Antioxidants to increase sperm count

Everyday chemicals may be lowering your sperm count, scrambling DNA sperm data, or causing sperm mobility problems. Antioxidants can prevent toxic substances from killing your sperms, you can find AGELOC family of supplements (zinc, vitamin C, Vitamin B complex, Vitamin D) here that resets your gene expression to a younger you:

http://www.clubalthea.pxproducts.com

Antioxidants—In addition to Dr. Clark’s study above, other studies have confirmed the benefits of antioxidants for male reproductive health. According to researchers at the University of Portsmouth, one bowl of tomato soup—which is high in lycopene—per day can boost a man’s fertility up to 12 percent. It’s believed that antioxidants may remove free radicals that have a negative impact on sperm.

You might already know that narrow bike seats and antidepressants can cause problems. MSN lists seven more you might not have heard about:

1. Cash register receipts

About 40 percent of receipts are coated with bisphenol-A (BPA), which has been linked to fertility problems and low sperm count and quality.

2. Canned food

The biggest source of BPA contamination is food packaging; almost all metal cans are coated with a BPA resin.

3. Sex toys

Sex toys made of out vinyl contain phthalates, which are linked to cancer, allergies, birth defects, and infertility.

4. Your shower

Phthalates are also found in scented soaps, shampoos, and cleaners — and in vinyl shower curtains.

5. Chemical-laced produce

Pesticides are meant to kill insect, but they can also affect your sperm.

6. Heated car seats

Heated car seats and heating pads increase testicular temperatures enough to decrease sperm production.

7. Contaminated fish

PCBs are a type of banned chemical, but enough remain in the environment to accumulate in fish.
Dr. Mercola’s Comments:
Infertility is more common than you might think these days. An estimated 1 in 6 American couples struggle with getting pregnant each year and there’s compelling evidence that lifestyle is in large part to blame.

Not only are you exposed to hundreds (if not thousands) of toxins each and every day, but some of the most commonly-prescribed drugs, poor diet, and common vitamin deficiencies have also been linked to reduced fertility, just to name a few.

The MSN article above primarily focuses on endocrine-disrupting chemicals (EDCs), which affect your hormones and have been shown to cause reproductive problems in both men and women. I will review these below, and then expand on several other commonly-ignored factors that contribute to rising infertility rates.

Two of the Most Common Chemicals Linked to Reproductive Problems
Hormone-disrupting chemicals are profoundly pervasive in today’s modern world. They lurk in personal care products, food containers, medical tubing, toys and more. Bisphenol-A (BPA) and phthalates are two of the most well known culprits.

Bisphenol A (BPA)

BPA is a common ingredient in many plastics, including those in water bottles and children’s toys, as well as the lining of most canned goods. It was recently discovered that even many cash register receipts contain this chemical.

BPA is so pervasive it has been detected in the umbilical cord blood of 90 percent of newborn infants tested!

Recent studies have confirmed suspicions that BPA is affecting male fertility, primarily by reducing semen quality. One such study, which provides the first epidemiological evidence of an adverse effect on semen quality, was published in the journal Fertility and Sterility. The study included 218 men with and without BPA exposure in the workplace, in four regions of China.

The researchers found that higher urine levels of BPA were significantly associated with:

Decreased sperm concentration
Decreased total sperm count
Decreased sperm vitality
Decreased sperm motility
Compared with those who did not have detectable levels, the men with detectable levels of BPA had more than:

three times the risk of lowered sperm concentration and lower sperm vitality
four times the risk of lower sperm count
twice the risk of lower sperm motility
According to the authors:

“Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population.”

In women, BPA can also reduce your chances of successful in vitro fertilization (IVF) by interfering with ococyte (immature egg cell) quality. Two recent studies attest to this. One, published last December, found an inverse association between BPA concentration and normal fertilization, and the other, published earlier last year found that “BPA was detected in the urine of the majority of women undergoing IVF, and was inversely associated with number of oocytes retrieved and peak estradiol levels.”

Phthalates

Phthalates are another group of chemicals that wreak havoc with your reproductive health. Exposure to phthalates can lead to incomplete testicular descent in fetuses, reduced sperm counts, testicular atrophy or structural abnormality and inflammation in newborns.

Phthalates are commonly found in vinyl flooring, detergents, automotive plastics, soap, shampoo, deodorants, fragrances, hair spray, nail polish, plastic bags, food packaging, garden hoses, inflatable toys, blood-storage bags, intravenous medical tubing, and yes, even sex toys, as pointed out by MSN.

Other Common Chemicals Linked to Fertility Problems
While BPA and phthalates have gotten most of the media attention, there are a number of chemicals that fall into this harmful category. Others to look out for include:

Perfluorooctanoic acid (PFOA) — Found in grease- and water-resistant coatings like Teflon and Gore-Tex, is a likely carcinogen.
Methoxychlor and Vinclozin– An insecticide and a fungicide respectively, have been found to cause changes to male mice born for as many as four subsequent generations after the initial exposure.
Nonylphenol ethoxylates (NPEs) — Known to be potent endocrine disrupters, these chemicals affect gene expression by turning on or off certain genes, and interfere with the way your glandular system works. They mimic the female hormone estrogen, and have been implicated as one reason behind some marine species switching from male to female.
Bovine growth hormones commonly added to commercial dairy have been implicated as a contributor to premature adolescence.
Non-fermented soy products, which are loaded with hormone-like substances.
MSG — A food additive that’s been linked to reduced fertility.
Fluoride — This chemical in the U.S. water supply has been linked to lower fertility rates, hormone disruption and low sperm counts.

