Gene WT1 impacts women’s fertility, study finds

Gene WT1 impacts women’s fertility, study finds

Article Provided By Science Daily and Leibniz Institute on Aging – Fritz Lipmann Institute (FLI).

It has been estimated that more than 80 million people in the world have an unfulfilled desire to have children. But for every 10th couple, the reasons therefor remain unclear. Now, researchers from the Leibniz Institute on Aging (FLI) in Jena/Germany have, together with clinical partners, found a new gene mutation that obviously leads to infertility in women. The mutated gene WT1 plays an important role in the early embryonic development controlling proteins (especially proteases) that are needed for the successful nidation in mother’s womb. The astonishing results were recently published in the journal Human Molecular Genetics.

For many couples, starting an own family remains an unfulfilled dream. According to estimations, this is true for about 80 million people worldwide. Some fight for years to have own children; some stay childless without any medical indication. Now, researchers from Leibniz Institute on Aging — Fritz Lipmann Institute (FLI) in Jena/Germany in collaboration with clinical partners discovered a formerly unknown gene mutation that could at least partly explain unwanted childlessness. The study’s results were recently published in the journal Human Molecular Genetics.

Newly discovered mutation of gene WT1

In collaboration with the Sophien and Hufeland Hospital Weimar and the Heidelberg University Women’s Hospital, researchers from FLI’s research group of Christoph Englert investigated samples of women younger than 40 years that suffer from unwanted childlessness. In one out of eight women, the gene WT1 showed a previously unknown mutation in one of its two alleles. “This result was really surprising,” explains Dr. Abinaya Nathan, who is the study’s first author. “Up to now, WT1 was only known as tumor suppressor gene important for the development and maintenance of organs like heart or kidney.” But which role does this gene play with regard to fertility?

Conserved gene function

To answer this question, the researchers from Jena conducted mouse experiments. What they found was that mice lacking one Wt1 copy had far less offspring than healthy wild type mice. Moreover, the researchers discovered that it is Wt1’s activity in the ovary that regulates fertility. After ovulation, the ovary is responsible for guiding the ovule into the womb. The ovary is also the place where fertilization takes place. If the ovule was inseminated, it travels down the fallopian tube to the womb, while dividing and developing continuously. “This process has to be strictly regulated,” explains Professor Christoph Englert, who leads a research group at the FLI. “If the embryo develops too quickly, a tubal pregnancy may occur; if the embryo develops too slowly, nidation into the womb won’t be successful. Hence, the communication between mother’s ovary tissue and the ovule is a highly important prerequisite for a successful pregnancy,” continues Prof. Englert.

Wt1 — Interacting with proteases

FLI’s researchers showed that so-called “proteases” are essential for this communication. They degrade proteins and “pre-digest” the embryo to prepare it for nidation. “Usually, these proteases are only active in the womb,” Professor Englert explains. “However, if the Wt1 gene is mutated, protease Prss29 already becomes active in the ovary, harming the embryo in a way that it cannot attach itself anymore to the uterine wall and finally is rejected. This could be the reason why these women cannot become pregnant even though there has been no clinical indication so far.”

“Results for mice and humans are very similar, showing that this function of the Wt1 gene is highly conserved in mammals,” Dr. Verena Holschbach from the Heidelberg University Women’s Hospital emphasizes. “The new WT1 gene mutation, which we have found, causing the premature activation of proteases already in the ovary, offers completely new approaches to help childless couples to fulfill their desire to have children,” the researchers conclude. The next steps will be even broader clinical patient screenings and a more detailed examination of how to alter the womb milieu.

Millions of Women Don’t Have Access to Fertility Treatments in the U.S.

Millions of Women Don’t Have Access to Fertility Treatments in the U.S.

Article Provided by Alexandra Sifferlin and Time.com.

Many Americans deal with fertility issues at some point in their lives, and more than 11% of women seek fertility services. But according to a new report, whether or not a woman has access to the clinics that provide these services depends on where she lives.

In the United States, about 40% of women of reproductive age—25 million women in total—have limited or no access to assisted reproductive technology (ART) clinics, according to a new study published in the journal Fertility & Sterility. Though OBGYNs can perform basic assessments of their patients’ reproductive needs, many will need to seek outside care at ART clinics for procedures like in vitro fertilization (IVF).

As of 2013, the year with the most recent available data, there are about 510 ART clinics in the United State. Among those clinics, 442 are in metropolitan areas, which leaves women in less-urban areas with fewer options.

