Link Between Infertility, Low Egg Reserve, and Breast/ovarian Cancer Gene (BRCA1) Suggested

A New York Medical College physician who specializes in restoring or preserving fertility in female cancer patients has discovered a possible link between the presence of breast cancer genes and infertility.

In a paper published last week in the Journal of Clinical Oncology, Kutluk Oktay, M.D., professor of obstetrics and gynecology and principal investigator on the study, concluded that mutations in the BRCA1 gene, which have been linked with early onset breast cancer, are also associated with an early loss of egg reserves. This finding may help to explain why women who carry a mutated BRCA1 gene have greater rates of infertility as well as a greater risk for breast and ovarian cancer.

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First birth after ovarian transplant

A Belgian woman has given birth to the first baby born after an ovarian tissue transplant, a medical advance that gives hope to young cancer patients whose fertility may be damaged by chemotherapy.

The baby, a healthy girl named Tamara, was born at 7:05 p.m. on Thursday in a hospital in Brussels and weighed 8.2 lb. Her mother is Ouarda Touirat, 32, a hospital spokeswoman said.

Read more: http://www.msnbc.msn.com/id/6089202

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Fertility First: Human Egg Cells Grow Up in Lab

For the first time, scientists have managed to grow mature human eggs from immature cells in the lab, a technique that may eventually help save the fertility of female cancer patients who aren’t eligible for traditional egg harvest.

Researchers from Northwestern University took immature egg cells, encased in a protective sac called a follicle, from 14 women who wanted to preserve their fertility before undergoing chemotherapy. By placing the cells in a unique three-dimensional growing environment for 30 days, the scientists coaxed the cells into becoming what appear to be healthy, functional human eggs.

“It is a major first,” said infertility expert Sherman Silber of St. Luke’s Hospital in St. Louis, who was not involved in the research. “No one has yet tested the eggs by in-vitro fertilization and pregnancy, but they look quite normal and we are all excited about it.”

Read more: http://www.wired.com/wiredscience/2009/07/humanegg/

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New technique could save cancer patients' fertility

The tiny translucent egg nestled in the special laboratory gel was a mere 30 days old, but its four-week birthday caused researchers to quietly celebrate. This was the first time anyone had successfully grown a woman's immature egg cells, contained in a tiny sac called a follicle, to a healthy and nearly mature egg in the laboratory. When an egg is fully mature, it is ready to be fertilized.

The researchers from Northwestern University Feinberg School of Medicine have completed the first critical step in the development of a new technique, which, if successful in the next steps, may eventually provide a new fertility option for women whose cancer treatments destroy their ability to reproduce.

The nearly mature follicles grown for 30 days in the laboratory had been plucked from ovarian tissue of cancer patients before they began chemotherapy and radiation treatments that would destroy their fertility. The cancer patients, from Northwestern Memorial Hospital, had agreed to participate in the experimental fertility study, which was funded by the National Institutes of Health.

"By being able to take an immature ovarian follicle and grow it to produce a good quality egg, we're closer to that holy grail, which is to get an egg directly from ovarian tissue that can be fertilized for a cancer patient," said Teresa Woodruff, chief of fertility preservation at the Feinberg School and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

"This represents the basic science breakthrough necessary to better accomplish our goals of fertility preservation in cancer patients in the future," added Woodruff, who developed the new technique with colleagues.

Woodruff is the senior author of a paper on the findings in the July 14 issue of the journal Human Reproduction.

The next step will be for Northwestern researchers to try to induce the egg's final division, called meiosis, so it sheds half of its DNA in order to be fertilized. The ultimate goal is for scientists to be able to freeze the immature follicles, then thaw and mature them in a culture to the point where they are ready to be fertilized.

"This is a very significant achievement because the early stage of the human ovarian follicle is really hard to grow in vitro. They're very fragile and delicate," said Min Xu, a paper coauthor and research assistant professor at the Feinberg School.

As the immature egg grew inside the follicle, it produced hormones just as it would inside a woman's body.

"That's a good sign that these follicles are healthy. The actual egg also is growing to the same size that we would see in an egg that a woman's body has ovulated," said Susan Barrett, a coauthor and post-doctoral fellow at the Feinberg School.

Women currently have few good options to save their ability to reproduce after cancer treatment. Men are able to freeze their sperm for later use before they begin fertility-destroying cancer therapies. The best option to preserve the fertility of a female cancer patient is to collect her eggs, fertilize them with sperm and freeze the resulting embryos. However, this option is often not a practical choice because it can delay cancer treatment, can't be performed on those who have not reached puberty, and requires fertilization -- a problem for those who do not have a male partner or do not wish to use donor sperm.