Vitamin D Deficiency Linked to Infertility

As I mentioned at the beginning of this article, toxic chemicals are not the only factors that play a part in rising infertility rates. In recent years, researchers have also identified vitamin D as an integral part of men’s reproductive health.

You may have heard that pregnant women are advised to get more vitamin D to promote fertility and ensure a healthy baby, but vitamin D is equally important for the father-to-be!

One 2008 infertility study revealed that vitamin D deficiency is common among men who are unable to impregnate their partners—almost a third of the 800 infertile men included in the study had lower than normal levels of vitamin D.

(Bear in mind here that “normal” does not equal “optimal.” So, by optimal standards, the rate of vitamin D deficiency was likely far higher than one-third.)

According to lead researcher Dr. Anne Clark, a fertility specialist:

“Vitamin D and folate deficiency are known to be associated with infertility in women, but the outcomes of the screening among men in our study group came as a complete surprise. Men in the study group who agreed to make lifestyle changes and take dietary supplements had surprisingly good fertility outcomes.”

In fact, of the 100 men who agreed to make and maintain certain lifestyle changes for three months prior to fertility treatment, 11 of them went on to achieve pregnancy naturally, without IVF treatment.

Lifestyle changes included quitting smoking, minimizing intake of caffeine and alcohol, weight reduction, along with a course of vitamins and antioxidants.

“The results clearly show that lifestyle changes and dietary supplements can be beneficial for the conception of a healthy on-going pregnancy,” Dr Clark said.

Another study published in November 2009 confirms these results as researchers discovered that human sperm does in fact have a vitamin D receptor.

Analysis also indicated that vitamin D is produced locally in the sperm, which suggests that vitamin D may be involved in the signaling between cells in the reproductive system. According to the authors, the study revealed “an unexpected significance of this hormone [vitamin D] in the acquisition of fertilizing ability,” and the results imply that vitamin D is involved in a variety of sperm signaling pathways.

Fertility – What Does Vitamins Have to Do With It?
So, it now seems quite clear you can add infertility to the list of health ailments that are made worse by too little sun exposure. But other vitamins and minerals can also be helpful in this area.

For example, did you know that vitamin C increases sperm quality and mobility?

Vitamin C — In one study, infertile men who were given 1,000 mg of vitamin C twice daily improved their sperm count, sperm motility, and sperm morphology.

The researchers stated vitamin C could be important as an additional supplement to improve semen quality and increase chances of a natural conception. Vitamin C is abundant in oranges, strawberries and sweet potatoes.

Vitamin E & Selenium — Vitamin E and selenium can also improve sperm motility. One study published in the Archives of Andrology confirmed the protective and beneficial effects of vitamin E and selenium on semen quality, and supported their use in male infertility treatment.

Men who are deficient in vitamin B12 can also suffer from poor motility (where the sperm don’t swim very well) so it is thought that taking this vitamin may be helpful as well.

Zinc — If low testosterone is the cause, zinc may help. In one study, 37 infertile men were given 60mgs of zinc a day for six weeks. 22 of the men with low testosterone dramatically increased their sperm counts and their testosterone, and 9 out of the 22 spouses became pregnant during the study. Good sources of zinc include nuts and seeds.

Antioxidants—In addition to Dr. Clark’s study above, other studies have confirmed the benefits of antioxidants for male reproductive health. According to researchers at the University of Portsmouth, one bowl of tomato soup—which is high in lycopene—per day can boost a man’s fertility up to 12 percent. It’s believed that antioxidants may remove free radicals that have a negative impact on sperm.

As usual, if you want to try the vitamin therapy approach, I recommend you try to get most of your vitamins naturally, from the food you eat. A whole food diet based on your nutritional type, and avoiding processed foods, is the best way to ensure you’re getting sufficient amounts of essential vitamins and minerals.

In the case of vitamin D, your best source is sun exposure. However, during winter months you may need to take a supplement, or use a safe tanning bed to maintain optimal vitamin D levels.

You should also be aware that certain drugs can interfere with your vitamin D absorption and metabolism, including cholestyramine (Questran), Dilantin, and phenobarbital. Additionally, because vitamin D is a fat-soluble vitamin, any drug or substance that interferes with fat absorption may cause problems, as may a low-fat diet.

Diet, Weight and Infertility

As I’ve mentioned before, insulin resistance is an underlying factor responsible for most chronic disease, and it should come as no surprise that it plays a role in fertility as well, for men and women alike.

One 2008 paper published in the Journal of Andrology explains how metabolic syndrome (characterized by obesity and insulin resistance) is connected with reduced fertility as follows:

“Adverse effects of obesity on male fertility are postulated to occur through several mechanisms. First, peripheral conversion of testosterone to estrogen in excess peripheral adipose tissue may lead to secondary hypogonadism through hypothalamic-pituitary-gonadal axis inhibition. Second, oxidative stress at the level of the testicular microenvironment may result in decreased spermatogenesis and sperm damage. Lastly, the accumulation of suprapubic and inner thigh fat may result in increased scrotal temperatures in severely obese men.”

Celiac disease (gluten intolerance) has also been linked to fertility problems in both sexes. In men, it’s associated with abnormal sperm, such as lower sperm numbers, altered shape, and reduced function. Men with untreated celiac disease may also have lower testosterone levels.

As with any other health problem, optimizing your insulin levels is very important for fertility, as is identifying potential gluten intolerance.

The treatment strategy for both is to reduce or eliminate grains along with sugars, especially fructose.

