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Fertility, Men's Health, Research, Sleep

Sleep apnea linked with male infertility

Sleep apnea linked with male infertility

14258396551_0d3b8edb81_zOver the past two decades, there have been a number of studies suggesting that men’s sperm counts have been steadily declining. Now research out of Spain and published in the journal Sleep suggests a connection between sleep apnea and decreased sperm production.

Michael Eisenberg, MD, a Stanford expert in male fertility, thinks the results are important but inconclusive. When reached for comment he told me:

My research focuses on the links between a man’s overall health and his reproductive health, so this study has a lot of connections. I think it shows another health factor that can impact fertility; we are seeing sleep apnea more and more commonly, and here’s something showing a link with decreased sperm production. A big drawback of the study is that before we can incorporate it in clinical practice the research needs to be replicated in humans.

The research, conducted collaboratively by research institutions in Spain, induced intermittent hypoxia (lack of oxygen) in male mice to mimic sleep apnea. These mice, along with a control group who had been experiencing normal oxygen levels, were mated, and researchers compared the numbers of pregnant females and fetuses, which were significantly lower for the hypoxic group.

Previously: Male infertility can be warning of hypertension, Stanford study finds, Poor semen quality linked to heightened mortality rate in men and Low sperm count can mean increased cancer risk
Photo by Kelsey

Big data, Cancer, Cardiovascular Medicine, Fertility, Men's Health, Research, Stanford News

Male infertility can be warning of hypertension, Stanford study finds

Male infertility can be warning of hypertension, Stanford study finds

sperm graffitiA study of more than 9,000 men with fertility problems links poor semen quality to a higher chance of having hypertension and other health conditions. The findings suggest that more-comprehensive examinations of men undergoing treatment for infertility would be a smart idea.

About a quarter of the adults in the United States (and in the entire world) have hypertension, or high blood pressure. Although it’s the most important preventable risk factor for premature death worldwide, hypertension often goes undiagnosed.

In a study published today in Fertility and Sterility, Stanford urologist Mike Eisenberg, MD, PhD, and his colleagues analyzed the medical records of 9,387 men, mostly between 30 and 50 years old, who had provided semen samples in the course of being evaluated at Stanford to determine the cause of their infertility. The researchers found a substantial link between poor semen quality and specific diseases of the circulatory system, notably hypertension, vascular disease and heart disease.

“To the best of my knowledge, there’s never been a study showing this association before,” Eisenberg told me when I interviewed him for a press release about the findings. “There are a lot of men who have hypertension, so understanding that correlation is of huge interest to us.”

In the past few years, Eisenberg has used similar big data techniques to discover links between male infertility and cancer and heightened overall mortality, as well as between childlessness and death rates in married heterosexual men.

Eisenberg sums it all up and proposes a way forward in the release:

Infertility is a warning: Problems with reproduction may mean problems with overall health … That visit to a fertility clinic represents a big opportunity to improve their treatment for other conditions, which we now suspect could actually help resolve the infertility they came in for in the first place.

Previously: Poor semen quality linked to heightened mortality rate in men, Men with kids are at lower risk of dying from cardiovascular disease than their childless counterparts and Low sperm count can mean increased cancer risk
Photo by Grace Hebert

Fertility, Research, Women's Health

PCOS linked with higher risk of type 2 diabetes even in young women who are not overweight, study finds

PCOS linked with higher risk of type 2 diabetes even in young women who are not overweight, study finds

Women with polycystic ovarian syndrome, which is present in 5 to 10 percent of women of childbearing age and is associated with reproductive and metabolic dysfunction, may be at higher risk for type 2 diabetes. Previous research has shown this correlation in women who are also overweight; now, an Australian study has shown that even young women with PCOS who are not overweight may be at a significantly higher risk for developing diabetes.

From a release:

Over 6000 women aged between 25-28 years were monitored for nine years, including 500 with diagnosed PCOS. The incidence and prevalence of type 2 diabetes was three to five times higher in women with PCOS. Crucially, obesity, a key trigger for type 2 diabetes, was not an important trigger in women with PCOS.

The women studied were aged 25-28 in 2003 and were followed over 9 years until age 34 to 37 years in 2012.

Findings from the large-scale epidemiological study were presented at the recent joint meeting of the International Society of Endocrinology and the Endocrine Society in Chicago.