The new report also found that 18 million women live in an area where there are no ART clinics, and another 6.8 million women live in areas with only one ART clinic. Since most people pay for fertility services out of pocket, having a choice of where to seek treatment is important, the researchers argue. Lack of access may limit their options.

People who want to undergo fertility treatments already face other barriers, including cost. Insurance or employer coverage of fertility treatments is uncommon, and the average cost of an IVF cycle in the U.S. is about $12,400. Even just an appointment with a fertility specialist can cost from $200-400.
The study authors argue that substantial travel for fertility treatments adds an additional barrier and expense for women without access to nearby clinics. “The major access issue is ability to pay for these services,” says study author Dr. John Harris, an assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine . “But I think there’s a subset of people who are really going to be affected by geography when it comes to getting treatment.”Using telemedicine to reach people where they live is one way to improve access to treatment, Harris says; more supportive policies from employers, with travel benefits or time off to go to appointments, are others. He adds that people who want to undergo fertility services should have more choices in the future.

New Research Shows Chance of Preserving Fertility in Cancer Patients

New Research Shows Chance of Preserving Fertility in Cancer Patients

Article Provided by Kathryn Sharkey and the Rivard Report.

A medication used to prevent infections in cancer patients shows promise of helping male cancer patients preserve their fertility and chance of having children, according to a new study led by an assistant professor at the University of Texas at San Antonio.

The study by Brian Hermann, an assistant professor of biology who has a doctorate in molecular and integrated biology, is another research study within the growing field of oncofertility, a medical specialty that brings together oncology and reproductive medicine with the goal of helping cancer patients and survivors protect their reproductive options and fertility.

The number of patients who survive cancer treatment is growing, but are they aware of their fertility risks and options?

“For certain cancers, treatments have become so successful that survivors can now focus on life after cancer,” said Dr. Alan E. Guttmacher, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in a 2014 issue of the National Institutes of Health’s MedlinePlus magazine, “and for many, the ability to have biological children is a major quality of life issue.”

Data from the National Cancer Institute (NCI) registry of cancer patients shows that there are about 10.5 million survivors of cancer, with 5% between 20 and 39 years old. That means there are at least 630,000 young cancer survivors, with the number increasing every year, according to Dr. Teresa Woodruff’s 2007 book “The Emergence of a New Interdiscipline: Oncofertility.” Woodruff, who coined the term oncofertility in 2006, is the director of the Oncofertility Consortium at Northwestern University.

“More than 25% of breast cancer patients are younger than 40 years old and more than 12,400 children and adolescents are diagnosed with cancer each year and the cure rate for all childhood cancers has reached 75%,” Woodruff states in her book.

This is in line with a 2013 estimate that there were more than 420,000 survivors of childhood cancer.

“We’re getting better at diagnosing cancer, we’re diagnosing it earlier, the treatment options are better, so patients are living,” said Dr. Terri Woodard, assistant professor in the department of Gynecologic Oncology and Reproductive Medicine and head of the Oncofertility Consult Service at The University of Texas MD Anderson Cancer Center in Houston.

There was a time when a cancer diagnosis was considered a death sentence, she said, but modern medicine has enabled people to live long, full lives after a history of cancer. Now, the option of reproducing after a cancer battle is no longer off the table.

“It’s highlighted fertility issues and thus the field of oncofertilty more so probably over the last 15 years,” Woodard said. “But our ability to freeze gametes like sperm or freeze embryos even has been around for some time. It’s just we’ve been a bit slower to adapt it to the population of patients with cancer.”

Cancer’s Effect on Fertility

There is a risk of infertility for cancer patients, and different treatments have different effects. The risk depends on many factors, including the patient’s age, type of treatment, type and dose of chemotherapy drugs used, amount and target area of radiation, type and extent of surgery, number of treatments used, and length of treatment, according to the UT MD Anderson Cancer Center. For men, the risk of infertility can come from the treatment itself.

“That’s because the cells that are in the testes responsible for making sperm – just like the cancer cells – are dividing. When they divide, they become susceptible to the chemotherapy,” Hermann said. “So unfortunately the effective nature of the chemotherapy itself is what causes the infertility, because the germ cells in the testes get killed off.”

Assessing infertility risk is a challenge for medical professionals, Hermann added, in part because there’s often a lag between the time patients are treated and the time they learn they’re infertile. In that time, the treatments may have changed.

“In general, there are some treatments that are more risky for sterilization,” Hermann said. Certain agents essentially create DNA damage that the cell can’t fix, causing it to die. These agents oftentimes cause infertility, depending on the dose, he added.