Some Drugs Can Also Cause Infertility

Prescription drugs can also throw a wrench in the works when you’re trying to conceive. While statin drugs have been shown to reduce your ability to achieve orgasm, especially in men, other drugs are known to cause infertility.

SSRI antidepressants are particularly notorious, and studies have linked SSRI’s with reduced sperm count and motility. Common side effects of many antidepressants also include impotence and delayed ejaculation.

How to Protect Your Reproductive Health
As you can see, there’s no shortage of assailants on your reproductive health, from diet and vitamin deficiencies to drugs, to a plethora of toxic exposures. If you’re planning a pregnancy, all of these are issues you’ll want to pay attention to.

And then there’s the issue of electromagnetic fields (EMF), which can also harm sperm quality! I haven’t even touched on that issue here, but you can read more about it in this previous article.

Optimizing your vitamin D levels, modifying your diet to normalize your insulin levels (i.e. avoid sugar/fructose/grains), and avoiding harmful drugs are a given. But how do you protect yourself from the onslaught of toxic chemicals?

It can seem like an impossible task, but there are a number of practical strategies you can implement to limit your exposure to endocrine disruptors and other common toxins. Here are one dozen practical measures you can take to protect yourself and your family from common toxic substances that may wreak havoc with your reproductive health:

As much as possible, purchase and consume organic produce and free-range, organic foods to reduce your exposure to pesticides and fertilizers.
Rather than eating conventional or farm-raised fish, which are often heavily contaminated with EDCs, PCBs and mercury, supplement with a high-quality purified fish or krill oil, or eat fish that is wild-caught and lab tested for purity.
Eat mostly raw, fresh foods, steering clear of processed, prepackaged foods of all kinds. This way you automatically avoid hidden fructose and artificial food additives of all kinds, including dangerous artificial sweeteners, food coloring and MSG.
Store your food and beverages in glass rather than plastic, and avoid using plastic wrap.
Have your tap water tested and, if contaminants are found, install an appropriate water filter on all your faucets (even those in your shower or bath).
Only use natural cleaning products in your home.
Switch over to natural brands of toiletries such as shampoo, toothpaste, antiperspirants and cosmetics. The Environmental Working Group has a great safety guide to help you find personal care products that are free of phthalates and other potentially dangerous chemicals. I also offer one of the highest quality organic skin care lines, shampoo and conditioner, and body butter that are completely natural and safe.
Avoid using artificial air fresheners, dryer sheets, fabric softeners or other synthetic fragrances.
Replace your Teflon pots and pans with ceramic or glass cookware.
When redoing your home, look for “green,” toxin-free alternatives in lieu of regular paint and vinyl floor coverings.
Avoid using pesticides and herbicides around your home, and opt for organic varieties instead.
Replace your vinyl shower curtain with one made of fabric or install glass shower doors.

Increasing Rates of Male Infertility + 5 Natural Remedies

Dr Axe

Male infertility - Dr. AxeIs a Western lifestyle to blame for increased rates of male infertility? All signs are pointing to yes. According to a recent report, sperm counts of men in North America, Australia, Europe and New Zealand have dropped by more than 50 percent in less than four decades, and show no signs of stopping.

Why is this occurring? And can be stopped/slowed down by adopting natural infertility treatments?


Increasing Rate of Male Infertility: What the Study Says

Researchers originally examined more than 7,500 studies published that looked at sperm counts and concentrations between 1973 and 2011. (1) Then, they conducted a meta-analysis of the 185 studies that met their criteria. These included studies of men who either didn’t know if they were fertile — like they’d never tried to have kids — and those who were known to be fertile. They eliminated any studies where men were suspected of being infertile. The studies were spread over the time period and included nearly 43,000 men in 50 different countries.

The findings were startling. The analysis found there was an almost 60 percent decline in the total sperm count over the nearly four decades. Importantly, researchers looked only at studies published after 1995, and it doesn’t seem like the decline in male fertility is slowing down.

Male infertility isn’t just related to procreation, either. Oftentimes, a decrease in sperm count is an indicator of an increased risk in premature death. (2) In fact, the study called it a “canary in the coal mine” for male health. And though the researchers didn’t set out to figure out why sperm counts were decreasing, they floated several theories, including environmental and lifestyle influences.

So what are the causes of male infertility the study suggests? Let’s take a closer look.


Causes of Male Infertility

What are the causes of male infertility? While there are a number of male infertility causes, ranging from hormone imbalances and certain medications to infections and chromosome defects, we’re going to focus on environmental and lifestyle factors today. (3)

For starters, what is the percentage of male infertility? It’s hard to come across hard figures, but studies suggest that in North America, male infertility is between 4 and 6 percent. (4) In cases of couples attempting to conceive, in about 1/3 of the cases, infertility is caused by male reproductive issues. (5)

What are the causes of male infertility? One of the reasons why so many scientists suspect manmade factors, like lifestyle and environment, for the increasing rate of male infertility is that the changes are happening too quickly to be attributed to genetics. These include both prenatal and adulthood exposure.

Prenatal

Endocrine-disrupting chemicals. Prenatal endocrine disruption because of chemical exposure is one major reason scientists believe male infertility is on the rise. (67Endocrine-disrupting chemicals, or EDCs, are all around us. They include things like phthalatestriclosan (yes, the stuff in your anti-bacterial gel!) and BPAs.

These substances interfere with our endocrine system, which regulates all of our body’s hormones and biological processes. And when EDCs mess with our endocrine systems, it can have serious developmental, reproductive, neurological and immune effects. Unfortunately, damage is thought to be most serious during prenatal or early pregnancy exposure.

