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7 things every woman should know before freezing her eggs


As women age, the likelihood of chromosomal abnormalities climbs, and with it, the risk of miscarriage, birth defects or disorders that makes conceiving more difficult. Egg freezing is seen by some as a way to stop the biological clock, expand reproductive options and preserve the younger, possibly healthier eggs. And for many women looking to extend their childbearing years, it has has become an increasingly attractive option.

The nation turned its attention to the issue in October when Facebook and Apple announced that they would cover up to $20,000 in costs for the procedure.
But just how successful is it? How invasive? How expensive? When it comes to the details, is this something women should seriously consider? And if so, who?
We turned to experts for the answers. Here’s what they told us.

What does egg freezing mean, exactly?

The process of egg-freezing, or in medical speak, oöcyte cryopreservation, involves stimulating the ovaries with hormones to produce multiple eggs, retrieving the eggs from the ovaries and taking them to the lab, where they’re cooled to subzero temperatures to be thawed at a later date.

Why might a woman opt to freeze?

Reasons vary. Some women choose to freeze their eggs for medical reasons. Cancer treatment, for example, can be toxic to the ovaries and cause premature menopause. Dr. Nicole Noyes, director of fertility preservation at New York University School of Medicine, said she’s overseen more than 200 cycles for medical reasons, mostly cancer, with women evenly divided between lymphoma, breast and gynecologic cancers.

But it’s not all medical. About three-quarters of the women who freeze their eggs do so because they don’t have a partner, Noyes said. She is the senior author of a New York University study released in May 2013.

“The primary reason given by women we surveyed is that they are not in a relationship conducive to childbearing,” Noyes said. “The second reason is women have something they need to get done before children, whether that’s their career or school.”

Indeed, among the first wave of egg freezers — those who froze their eggs from 2005 to 2011 — more than 80 percent had no partner, said Sarah Elizabeth Richards, author of the book, “Motherhood Rescheduled: The New Frontier of Egg Freezing.”

But the “why” is shifting, Richards said. Women are increasingly deferring childbearing in order to focus on demanding careers, and the age has dropped.

“The average age at which a woman freezes her eggs is now 36,” she said, down from 38. “Now, and really starting with [the Facebook and Apple announcement], we’re seeing women freeze their eggs younger and younger, and the public narrative around it is changing. Women are doing it for work now, which is very different from the first wave of freezers.”

How invasive is the procedure, and how risky?

The process of retrieving eggs is identical to the first phase of in vitro fertilization, or IVF.

“You are going to get anesthesia and there will be a needle puncturing your vaginal wall,” said Dr. Jaime Knopman, an endocrinologist and infertility specialist with the Reproductive Medicine Associates of New York. “That has a risk for infection, but as far as surgical procedures go, it’s a low-risk one.”

The procedure goes like this: The woman receives a round of hormone injections that stimulate the ovaries to produce multiple eggs. This stage involves frequent visits to the fertility clinic, about five in 10 days, while the ovaries are regularly monitored by vaginal ultrasound. After roughly a week or two of hormone treatments, the eggs are retrieved.

“I think people picture that it’s months of shots and invasive procedures, but in the end it’s a maximum of two weeks,” Knopman said.

The egg retrieval process takes about 10 minutes and is done under mild anesthesia or sedation. Using an ultrasound, the doctor guides a needle through the vagina to the ovarian follicle containing the egg. A suction device at the end of the needle removes the eggs from the follicles.

Retrieving the eggs is technically not that different from getting blood drawn, Noyes said. A needle goes into the ovary and the eggs get gently aspirated out.

“It’s just in a different area of the body: the vagina,” she said. “That makes people eyes bulge when I say it. But it’s exactly the same as a routine IVF retrieval.”

While the surgical procedure is mostly safe, the hormone shots do carry a risk of ovarian hyperstimulation syndrome, or OHSS, which makes some women ill, said Dr. Samantha Pfeifer, chair of the American Society for Reproductive Medicine practice committee. That occurs when a woman responds too aggressively to the hormones and the ovaries become swollen and painful. It can be accompanied by nausea, vomiting and abdominal pain.

When hyperstimulated, the ovaries produce a lot of fluid, which has to be drained from the abdomen with a needle. OHSS tends to happen in younger women in their 20s and 30s, she said, and occurs in less than 5 percent of patients. But in severe cases, OHSS increases the risk of kidney failure and blood clots and in very rare instances, can be fatal.

“It can be managed,” Pfeifer said. “But you can’t always predict who will get it or 100 percent prevent it.”

Will the hormone shots make me crazy?

Not really, but they do cause moodiness and bloating. Noyes compared it to eating too much pie after Thanksgiving.

