New procedure may restore fertility in girls who survive childhood cancer

Leukemia treatments often leave girls infertile, but a procedure developed by researchers at the University of Michigan working with mice is a step toward restoring their ability to be biological mothers.

Ovarian follicles are the “nests” that carry eggs and support them to grow and become viable. The researchers demonstrated that they could dramatically improve the rate at which follicles develop mature eggs by surrounding the follicles with adipose-derived adult stem cells in a 3D scaffold that mimics the environment of the ovary. Adipose-derived stem cells can be obtained from readily available fat tissue in adults.

The approach increased follicle survival from less than 5 percent to between 42 percent and 86 percent depending on the size of the follicle. The research was recently published in Stem Cell Research & Therapy Journal.

The researchers point out that utilizing this approach in women is a ways off, but it could offer hope for many. “This is a huge step toward being able to preserve the fertility of women and girls undergoing chemotherapy and radiation for cancer since those treatments are toxic to the follicles,” said Claire Tomaszewski, a U-M doctoral student in biomedical engineering and member of the research team.

“Once a patient is cancer-free and they want biologically related children, we hope we’ll be able to take their ovarian follicles, grow them in vitro and obtain healthy eggs for these young, otherwise healthy women,” said Ariella Shikanov, associate professor of biomedical engineering.

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Smoking, pre-eclampsia may cause fertility problems for offspring

Low levels of oxygen in the womb, which can be caused by smoking or conditions such as pre-eclampsia, may cause problems with fertility later in life, a study carried out in rats suggests.

The research, led by scientists at the University of Cambridge, England, found that exposing fetuses to chronic hypoxia (low oxygen levels) during development led to them having advanced aging of the ovaries and fewer eggs available.

Hypoxia in the womb can be caused by a number of factors, including smoking, pre-eclampsia, maternal obesity, and living at high altitude. The condition is already known to have potential long-term effects on the health of offspring, including increased risk of heart disease. However, this study, published today in The FASEB Journal, is the first time it has been shown to affect fertility.

To investigate the effects of hypoxia, researchers from the Metabolic Research Laboratories at the University of Cambridge placed pregnant female rats in reduced levels of oxygen (13%, compared to the standard 21% found in air). They then examined the reproductive tract of their female pups at a later age and found a decrease in the number of ovarian follicles in the reproductive tract.

“It’s as if low levels of oxygen caused the female’s ovarian tissue to age faster,” says Dr. Catherine Aiken from the University of Cambridge. “Biologically, the tissue appears older and the female would run out of eggs — in other words, become infertile — at a younger age.”

Although the research was carried out in rats, Aiken says there is every reason to expect that the findings could be translated to humans, as previous studies looking at hypoxia during pregnancy in relation to other conditions such as heart disease have been shown to be relevant in humans.

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New podcast: How are fertility success rates determined?

What are your chances of getting pregnant during an IVF cycle? In our latest podcast, Dr. William Ziegler discusses what success rates are and how they are determined for IVF and other fertility treatments.

You can listen to the podcast here.

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Study links air pollution with reduced sperm production in mice

Exposure to tiny air pollution particles may lead to reduced sperm production, suggests new research in mice that was presented at ENDO 2019, the Endocrine Society’s annual meeting in New Orleans in March.

“Infertility rates are increasing around the world, and air pollution may be one of the main factors,” said lead researcher Elaine Maria Frade Costa, M.D., Ph.D., of Sao Paulo University in Sao Paulo, Brazil. The World Health Organization (WHO) estimates that approximately 15 percent of the global population has difficulty with fertility, and male infertility accounts for about half of those problems.

The study looked at the effect of particulate matter (PM) on sperm production. PM is a mixture of solid particles and liquid droplets found in the air. Researchers studied PM2.5, a fine inhalable particle that is 30 times smaller than the diameters of a human hair. PM2.5 is known to disrupt the endocrine system, which is involved in reproduction, including the production of sperm.

The tubes in the testes that produce sperm of all the exposed mice showed signs of deterioration. The research demonstrates for the first time that exposure to air pollution of a large city impairs production of sperm, mainly in exposure after birth, Costa said. “These findings provide more evidence that governments need to implement public policies to control air pollution in big cities,” she said.