Other researchers have experimented with freezing entire ovaries or strips of ovarian tissue and implanting them in a woman's body once she is ready to have children. But for cancer patients, it is possible that cancer cells may be present in the ovarian tissue and result in a new cancer after the tissue is implanted. However, if follicles could be removed from the tissue and grown in the laboratory successfully, as this study suggests, then a new fertility preservation technique might become available for women who could not safely have an ovarian transplant.

The new Northwestern findings build on earlier research by the scientists, who grew mouse follicles in a culture, induced the eggs they contained to mature, fertilized them with mouse sperm and implanted them into female mice to establish pregnancy. The technique produced healthy, fertile generations of mice.

Woodruff, working with Lonnie Shea, professor of chemical and biological engineering at McCormick School of Engineering and Applied Science, achieved the new advance by suspending the human ovarian follicle in two different kinds of three-dimensional gels. Previous attempts to grow ovarian follicles had been on a flat surface, which the researchers now believe does not replicate conditions inside the body. These earlier attempts failed to develop good quality eggs that were healthy enough for fertilization.

Woodruff said the research also is significant because it is the first time scientists have been able to isolate and study a functioning individual human ovarian follicle.

"Because you don't take an ovary out of young women, we've never before been able to look inside the follicle of the human and ask how does it work, how do hormones change, how does the estrogen change in the follicle?" explained Woodruff, who also is the Thomas J. Watkins Professor of Obstetrics and Gynecology. "We never knew how an individual follicle regulated these hormones. This paper for the first time shows these individual hormones being regulated by one growing follicle."

The discovery, Woodruff said, will enable researchers to understand how nurse cells (granulosa cells), the cells that support and surround the maturing egg, communicate with the egg. "They provide a lot of information that the egg needs to grow and develop properly," Woodruff said. "It's a big priority for us to understand how the nurse cells talk to the egg." The information, she said, will help scientists understand how eggs grow and develop properly.

For additional information on Woodruff's research visit her laboratory web site at http://www.woodrufflab.org.

Source: http://www.eurekalert.org/pub_releases/2009-07/nu-ntc071309.php

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New Ovarian Transplant Technique Successful

A new, two-step method of ovarian transplant has had excellent results, giving women a greater ability to conceive after cancer treatment or when older, doctors announced Monday.

The technique successfully and quickly restored ovarian function enabling two patients to become pregnant.

Scientists have performed ovarian transplants in women with cancer before, since chemotherapy often leaves them infertile. The ovaries are removed before the toxic treatment begins in order to re-implant them later.

Up to this point, cost and uncertainty yielded only a handful of successful transplants, but since women with diseases have limited options, they found it worth a shot.

Read more: http://www.redorbit.com/news/health/1713205/new_ovarian_transplant_technique_successful/

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Exposure to combustion by-products linked to male infertility

Picture by vierdrie
A new study adds to the growing literature suggesting that chemical exposure may affect male fertility.

Men exposed to higher levels of combustion by-products had an increased risk of infertility, according to results from a study conducted in China.

A decline in male fertility has been observed in recent years, and some scientists have proposed that exposure to endocrine disrupting chemicals, such as PAHs, may be to blame. PAHs are a class of chemicals that are released in the atmosphere, soil and water as a result of the incomplete burning of a range of substances including coal, oil, gas, wood, refuse and other organic substances. These chemicals are classified as probable carcinogens by the International Agency for Research on Cancer.

Researchers found that infertile males with abnormal semen quality (based on sperm concentration, number of sperm per sample, sperm motility and semen volume) had a 14 percent increase in median exposure to total PAHs relative to fertile men and slightly higher median PAH concentrations than infertile men with otherwise normal semen quality. Men with higher PAH exposure had a 53 percent increased risk of infertility than men with lower exposure.

The influence of the pollutants on infertility varied. Some PAHs had more of a risk of affecting the men's semen quality than others. Two in particular – called I-OHP (I-hydroxypyrene) and 2-OHF (2-hydroxyfluorene) – showed the strongest associations. I-OHP is one of highest measured PAHs in the US population and has been found in prior human and laboratory studies to affect semen quality at everyday exposure levels.

These results were obtained after researchers compared PAH residues in the urine of 513 infertile men with 273 fertile men.

It is however limited by the fact that exposure could not be directly determined. Instead, PAH residues in urine were measured, representing only a few days of exposure.

Source: http://www.environmentalhealthnews.org/ehs/newscience/exposure-to-pahs-may-affect-male-fertility

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New Tool Guides Doctors To Save Cancer Patients' Fertility

Picture from oncofertility.northwestern.edu
ScienceDaily (Feb. 26, 2009) — The powerful chemotherapy and radiation used to save cancer patients' lives can also destroy their fertility.

Research in a new field called oncofertility has advanced the ability of doctors to preserve the reproductive health of women, men and children who are diagnosed with cancer. Yet, many oncologists aren't familiar with these new strategies to help their patients.

Full story: http://www.sciencedaily.com/releases/2009/02/090226122728.htm

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