“You feel more bloated than you do after eating pie. The hormones make the ovaries swell a little bit, because they have to create space to accommodate the multiple expanding follicles, each containing a maturing egg,” Noyes said.

“It’s funny sometimes hearing how people say they feel,” Knopman said. “I’ve had patients tell me they feel amazing and awesome. I’ve had people say they feel great and others say they feel tired. In general the emotions are steady, and I don’t see patients having a crazy, emotional response.”

What are my chances of having a baby later if I freeze my eggs now?

The chance that a single frozen egg will lead to a live birth is about 2 to 12 percent,according to the American Society for Reproductive Medicine. That’s why doctors often recommend having a couple dozen eggs frozen to maximize success.

Success is based on a number of factors, from a woman’s age to the quality of her partner’s sperm, Pfeifer said. According to one study published in the journal Fertility Sterility in May 2013, a 30 year-old woman with two to six thawed eggs had a 9 to 24 percent chance of one of those eggs progressing to a live birth, depending on the method of freezing. At age 40, that number dropped to between 5 to 13 percent.

In a January 2013 report, ASRM said that egg freezing technology has “improved dramatically” and that it should no longer be considered experimental. But the study concluded that there wasn’t enough data to recommend egg freezing for the purposes of delaying childbearing. More data is needed on safety, efficacy, ethics, emotional risks and cost effectiveness.

Is a 35-year-old egg that’s been frozen really healthier than a 40-year-old egg that’s been freshly harvested?
It may be hard to believe that an egg removed from its natural state and frozen for years could more readily lead to a baby than a slightly older egg that’s remained inside your body. But Knopman insists that if you’re a woman in your early 40s, eggs that were frozen in your late 30s are your best chance of conception.

“The most important thing for eggs is time. The younger the egg, the healthier it is,” Knopman said.

Noyes agreed.

“Absolutely. Those younger eggs are healthier,” she said.

But freezing the eggs can cause some damage. Once fertilized, the egg becomes an embryo. Doctors often follow embryo development for about five days in the incubator looking for “blastocyst” formation at the end of this time period. The blastocyst is comprised of two parts; an outer layer, known as the trophectoderm, which is destined to become the placenta and an internal cellular ball called the inner cell mass, which ultimately forms the embryo. Fewer frozen eggs make it the blastocyst stage, Noyes said. But, she added, “the eggs that do seem just as good as fresh eggs.”

But there have been no studies yet on how long eggs can be frozen and survive the thawing process, Pfeifer says. She chaired the American Society for Reproductive Medicine’s committee that declared egg freezing no longer an experimental procedure. At the time, the longest any egg had been frozen was four years, she said. In the majority of studies, the eggs were frozen for a few weeks or months. That’s something that women who don’t plan on having children for a long time need to consider, she said.

“The expectation is they should be fine, but has anyone frozen an egg for 20 years and used it? No,” she said. When to freeze is a matter of opinion; many doctors see 34 as a good age to freeze eggs, though some recommend younger, Pfeifer said.

But Noyes said her clinic recently had success with eggs frozen for seven years — a promising sign, she added.

“Women definitely feel empowered by the experience,” she said. “They come in scared of not having a baby and they leave with their eggs in the bank. They feel like they have a much higher chance of having a baby later.”

Is this an elitist thing? How much does the procedure cost?

At most centers the egg retrieval procedure costs about $10,000, and that doesn’t include the drugs, which alone can range from $3,000 to $5,000.

“Some people will have their medication covered by insurance companies and some will not, because it’s considered an elective procedure,” Knopman said.

Cold storage costs from $500 to $1,000 in annual fees. And when you’re ready to use the eggs, they must be thawed and then fertilized to prepare for the IVF process. Each round of IVF costs somewhere between $3,500 and $5,000.

“So, for now, without insurance coverage, it’s a rich person’s game,” Noyes said.

With no guarantee on how long the eggs will be viable, freezing eggs isn’t always a financially or medically sound choice, especially when women don’t know when — or if — they will want to use them. It’s better to freeze eggs when women are young and healthy, but a woman in her 20s should carefully consider the costs and risks, Pfeifer said.

Egg production starts declining after age 35, Pfeifer said, so a woman in her late 30s or 40s may need to go through the hormone treatments and collection cycles several times. And not all the eggs will be good. Among women over 40, about 15 percent of the eggs produced will be normal, Pfeifer said.

Many doctors recommend freezing about 20 eggs.

“These cycles are not cheap,” Pfeifer said. “You have to think about an individual going through this four times to store up to 20 eggs.”