EDCs are especially tricky because even teeny doses of exposure can have serious effects, but it can be years or even decades until the health impact fully manifests.

Smoking. Hopefully, you’re already well aware of the impact that smoking has on your health. In fact, it’s the leading preventable cause of death in America — causing more deaths than HIV, illegal drug use, alcohol use, car accidents and firearm-related incidents combined. (8)

But while smoking as an adult can affect infertility in men (more on that later), prenatal exposure to smoking can play a role, too. One small study found that European men who had prenatal exposure to smoking had a 20 percent lower sperm density than those without. (9) Exposure to second-hand smoke may play a role, too.

Adult life

Exposure to pesticides. In the last 40 years, we’ve been exposed to a variety of pesticides that haven’t always been around, like Monsanto Roundup. All of these pesticides are affecting male infertility, and we’re not always sure exactly how, because enough research hasn’t yet been done. Remnants of pesticides can stay on our foods long after the pesticide has been sprayed. There’s also pesticide drift, where the chemicals travel even to foods that haven’t been sprayed with pesticides.

Is it just a coincidence that male infertility has increased in the last four decades, around the same time that powerful pesticides have come into play? It could be, but I find that unlikely.

Smoking. As I mentioned before, smoking affects male infertility. There are more than 4,000 toxins in tobacco smoke, which combine to harm male fertility.

If you’re a smoker, you can expect lower-quality semen, reduced sperm function, a dysfunctional reproductive hormonal system, impaired sperm maturation and other reproductive side effects. (10)

How much you’re smoking matters, too. Heavy smokers are likely to experience more negative effects in their fertility than casual smokers, though, to be clear, any type of smoking can have an effect on male infertility. (1112)

Stress. We already know that chronic stress is harmful to your health. Did you know that it also plays a role in a man’s fertility?

Men who are stressed tend to have lower sperm concentrations during ejaculation and reduced sperm quality, which makes it more difficult for a sperm to fertilize an egg. This holds true even once other health issues are accounted for. (13)

Obesity. Obesity has been on the rise in the past few decades, and it’s playing a role in male infertility. While we’ve known for some time that an obese woman may have difficulty conceiving, an obese male partner plays a role, too. It seems that obesity affects the sperm’s ability to fertilize an egg. (14) This is likely due to impaired semen quality.

Obesity comes with its own set of other health issues, too, which can affect male infertility, like hormonal changes and sexual dysfunction. (15)

Growth hormone in male infertility

Abstract

Growth hormone (GH) is expressed in a variety of tissues, including the testes, and has autocrine and paracrine functions as well. This, along with other factors, exerts autocrine and paracrine control over spermatogenesis. GH, used as an adjuvant therapy, induces spermatogenesis in non-responder patients with hypogonadotropic hypogonadism, who are not responding to gonadotropin or pulsatile luteinizing hormone (LH) therapy. GH has an important physiological role to play in spermatogenesis and male fertility.

Keywords: Growth hormone, infertility, male, pituitary, spermatogenesis

Growth hormone (GH) expression is not limited to the pituitary, neither is its function limited to simple endocrine effects on growth. GH is expressed in a variety of tissues, including the testes, and has autocrine and paracrine functions as well.

The process of spermatogenesis is essential for human reproduction. A simple sounding process is mediated by a variety of factors, including multiple hormonal influences. The gonadotropin-releasing hormone (GnRH), LH, Follicle-stimulating hormone (FSH), and testosterone all play an important role in the development and maturation of sperms. At the same time, various locally secreted peptides and proteins such as GH, IGF-1, cytokines, activin, inhibin, follistatin, and estrogen, exert autocrine and paracrine control over spermatogenesis.[1]

The growth hormone acts directly and indirectly via hepatic IGF-1, at the testicular level, to promote sperm production. The locally produced GH may act in a paracrine or autocrine fashion to regulate local processes that are strategically regulated by pituitary GH. GH promotes early development of spermatogonia, and ensures complete maturation as well.

Growth hormone–deficient men have small-sized testes. GH has been found to be deficient in phenotypically normal, azoospermic men, with maturation arrest, a finding confirmed by clonidine stimulation tests.[2] Conversely, the sperm count is low or nil in men with GH deficiency. GH resistance in men is also associated with reduced fertility.[3]

Growth hormone restores sperm concentration, morphology, and motility in GH-deficient rats[4] as well as men. GH, used as adjuvant therapy, induces spermatogenesis in non-responder patients with hypogonadotropic hypogonadism, who are not responding to gonadotropin or pulsatile LH therapy. A study on nine oligozoospermic and nine asthenozoospermic men treated with GH for 12 weeks reported increased sperm motility in both groups, and three pregnancies were reported in asthenozoospermia, but not in oligozoospermia.[5]

An Indian prospective, open-label, non-randomized observational study of 14 men, aged between 26 and 35 years, with normogonadotropic idiopathic oligoasthenospermia has described the beneficial effects of growth hormone 1.5 IU / day, administered for six months. Semen volume, count, and motility were improved in all patients. The increase was most marked during the first three months of therapy. Not much improvement was noticed during the latter half of the treatment. None of the patients experienced any side effects. Three subjects fathered children over the next one year, two with the help of intrauterine insemination.[6]

At the same time, other authors have also reported lack of beneficial effect with this therapy.[7] Therefore, GH cannot be promoted as a panacea for all subfertile men.