“Our research found that there is a clear link between PCOS and diabetes,” study author Helena Teede, PhD, said in the release. “However, PCOS is not a well-recognised diabetes risk factor and many young women with the condition don’t get regular diabetes screening even pre pregnancy, despite recommendations from the Australian PCOS evidence based guidelines.”

Previously: Study shows bigger breakfast may help women with PCOS manage symptoms and NIH study suggests progestin in infertility treatment for women with PCOS may be counterproductive

Cancer, Fertility, Parenting, Pregnancy, Women's Health

A cancer survivor discusses the importance of considering fertility preservation prior to treatment

pregnancy_testBack in 1998, Joyce Reinecke, JD, was on a cross-country business trip when her increasing fatigue and lightheadedness resulted in her being admitted to the emergency room and the discovery that she had tumors in her stomach, one of which was necrotic and bleeding causing her to be severely anemic. She was diagnosed with leiomyosarcoma, and the tumors, as well as all of the surrounding lymph nodes, were surgically removed. Before she was discharged from the hospital an oncology fellow casually mentioned to Reinecke that since she was scheduled to start chemotherapy she might want to consider options to preserve her fertility.

At the time, Reinecke and her husband hadn’t considered how her treatment would affect their future plans to have a family. The couple eventually decided to complete a round of in vitro fertilization and work with an agency to select a gestational carrier. Their twin daughters were born in February 2000. Reinecke, executive director of the Alliance for Fertility Preservation, shared her patient perspective during a keynote speech at the Family Building After Cancer: Fertility Preservation and Future Options Symposium held at Stanford earlier this month.

To continue the conversation, I reached out to Reinecke about the issue of fertility and cancer survivorship. In the following Q&A, she discusses advancements in the field, why patients need to be proactive in sharing their wishes to have a family with providers, and questions to consider prior to treatment.

What motivated you to focus your career on expanding patient and provider awareness of fertility preservation?

When my girls were around two, I received several inquiries from family acquaintances who had young adults in their lives who were newly diagnosed with cancer. These people had reached out to my parents, to try to understand more about what I had done, where I had gone, etc. in order to preserve my fertility. In speaking to others and hearing about their challenges in finding fertility information and services, I started to really feel that something about the status quo was not right. These patients/family members had learned about possible infertility because they knew of my story, not because their doctors had discussed it with them. This really emphasized to me that my situation – learning about my possible infertility in a very ad hoc way – was not unique, not unusual, but the norm, and perhaps, lucky.

I began doing research around the issue, to see what was out there, what information was available online, etc. I found very little, but I did stumble upon information that Fertile Hope was having a fundraiser. I was in complete shock that a new nonprofit focused on this very issue existed, not to mention that it was based in New York. I went to the fundraiser, signed up to volunteer, met with Lindsay Beck, and signed on as Employee #2. The rest is history.

A past study shows that less than half of U.S. physicians are following the American Society of Clinical Oncology’s guidelines suggesting all patients of childbearing age be informed about fertility preservation. How can patients make sure they get the necessary information about their fertility options prior to treatment?

This question is tricky, because I feel like the onus for initiating this discussion has to be on the provider. Newly diagnosed patients are overwhelmed with all sorts of medical information and decisions to make, not to mention the emotional distress of the diagnosis. Also, patients don’t know what they don’t know. Sometimes providers mistakenly believe a patient isn’t interested in fertility preservation because they don’t ask about it. However, providers have to remember that newly diagnosed young adults probably have very little understanding about how chemotherapy and radiation work – unless they have a cancer that has a direct impact on their reproductive system they probably have no inkling that their fertility is at stake.

That being said, patients need to advocate in their own interest (or enlist a family member to help them do this if they cannot during this difficult time). That means communicating their wishes and values about future parenthood with their providers. That means asking the right questions: Will I be able to have children in a few years? Ever? What can I do about it? It might also mean being able to challenge their doctor’s disapproval or ask that treatment be pushed back [so the patient has time to] bank sperm or eggs. Which is sometimes hard to do.

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Fertility, Health and Fitness, Men's Health, Public Health, Research, Stanford News

Poor semen quality linked to heightened mortality rate in men

Poor semen quality linked to heightened mortality rate in men

sperm graffitiMen with multiple defects in their semen appear to be at increased risk of dying sooner than men with normal semen, according to a study of some  12,000 men who were evaluated at two different centers specializing in male-infertility problems.

