Connect with us

Fertility 360

Putting Reproductive Genomics at the Heart Of IVF Treatment

Published

on

Reproductive Genomics

Dr. Elizabeth Barbieri of Oregon Reproductive Medicine explains some of the incredible advances in reproductive genomics that are now at the heart of IVF treatments and are increasing patients’ chances for success and a healthy baby.

When our patients embark on their fertility treatment journey they are bombarded with the terms “genetics” and “genomics.” Even just five years ago, this was not the case – but as genetic medicine continues to have an impact on reproductive care, patients increasingly face decisions about genetic screening and testing. Here we discuss the most common genetic tests offered in our fertility clinic.

Genetic disorder carrier screening

Carrier screening refers to DNA testing that investigates whether you or your “reproductive partner” (whether your actual partner, or an egg or sperm donor) has, or “carries,” recessive gene changes – also called mutations – that could cause certain serious genetic diseases in your children.

Genes are the units of heredity – small pieces of DNA that code for certain traits or functions of the body. Genes are inherited in specific ways. One of the basic patterns of inheritance is autosomal recessive. To develop a recessive genetic condition, you must have inherited two copies of a mutation in that gene – one from the egg cell and one from the sperm cell.

If you have just one recessive mutation, you are a carrier for that condition. If you are a carrier, you probably have no idea that you have such a mutation – why would you, when you are likely healthy? Carriers are not expected to have signs or symptoms of the disease they carry (although there are a few exceptions). Carriers usually do not have anyone in their family with the disease they carry; recessive gene mutations can remain hidden in families for generations because generally both members of a reproductive couple must be carriers in order for the disease to appear in a family.

If you are a carrier, you are only at risk to have a child with the disorder if your reproductive partner (or egg donor or sperm donor) happens to be a carrier of the exact same disorder. If this is the case, then you have a 25% chance for that condition to occur in each of your children.

In our clinic we offer “expanded carrier screening (through the Counsyl laboratory’s Family Prep Screen) to all of our patients. Expanded carrier screening refers to testing for a large number (generally 100 or more) genetic conditions simultaneously on one test. There are thousands of rare genetic conditions, and even expanded carrier screening cannot screen for all of these. While 30-50% of patients that we screen at ORM are found to be a carrier of at least one genetic condition, only 1-2% of couples or reproductive partners (intended parent + sperm or egg donor) are found to be carriers for the same condition and have a 25% chance to have a child with the condition.

For most people having children, genetic carrier screening is unfortunately not offered by their physicians until a pregnancy has already been conceived. But testing before pregnancy allows us to discuss options for prevention of genetic disease with you, rather than coping with this information during the pregnancy or after a baby is born with the condition. For example, if you are using an egg donor or sperm donor, knowing your carrier status can help you choose a donor who is unlikely to carry the same condition as you. And if you and your partner are found to be a carrier-carrier couple, you may wish to consider in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) to prevent passing on the disease to your child.

Genetic Disorder Carrier Screening

Genetic testing of the embryos

There are 2 possible types of tests when it comes to genetic testing of the embryos. The first is analysing embryos to determine the number of chromosomes in their cells, which we call comprehensive chromosomal screening (CCS; also known as PGS, preimplantation genetic screening). The second is testing for a specific disease that the embryos are known to be at risk for due to the family history or positive carrier screening results. This is called preimplantation genetic diagnosis (PGD).

In both CCS and PGD, transferring “normal” embryos can help reduce the chance of the embryo and baby having a chromosome abnormality or inheritedgenetic disorder.

CCS is the removal and testing of cells from embryos created through the IVF process to count the number of chromosomes present in these cells. Chromosomes are packages of genes, or DNA, within the cells. Humans normally have 46 chromosomes in each cell; 23 come from the sperm cell and 23 from the egg cell. The first 22 pairs of chromosomes are identified by number, 1 through 22, while the last pair reflects the gender of the embryo: XX for female, XY for male. A normal chromosome result for a female is 46, XX and for a male, 46, XY.

Surprisingly, a large percentage (30- 80%) of healthy-appearing embryos have too many (e.g. 47) or too few (e.g. 45) chromosomes or very large extra or missing pieces of chromosomes. These abnormal embryos have a very high chance of failing to implant or miscarrying. Other embryos with an abnormal number of chromosomes can lead to the birth of a baby with physical or intellectual disorders, such as Down syndrome, which is linked to having an extra copy of chromosome 21.

CCS can identify the embryos with the normal number of chromosomes (46). Preferentially transferring these embyros into the uterus can improve the chance of an ongoing, healthy pregnancy. In our laboratory, we use the most advanced technology available – next-generation sequencing (NGS) – to perform CCS.

Many women have fertility problems because of advancing age, which leads to a decreased number and quality of eggs as well as a higher risk for chromosome abnormalities. Our own success rates at ORM demonstrate that pregnancy rates through IVF decrease as women age, but transferring CCS-normal embryos provide women of all ages, up to 43 years old, the same chance for success. Furthermore, since many miscarriages are the result of chromosomally abnormal embryos, CCS can help reduce the chance of pregnancy loss.