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Sperm DNA damage may contribute to repeated miscarriages, study reports

Some cases of recurrent pregnancy loss may be caused by sperm DNA damage in the male partner, rather than by a problem in affected women, according to research presented at ENDO 2019, the Endocrine Society’s annual meeting in New Orleans in March.

Between 1 and 2 percent of couples have recurrent pregnancy loss (RPL), defined as the consecutive loss of three or more pregnancies before 20 weeks’ gestation. “Affected women undergo many tests to determine the cause, but many cases have no identified cause,” said lead researcher Channa Jayasena, M.D., Ph.D., of Imperial College London in London, U.K. Male partners of women with RPL do not routinely undergo assessment to see if they play a role. “However, we know that sperm play an important role in the formation of the placenta, which is critical for survival of an unborn baby,” Jayasena said.

The study was designed to assess whether male partners of women with RPL may have an increased risk of sperm DNA damage, which is known to impair fertility. The researchers compared 50 healthy men whose partners had not experienced miscarriages with 63 men whose partners were affected by RPL. They measured levels of sex hormones such as testosterone, the number and behavior of sperm using a microscope, and further molecular tests. They also measured the level of damage to sperm DNA, and level of a chemical entity called reactive oxygen species, which can damage cells such as sperm in the semen of men.

They found that men affected by RPL had twice as much sperm DNA damage compared with the unaffected men. Men whose partners had suffered miscarriage also had a four-fold increase in the amount of reactive oxygen species compared with unaffected men.

“Our study suggests that it may be useful to investigate if male partners of women with RPL have abnormalities in their reproductive function,” Jayasena said. “It also opens up a new potential ‘drug target’; it may be possible to design future drugs to stop sperm DNA damage to treat couples with RPL and reduce the risk of miscarriage.”

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Study shows household contaminants cut male fertility

New research by scientists at the University of Nottingham suggests that environmental contaminants found in the home and diet have the same adverse effects on male fertility in both humans and in domestic dogs.

There has been increasing concern over declining human male fertility in recent decades, with studies showing a 50% global reduction in sperm quality in the past 80 years. A previous study by the Nottingham experts showed that sperm quality in domestic dogs has also sharply declined, raising the question of whether modern day chemicals in the home environment could be at least partly to blame.

In a new paper published in Scientific Reports, the Nottingham team set out to test the effects of two specific human-made chemicals—namely, the common plasticizer DEHP, widely abundant in the home (in carpets, flooring, upholstery, clothes, wires, toys) and the persistent industrial chemical polychlorinated biphenyl 153, which although banned globally, remains widely detectable in the environment, including in food.

The researchers carried out identical experiments in both species using samples of sperm from donor men and stud dogs living in the same region of the UK. The results show that the chemicals, at concentrations relevant to environmental exposure, have the same damaging effect on sperm from both man and dog.

Leading the work, Associate Professor and Reader in Reproductive Biology at the School of Veterinary Medicine and Science, Richard Lea, said, “This new study supports our theory that the domestic dog is indeed a ‘sentinel’ or mirror for human male reproductive decline and our findings suggest that human-made chemicals that have been widely used in the home and working environment may be responsible for the fall in sperm quality reported in both man and dog that share the same environment.”

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New chlamydia treatment could lower infertility risk

Researchers in Canada have developed a new way to prevent and treat chlamydia, the most common sexually transmitted bacterial infection in the world. Left untreated, chlamydia can infect other parts of the female reproductive system and cause pelvic inflammatory disease (PID). About one in five women with chlamydia develop PID, making chlamydia the most common cause of infertility in women.

The new treatment differs from the traditional anti-biotic treatment. It is a type of gene therapy that is delivered via nanotechnology. The researchers claim it shows a 65% success rate in preventing chlamydia infection on a single dose.

“As antibiotic resistance continues to develop, people may experience chlamydia infections that cannot be treated through conventional means, which is causing increasing public health challenges,” said Emmanuel Ho, a professor at the University of Waterloo’s School of Pharmacy. “If left untreated or if treatment takes an extended period of time it can lead to infertility and other reproductive issues so finding new ways to treat this common infection is important.”

