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UCLA research may explain some causes of infertility and miscarriage Study examines how early embryonic development can go awry

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A new study in the journal Nature Cell Biology has uncovered information about a key stage that human embryonic cells must pass through just before an embryo implants. The research, led by UCLA biologist Amander Clark, could help explain certain causes of infertility and spontaneous miscarriage.

Infertility affects around 10 percent of the U.S. population, and roughly 15 to 20 percent of all pregnancies in the U.S. end in miscarriage. In many cases, the causes of infertility and miscarriage are unknown.

A team led by Clark, a UCLA professor of molecular cell and developmental biology and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, set out to find how epigenomic changes — non-genetic influences on gene expression — in human embryonic stem cells could explain why some embryos are not viable.

They started by analyzing cells within the early embryo; these cells are pluripotent, meaning that they can turn into any cell within the human body.

“For many years, researchers thought that human pluripotency was a single state,” Clark said. “However, over the past three years, the field has discovered that human pluripotency involves at least two major states, and as embryos grow the stem cells pass through these two different states of pluripotency on the way to the embryo establishing a pregnancy.”

After a human embryo is fertilized and before it implants in the uterine lining, cells in the embryo are in a very immature state of pluripotency called the “naive” state. Little is known about the naive state, but scientists believe that if embryonic cells cannot first enter this state, the embryo is not viable and a miscarriage would occur. Around the time an embryo implants, its cells enter the “primed” state. Primed cells are ready to differentiate into all of the various cell types in the body.

“Although no one knows exactly why the naive state of pluripotency exists, or what helps naive cells stay in that state for a period of time, it could be to provide a protective mechanism that prevents the embryonic cells from differentiating too quickly, which would ensure the timing of implantation is right,” Clark said.

To better understand what helps regulate the naive state, the researchers compared epigenomic changes in lab-created naive and primed embryonic stem cells. They discovered that both cell types have different sequences of open chromatin throughout their DNA. Chromatin consists of DNA and protein that condense to form the chromosomes within a cell’s nucleus.

Unique sequences of open chromatin within any cell type act as bar codes. Gene-regulating proteins called transcription factors in the open areas of chromatin “scan” the bar code and then bind to it, which influences genetic activity in the cell.

“We looked specifically at open chromatin and found a bar code that is unique to naive embryonic stem cells repeated over and over again, so we asked what transcription factor recognizes that bar code,” Clark said.

The researchers discovered that a transcription factor called TFAP2C recognizes the bar code. To learn more about its specific role, they deleted the gene that makes the TFAP2C protein from both primed and naive embryonic stem cells in the laboratory using a gene editing tool called CRISPR-Cas9.

They found that the deletion had no effect on primed stem cells. Conversely, when TFAP2C was deleted from naive stem cells, the areas of open chromatin associated with the naive state closed and the naive stem cells passed into a primed state.

The research also revealed about 1,500 regions of open chromatin that are very sensitive to the loss of TFAP2C and showed that there are hundreds of genes associated with early embryonic development in those areas.

“We’ve discovered that the presence of TFAP2C marks an important difference between the naive and primed states of pluripotency, and that TFAP2C is necessary to maintain the naive state of pluripotency,” Clark said. “We also showed that without TFAP2C, hundreds of genes aren’t expressed correctly, which would most likely result in early miscarriage.”

In addition, the researchers verified that the regions of open chromatin present in lab-created naive embryonic stem cells are also present in embryos before the stage associated with implantation.

“Our findings are relevant to the natural process of human development because they match up with what we see in human pre-implantation embryos,” Clark said. “This provides new information about a time in the lifecycle that we know little about. Fundamental knowledge like this could help better predict infertility or embryo quality.”

The study also could lead to important advances in an area of medicine that historically has been underfunded and underappreciated — in part because the subject of infertility is sometimes seen as taboo and because it doesn’t attract the attention of deadly diseases like cancer.

“People who experience infertility and miscarriage may tell close friends or family, but too often, these issues are not discussed,” Clark said. “But infertility is a significant health concern. It deserves our attention, and we as a society need to be more open about it.”