The GH and recombinant human insulin-like growth factor-I (rhIGF-I) can be utilized in improving the outcome of IVF as well. These drugs have been reported to maintain sperm motility longer after a 24-hour treatment at room temperature in mature equine spermatozoa, without any deletiroius effects. This property can be utilized to store spermatozoa longer at room temperature in Assisted Reproductive Technology (ART) centres.[8]

In conclusion, GH has an important physiological role to play in spermatogenesis and male fertility. More studies are required to define the exact place of GH therapy in clinical practice. Although it certainly merits a trial in GH-deficient patients, it may be used in non-responding normogonadotropic idiopathic oligoasthenospermia. A close watch must be kept for metabolic side effects. Its true potential will be realized only if endocrinologists: both medical and reproductive, team together to analyze the patient populations and where it can be used.

MALE INFERTILITY COULD SIGNAL MORE SERIOUS HEALTH PROBLEMS LATER IN LIFE, NEW RESEARCH SUGGESTS

MALE INFERTILITY COULD SIGNAL MORE SERIOUS HEALTH PROBLEMS LATER IN LIFE, NEW RESEARCH SUGGESTS

This article was originally published on The Conversation. Read the original article.

Poor sperm quality affects about one in 10 men and may lead to fertility problems. These men also have an increased risk of developing testicular cancer, which is the most common malignant disease of young males.

And, even if they don’t develop testicular cancer, men with poor sperm quality tend to die younger than men who don’t have fertility problems. The Conversation

Couples who can’t achieve pregnancy usually go to fertility clinics for treatment. At these clinics, emphasis is put on deciding whether the couple needs assisted reproduction or not, and, if so, to choose between different methods (such as IVF, IUI, or ICSI) for doing this. In most cases, these treatments lead to pregnancy and a live birth. So the problem seems to be solved. But if infertility is an early symptom of an underlying disease in the man, fertility clinics won’t pick it up.

Missed opportunity

Testicular cancer is easy to detect. In men seeking treatment for fertility problems, a simple ultrasound scan of the testes can reveal early cancer, so a life-threatening tumour can be prevented. If detected, 95% of all cases can be cured. But, unfortunately, testicular ultrasound scans are rarely performed at fertility clinics as the focus tends to be on sperm numbers and which method of assisted reproduction to use.

And testicular cancer is not the only threat to young infertile men’s health. Serious health problems, such as metabolic syndrome (high blood pressure, high blood sugar and obesity), type 2 diabetes and loss of bone mass are also much more common conditions among infertile men. These disorders are possible to prevent, but if left untreated often lead to premature death.

A possible culprit

At Lund University in Malmö, Sweden, we have – together with other research groups – made a number of studies focusing on the link between male fertility problems and subsequent risk of serious diseases. We cannot yet explain the causes, but testosterone deficiency is a strong candidate.

My research team found that 30% of all men with impaired semen quality have low testosterone levels. And men totally lacking the hormone have early signs of diabetes and bone loss.

We recently conducted a study in which we investigated almost 4,000 men below the age of 50 and who had had their testosterone measured 25 years ago. We found that the risk of dying at a young age was doubled among those with low testosterone levels compared with men with normal levels of this hormone.

Although testosterone treatment may not necessarily be the best preventive measure, these findings makes it possible to identify men at high risk so that they can be advised about lifestyle changes, such as losing weight or quitting smoking – lifestyle changes that will help reduce the risk of developing type 2 diabetes, cardiovascular disease and osteoporosis.

A relatively high proportion of men get in touch with their doctor about infertility problems and, as they represent a high-risk group for some of the most common diseases occurring later in life, perhaps it is time to change the routines for managing them. With the knowledge we now have regarding these men’s health, the least we can demand from doctors is to identify those who are at risk of serious diseases after they have become fathers. This is cheap and only requires simple tests. It is no longer enough to just evaluate the number of sperm.

Aleksander Giwercman is Professor of Reproductive Medicine, Lund Universityand Yvonne Lundberg Giwercman is Associate Professor in Experimental Urology, Lund University.

Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study

Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD.

These analyses included 537 ASD cases and 381 TD controls. Parents of children with an ASD were slightly older than TD control parents, and case mothers were slightly more likely to have had a history of smoking; other demographic and lifestyle factors were similar between the groups (Table 2).

Table 2

Basic characteristics of the study population (n = 918).

Nine percent of both ASD cases and TD controls had used at least one type of infertility treatment for the index birth. Numbers were small for rarer types of therapies, but overall, frequencies were remarkably similar between the ASD and TD groups (Table 3). The ASD case group also did not differ from TD controls by infertility diagnosis or according to hypothesized pathways.

Table 3

Infertility and infertility treatments by case status.

In adjusted analyses comparing ASD cases to TD controls, fertility therapies and infertility continued to show no association with odds of ASD (Table 4). Overall, odds ratios were all close to 1 (OR for overall infertility treatment use = 1.16, 95% CI 0.70, 1.93), though for certain therapies, confidence intervals were imprecise due to small numbers. In particular, any male treatment had only nine exposed cases in the primary analysis, and while similar point estimates were similarly elevated across subgroup analyses for this treatment type (OR approaching 2), these results were not significant. Contrary to our hypotheses, no differences were noted according to hypothesized underlying pathways (Appendix, Table S1). Results were similar across models tested, including in weighted (Model 3, Table 4) and unweighted (Model 2, Table 4) analyses, and did not materially change when using reduced models including only maternal age, child year of birth, and matching factors, or conversely, when considering further adjustment for pre-pregnancy smoking and BMI, which have been associated with both the exposures and outcome under study in some investigations [30,34,35,36].

Table 4

Odds of ASD according to infertility and treatments.