In his research on mice, Hermann said he used such an agent called busulfan, which can be used to treat people before they get bone marrow transplants, to reflect the kind of treatment that can cause long-term or permanent infertility in men. The study that he originally started on primates showed that the drug granulocyte colony-stimulating factor (G-CSF), given to stimulate white blood cell production in the bone marrow to fight off infections associated with a bone marrow transplant, also stimulated sperm cell production. By stimulating cell production, the drug helped replace the sperm cells killed during the busulfan treatment.

A 2013 study performed on female mice at the University of Pittsburgh School of Medicine found that the G-CSF drug decreased ovarian follicle loss and extended time until premature ovarian insufficiency, meaning that in the mice treated with the G-CSF drug the cancer treatment didn’t destroy as many follicles that contain egg cells and they were able to keep those follicles and egg cells longer than the mice who weren’t. Women are born with all of the egg cells they will have in their lifetime, and those egg cells are kept in small pockets called follicles. Cancer treatments can damage the follicles, leading to a decreased number of eggs and earlier onset of menopause.

“I would say the female fertility preservation field is maybe 10, 15 years ahead of male, so for sure there’s a need,” Hermann said. While infertility is not life-threatening, he believes it nonetheless warrants effort and attention, especially among people who might have the ability to have their own children despite a cancer diagnosis.

Cancer Patients and Fertility

“I think we do a bad job with everybody, honestly,” Woodard said. “The sad thing is for men we have a good option, which is sperm-banking, which can be done quickly, the same day before chemotherapy. And we still miss a lot of these men.”

A 2009 survey, published in the Journal of Clinical Oncology, found that less than half of U.S. physicians followed guidelines from the American Society of Clinical Oncology (ASCO), which suggests all patients of childbearing age should be informed of fertility preservation options. According to a 2011 article in Mayo Clinic Proceedings, 95% of oncologists reported that they routinely discuss the effect treatment may have on patients’ fertility, but only 39% routinely referred patients to a specialist in reproductive medicine. In sperm conservation, 91% of oncologists agreed it should be offered to eligible men, but only 10% reported actually offering it.

“For certain cancers, like breast cancer, lymphoma, gynecologic cancers, they do a really good job at referring, because they’re used to dealing with young patients,” Woodard said. But when it comes to types of cancer that are associated with older patients, many oncologists fail to thoroughly discuss fertility or refer younger patients to specialists, she added.

The goal is to lessen the oncologists’ burden, she said, by providing patients with pertinent information ahead of time to empower them to talk to their oncologists about their fertility options and get referrals to specialists.

“It’s hard to rely on already overworked oncologists to cover that in any significant depth or in a way that patients can understand,” she said.

Woodard ultimately sees the patient as the best source for improving fertility discussions about risks and options.

“They have to say what they want,” she said. “We’re starting to get patients advocating for themselves and saying, ‘Hey, what about my fertility? Is there anything I can do?’”

Some doctors struggle with the ethical decisions of discussing fertility options as it can mean delaying or decreasing treatment with less toxic chemotherapy regimens, but Woodard doesn’t see fertility concerns compromising care.

“I think most oncologists are still picking [treatment] regimens that are reasonable,” she said.

Woodard believes that just having the fertility discussion – whether the patient ultimately pursues any of the options or not – is valuable. Ideally, the conversation would move beyond the patients to insurers to make sure the options are covered by insurance.

Hermann’s study on male fertility shows promise of options for men beyond sperm banking, but he cautions that the study is still in its infancy and needs more follow-up research to see if the G-CSF drug can preserve fertility in humans.

“This is just the tip of the iceberg,” he said. “We still have a lot of work to do to understand whether this is something that will be effective in the clinic.”

Study finds most women unable to track fertility

Study finds most women unable to track fertility

Article provided by Mercatornet.

With infertility more common than ever and birth rates around the world at a record low, a crucial first step for couples trying to get pregnant is to clearly understand exactly when they are fertile. Yet that is something just 13 per cent of women surveyed were able to identify according to a new study just published in the Australian and New Zealand Journal of Obstetrics and Gynaecology which surveyed over 1000 New Zealand women. That was despite a third of the women reporting that they monitored their ovulation.