The pluripotent stem cell research was supported by the Jane Coffin Childs Memorial Fund for Medical Research, the Chinese Scholarship Council, the National Institute of Child Health and Human Development, Australia’s National Health and Medical Research Council, the Silvia and Charles Viertel Senior Medical Research Fellowships and the Howard Hughes Medical Institute. The human embryo research was funded by the UCLA Broad Stem Cell Research Center and its training program.

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NEWS: Get access to adult photos of the Cryos sperm donors

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Adult Cryos Sperm Donors Photos

Viewing adult photos of Cryos sperm donors is now a reality. Visit dk.cryosinternational.com today and get access to the new feature.

At Cryos it is now possible to access adult photos of sperm donors on our website, thus adding another dimension to your search for the perfect donor.

The unique chance to see both childhood and adult photos of your sperm donor, provides you with a more comprehensive idea of who your sperm donor is and moreover of the features of your future child. We hope that this extra dimension will upgrade your experience making your decision of a sperm donor easier.

The 5-6 adult photos are taken by a professional photographer and are a part of the donors extended profile where you also have access to childhood photos, an audio recording of the donor’s voice, a handwritten message, an emotional intelligence profile, and finally our staff impressions of the donor, amongst other exclusive features.

The adult photos require special access on our website. Visit our website and find out more and get access to this new feature now.

Please note that the person in the photos is a model and not a Cryos donor.
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Fertility And Sex: Why Her Orgasm Matters

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Why her orgasm matters

For many couples, trying to conceive can make sex feel less fun and more pressured. Instead of being an intimate and enjoyable experience, baby-making sex can start to seem like a finely choreographed routine. Often, the female orgasm is one of the first things to go, but the maleorgasm is not the only orgasm that matters when it comes to fertility.

Before I dive into discussing the potential benefits of the female orgasm for fertility, it’s important to note that reaching climax is not technically essential for conception. If you never, or rarely, achieve orgasm, don’t worry, you can still get pregnant! Around 1 in 10 women don’t experience orgasm, ever. What’s more, the exact nature of the female orgasm remains somewhat elusive. Some experience orgasm through clitoral stimulation, some through vaginal intercourse, some through both, and others through something else entirely, or not at all.

Even without reaching orgasm, sexual arousal is itself beneficial to fertility. Like an orgasm, arousal is, first and foremost, a good indication that sex is enjoyable. Sexual arousal and climax causes significant changes in your levels of neurotransmitters including noradrenaline, oxytocin, prolactin, dopamine, and serotonin. These ‘reward’ neurohormones help you bond to a sexual partner and make it more likely that you’ll have sex more often, thereby increasing your chances of conception.

Second, orgasm and arousal have a range of physiological effects that might aid conception, which I’ll discuss in a moment. And, third, sexual arousal and orgasms for everyone can help sperm-producing partners avoid feeling like they’re being used just for their sperm. In fact, some studies show that male partners who engage in cunnilingus prior to vaginal intercourse have greater sexual arousal and produce more semen!

HOW ORGASMS ENHANCE FERTILITY

The female orgasm can help relieve stress, and promote healthy circulation and balance in the body. Stress is a key cause of diminished libido and may also reduce the chances of conception by raising levels of the stress hormone cortisol. Conversely, good sex can help raise levels of oxytocin and the other neurohormones mentioned above. These help you to relax and bond to your partner.

Published in 1967, the author even went as far as suggesting that the increase in these hormones after orgasm help support conception by temporarily incapacitating you. Put simply, this ‘poleax’ effect means you’ll feel so relaxed that you’ll stay lying down, which may increase your chance of conceiving. Whether staying supine does make conception more likely is still under debate, but I’m all for promoting relaxation, so if this theory provides added motivation, go for it!

CERVICAL TENTING

There is some suggestion that orgasm affects the shape and function of the cervix. These effects, which may include cervical ‘tenting could enhance the likelihood of conception by promoting the movement of sperm into the uterus and beyond. If you are curious as to what your cervix looks like during different stages of your cycle, check out these photos.