In subgroup analyses among mothers of advanced age (n = 237) and by diagnostic subgroup (367 autistic disorder and 170 broader ASD), results were very similar, and again non-significant for any associations with infertility and infertility treatments (data not shown; OR for any infertility treatment in the advanced maternal age group: 1.20, 95% CI 0.56, 2.59; in the autistic disorder case group, the corresponding OR was 1.27, 95% CI 0.73, 2.20). However, it should be noted that numbers were small within these groups; only 27 cases used any fertility therapies among the advanced maternal age subgroup, with numbers for individual types of therapies around 10 or fewer. Likewise, sensitivity analyses utilizing only self-reported information, or only information from medical records, also did not demonstrate any significant associations.

Discussion

The results of this case-control study do not provide evidence for an association between fertility therapies and autism spectrum disorders. We examined a number of different types of therapies and conditions underlying the infertility being treated, and overall found remarkable similarity between ASD cases and typically developing controls. However, due to the low power to detect subtler effects in our study, we cannot exclude the potential for modest associations with rarer therapies or conditions. These topics should therefore be further explored in very large studies with standardized outcome ascertainment and rigorous exposure information.

A major strength of this study, and an improvement over a number of prior studies examining infertility and/or its treatments in association with ASD, is the confirmation of both case status and exposures through rigorous, gold standard measures. All children included in these analyses were evaluated at the UC Davis MIND Institute for diagnostic confirmation, and detailed interviews were conducted and medical records abstracted (in the majority of the study group) for exposure information. In contrast, none of the prior studies examining these factors have confirmed case and comparison group status at this level of detail. We also had information on a full range of infertility diagnoses and treatments, which is lacking in other studies. Our estimates of frequency of use of a wide range of therapies according to ASD status thus fill a needed gap in the literature. Despite using retrospective reporting, as had been previously utilized in a number of prior investigations, we also collected medical records in a large majority of the group for confirmation. We also carried out a thorough confounder identification strategy, whereas many of the prior studies of infertility treatments and ASD failed to adjust for even basic sociodemographic risk factors [16,20,21,22,25,27]. We further took advantage of the linkage of all our cases and controls to the population birth files that included all non-participants in order to account for potential differential participation (selection bias) through weighted analyses, which has not been done in previous case-control studies of this topic.

However, a number of limitations in our work should be noted. Despite a sample size of nearly 1,000 mother-child pairs, our study was limited by the relatively rare exposures, leading to small numbers in many categories. Thus, while we had sufficient power to detect odds ratios of at least 1.75 for treatments and diagnoses with prevalence over 5%, power was reduced to detect associations for specific therapy types with infrequent use. To date, only Hvitjorn and colleagues [17] have had adequate numbers to examine rarer therapies, but unfortunately, they did not have information on many different types of treatments. We cannot rule out bias due to participation, a common problem in case-control studies, by demographic factors that could be related to the exposures studied here; however, our use of sampling weights strove to mitigate any such biases. While we did rely on retrospective reporting, between 70–80% of our exposures were confirmed in medical records. Another potential limitation, not restricted to our own study, is the definition of infertility itself; how different couples perceive “regular intercourse” is open to interpretation, and timing, diet, lifestyle and cultural factors all may influence reported infertility in ways not related to hypothesized biological pathways.

Consistent with our results, the majority of prior work suggests that use of assisted technologies does not increase risk of adverse child outcomes (with the notable exceptions of multiple births, pre-term birth and low-birth weight). A handful of studies have suggested increased risks of autism, or developmental delay, cerebral palsy, and imprinting disorders with use of ART [15,19,22]. However, our study and four other investigations [17,18,25,27], including the largest study of ASD and assisted conception to date, with over 3,600 cases and approximately 33,000 children exposed to assisted conception [17], found no association between ART and risk of ASD specifically. We also did not see associations with IVF or other ART subtypes, though numbers were small. Two prior studies have also found no association between ASD and IVF or ICSI [25,26], while results from few others have been inconsistent for more broadly defined developmental outcomes and ART subtypes [19,22,24,27].

For other types of infertility treatments, there is limited information on associations with ASD specifically. A handful of prior studies have suggested associations with ovulation drugs or medications (three studies, each of which found associations only in different subgroup analyses) [17,18,28], specific hormones (two studies) [17,28], and artificial insemination/intrauterine insemination (two studies) [18,28]. Specifically, an investigation in the Nurses’ Health Study II found a significant association between ASD and OID in an advanced maternal age subgroup [18], which was a larger subgroup than the current study; thus, smaller numbers here could account for the differences seen. The Danish study conducted by Hvitjorn and colleagues [17] found significant associations with ASD for female offspring exposed to OID as well as for use of follicle-stimulating hormone (FSH)-containing medications, while another study saw an association with urofillitropin, a purified form of FSH, only among multiple births [28]. Given that FSH-containing medications are indicated for a range of underlying problems, the meaning of these findings is not immediately evident. We did not see an association with FSH specifically, and a larger investigation than ours will be needed to replicate results. Another recent study found no association with a general category of infertility medications (that included OID) and ASD among singleton births [28], but did find a significant association among multiple births. Our results did not differ in multiple or singleton births, though as in the work by Grether and colleagues, exposed numbers among multiples were small, thereby limiting conclusions.

The Nurses’ investigation also saw an association with AI, which the CHARGE study did not replicate; however, the source of infertility treatment information in the Nurses’ study was not as rigorous as in the current study. We did find increased odds ratios for male treatments in our study; though non-significant, use of AI is sometimes indicated for male factors. Again, Grether and colleagues’ study found an association with IUI and ASD only among multiple births but not in singletons, providing mixed results. Given that Hvitjorn and colleagues’ definition of OID included use with and without AI, future studies should also investigate AI in association with ASD, both in singleton and multiple births.