The authors concluded that fertility knowledge needs to be better addressed among women intending to conceive. Professor Wayne Gillett, a researcher at the university’s Dunedin School of Medicine and medical director at Fertility Associates Dunedin commented:

“When a couple are trying to have a baby, problems like age, endometriosis and male problems are always touted – but no one ever considers knowledge, and that’s one of the things we often see,”

Gillett said there was one enduring myth that the best time in the menstrual cycle to conceive was during, or even after, ovulation, when the reality is that the fertile window is pre-ovulation. He expressed concern that even health professionals are not well-educated about a woman’s fertile window.

An article discussing infertility published in the New Zealand media this month comically writes “at high school we’re taught that if you so much as look at a girl strangely, she’ll get pregnant.” Sadly many indeed carry this idea into adulthood after years of only being told how not to get pregnant. However, given that interest in natural family planning continues to grow, it is hopeful that fertility knowledge will be better circulated, including the knowledge that fertility begins to reduce in a woman’s late twenties and more drastically after the age of 35.

One in six couples in Australia use IVF, and one in every 25 Australian children are now born as a result of IVF. In Denmark one in 15 children are IVF babies. Yet it is questionable whether people are first given good advice about the other more simple and inexpensive options available to them – including accurate knowledge about their exact fertile window which is normally only 6 days long if not shorter. To some, IVF services are a business and there is little incentive to first offer easier, cheaper options to couples.

John Aitken, Newcastle University laureate professor, Director of the University of Newcastle’s large 50-staff Priority Research Centre for Reproductive Science, and the 2012 NSW Scientist of the Year, recently commented:

“We should guard against recklessly marching into a future where we use too much assisted conception in order to compensate for our loss of fertility … It’s an inexorable upward trend. We are taking recourse to IVF in increasing numbers and the thing we have to remember as a society is that the more you use assisted conception in one generation, the more you’re going to need it in the next.”

When should you stop fertility treatment?

When should you stop fertility treatment?

Article provided by NetDoctor.

For people going through IVF it can sometimes seem like there are babies and success stories everywhere. However the Human Fertilisation and Embryology Authority which regulates assisted conception treatment in the UK states that for women under 35 the national average success rate for IVF is just 33%.

So even for ‘younger’ women that means that nearly 67 out of every hundred women either choose to undergo further treatment or explore other options.

For people who do choose to move on, there are many fulfilling alternative nurturing options such as donor conception, adoption, fostering, mentoring or taking on a more participative role with a child in your wider networks. But you don’t have to choose right away.

When is the right time to consider my treatment options?

This is a question I get asked a lot by people going through IVF. The reality is that there is no ‘right time’ to end IVF treatment and try something else, and to be wholly contradictory, any time can be the ‘right time’. For some the odds of success can feel too low or the financial pressures too high, but if the chances of success remain the same and the money is available, then making the decision to stop treatment can feel impossible.

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For people who feel like this I would say it signifies that you are not ready to make that decision. I would tell people to listen to their instincts, which sounds oversimplified but if a decision feels 51% or more ‘right’, then I believe we have the strength to cope with the ifs, buts and maybes.

Accessing support from the counsellor at your fertility clinic can help to manage the limbo time whilst you come to a decision that you are comfortable with. Talking with friends and family can sometimes be helpful, but try not to let their own thoughts or feelings weigh you down too much, as this can add to an already stressful situation. Objective support from your clinic counselling service should always be available for you.

Embryo selection for IVF light micrograph
Getty Science Photo Library – ZEPHYR

Coping with your decision

For most couples or individuals trying to conceive with assistance, beginning treatment means grieving the loss of the fantasy of conceiving naturally. When choosing not to pursue a certain type of treatment further, it’s natural to also grieve.

This can be the case for both primary and secondary infertility. We recognise that grief can bring on many emotions, and can often feel like a rollercoaster. The different stages to grief that people may experience include:

Shock, which can include fear and confusion as we cannot believe the situation we find ourselves in.
Anger, which can include anxiety, shame and embarrassment as it should not be like this, thoughts and feelings can be amplified if others see our discomfort.
Depression and detachment, as we begin to experience more holistically we can feel overwhelmed, depression is appropriate and detachment can help a situation to feel more manageable if we’re not exactly feeling part of it.
Dialogue and bargaining, where we have a chat inside our own heads internally, externally with other people, non-verbal communication plays a part too as does our intuition or ‘gut feel’
Acceptance, finding meaning to our situation, not necessarily happy with our situation, but accepting of it and managing.
Acknowledging the immense lows and highs and working through them with support, rather than battling with each emotion can create a smoother journey to acceptance of your situation.
Acceptance

Acceptance of your situation might mean that you are now exploring alternative parenting options. Or acceptance might mean focussing on you and self-nurturing.