And Richards pointed out that in certain markets, costs are declining, making the procedure more accessible. Some clinics now offer package deals, where they’ll lower the price if you do three or more rounds of egg retrieval.

“There are some markets offering it for as low as $4,000. When I froze my eggs it cost $13,000, so that’s a big difference,” Richards said. “And at the moment, there is some theoretical talk about parents gifting egg freezing to law school graduates. In reality, when parents know more about egg freezing, it will become more common to have that conversation.”
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No Date, no money, and working stress — over 80% Taiwanese women are not married

Figure the percentage of unmarried female with the different age spans

Original article: (Chinese news)
Translated by Andrea Chuang

Directorate-general of Budget and Accounting, Taiwan, has published a survey investigated the marriage and occupation statuses of nationwide females over 15 years old. It pointed that the percentage of getting married late in life is much higher than before, and the total percentage of unmarried female is 32.55%, and the peak is in the group of 25-29 years (~80%), which increases most in last 20 years.

As the figure displayed, the percentage of unmarried female is 28.52% in 1993, 29.71% in 2003, and 32.55% in 2013 ( increase around 3% in the last decade). The ascending trend seems getting faster and faster recently.

Universal higher education universal higher employment rate are the main reasons

Under 24 years old, the females mostly concentrate on their academic works, and then it makes the percentage of unmarried is as high as 97%. Receiving higher education was not that common in the early stage of Taiwan, however, the social concepts and structure has been changed dramatically and the education period in the females' lives has extended currently. Thus the extending education period delays both in getting into employment and marriage. Otherwise, most female labors are in the industry of commerce and services, and their working places may be broader than before, so these working women would not decide to enter into another family life that soon.

Financial and working stress are the associated reasons

According to the results of this survey, three main reasons to make the females unmarried are "lacking dates", "lacking money", and "working stress." Except the first reason, the other two are related to the recent social structure. Since the modern females mostly are working, they have more responsibility to help the financial status of their original families. Additionally, lower wages and higher house prices are another concerns. In conclusions, stable wages, sharing the housework, and having similar family plans are three main incentives for the modern women to get married. If they could keep their jobs, it motivates them to get married.

Related articles:
Career first, children later: Taiwan women put their eggs on ice
AMH test: To Know More about Your Ovaries!! (online test)
Women-Friendly Industry: Apple/Facebook offer to cover your egg freezing now!
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What’s next for the world’s 5 million IVF babies?

Studying 20 years’ worth of data is helping scientists to understand the long-term health effects of IVF – and how to improve its success rate and safety

by Helen Massy Beresford

When in-vitro fertilisation (IVF) began in 1978, some scientists were worried that the babies born as a result of it might suffer birth defects and health problems.

Intensive research in the early years, and a thriving population that has now grown to more than 5 million IVF children worldwide, have reassured scientists, but they have not stopped studying and trying to improve the process.

Recent discoveries in epigenetics – the study of how environmental factors can affect gene activity, and how a person’s risk of getting chronic diseases is “programmed” into them before they are even born – have opened up new possibilities.

In IVF, eggs are removed from the ovaries and fertilised with sperm in a laboratory before being placed in the uterus. Initially, women are often given drugs to suppress their menstrual cycles before taking fertility hormones designed to make them produce more eggs to be collected and fertilised. The technique can be used to overcome infertility caused by blocked fallopian tubes, reduced fertility in the male partner or unexplained infertility, among others.

Researchers are looking into the subtle effects each part of the IVF process can have on a developing embryo – effects that continue into later life.

A priority is finding out how elements of the IVF process – such as freezing the embryos, how they are grown in the lab, how long they are kept out of the mother and how they are stored – could be responsible for those effects and how tweaks to the process could make it even safer.

Much of today’s research stems from the Barker hypothesis, which proposes that birth weight may be linked to the likelihood of getting certain diseases. IVF babies are known to have lower average birth weights – even if the difference, at about 20-30 grams, is small. Scientists are now investigating whether IVF conception equates with more hospital admissions, and an increased risk of cardiovascular disease, high blood pressure and diabetes in later life.

Researchers take great pains to point out that the risks for an individual born after IVF are tiny – but they could be significant for society.

“I’m involved in IVF treatment myself,” says Professor Daniel Brison, scientific director of the department of reproductive medicine at Central Manchester and Manchester University Hospitals NHS Foundation Trust, who is looking at the long-term health of IVF children as part of the EpiHealth consortium, an EU research project.

“On an individual level, things that children will do in their later life will have much more influence on their health,” Brison says.

But across the broader population, the subtle effects the process may have on those born from IVF could have an impact – for example on the kind of healthcare they might need in later life.