In that study, led by Michael Eisenberg, MD, PhD, Stanford’s director of male reproductive medicine and surgery, men with more than one such defect such as reduced total semen volume, low sperm counts or motility, or aberrant sperm shape were more than twice as likely to die, over a seven-and-a-half-year follow-up period, than men found to be free of such issues.

Given that one in seven couples in developed countries encounter fertility problems at some point, Eisenberg told me, a two-fold increase in mortality rates qualifies as a serious health issue. As he told me for an explanatory release I wrote about the study:

“Smoking and diabetes — either of which doubles mortality risk — both get a lot of attention… But here we’re seeing the same doubled risk with male infertility, which is relatively understudied.”

Moreover, the difference was statistically significant, despite the fact that relatively few men died, due primarily to their relative youth (typically between 30 and 40 years old) when first evaluated. And the difference persisted despite the researchers’ efforts to control for differences in health status and age between the two groups.

Eisenberg has previously found that childless men are at heightened risk of death from cardiovascular disease and that men with low sperm production face increased cancer risk.

Previously:  Men with kids are at lower risk of dying from cardiovascular disease than their childless counterparts and Low sperm count can mean increased cancer risk
Photo by Grace Hebert

Fertility, Women's Health

Mother's Day and not-by-choice non-mothers

Mother's Day and not-by-choice non-mothers

mother's day partyThe fictional character Bridget Jones drew melancholy in the presence of “smug marrieds” as a single woman. I thought of her term, and other ways experience shapes one’s perspective and perceived status in social interactions, when reading a CommonHealth blog post today by guest contributor and executive producer Karen Shiffman.

Shiffman explains why, through no fault of the happy parents, someone else’s celebration can feel particularly abrasive to the childless-not-by-choice around Mother’s Day. Whether because of infertility, previous illness, divorce or other reasons for not becoming pregnant, or losing a child through miscarriage, death or estrangement, she writes, Mother’s Day isn’t “flowers, manicures, homemade cards” to every woman.

From the piece:

…For me, Mother’s Day is the hardest date on the calendar: I can’t have children and will never be a biological mother. Bad genes, bad luck and a huge cancer scare a while back left me without a womb and a few other body parts.

…As Mother’s Day approached, I didn’t do much better. My family went out for a celebratory brunch; I stayed home. I said it was too painful to be out with all those happy moms and families. I took my mother out to dinner later that week.

She later advises: “So on Mother’s Day, celebrate to the hilt. And the week after, check in on a friend who might have struggled that day.”

Previously: An in-depth look at fertility and cancer survivorshipStudy highlights fertility-related concerns of young cancer survivorsA need to provide infertility counseling to cancer patients and Ask Stanford Med: Director of Female Sexual Medicine Program responds to questions on sexual health
Photo by Quinn Dombrowski

Fertility, Men's Health, Research, Stanford News

Researchers create primordial germ cells from stem cells of infertile men

Researchers create primordial germ cells from stem cells of infertile men

New research from Stanford and Montana State University shows that stem cells made from the skin of adult, infertile men can be used to create primordial germ cells, which are cells that normally become sperm, when transplanted into the reproductive system of mice.

The findings hold the potential to shed light on the earliest steps of human reproduction and could lead to the development of future therapies for men diagnosed with azoospermia, the most severe form of male factor infertility, or those rendered sterile after cancer treatments. My colleague Krista Conger explains the work in a release:

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

The germ cells made from stem cells stopped differentiating in the mice before they produced mature sperm (likely because of the significant differences between the reproductive processes of humans and mice) regardless of the fertility status of the men from whom they were derived. However, the fact that the infertile men’s cells could give rise to germ cells at all was a surprise.

Previous research in mice with a similar type of infertility found that although they had germ cells as newborns, these germ cells were quickly depleted. The Stanford findings suggest that the infertile men may have had at least a few functioning germ cells as newborns or infants. Although more research needs to be done, collecting and freezing some of this tissue from young boys known to have this type of infertility mutation may give them the option to have their own children later in life, the researchers said.

The findings were published today in Cell Reports.