Although at this time of year it can seem like the end of the road, we also have the opportunity to make a new start too. Sometimes it’s most important to just give yourself some time and space to explore the options available to you.

Smartphone app could allow men to test their fertility at home

Smartphone app could allow men to test their fertility at home

Article Provided by The Guardian.

Men may soon be able to measure their own sperm count and quality at home, using a smartphone app developed by scientists. In early tests the gadget, designed to clip onto a smartphone, detected abnormal sperm samples with an accuracy of 98%.

In more than 40% of cases where couples struggle to conceive, the underlying fertility issue is linked to sperm abnormalities, but the researchers said that social stigma and lack of access to testing meant than many men never seek evaluation.

Hadi Shafiee, who led the work at Brigham and Women’s Hospital in Boston, US, said: “We wanted to come up with a solution to make male infertility testing as simple and affordable as home pregnancy tests.”

The team put the device together using spare parts from DVD and CD drives at a total cost of $4.45. Using the device simply involves drawing semen into a disposable holder that is plugged into one side of the phone attachment, in a similar way to a USB. In seconds, results of the analysis are displayed on the phone’s screen.

In the study, published in the journal Science Translational Medicine, the research team recruited 10 volunteers with no formal training, including administrative assistants employed at a Boston fertility clinic. They correctly classified more than 100 semen samples using the app.

Overall, the scientists examined 350 clinic samples and were able to identify those with low sperm counts and inactive or poorly motile sperm with 98% accuracy.

John Petrozza, director of the Massachusetts General Hospital Fertility Center and a co-author, described the device as a “true game-changer”. “Men have to provide semen samples in these rooms at a hospital, a situation in which they often experience stress, embarrassment, pessimism and disappointment,” he said.

“Current clinical tests are lab-based, time-consuming and subjective. This test is low-cost, quantitative, highly accurate and can analyse a video of an undiluted, unwashed semen sample in less than five seconds.”

Allan Pacey, professor of andrology at the University of Sheffield, who was not involved in the research, said that the techniques used for sperm quality assessment have not changed significantly since the 1950s, and that even when carried out at specialist centres can be prone to errors if the laboratory worker has not had sufficient training.

“As such, the development of an easy, cheap and accurate method to evaluate the sperm present in a sample of semen would be very welcome, particularly if it could be carried out by someone without specific training and in any location,” he said.

However, he added that the smartphone device could not replicate all the tests carried out in a specialist lab and did not analyse morphology – sperm size and shape.

“For a small number of men whose sperm are badly made, and have poor morphology, it would be important to get this diagnosed correctly,” he said. “So any man who struggles with infertility for a significant length of time, say more than 12 months, should consider getting their test repeated in a specialist laboratory, regardless of what the phone app might have concluded.”

The team behind the device are planning to perform additional testing and will file for approval from the FDA, the US regulator.

Injured Vets Finally Gain IVF Coverage from the VA

Injured Vets Finally Gain IVF Coverage from the VA

Article Provided by The Huffington Post.

Every couple dealing with infertility faces challenges. This often includes problems with access to affordable infertility services such as in vitro fertilization (IVF). For one group – wounded American veterans – an outdated 30-year ban on funding for IVF made family-building a distant dream for those already dealing with devastating service-related injuries.

Back in the early 1990’s, Congress enacted a ban that prevented the Veterans Administration (VA) from providing IVF to patients at a time when it was new and a bit controversial. Although IVF has now been a well-accepted treatment for some time, vets still lacked coverage until recently.

With strong advocacy by patients and organizations including the American Society for Reproductive Medicine (ASRM), RESOLVE: The National Infertility Association, ARC Fertility and others, Congress in 2016 temporarily lifted – but did not overturn – the prohibition on VA funding of medically appropriate IVF.

VA funding is now in place through September 2018 to offer IVF to severely wounded veterans with a service-connected injury. This means they will now receive the same infertility benefit as their active duty counterparts under the Department of Defense, fixing an inequity between care offered to active duty service members vs. veterans. The VA is currently in the process of signing up clinics to participate in their provider network to deliver the finally available infertility services.

Applauding Congressional action on VA funding, Owen K. Davis, MD, ASRM President referred to the ban as “outdated and cruel” adding “Modern medicine cannot undo their wounds, but by lifting the ban on IVF treatments, we can at least deploy our best tools to help them.”