“We have 2% of babies born through IVF every year, so this is an important issue for them and for society,” Brison adds.

His team is linking a database of 110,000 IVF births dating from 1991 to 2009 held by the Human Fertilisation and Embryo Authority (HFEA) to other health databases to investigate patterns in IVF children’s health.

His is not the first such study. Alastair Sutcliffe, professor of general paediatrics at University College London’s Institute of Child Health, carried out a study last year using the HFEA database and cancer registries that showed there was no overall increased risk of cancer among children born from IVF compared with the population at large.

“We will revisit the data in five years to see if we continue to get good news, as cancer is a major outcome and normal risk is a measure of normal resilience,” Sutcliffe says.

Brison’s current project is linking the HFEA babies’ data to Scottish medical records to find out whether IVF babies have an increased risk of hospital admissions and growth abnormalities.

“We’re interested in following up the long-term health of babies, but it’s a long time to wait,” Brison says.

That’s where the study of early human embryos comes into its own – as part of EpiHealth they are also being studied to determine whether the length of time they are kept in culture in the lab, or whether they are frozen, changes the embryos in a way that could make them more susceptible to disease in the long term.

Patients at Brison’s Manchester fertility clinic who have used all the embryos they need to conceive their children are given the option of donating their extra frozen embryos either to others to help them conceive, or to research such as this. “We see that human embryos have stress pathways and they do seem to be changed in response to different conditions in the environment,” Brison says. “This may allow us to improve IVF conditions to reduce stress to embryos and increase success rates and safety.”

Brison adds: “IVF has been of tremendous benefit to millions of couples – we just need to make sure we’re practising this technology in the safest possible way.”

He is also working closely with Tom Fleming, professor of developmental biology at the University of Southampton, who is taking advantage of the shorter lifecycle of mice to gather data from in-vitro fertilisation of their embryos.

Fleming’s team, also part of EpiHealth, is focusing on the effects of maternal age, of embryo vitrification – a form of freezing – and of different periods of embryo culture: three common themes within IVF-related medical treatment.

The mouse studies can be used as a starting point to look for similar effects in humans. The team has found that mouse embryos that are transferred to the mother later in their development as blastocysts – fertilised eggs that are left for five or six days to mature before transfer – grow into babies with a greater risk of cardiovascular problems in adulthood.

Blastocyst culture is often used in human IVF because it allows embryologists to select the embryos that seem to have the best chances. The mouse study led clinicians to study data on human IVF children and find that they, too, showed signs of raised blood pressure.

“There’s evidence that some aspects of the cardiovascular and metabolic health of IVF children is affected – high blood pressure and body fat composition may be different, as well as evidence of more advanced bone age,” Fleming says.

“There are a number of not life-threatening, but important changes in health, and the population is still young. How the health of these people will be in the future, we honestly don’t know,” Fleming adds. Some of these findings seem to fit in with the results of animal studies that suggest some of the technologies used to aid fertility may increase the risk of cardiometabolic diseases in later life.

Studying mice also has another advantage: they are not generally infertile, meaning that the effects of the different technologies on the embryos can more easily be seen.

Nick Macklon, professor of obstetrics and gynaecology at the University of Southampton, who is also carrying out research as part of EpiHealth, agreed that separating the effects of underlying infertility from the effects of the process to correct it was a challenge for IVF researchers, for example when looking at birth weight.

“One of the problems has been finding out if it is something about the parents’ infertility itself which means that when the baby is born it’s slightly lighter, or if it’s the IVF process. Where the consensus seems to be going is a bit of both.”

Macklon, who is also director of the Complete Fertility Centre in Southampton, foresees a move towards more natural IVF that is less reliant on administering hormones to the mother. “I think what we’re seeing is a general trend towards recognition that the more natural the process can be the better.”

New, safer techniques for freezing embryos open up greater possibilities for storing them until they can be transferred, so the use of hormones to artificially stimulate the mother’s cycle can be avoided or minimised.

Techniques to analyse the fluid in the uterus into which the embryo is placed have shown that the environment in the uterus is changed by the hormones, Macklon says. “Therefore there could be some benefit in avoiding them.”

Macklon is looking for ways in which IVF patients can improve their chances by ensuring their health is as good as it can be and that their embryos are of the best possible quality.

“We have for the first time been able to analyse the nutritional content of the uterine fluid in which the embryo develops. We’ve found out the amino acids that are in there and we’ve shown that this can be affected by diet.”

Fleming’s team has also shown, in mice, that the mother’s diet changes amino acid levels in the uterine fluid with lasting consequences.