One of the most important factors in reducing the risk of CCS and having success with the process is the experience of the fertility clinic. At ORM, our embryologists have biopsied over 12,000 embryos since 2010. Since over 80% of our patients now choose to have to CCS testing on their embryos, it is a routine part of the IVF patient workflow at ORM and our clinical and laboratory teams have facilitated the process on over 2,000 patients to date.

PGD is the testing of embryos for a specific genetic or chromosomal condition that is carried by one or both parents. Patients choose to do IVF with PGD in order to significantly decrease the chance of having a child with that condition.

Examples include:

  • A couple has had a previous child or pregnancy with a serious genetic condition.
  • A woman or a man has a serious heritable condition and their children have a 50% risk to inherit the disease gene.
  • A couple learn that they are both healthy carriers of the same recessive genetic disease, often without having any family history of the condition.
  • A woman or man learn that they are carriers of a chromosome change predisposing them to making eggs or sperm with a chromosomal imbalance that increases the risk for miscarriage or birth defects in their pregnancies.

Some examples of conditions for which PGD can be done are:

  • Pediatric conditions such as cystic fibrosis, spinal muscular atrophy, thalassemia, Tay-Sachs disease, and sickle cell anemia.
  • Hereditary cancer syndromes such as breast/ovarian cancer predisposition (known to be associated with BRCA1 or BRCA2 genes) and Lynch syndrome
  • Inherited neurologic and muscular conditions such as Huntington’s disease, frontotemporal dementia, and muscular dystrophy.
  • X-linked conditions such as Fragile X syndrome, and adrenoleukodystrophy.
  • Inherited heart disease such as hypertrophic or dilated cardiomyopathy.
  • Hundreds of other autosomal recessive, autosomal dominant, and X-linked genetic disorders.
  • Chromosomal conditions such as translocations and inversions that can cause embryos to not implant or miscarry.

Reproductive Genomics Twitter
PGD is available for the vast majority of serious genetic conditions as long as the particular gene mutation or chromosomal condition in the family has been identified through genetic testing.

To test for “single-gene” disorders, because only a very small amount of DNA is available, special genetic testing techniques are necessary. Most PGD for single-gene conditions are now done via a technique called karyomapping. DNA samples from the sperm and egg providers, as well as from one or more family member(s) of known genetic status (gene carrier or non-carrier) are examined to identify a unique DNA “fingerprint” that is associated with the gene mutation(s) in the family. Embryos can then be tested to determine whether they carry the DNA fingerprint associated with the “normal” gene or the gene with the mutation. Overall, the accuracy of PGD is quite high and the risks are low, but we always recommend discussing the specific details with your providers.

Genetic testing in recurrent pregnancy loss

When an individual or couple has suffered two or more first-trimester pregnancy losses, part of their evaluation includes “genetic testing.” This testing is a karyotype, a blood test to evaluate the total number and arrangement of chromosomes in an individual. A normal karyotype for women is 46, XX and for men, is 46, XY. The most common cause of miscarriage is aneuploidy (abnormal number of chromosomes) in the embryo/fetus, which is most often a sporadic event.

However, in 2-5% of patients with recurrent pregnancy loss, there is an inherited chromosome abnormality in one of the parents which contributes to abnormal chromosomes in the pregnancy, resulting in a miscarriage. The most common inherited chromosome abnormality is a balanced translocation (in which two chromosomes “break” and exchange pieces, leading to the possibility of “unbalanced” eggs/sperm and embryos). IVF with PGD can be used to identify viable, balanced embryos to help such couples conceive a healthy pregnancy.

Genetic testing in male factor infertility

A critical part of the evaluation of men with azoospermia or severe oligospermia (sperm count <5million/mL) includes two genetic tests. The first is a karyotype to assess for chromosome number and arrangement. 10-15% of men with azoospermia and 5% of men with severe oligospermia have an abnormal karyotype, most often a sex chromosome abnormality (Klinefelter’s syndrome, 47, XXY) or a translocation (chromosome rearrangement) which can result in decreased sperm production. Such tests provide not only an explanation for the low sperm count, but also information about the man’s ability to successfully conceive a healthy pregnancy.

The second genetic test is Y microdeletion testing. 16% of men with azoospermia or severe oligospermia are found to be missing a very small piece of the Y (male) chromosome. Specific regions of this chromosome, known as AZFa, AFZb, and AFZc region contain genes that are important for sperm development. Microdeletion of the AFZc region has been associated with severe oligospermia, while microdeletions of the AFZa and AFZb regions are associated with no sperm production. Couples in which the male partner has an AFZa or AFZb deletion will most often need donor sperm to grow their families. Sons born to men with the AFZc microdeletion are expected to be healthy and will likely have severe oligospermia as well.

These are just a few of the ways in which we can use genetic technologies to improve outcomes for our patients. It is an exciting time in reproductive genetics, and we look forward to continuing to educate our patients about these promising advances.

More information can be found on the Oregon Reproductive Medicine and ORM Genomics websites oregonreproductivemedicine.com and ormgenomics.com.

Continue Reading
Advertisement
Comments

Fertility 360

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

Published

on

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.
Continue Reading

Fertility 360

Fertility And Sex: Why Her Orgasm Matters

Published

on

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!

Continue Reading

Fertility 360

What Is Polycystic Ovary Syndrome (PCOS)?

Published

on

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

Continue Reading

Trending