Our analyses of these infertility treatments considered adjustment for a number of potential confounders. Prior studies examining potential effects of infertility treatments have adjusted for or stratified on multiple births in attempt to assess the effect of the treatments on the various outcomes studied, not mediated by multiplicity. For comparison to this work, we examined exposures stratified by singleton and multiple births and found that results did not differ (data not shown; nor did results materially change when adjusting for birth order, which has similar issues when considering effects of infertility and its treatments). However, conditioning on a downstream consequence of exposure can introduce bias. Another example is adjustment for birth weight, a common flaw in studies of prenatal exposures; again, we did not include birth weight in our multivariable models for this reason. Future large studies may benefit from the use of more sophisticated statistical methods, such as marginal structural models (MSMs) [37,38], to determine controlled direct effects not mediated by these factors. Alternatively, using mediator analyses [39,40] may also be useful in determining the impact of factors that may be downstream of infertility therapies, assuming confounding of the intermediate-outcome association is adequately accounted for. Given the null findings for exposures in our study, we did not see significant associations with potential mediators when we conducted such analyses (results provided in Appendix, Table S2); however, pregnancy complications, low birth weight, and multiple births had fairly large estimates of percent mediation. Little prior work has investigated underlying infertility, rather than just its treatments, in association with ASD. While two small studies reported increased prevalence of infertility among mothers of affected children [16,21], and a third study reported an association only for multiple births [28], two larger studies (one registry-based and one nested case-control) have not found associations between maternal infertility and risk of ASD [17,18]; our work is consistent with these recent findings.

Infertility treatments have been hypothesized to influence ASD through a number of mechanisms, including hormonal influences of the medications, effects of invasive procedures on DNA methylation or other direct effects of the procedure/treatment, impaired egg quality, influences of the underlying infertility, or simply through associations with downstream consequences of the treatment (such as multiple birth, pregnancy complications, low birth weight, or pre-term birth) [15,18,41]. While we had hypothesized that hormonal or inflammatory pathways may be involved, we did not see associations with these pathways as related to infertility and its treatments. However, power was limited to detect modest associations (i.e., those on the order of OR = 1.5 or less), given the number of exposed cases in each of the pathway groups. Continued investigation of such pathways and groupings as conducted here may be useful in learning more about potential underlying mechanisms.

Conclusions

Our work and that of others highlights the need for very large studies in order to fully address the topic of infertility and its treatments in association with ASD. Overall, the evidence to date suggests that women using infertility therapies do not need to be concerned about strong increases in risk of ASD. However, the known risks associated with infertility therapies, such as prematurity, low birth weight infants and multiple births, remain as concerns associated with use of these therapies, and evidence suggests the need for continued long-term follow-up of children conceived using these procedures [14]. Women using these therapies appear to also be at higher risk for pregnancy complications, although this increased risk could be a result of the primary infertility and its root causes. Thus, further investigations are needed to disentangle the complex role of underlying infertility, its treatments, and possible mediators of hypothesized effects on risk of ASD. The limited power to detect modest associations in our study suggests further work may be required to (a) detect subtler risks associated with specific infertility therapies and underlying infertility pathways, and (b) better understand associations in groups such as multiple births and women with advanced maternal age, for whom these treatments and issues are more common.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774465/

Genetics of infertility, zinc, pituitary gland and Endocrine disruptors

About 10–15% of human couples are infertile, unable to conceive. In approximately in half of these cases, the underlying cause is related to the male. The underlying causative factors in the male infertility can be attributed to environmental toxins, systemic disorders such as, hypothalamic–pituitary disease, testicular cancers and germ-cell aplasia. Genetic factors including aneuploidies and single-gene mutations are also contributed to the male infertility.

Patients suffering from nonobstructive azoospermia or oligozoospermia show microdeletions in the long arm of the Y chromosome and/or chromosomal abnormalities, each with the respective frequency of 9.7% and 13%. A large percentage of human male infertility is estimated to be caused by mutations in genes involved in primary or secondary spermatogenesis and sperm quality and function. Single-gene defects are the focus of most research carried out in this field.[1][2]

NR5A1 mutations are associated with male infertility, suggesting the possibility that these mutations cause the infertility. However, it is possible that these mutations individually have no major effect and only contribute to the male infertility by collaboration with other contributors such as environmental factors and other genomics variants. Vice versa, existence of the other alleles could reduce the phenotypic effects of impaired NR5A1 proteins and attenuate the expression of abnormal phenotypes and manifest male infertility solely.

NR5A1 roles in sex development and related disorders

Nuclear receptor subfamily 5 group A member 1 (NR5A1), also known as SF1 or Ad4BP (MIM 184757), is located on the long arm of chromosome 9 (9q33.3). The NR5A1 is an orphan nuclear receptor that was first identified following the search for a common regulator of the cytochrome P450 steroid hydroxylase enzyme family. This receptor is a pivotal transcriptional regulator of an array of genes involved in reproduction, steroidogenesis and male sexual differentiation and also plays a crucial role in adrenal gland formation in both sexes. NR5A1 regulates the mullerian inhibitory substance by binding to a conserved upstream regulatory element and directly participates in the process of mammalian sex determination through mullerian duct regression.