“Poor maternal diet causes the amino acid levels to decline and embryos can sense this,” Fleming says. Embryos react to the information they get from their environment, using it to “decide” how efficient the placental tissue should be later in pregnancy. “In mice, if the wrong decisions are made, it leads to long-lasting effects, associating with adult cardiovascular disease,” Fleming says.

Macklon’s team is halfway through a randomised study that should show whether a Mediterranean diet could help improve embryo quality.

The scientists all stress the importance of continued research into one of the most closely studied groups of people in history, who are still only in their early 20s. It will be important to study them as they reach middle age, when they are more likely to start to pick up early onset diseases such as type 2 diabetes and cardiovascular problems, as predicted by the Barker hypothesis.

Macklon says: “We know that the environment in which we are conceived and in which we develop in the uterus can have effects right through our lives. It is important that we follow up children right through into late adulthood and look at their offspring to make sure that we don’t just consider the sense of reassurance we have now – which is considerable, a closed book. We’ll only know the answers to some of these questions in 20, 30 years, but so far it looks good.”

What's next for IVF?
Freezing embryos

The first baby born from IVF using a frozen embryo was in Australia, in 1984. Freezing embryos maximises the chances of conception from one artificially stimulated cycle – more are produced than are needed, some can be frozen, stored and transferred at a later date. Freezing also opens up the possibility of cutting the use of artificial hormones as embryos can be placed in the mother later, at the appropriate point in her natural cycle.

The more recent introduction of a fast-freezing technique, known as vitrification, has improved the chances of frozen embryos surviving. Data from a Danish study has shown that babies born from frozen embryos are slightly heavier than other IVF babies, but it is not clear whether that is to do with the freezing process itself, or the fact that hormones were not needed, Nick Macklon, professor of obstetrics at the University of Southampton, says: “We’re just beginning to understand some subtle effects of freezing and thawing on the embryo. It may well be that, in the future, it will be routine to freeze all embryos and transfer them in the normal cycle.”

Avoiding hormones
“Using a natural cycle would be best, but it is hard,” says Alastair Sutcliffe, professor of paediatrics at the University College London. Macklon agrees – his team has been researching the hormone-stimulation phase of the IVF process. “If you stimulate more mildly, you get better quality embryos and perhaps a healthier uterine environment. If you take that to its logical conclusion, people are beginning to ask if one reason why the babies are slightly different in weight is because of the effect of these hormones on the uterus.” With advances in freezing techniques, there is a trend towards putting embryos back into a much more natural, physiological cycle, Macklon adds.

Fewer embryos
Improvements in IVF techniques and success rates have led to a trend towards transferring fewer embryos to the mother to cut the risks of miscarriage and health problems related to multiple pregnancies.

Time-lapse technology
A recent important development is time-lapse incubators containing cameras, allowing IVF doctors to leave embryos undisturbed between fertilisation and transfer. Previously, embryos had to be removed from their incubators every day for analysis under a microscope. Time-lapse technology also gives more detailed information on how the embryo is developing. “This is a tremendously powerful technology which we think will improve IVF treatments considerably,” Daniel Brison, of Central Manchester and Manchester University Hospitals trust, says.

Natural incubation
Reviewing how the embryos are cultured should be part of the drive to get as close as possible to a natural process, Macklon says. “There are companies looking at developing devices which you can load embryos into, put them in the uterus and use the uterus as an incubator. I think that’s going to be something that we’ll see coming on line in the next year or so. It’s quite an important possible development.”

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Individualized IVF Program for overseas customers

Individualized Program
The procedure of overseas customers undergoing IVF is as follows,

Step 1. Paper Work
For registration of IVF related treatments (e.g. autosomal IVF, oocyte-donating, sperm-donating ...) in Taiwan, the Department of Health Promotion Administration
required paper works as follows,

a. Two forms of picture IDs (Your passport must be necessary)
b. Certificate of Marriage which must be certified by Overseas Office of Republic of China, Taiwan
c. Agreements of IVF/Oocyte Recipient/Sperm Recipient programs

(Notes: If you are taking an oocyte/sperm donating cycle, both agreements for IVF treatment and oocyte recipient are required.)

Step 2. First visit and Examinations
Before starting the main treatments, several checkup exams must be done to confirm the uterine condition and male factors. They are listed as follows, (You can provide the clinical reports at your local hospitals, or just take the exams when you visit Stork Fertility Center. )

a. Sperm Analysis
b. Hormone tests (AMH, TSH, PRL ...)
c. Hysteroscopy (The clinical report within half year is more recommended.)
d. Hysterosalpingography (The clinical report within half year is more recommended.)
e. Cervical culture (Chlamydia DNA test and HPV test are also recommended.)
f. Sperm Cryopreservation: If your spouse cannot visit us on the oocyte retrieval date, it is better to preserve his sperm sample in advanced.
g. Bring the prescribed medicines

(Notes: You may spend two to three days staying in Taiwan to complete the exams and required documents. For this visitation, it's necessary for both you and your husband.)