The new treatment prevents the majority of bacteria from entering cells in the genital tract and destroys any bacteria that is able to penetrate a cell wall. “We’re able to stop the creation of the protein that chlamydia will use to enter genital tract skin cells,” said Ho. “As a result, an incoming infection has fewer targets to latch onto and infection is less likely to occur.”

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New fertility hope for childhood cancer survivors

One in three childhood cancer survivors is at risk of becoming infertile due to chemotherapy or radiation, and since their sperm or eggs have not matured, assisted reproduction using those sperm or eggs is not an option when they become adults. Now, in a major first, researchers at the University of Pittsburgh School of Medicine and the Magee-Womens Research Institute (MWRI) have reported in a non-human primate model that immature testicular tissue can be cryopreserved, and later used to restore fertility to the same animal.

The advance, reported in Science, offers hope for fertility preservation in prepubertal boys who are about to undergo cancer treatments, the researchers report. “This advance is an important step toward offering young cancer patients around the world a chance at having a family in the future,” said the study’s senior author Kyle Orwig, Ph.D., professor of obstetrics, gynecology and reproductive sciences at Pitt’s School of Medicine and an MWRI investigator.

In the study, Orwig and his team developed a non-human primate model of cancer survivorship. Prior to treating with chemotherapy, the researchers cryopreserved immature testicular tissue. They later thawed and transplanted pieces of the tissue under the skin of the same animal. Eight to 12 months later, after the animals entered puberty, the researchers removed the grafts and found large numbers of sperm to be present. They sent the sperm to their collaborators at the Oregon National Primate Research Center at Oregon Health and Science University who were able to generate viable embryos, which were then transferred to recipient females.

In April 2018, one of the females gave birth to a healthy female baby, which Orwig named “Grady” — a portmanteau of “graft-derived” and “baby.” “With Grady’s birth, we were able to show proof-of-principle that we can cryopreserve prepubertal testicular tissue, and later use it to restore fertility as an adult,” the researchers said.

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Thank your doctors on National Doctor’s Day

March 30, which is designated National Doctor’s Day, was established to recognize physicians, their work and their contributions to their community. Please join us as we wish our physicians–Dr. Alan Martinez, Dr. William Ziegler and Dr. Virginia Mensah, left to right–a Happy National Doctor’s Day.

This day was first observed on March 30, 1933, in Winder, Georgia. The wife of Dr. Charles B. Almond, Eudora Brown Almond, wanted to have a day to honor physicians. On that first day, she encouraged supporters to mail cards and put flowers on the graves of deceased doctors. The red carnation, in fact, is the symbolic flower for National Doctor’s Day.

On National Doctor’s Day this Saturday, give thanks to the doctors in your life. The organization National Today suggests you recognize the hard work and dedication that physicians demonstrate each day. Send your doctor an appreciation card or email, donate to your local medical center, or even nominate your doctor for an award. With nearly 700,000 people working as physicians and surgeons across the United States, your doctor would be thrilled to know that their hard work has been valuable to your health.

Our doctors have helped hundreds of couples achieve their dream of having a family. If an RSCNJ doctor has helped your family, please share your experience with us.

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Can ‘sperm races’ help IVF succeed?

Perhaps, according to a presentation at the American Physical Society March Meeting in March. A microchip device that pits sperm racing against one another is being developed by Afrouz Ataei from Florida Atlantic University and may help to improve IVF success rates in the future.

“An integral part of in vitro clinical procedures is the isolation of motile and morphologically normal viable sperm from the semen,” said Ataei, who explained that this step increases the chances of successful egg fertilization in plastic dishes outside the body (in vitro).

However, the conventional method used to sort the speediest sperm involves centrifugation and several high-speed, spinning steps, which can damage the delicate DNA encased within a sperm’s head. And an egg fertilized with sperm damaged in this manner is unlikely to progress to a viable embryo for implantation into the womb.

Ataei’s device manages to select the faster swimmers without any damaging steps. Her device exploits the observation that sperm swim against an opposing flow of liquid at certain flow rates. The microchip is designed to generate liquid flow without the use of other equipment. “No other devices generate the flow in this way, and our device is much easier to use,” said Ataei. “We found that at a specific flow rate, we get the most motile sperm with highest motility. I think this device has potential for clinical use.”

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