Previously: Stanford researchers work to increase the odds of in vitro fertilization success and New York Times shows how Stanford researchers solved the “egg maturation puzzle”

Ethics, Fertility, Genetics, In the News, Pregnancy, Stanford News

Daddy, mommy and ? Stanford legal expert weighs in about "three parent" embryos

Daddy, mommy and ? Stanford legal expert weighs in about "three parent" embryos

3519855504_9000d95a2aIt’s an interesting question that got a lot of traction in the media last week. Does the contribution of a tiny amount of DNA from a third person during in vitro fertilization really mean that the resulting child would have three genetic parents? Researchers in Oregon have proposed the technique as a way to avoid genetic diseases arising from faulty mitochondrial DNA by replacing an egg’s mitochondria with one from a second, healthy woman either before or after fertilization with a man’s sperm. They’ve shown that it works in monkeys, and the FDA met last week to consider whether the technique is safe enough to be used in humans.

Yesterday, Stanford law professor and bioethicist Hank Greely, JD, posted a great analysis of the topic on the university’s Law and Biosciences blog, complete with an elegant explanation of the problem for women with mitochondrial DNA mutations:

The mitochondria (high school biology’s “energy powerhouses of the cell”) have their own very short stretch of DNA, separate from the 6.8 billion base pairs found on 46 chromosomes in the cell’s nucleus (the nuclear DNA).  The 16,569 base pairs of the mitochondrial DNA (hereafter “mtDNA”) hold 37 (some say 38) genes, providing instructions for making 13 (or 14) proteins and another 24 RNA molecules.  The full importance of these genes is unknown, but it is clear that some (happily rare) variations in the mtDNA cause quite severe illnesses. Unfortunately, each child gets all of its mitochondria (and hence its mtDNA) in the egg from its mother; if the mother’s mtDNA is dangerously flawed, so will be the mtDNA of all her children. With almost all other genetic diseases, no matter how inevitably the “bad” genetic variation leads to a disease (how “penetrant” the genetic variation is), a woman will have only a 50% or 25% chance of passing on the condition.  With these, her genes can give rise to no healthy children.

Greely gets at the heart of the matter when he compares the statistically minute contribution from the donated mitochondria to a hypothetical child he calls Heather:

I have DNA from four people in each of my cells:  my mother’s mother, my mother’s father, my father’s mother, and my father’s father. Actually, my DNA really came from all eight of my great-grandparents, and all 1024 of my great great great great great great great great grandparents, and all roughly one million of my great (18) grandparents. Yes, all that DNA passed through my (genetic) parents before coming to me, but why does that matter?

Heather gets her DNA from more than two people a bit differently from the way the rest of us do, but so what? How does getting what is, in effect, “gene therapy,” where the gene is delivered in a natural package called the mitochondrion, turn our hypothetical (and healthy) child into a powerful argument against the procedure?

It shouldn’t.  Heather will not be getting superpowers, she will not be in any meaningfully way “designed” (except to avoid a nasty genetic disease), and she will not be given a newly made DNA sequence never before found in the human gene pool. She will get mitochondria with mtDNA that will allow her to have normal health, not a grave disease. That mtDNA will have been taken from a woman, who, though not a source of Heather’s nuclear DNA, is certainly a participant in the human gene pool.

“Heather has three parents” is NOT an argument. It is an irrelevant but attention-getting slogan that is uncritically put forward as, and sometimes mistaken for, a real argument. Yes, the proposed process is a way of bringing forth living and healthy babies that is somewhat new and different, but so were obstetric forceps, (safe) C-sections, and in vitro fertilization. Novelty is not, in itself, a respectable argument against it.

Previously: Medical practice, patents and “custom children”: A look at the future of reproductive medicine, Five million babies and counting: Stanford expert offers conversation on reproductive medicine and Stanford researchers work to increase the odds of in vitro fertilization success
Photo by Christian Pichler

Clinical Trials, Fertility, NIH, Research, Women's Health

Testosterone therapy not effective for primary ovarian insufficiency-related depression, study finds

Testosterone therapy not effective for primary ovarian insufficiency-related depression, study finds

Primary ovarian insufficiency (POI), a condition affecting approximately 1 percent of women and teenage girls in the U.S., is characterized by ovaries that stop functioning normally before a woman is 40. POI may be a cause for irregular periods, reduced fertility, or health problems such as osteoporosis, and women with POI may also be at risk for depression and decreased quality of life. Treatments for POI may include hormone replacement therapy to restore estrogen and progesterone levels.

A recent study from the National Institutes of Health Clinical Center has examined the effect in women with POI of one year of hormone treatment that included testosterone.