THE ‘UP-SUCK’ THEORY

One of the main ways in which female orgasm has been linked to fertility is something called the ‘upsuck’ theory (or, sometimes, the ‘insuck’ theory). This theory proposes that the female orgasm causes uterine and vaginal contractions that actively draw semen up into the uterus and towards the fallopian tubes, thereby increasing the chances of an egg being fertilized.

Scientific evidence to support this theory is rather inconsistent, but there’s certainly no harm in trying! One proposed underlying mechanism of this theory is oxytocin-mediated uterine peristalsis, i.e. the same mechanism that causes uterine contractions during labour could be partially responsible for increasing the likelihood of conception. Indeed, some research has found higher pregnancy rates in women shown to experience this ‘insuck’ phenomenon.

SPERM RETENTION AND FERTILITY

More recently, one small study found that orgasm may increase sperm retention. This study involved women using a syringe to insert a sperm simulant (lube) prior to external stimulation to orgasm. As such, the study’s findings may be especially applicable to anyone undergoing artificial insemination (IUI).

The take-away: Chances are that if you orgasm 1 minute before or up to 45 minutes after insemination (whether artificial or otherwise), you will probably retain more sperm, which may increase your chance of conceiving.

IN CONCLUSION

To sum up, the female orgasm might enhance fertility in a variety of ways, but it isn’t essential to conception.

The take home message is that orgasm and sexual arousal itself have many benefits to fertility, partner relationships and stress relief. Don’t worry though, if you have a low libido, conception can still happen even in the absence of arousal and orgasm!

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What Is Polycystic Ovary Syndrome (PCOS)?

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Polycystic Ovary Syndrome

Polycystic Ovary Syndrome or PCOS is a hormonal imbalance that affects 5 to 10 percent of women of reproductive age across the world, and results in irregular or absent periods, acne, excess body hair and weight gain. It is also a major cause of infertility and yet is frequently misdiagnosed and often missed completely.

PCOS gets its name because under an ultrasound scan, the ovaries can look like a bunch of grapes, each one covered in what look like multiple cysts. In fact, these aren’t cysts at all, but are small, undeveloped follicles.

Symptoms

Not every woman with PCOS will get the same symptoms, but common signs to look out for include:

  • Few or no periods
  • Excess hair on the face or breasts or inside of the legs or around the nipples
  • Acne
  • Oily skin
  • Scalp hair thinning or loss (male pattern baldness)
  • Skin tags (known as acrochordons)
  • Skin discolouration (known as acanthosis nigricans) where the skin looks ‘dirty’ on the arms, around the neck and under the breasts
  • Mood swings
  • Depression
  • Lack of sex drive
  • Weight gain especially around the middle of the body
  • Difficulty in losing weight
  • Cravings and binges
  • Irregular or no ovulation
  • Difficulty in becoming pregnant
  • Recurrent miscarriages

PCOS creates a vicious cycle of hormone imbalances, which has huge knock-on effects throughout the rest of your body. With PCOS, the problem often starts with the ovaries, which are unable to produce the hormones they should, and in the correct proportions. But linked to this is the very common problem of insulin resistance. Women with PCOS very often have difficulties with blood sugar levels which can cause weight gain and the excess insulin can stimulate your ovaries to produce yet more testosterone. Half of all women with PCOS do not have any problems with their weight, yet they can still have higher insulin levels than normal.

How is Polycystic Ovary Syndrome diagnosed?

The most widely accepted criteria for the diagnosis of PCOS says that you should have two out of these three problems:

  • Infrequent or no ovulation
  • Signs (either physical appearance – hirsutism or acne – or blood tests) of high levels of male hormones
  • Polycystic ovaries as seen on an ultrasound scan

The Seven Nutritional Steps to beat Polycystic Ovary Syndrome

Good nutrition is the foundation of your health and you should never underestimate how powerful it can be. It is the fuel that provides you with the energy to live your life and it gives your body the nutrients it needs to produce your hormones in the correct balance. The better the supply of those nutrients, the more healthily your body will function.

The fundamental aim of my nutritional approach to PCOS is to target a number of areas simultaneously so that you get the maximum effect in the minimum amount of time.  