Step 3. Stimulation Cycle

IVF treatment is divided into two cycles: oocyte retrival cycle and transfer cycle.
For either cycle, please tell your consultant that you are ready to start the treatment when you get your period on the first day. Then the medication instruction, embryo culture information, medical reports, etc. will be sent on Stork Fertility Center APP. Please allow to enable push notification and keep an eye on it.

oocyte retrival cycle

transfer cycle

 Register:Oversea Form
 Facebook:e-Stork FB Page

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IVF program in Stork Fertility Center

Hystereoscopy (H-scopy)and Cervical Bacteria Culture:

Uterine condition plays a crucial role for embryo implantation. H-scopy is better to be arranged on MC day 7 to 11, when the endometrial thickness would not affect the examination of uterus lining. Fasting is required for eight hours prior to H-scopy, because of anesthesia safety for the uterine polyps removal.

Cervical Bacteria Culture prevents infection or inflammation during embryo transfer going through female vagina. There are three tests included in the exam,

More info:
➤ Examinations before the transfer

Ready to My IVF program in Stork Fertility Center

Follicle stimulation It starts from the 3rd day of your menstrual cycle, and the specialist will prescribe the most adequate medications of human recombinant follicle-stimulating hormones based on your original ovarian status. When it comes close to the date of ovulation (commonly on MC day 14), ultrasound monitoring and serum hormone exams are required to provide the actual size and maturation progress of stimulated follicles for the specialist.

Caution: Herbal medicines and other medicines containing hormones are forbidden during stimulation, and they may affect the outcomes of stimulation.

Oocyte retrieval 
Through transvaginal ultrasound-guided probe, the oocyte-pickup needle aspirates the follicle and also removes the oocyte inside. The lab technician then check the existence and quality of oocyte under a microscope immediately. After removing the cover of cumulus cells, the maturity of oocyte is confirmed. Only the mature oocyte (MII) is able to be fertilized.

Ferilization and Fresh transfer/Cryopreservation

The mature oocyte is fertilized by the washed sperms either by direct insemination or intracytoplasmic sperm injection (ICSI). After culturing for 5 to 6 days in vitro, the best embryos are at blastocyst stage and ready to be transferred into the womb if the hormone levels and uterine condition are both appropriate. Otherwise, cryopreserving these blastocysts in the liquid nitrogen until your favorite transferred month is quite popular in recent IVF programs. Frozen-thawed blastocyst transfer (FBT) is more patient-friendly for the women with tight schedules or overseas customers.

Luteal Support
After transferring of the precious blastocyst into the womb, the specialist would prescribe suitable medications to maintain the steadiness of your endomerium. The implantation of embryo may happen during the 4th day to 7th day after transferring. The serum β-HCG could be detected after 14 days to check the pregnancy.

Cautions: Smoking, drinking and caffeine are forbidden after embryo transfer.
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Twins born through IVF "more likely to suffer problems"

Giving birth to twins through fertility treatment substantially increases the risk to both mother and children, new research finds

by Sarah Knapton

Twins born through fertility treatment and their mothers are far more likely to suffer problems than single births, new studies show. Until recently fertility clinics implanted several embryos to increase the chance of conception, but the practise led to women regularly having more than one child.

Now new research has shown that even giving birth to twins through fertility treatment, such as IVF, substantially increases the risk to both mother and children. They were five times more likely to need a Caesarean section and 10 times more likely to be born prematurely.

Prof Barbara Luke, at Michigan State University, looked at the birth outcomes for 6,000 single pregnancies and 2,500 twins. "And what we found was that being a twin versus a singleton at birth increased the risk for all outcomes except for of course large for age," she said. Multiple pregnancy is the single biggest risk of fertility treatment, according to the Human Fertilization and Embryology Authority.

It increases the risk of stillbirth, neonatal death and disability in children born. It also increases the risk of dangerous complications to the mother, such as late miscarriage, high blood pressure and pre-eclampsia.

On average, one-in-five IVF pregnancies are a multiple pregnancy compared to one-in-80 for women who conceive naturally. UK guidelines advise that wherever possible a single embryo only should be transferred, but some clinics still put back more – sometimes because the patient wrongly thinks it improves their chances. However, the research suggests that it is safer to transfer single embryos.

Dr Rebecca Sokol, president of the American Society for Reproductive Medicine, said: "We have long known the dangers of high order multiple pregnancies.