From a release:

In the randomized, double-blind, placebo controlled study, 61 women used placebo patches and 67 women used patches that delivered 150 micrograms of testosterone a day, similar to the Intrinsa patch that was rejected by FDA as a treatment for low sexual desire in women.

After 12 months, testosterone levels were back up to normal for the women who got the treatment. The investigators saw no detrimental effects of testosterone, but they found no significant improvement either in measurements of quality of life, self esteem and mood compared with placebo.

Bringing testosterone back to normal doesn’t help these aspects of life, suggesting that it’s something other than testosterone that plays a role in mood problems for women with POI, concluded the researchers.

“This study makes an important contribution toward understanding what testosterone can and cannot do. With all the hype about testosterone and aging, it is important that the public have the facts,” NAMS Executive Director Margery Gass, MD, said in the release.

The study was published online in the journal Menopause.

Previously: An in-depth look at fertility and cancer survivorshipAsk Stanford Med: Expert in reproductive medicine responds to questions on infertility, Researchers describe procedure that induces egg growth in infertile women and Oh, baby! Infertile woman gives birth through Stanford-developed technique

Cancer, Fertility, Research, Stanford News, Women's Health

An in-depth look at fertility and cancer survivorship

An in-depth look at fertility and cancer survivorship

Pregnant_woman2The physical and emotional after-effects of cancer treatment – things like fatigue, pain and depression – have been well-documented. And because some treatments cause havoc on parts of the body’s reproductive system, younger patients often must also contend with fertility issues.

In a paper recently published online in CA: A Cancer Journal for Clinicians, a group of Stanford researchers review the existing literature on fertility and cancer survivorship. The topic, they explain, is an increasingly important one, given that around 9 percent of patients diagnosed with cancer in the United States are younger than 45 years old and that infertility has been shown to negatively impact quality of life among cancer survivors. They write:

The distress resulting from the interruption of fulfilling one’s reproductive goals as a result of a cancer diagnosis and treatment  persists several years after the diagnosis, particularly for those who never conceive.

The goal of the review, which was led by Lynn Westphal, MD, associate professor of obstetrics and gynecology, was to aid in pre- and post-treatment fertility counseling for patients. In their lengthy article, Westphal and her colleagues summarize what is known about infertility and survivorship – and what we still need to study further. Among the information shared about patients’ reproductive health and the health of their offspring:

  • Since it varies with type of treatment and patient age, among other things, there isn’t an accurate estimate of women’s risk of infertility or primary ovarian insufficiency after cancer treatment. But, the researchers write, studies have shown the incidence of acute ovarian failure or premature menopause among childhood cancer survivors varies from 6 to 12 percent.
  • In the landmark Childhood Cancer Survivor Study, exposure of the ovaries to radiation was shown to be to be one of the highest risks for acute ovarian failure and premature menopause in women.
  • In several studies comparing pregnancies in cancer survivors with those in the general population, “the vast majority of pregnancies occurring in cancer survivors are routine  and uneventful.” But patients who have undergone abdominal or pelvic radiotherapy are known to face a higher risk of preterm birth, low birth-weight offspring, stillbirth and early neonatal death.
  • Testicular and hematologic malignancies are the most common cancers that are associated with impaired sperm production in men.
  • Recent estimates suggest that up to two-thirds of all pediatric cancer survivors will face male germ cell dysfunction.
  • For most cancer survivors, there is no increase in cancer or birth defects in their children. One study comparing more than 2,100 offspring of cancer survivors with more than 4,500 offspring of controls in the United States found no difference in birth defects between the two groups.

The authors discuss specific types of fertility preservation, including egg and embryo freezing, and note that techniques to help survivors have children have improved over the past decade. Yet, they write, only “a subset of oncologists discuss the gonadotoxic effects of cancer treatments with patients of reproductive age, and even fewer refer them for fertility preservation consultations.”

In light of research showing that treatment-related infertility is significantly associated with depressive symptoms among survivors, Westphal and her colleagues encourage clinicians to address these issues – and the options – with their patients.

“Discussion of the changes to a patient’s reproductive health after cancer treatment is essential to providing comprehensive quality care,” they conclude.

Previously: Study highlights fertility-related concerns of young cancer survivorsUnique challenges face young women with breast cancer and A need to provide infertility counseling to cancer patients
Photo by Canwest News Service

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