According to Wounded Warrior Project Chief Strategy Officer, Jeremy Chwat “Because of injuries, especially blast injuries from improvised explosive devices, many veterans of the Iraq and Afghanistan conflicts have tragically lost the ability to have children. After they transition out of the military, affected veterans are left without the basic ability to start a family and move on with their lives.”

While waiting for Congress to act, members of the Society for Assisted Reproductive Technology (SART) decided to offer help through member clinics across the country. Through participation in the ASRM/SART’s “Service to Veterans” program, individual infertility clinics stepped up to provide deeply discounted IVF services to injured veterans. While program details varied from clinic to clinic, most offered at least a 50% discount to veterans whose service-related injuries impaired their fertility. Clinics used the same eligibility criteria developed by the Department of Defense for active-duty personnel.

Enacting this much-needed change in policy took 5 years and work is not yet finished. Members of Congress will be introducing legislation to permanently overturn the VA IVF funding prohibition. To help with getting the legislation introduced, co-sponsored, and passed, once again, groups that advocate for patient access to infertility services – including ASRM, RESOLVE and ARC Fertility – will be active in promoting patient awareness.

On May 18, RESOLVE will hold its annual Advocacy Day to promote awareness of infertility and advocate for coverage for needed care. This year – in partnership with ASRM – those visiting Capitol Hill to meet with Members of Congress will make sure to discuss the need for permanently overturning the VA ban on IVF funding.

To describe what’s needed for the most effective advocacy, Barbara Collura, President/CEO of RESOLVE notes that “members of Congress have asked me and our advocates – ‘Where are the doctors? We need the entire community, including physicians and nurses and embryologists, to come to Advocacy Day. Access to Care is supported by all of us, and showing up and advocating is the best way to see real change happen for our community.”

Mystery of how sperm swim revealed in mathematical formula

Mystery of how sperm swim revealed in mathematical formula

Article provided by Science Daily and The University of York.

Researchers have developed a mathematical formula based on the rhythmic movement of a sperm’s head and tail, which significantly reduces the complexities of understanding and predicting how sperm make the difficult journey towards fertilizing an egg.

Researchers at the Universities of York, Birmingham, Oxford and Kyoto University, Japan, found that the sperm’s tail creates a characteristic rhythm that pushes the sperm forward, but also pulls the head backwards and sideways in a coordinated fashion.

Successful fertility relies on how a sperm moves through fluid, but capturing details of this movement is a complicated issue.

The team aim to use these new findings to understand how larger groups of sperm behave and interact, a task that would be impossible using modern observational techniques. The work could provide new insights into treating male infertility.

Dr Hermes Gadêlha, from the University of York’s Department of Mathematics, said: “In order to observe, at the microscale, how a sperm achieves forward propulsion through fluid, sophisticated microscopic high precision techniques are currently employed.

“Measurements of the beat of the sperm’s tail are fed into a computer model, which then helps to understand the fluid flow patterns that result from this movement.

“Numerical simulations are used to identify the flow around the sperm, but as the structures of the fluid are so complex, the data is particularly challenging to understand and use. Around 55 million spermatozoa are found in a given sample, so it is understandably very difficult to model how they move simultaneously.

“We wanted to create a mathematical formula that would simplify how we address this problem and make it easier to predict how large numbers of sperm swim. This would help us understand why some sperm succeed and others fail.”

By analysing the head and tail movements of the sperm, researchers have now shown that the sperm moves the fluid in a coordinated rhythmic way, which can be captured to form a relatively simple mathematical formula. This means complex and expensive computer simulations are no longer needed to understand how the fluid moves as the sperm swim.

The research demonstrated that the sperm has to make multiple contradictory movements, such as moving backwards, in order to propel it forward towards the egg.

The whip-like tail of the sperm has a particular rhythm that pulls the head backwards and sideways to create a jerky fluid flow, countering some of the intense friction that is created due to their diminutive sizes.

Dr Gadêlha said: “It is true when scientists say how miraculous it is that a sperm ever reaches an egg, but the human body has a very sophisticated system of making sure the right cells come together.

“You would assume that the jerky movements of the sperm would have a very random impact on the fluid flow around it, making it even more difficult for competing sperm cells to navigate through it, but in fact you see well defined patterns forming in the fluid around the sperm.

“This suggests that to achieve sperm stirs the fluid around in a very coordinated way locomotion, not too dissimilar to the way in which magnetic fields are formed around magnets. So although the fluid drag makes it very difficult for the sperm to make forward motion, it does coordinate with its rhythmic movements to ensure that only a few selected ones achieve forward propulsion.”