Targeted disruption of NR5A1 (Ftzf1) in mice results in gonadal and adrenal agenesis, persistence of Mullerian structures and abnormalities of the hypothalamus and pituitary gonadotropes. Heterozygous animals demonstrate a milder phenotype including an impaired adrenal stress response and reduced testicular size. In humans, NR5A1 mutations were first described in patients with 46, XY karyotype and disorders of sex development (DSD), Mullerian structures and primary adrenal failure (MIM 612965). After that, heterozygous NR5A1 mutations were described in seven patients showing 46, XY karyotype and ambiguous genitalia, gonadal dysgenesis, but no adrenal insufficiency. Since then, studies have confirmed that mutations in NR5A1 in patients with 46, XY karyotype cause severe underandrogenisation, but no adrenal insufficiency, establishing dynamic and dosage-dependent actions for NR5A1. Subsequent studies revealed that NR5A1 heterozygous mutations cause primary ovarian insufficiency (MIM 612964).[3][4][5][6]

NR5A1 new roles in fertility and infertility

Recently, NR5A1 mutations have been related to human male infertility (MIM 613957). These findings substantially increase the number of NR5A1 mutations reported in humans and show that mutations in NR5A1 can be found in patients with a wide range of phenotypic features, ranging from 46, XY sex reversal with primary adrenal failure to male infertility. For the first time, Bashamboo et al. (2010) conducted a study on the nonobstructive infertile men (a non-Caucasian mixed ancestry n = 315), which resulted in the report of all missense mutations in the NR5A1 gene with 4% frequency. Functional studies of the missense mutations revealed impaired transcriptional activation of NR5A1-responsive target genes. Subsequently, three missense mutations were identified as associated with and most likely the cause of the male infertility, according to computational analyses.[7] The study indicated that the mutation frequency is below 1% (Caucasian German origin, n = 488).[7] In another study the coding sequence of NR5A1 has been analysed in a cohort of 90 well-characterised idiopathic Iranian azoospermic infertile men versus 112 fertile men.[8] Heterozygous NR5A1 mutations were found in 2 of 90 (2.2%) of cases.[8] These two patients harboured missense mutations within the hinge region (p.P97T) and ligand-binding domain (p.E237K) of the NR5A1 protein.[8]


Zinc in Semen

Semen is only one percent sperm; the rest is composed of over 200 separate proteins, as well as vitamins and minerals including vitamin C, calcium, chlorine, citric acid, fructose, lactic acid, magnesium, nitrogen, phosphorus, potassium, sodium, vitamin B12, and zinc .

zinc.JPG

Endocrine disruptors or Toxins

Endocrine disruptors are chemicals that, at certain doses, can interfere with endocrine (or hormone) systems. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders. Any system in the body controlled by hormones can be derailed by hormone disruptors.

EDS.JPG

Pituitary Gland

Pituitary Gland in the brain is responsible for sleep, sex hormones, food cravings and stress hormones.

Table of pituitary hormones

Hormone Target(s)   Function
ACTH Adrenals Stimulates the adrenal gland to produce a hormone called cortisol. ACTH is also known as corticotrophin.
TSH Thyroid Stimulates the thyroid gland to secrete its own hormone, which is called thyroxine. TSH is also known as thyrotrophin.
LH & FSH Ovaries (women)

Testes (men)

Controls reproductive functioning and sexual characteristics. Stimulates the ovaries to produce oestrogen and progesterone and the testes to produce testosterone and sperm. LH and FSH are known collectively as gonadotrophins. LH is also referred to as interstitial cell stimulating hormone (ICSH) in males.
PRL Breasts Stimulates the breasts to produce milk. This hormone is secreted in large amounts during pregnancy and breast feeding, but is present at all times in both men and women.
GH All cells in the body Stimulates growth and repair. Research is currently being carried out to identify the functions of GH in adult life.
MSH Exact role in humans is unknown.
ADH Kidneys Controls the blood fluid and mineral levels in the body by affecting water retention by the kidneys. This hormone is also known vasopressin or argenine vasopressin (AVP).
Oxytocin Uterus

Breasts

 Affects uterine contractions in pregnancy and birth and subsequent release of breast milk.

 

Study reveals gene’s role in male infertility

By Tom Gresham

Study reveals gene's role in male infertility
In this figure a transmission electron microscopic image (top) shows the array of manchette microtubules running lateral to the nucleus and extending toward the forming sperm tail. In the confocal fluorescence images (bottom) SPAG16 protein …more

A Virginia Commonwealth University-led research team has opened a fresh direction in the field of male infertility with a new study that examines the role of a particular gene in the formation of sperm flagella, which is the appendage that propels sperm.

The paper, “Intraflagellar Transport Protein IFT20 is Essential for Male Fertility and Spermiogenesis in Mice,” was published online in Molecular Biology of the Cell. It will be published in a future print issue of the journal. In the paper, researchers studied the role of the intraflagellar transport protein IFT20 in male germ cell development. They learned that the gene was important for sperm flagella formation and therefore . Without flagella, sperm cannot swim.

“Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation,” said lead researcher Zhibing Zhang, M.D., Ph.D., associate professor in the Department of Obstetrics and Gynecology in the VCU School of Medicine. “Our study also uncovered a novel genetic factor for male infertility.”

In humans, accounts for 40-50 percent of infertility, and it affects approximately 7 percent of all men. Many different medical conditions and other factors can contribute to fertility problems, but the most common issues that lead to infertility in men are problems that affect how the testicles work. Many of the etiologies are unknown, but this accounts for about 50 percent of patients. Genetic factors are the major issues.

There are two kinds of cilia, and primary cilia. Motile cilia are present in sperm, epithelial cells of trachea and brain ventricles; the major function of motile cilia is for motility. Primary cilia are present in almost all the mammalian cells; t

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