"This research shows us how risky even twin pregnancies can be. Clearly, the trend toward using single embryo transfer needs to continue."

The research was presented at the American Society for Reproductive Medicine annual meeting in Honolulu, Hawaii.

Data Source: Stork Fertility Center, 2011

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Women-Friendly Industry: Apple/Facebook offer to cover your egg freezing now!

Facebook, Apple offer to cover costs of freezing eggs for female staff

by Michelle Starr

Data source:, 2012

-- Apple and Facebook have updated their company benefits policies to include fertility treatments in a bid to retain female staff.

From January 2015, Apple will cover up to $20,000 for freezing eggs for both full- and part-time staff in the US, including the extraction procedure and storage costs, while Facebook has been offering the benefit up to the same amount from January this year.

"We continue to expand our benefits for women, with a new extended maternity leave policy, along with cryopreservation and egg storage as part of our extensive support for infertility treatments," Apple said in a statement. "We want to empower women at Apple to do the best work of their lives as they care for loved ones and raise their families."

The company also introduced extended parental leave, while Facebook offers four months of parental leave for both mothers and fathers, as well as adoption and surrogacy assistance, and other fertility services for male and female staff. Apple offers assistance for adoption, too.

"Egg freezing gives women more control," said Jennifer Tye, marketing lead for fertility app Glow. "When I turned 30, I had this notion that my biological clock was ticking, but I didn't know what my options were. These employers should be commended."

Warwick Business School professor of human resource management James Hayton, who researchers how companies attract and retain talent, noted that the policies, though bold, are likely to benefit those companies who are brave enough to offer them.

"Egg freezing is one in a long line of innovative HR practices intended to be attractive to educated people with many employment options, seeking a focus on flexibility in the difficult balance between work and life," he said.

"The costs appear to be moderate, although not trivial, at about 20 percent of average annual salary at these firms. The benefits, in terms of attracting and retaining employees, can be expected to significantly outweigh the costs. The positive PR will pay for itself by signalling these employers' values, with respect to women's control over this important life choice, to prospective female employees."

Original Source:

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Advances May Improve Success Rate for In-Vitro Fertilization

Two New Techniques Aim to Make It More Likely That a Single Embryo Will Lead to a Pregnancy

by Lisa Ward

New techniques offer the possibility of improving a patient's odds of having a baby through in-vitro fertilization. A single IVF cycle has about a 32% chance of resulting in a live birth, according to statistics from the Centers for Disease Control and Prevention. To improve the odds, doctors often implant multiple embryos in the uterus during a single IVF cycle, leading to a high rate of twins and triplets. Multiple births can lead to serious health complications for mother and child and significantly increase health-care costs, says Emre Seli, director of the Yale School of Medicine's division of reproductive endocrinology and infertility.
Two new techniques aim to improve the likelihood that implanting a single embryo will allow a patient to have a baby.

A. Screening Chromosomes
The technique furthest along, and already used in select clinics around the world, is called preimplantation genetic screening. In this procedure, cells are removed from the embryo on day five (or day six) to see if the normal amount of genetic material is present. An embryo should have 23 pairs of chromosomes; those with extra chromosomes or missing chromosomes are considered less viable.

"Chromosome abnormality is the main cause of miscarriage," says Richard Scott, clinical and scientific director at Reproductive Medicine Associates of New Jersey, a fertility clinic and the reproductive endocrinology and infertility division of Rutgers University's Robert Wood Johnson Medical School.

(The process is different from searching for a specific disease or genetic disorder that is likely to manifest later in life, which is known as a preimplantation genetic diagnosis.)

Chromosomal screening has shown promise in three small, randomized studies. A study co-authored by Dr. Scott, for instance, found that transferring a single embryo after chromosomal screening resulted in a similar rate of live births as transferring two untested embryos.

Still, some experts say more research is needed.
"A major study with an adequate number of patients is needed to definitively determine the degree of benefit," says Christos Coutifaris, chief of reproductive endocrinology at the Perelman School of Medicine at the University of Pennsylvania, adding that this is especially true given the price tag. The procedure costs about $4,000—a hefty fee on top of an already expensive process that often is paid for out-of-pocket. The average IVF cycle costs about $12,400, according to the Society for Assisted Reproductive Technology.

B. Monitoring Cell Division

Time-lapse imaging, which costs about $1,500, is a less invasive method of evaluating embryos. It's already used in clinics around the world, but new types of time-lapse screening are just becoming available commercially. With time-lapse imaging, thousands of pictures are taken to record a fertilized egg cell dividing. Eggs dividing atypically are unlikely to survive.