Now that the team has a mathematical formula that can predict the fluid movement of one sperm, the next step is to use the model for predictions on larger numbers of cells. They also believe that it will have implications for new innovations in infertility treatment.


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Materials provided by University of York. Note: Content may be edited for style and length.

Gene mutation may be linked to unexplained female infertility

Gene mutation may be linked to unexplained female infertility

Article provided by Science Daily and Baylor College of Medicine.

Researchers at Baylor College of Medicine, Texas Children’s Hospital and Rice University have uncovered a gene mutation that may provide answers to unexplained female infertility. The study appears in Scientific Reports, a member of the Nature family of journals.

“Experts cannot identify the cause of the problem in an estimated 10 to 15 percent of couples with infertility and 50 percent of women with recurrent pregnancy loss,” said senior author Dr. Ignatia B. Van den Veyver, professor of obstetrics and gynecology and molecular and human genetics at Baylor, and director of clinical prenatal genetics at Baylor and Texas Children’s Hospital. “Researchers have found that women with mutations that lead to loss-of-function of some of the genes of the NLRP family can fail to reproduce for reasons that may include recurrent loss of pregnancies with abnormally developing placentas, loss of the embryo before implantation, or, more rarely, having a baby with developmental disabilities.”

“Women carrying these mutations are healthy in all other physical aspects, so they are unaware that they have these mutations that do not allow them to carry a pregnancy,” said first author Dr. Sangeetha Mahadevan, a graduate of the Translational Biology and Molecular Medicine program and currently a postdoctoral fellow in the Van den Veyver lab. “To investigate the mechanisms by which the inactivation of the human NLRP2 and NLRP7 genes might affect reproductive success and fertility, we developed a mouse model.”

Mice, however, only carry the Nlrp2 gene, and the researchers hypothesized that it might assume the role of both NLRP2 and NLRP7 in humans.

A closer look at the role of Nlrp2

“When we genetically engineered mice to lack the Nlrp2 gene, the animals looked completely normal. However, when the females mated, we observed three different types of outcomes: some did not get pregnant, others had stillborn pups with abnormalities and a third group of females gave birth to live pups of normal appearance, but fewer per litter. Some of the pups were smaller or larger than expected,” Mahadevan said. “Thus, there was a spectrum of reproductive outcomes when the females lacked the Nlrp2 gene. However, when male mice lacked the gene, there was no impact on fertility or offspring.”

“From prior studies by us and others, we knew that DNA methylation of genes that are normally methylated when the mother passes them on, was absent in pregnancies of women with mutations in the NLRP7 gene,” Van den Veyver said. “Methylation is a small chemical modification on DNA that controls which genes are expressed and which are not.”

In the mouse model lacking the Nlrp2 gene, the scientists also observed abnormal DNA methylation in the offspring, which allowed them to draw stronger parallels between the human and the mouse systems.

Connecting NLRP2, the subcortical maternal complex and fertility

“We were very interested in learning how NLRP2 aids in passing on DNA methylation marks to the next generation,” Van den Veyver said. “Initially we thought we had to focus on the nucleus of the cell and the proteins that carry out methylation there, but instead we discovered that NLRP2 proteins are mostly outside the nucleus. They are part of a large protein complex inside the egg called the subcortical maternal complex.”

The subcortical maternal complex is part of the proteins and other molecules packed inside the egg as it prepares for fertilization. After the egg is fertilized and begins to divide, there is a period of time during which the fertilized cell and early embryo relies heavily on the proteins and other compounds that the egg has stored to carry on essential functions — including DNA methylation — until the embryo can switch on its own genes. These stored compounds are all of maternal origin.

“We also found that when the Nlrp2 gene is absent or inactive in the mother, the subcortical maternal complex does not form properly anymore in the egg and that, in addition, one of the proteins that plays a role in DNA methylation seems not to be in the right place in early embryos,” said Mahadevan. “This might help explain the disturbances in DNA methylation observed in offspring of female mice lacking Nlrp2.”

“Finding NLRP2 proteins in the subcortical maternal complex was not unexpected but this is the first time scientific evidence shows that NLRP2 proteins are part of this important cellular complex, providing more support to the idea that the complex is critical for fertility and embryonic development,” Van den Veyver said.

Implications for in vitro fertilization

The researchers also investigated whether lack of the Nlrp2 gene in mouse eggs would affect their survival when cultured in the lab. This is relevant to in vitro fertilization, a procedure in which eggs are collected and cultured in special conditions in the lab in preparation for fertilization.