Here’s how:

  1. Switch to unrefined carbohydrates (eaten with protein) and never go more than 3 hours without food to keep your blood sugar levels balanced
  2. Eat oily fish and foods rich in Omega 3s to help your body to become more sensitive to insulin so it can overcome insulin resistance
  3. Cut out all dairy products for 3 months to bring levels of male hormones under control
  4. Eat more vegetables and pulses to which helps control male hormones
  5. Cut right back on or cut out alcohol for 12 weeks to allow your liver function to improve
  6. Cut down on caffeine to give your adrenal glands a rest
  7. Cut down on saturated fats and eliminate trans fats to help control the potentially damaging inflammatory processes PCOS causes in the body

PCOS Symptons

Best Supplements for PCOS

The use of certain vitamins and minerals can be extremely useful in helping to correct Polycystic Ovary Syndrome, along with a good diet.

Chromium

Chromium helps to encourage the formation of glucose tolerance factor (GTF), which is required to make insulin more efficient. A deficiency of chromium can lead to insulin resistance.  It also helps to control cravings and reduces hunger. Can help to reduce insulin resistance associated with PCOS

B vitamins

The B vitamins are very important in helping to control the symptoms of PCOS. Vitamin B2 helps to burn fat, sugar and protein into energy. B3 is a component of GTF which is released every time blood sugar rises, and vitamin B3 helps to keep the levels in balance. Vitamin B5 has been shown to help with weight loss and B6 is also important for maintaining hormone balance and, together with B2 and B3, is necessary for normal thyroid function.

Zinc

Zinc helps with PCOS as it plays a crucial role in the production of your reproductive hormones and also regulates your blood sugar.

Magnesium

Magnesium is an important mineral for dealing with PCOS because there is a strong link between magnesium levels and insulin resistance – the higher your magnesium levels the more sensitive you are likely to be to insulin.

Co-Enzyme Q10

Co-Q10 is a substance that your body produces in nearly every cell.  It helps to balance your blood sugar and lowering both glucose and insulin.

Alpha lipoic acid

This powerful antioxidant helps to regulate your blood sugar levels because it releases energy by burning glucose and it also helps to make you more insulin sensitive. It also has an effect on weight loss because if the glucose is being used for energy, your body releases less insulin and you then store less fat.   

Omega 3 fatty acids

Omega 3 fatty acids taken in supplement form have been found to reduce testosterone levels in women with Polycystic Ovary Syndrome.

Amino Acids

Certain amino acids can be very helpful for PCOS as they can improve your insulin sensitivity and also can have an effect on weight loss.

N-Acetyl cysteine

In women with PCOS this amino acid helps reduce insulin levels and makes your body more sensitive to insulin. Study using NAC in women who were clomiphene resistant and had ovarian drilling.  After ovarian drilling, the women given NAC compared to a placebo showed a significantly higher increase in both ovulation and pregnancy rates and lower incidence of miscarriage.

Arginine

Arginine can be helpful in reversing insulin resistance. In one study, a combination of both arginine and N-acetyl cysteine were given to women with Polycystic Ovary Syndrome.  The two amino acids help to improve blood sugar and insulin control and also increased the number of menstrual cycles and ovulation with one women becoming pregnant on the second month.

Carnitine

Carnitine helps your body break down fat to release energy and can help improve insulin sensitivity.

Tyrosine

Tyrosine is helpful for women with PCOS who are overweight as it helps to suppress the appetite and burn off fat.

Glutamine

This amino acid is useful for helping with sugar cravings as it can be converted to sugar for energy and so takes away the need to eat something sweet.  It also helps to build and maintain muscle which is important for fat burning.

Branched Chain Amino Acids (BCAAs)

BCAAs include three amino acids leucine, isoleucine and valine. They are important in PCOS because they help to balance blood sugar and having good levels of these BCAAs can have a beneficial effect on your body weight

Inositol

A study used inositol (2,000mg) in combination with NAC (600mg), a significant increase in ovulation rates.

Having a good diet, regular exercise, controlling stress and taking key nutrients will help in getting your hormones back in balance and reducing the negative symptoms associated with PCOS.

More information can be found on www.naturalhealthpractice.com

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