’t have the right number of chromosomes, making it impossible to have a successful pregnancy.

The eggs in your ovaries also need energy in order to split after fertilization. Your eggs contain mitochondria, which are tiny cell organelles that provide the energy for the egg. Without mitochondria, your egg wouldn’t have the energy to survive. As you age, these mitochondria produce less and less energy. As a result, any egg that is fertilized will eventually run out of energy and will be unable to divide.

Egg quality is greatly affected by your age. In your 20s and early 30s, you should have a large number of good quality eggs available for fertilization. Yes, you will have a few bad eggs too, but the good ones should vastly outweigh them. However, as you age your eggs will begin to decline in quality as well as in number. By the time you are in your late 30s or early 40s, you will probably have more poor quality eggs available than good quality eggs.

However, you don’t have to be over the age of 40 to have poor quality eggs. Some younger women can also have a poor ovarian reserve, either as a result of health problems or genetics. In particular, smoking, radiation therapy, and chemotherapy have been known to cause eggs to decline in health. If you suffer from endometriosis, you may also find that your egg quality is poorer than you would like it to be.

Egg quality has a huge impact on your fertility. If you have poor quality eggs, you will probably have a difficult time getting pregnant and staying pregnant. The impact of poor quality eggs is reflected in the general decline in pregnancy rates as women age. Women between the ages of 15 and 25 have a 40% chance of conceiving every cycle. Women who are over 40 however, have less than a 25% chance of becoming pregnant naturally. This is due to the fact that women who are older tend to have fewer eggs and eggs of a poorer quality. Poorer quality eggs can be one of the major causes of infertility in a number of ways. Firstly, poor quality eggs can make conceiving a child very difficult. If a baby is conceived, a poor quality egg can make the difference between carrying your baby to term or losing it in the first few weeks. Many poor quality eggs do not implant properly into the uterus once they are fertilized. Others implant properly but are simply not healthy enough to grow and divide, resulting in a miscarriage.

If you think you may be struggling with fertility issues, it is important to get checked out by a health care professional. In particular, you should probably make sure that your eggs are healthy and of a good quality. Women who are struggling with infertility and are over the age of 37 are usually tested for this.t is difficult to determine the quality of an egg simply by looking at it. Doctors usually have to implant the egg using in vitro fertilization to see whether it will grow or not. However, there is fertility testing to determine if you may be suffering from poor egg quality. Typical tests that evaluate your egg equality include:
Day 2/ 3 FSH Test: Measures your levels of FSH. Elevated levels may indicate poor egg quality.
Clomid Challenge Test (CCCT): The clomid challenge test is a blood test.

If you are suffering from poor egg quality there are a variety of fertility treatments that you can pursue to help you to conceive. Just because you have poor quality eggs does not mean that it is impossible for you to become pregnant. Using fertility drugs is one way to possibly increase the quantity and quality of your eggs. Typical female infertility drugs include clomiphene and cabergoline. In vitro fertilization is another treatment option. However, if your eggs are of too poor quality, you may be encouraged to use an egg donor.

Research into improving egg quality is ongoing. One treatment currently in the trial phase is cytoplasmic transfer. This form of treatment involves putting cytoplasm (the watery, outside layer of a cell) from a healthy donated egg into a poor quality egg in order to help it divide. Nuclear transfer is another form of treatment currently under investigation. Nuclear transfer involves taking a healthy nucleus from a donated egg and transferring it into an egg with an unhealthy nucleus. This helps to improve the quality of the egg thereby increasing the chances of conception occurring. Though neither of these procedures are currently available to the general public, there is hope that they may come to fertility clinics in the near future.