“When we attempted to grow the eggs of a female mouse carrying the mutation in the Nlrp2 gene in an artificial environment in the lab, they did not develop,” said Mahadevan. “This finding has implications for in vitro fertilization. It is important to recognize that there will be women who may not be candidates for this procedure because their embryos would likely be unable to grow in culture as a result of the females carrying these mutations in NLRP genes.”

“I think that in addition to establishing a connection with fertility and pregnancy loss, understanding these basic early mechanisms associated with NLRP genes is very important for developmental disorders in general, and particularly for those with DNA methylation abnormalities,” Van den Veyver said. “It is a very rare human condition with a very unique mutation that teaches a lot about different aspects of development.”

 

Smartphone App Helps Diagnose Male Infertility

Smartphone App Helps Diagnose Male Infertility

Article courtesy of Medscape and Science Translational Medicine.

An easy-to-use smartphone-based app could help diagnose male fertility at home, according to a study published today in Science Translational Medicine.

Infertility affects roughly 45 million couples worldwide, and male infertility contributes to more than 40% of those cases. However, men can be uncomfortable with seeking fertility testing in the clinical setting, explained Hadi Shafiee, PhD, the senior author of the study and assistant professor of medicine at Brigham and Women’s Hospital in Boston, Massachusetts. Moreover, clinical testing of semen samples can be expensive, time-consuming, and subjective. These barriers, as well as cultural or social stigma associated with infertility, may prevent many men, especially those in resource-poor settings, from undergoing testing at all.

“We wanted to come up with a solution to make male infertility testing as simple and affordable as home pregnancy tests,” said Dr Shafiee in a press release. “This test is low-cost, quantitative, highly accurate and can analyze a video of an undiluted, unwashed semen sample in less than five seconds.”

To do this, Dr Shafiee and colleagues developed a mobile phone app that uses the phone’s camera and an inexpensive microfluidic device to measure sperm concentration and motility, along with a device to position and illuminate the sperm-containing sample. The total materials cost for the device was less than $5.

The researchers tested the device on 350 semen specimens from a fertility clinic and compared the results to those of traditional laboratory-based semen testing. They found that according to World Health Organization guidelines for assessing semen quality, the device was about 98% accurate. They also showed that the device performed well with both trained and untrained users.

The study was thoughtful and well carried out, said Michael L. Eisenberg, MD, director of male reproductive medicine and surgery at Stanford University School of Medicine in California.

The app is one of a growing number of devices in development that aim to provide at-home fertility testing for men, Dr Eisenberg told Medscape Medical News. He noted that many at-home fertility tests and ovulation tracking devices are available for women, but men “are largely ignored.” In fact,  about 20% to 25% of the time, US men who are in a couple experiencing infertility are never evaluated, he said. But at-home testing could help boost the number of men who are assessed.

“It lowers the barriers,” Dr Eisenberg said.

While he didn’t think such tests would replace traditional fertility care, Dr Eisenberg said the tests might act as a preliminary male fertility screen to alert couples of a problem early on and allow them to seek help. They might also allow men to longitudinally track their semen quality. He noted that some other apps in development provide men with assessments of habits that can affect fertility and recommend changes.

“There are a lot of things men do that can impact fertility,” Dr Eisenberg said. “As men work to improve their health, they can improve semen quality over time.”

The authors also suggest that the device could help make male infertility testing accessible and affordable in resource-poor settings and eliminate the need for expensive laboratory testing.

It might also be useful for home monitoring of sperm levels after vasectomy. Currently, such follow-up testing is recommended to ensure the success of the procedure, but many man don’t follow through on the testing, Dr Shafiee and colleagues write.

Dr Eisenberg cautioned that if the test is used to track semen after vasectomy, it should be made clear that men are looking to have nonmoving sperm, not just a sperm count below a particular threshold.

Although the app tested by Dr Shafiee and colleagues is still in an early phase of development, Dr Eisenberg noted other products closer to becoming available. In the long term, he said, the growing availability of male fertility tests would help to raise awareness among the public and physicians, just as the growing availability of medications to treat erectile dysfunction has boosted awareness about the condition and its treatment.

“A lot more people will learn there are options and things you can do about it,” he said.

Dr Hadi Shafiee and Brigham and Women’s Hospital hold a patent on their home semen evaluation technology. The other authors have disclosed no relevant financial relationships. Dr Eisenberg has served as an advisor for several companies with reproductive products: Sandstone Diagnostics, Glow, Embraceher, and Reprovantage.

Sci Transl Med. Published online March 22, 2017. Abstract