"The embryo's fate can be determined very early in development," says Barry Behr, director of Stanford University Medical Center's IVF laboratory.

Dr. Behr co-wrote a study identifying three markers that determine if a four-cell embryo (on day two) is likely to reach blastocyst, a critical stage where it has divided into about 120 cells (on day five) and has a better chance of implanting in the uterus. The study created an algorithm to do the analysis automatically.

Auxogyn Inc., based in Menlo Park, Calif., and Unisense FertiliTech AS, based in Copenhagen, make devices that use time-lapse imaging. Both companies are coming to market with products that use algorithms to automate the evaluation process. Currently most clinicians analyze time-lapse imaging subjectively.

Time-lapse imaging may also work in tandem with chromosomal screening, since it provides information about an embryo's metabolisms unavailable through genetic testing. An initial study was promising.

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The Success Rate of Oocyte Donation Program in IVF

baby, child, father

Having a baby was so arduous when you could get only one or two eggs in every IVF program...

According to the statistical results made by Department of Budget and Accounting in Taiwan, the average age of women getting married was 29.4 in 2011. Late marriage becomes more common, and the percentage of pregnant women with advanced maternal age (>35 yrs) has reached 17.7% last year. Busy work and deteriorating environment are the main causes to the decline of female fertility, and they force the modern women to face the problems of premature ovarian function failure or embryo chromosome abnormalities.

To choose the oocyte donation program seems like an easier and more efficient way. 

Because young women provide their eggs with better quality and remarkable amount, the pregnancy rate of the oocyte-recipient group increases to 70% in many published data. Spanish researcher, Dr. Garrido and his team calculated the cumulative live-birth rate of 8,895 couples undergoing oocyte recipient program from 1998 to 2010. They also analyzed the effects of the maternal age, primary infertile cause, and date of embryo culture of these cases.

As Figure 1 displayed, a single transferred embryo generated the cumulative live-birth rate as 64.8% in oocyte-recipient program, and each additional transferred embryo increased the cumulative live-birth rate with 12.3%. The cumulative live-birth rate reached 85.2% when the amount of transferred embryos was 10, and it came to the maximum as 96.8% when the transferred number was 25.

Figure 1

Similar curves was obtained when the study group was separated either by the maternal ages (Figure 2), or by the infertile causes (Figure 3). Thus the advanced age and other clinical factors affected fertility seemed not that critical in the oocyte-recipient program.

Figure 2                                                    Figure 3

Then the curves generated by different dates of embryo culture showed the cumulative live-birth rate was better in Day 5/ Day 6 blastocyst group than that of Day 3 cleavage-embryo group (Figure 4). Therefore, accepting donated oocytes plus blastocyst culturing were strongly recommended for the women suffering with declined ovarian reserve and repeated IVF failure. 

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Next-Gen Sequencing Gets a Fix on Disease

Article Author: Neil McKenna
Original Source:

Recent years have seen rapid advances in the capacity of molecular biological techniques to simultaneously interrogate multiple targets on omics platforms.

While these techniques are well established in basic research, they have more recently gained a foothold in clinical diagnostics, with an increasing number of laboratory tests incorporating some type of high-throughput or global-scale molecular analysis. Of these techniques, the one that arguably has the greatest potential to revolutionize our approach to diagnosing disease and tailoring therapies is next-generation sequencing (NGS).

NGS, which refers to a constellation of techniques in which DNA or RNA fragments are sequenced in parallel, offers significant increases in speed, scalability, and resolution over traditional sequencing methodologies. Testament to the considerable interest in NGS is the increasing number of conferences exclusively devoted to the topic.

One such event, GTCBio’s “Next-Generation Sequencing” conference, was recently held in San Diego. Presenters showcased the application of NGS-based diagnostic platforms in a variety of clinical settings.

Preimplantation Genetic Screening

Varied genetic prenatal conditions impact pregnancy and fetal development. Accordingly, preimplantation genetic screening (PGS) has emerged as an important clinical tool for identifying chromosomal aberrations.

Traditional prenatal screens have a number of limitations. Some screens, such as amniocentesis or chorionic villi sampling, are invasive; others, such as ultrasound or biochemical screening, are less invasive but limited in their sensitivity and specificity.

“In contrast to these techniques, noninvasive PGS-based on NGS has both superior detection sensitivity and specificity for chromosomal abnormalities,” said Keith Jones, Ph.D., vp of development at Illumina. “The Illumina verifi® test detects greater than 99% of all true-positive cases and has a cumulative false-positive rate of <0 .2="" br="">
The verifi test uses sequence information from across the genome. This approach, Dr. Jones suggested, allows for the rapid adoption of additional tests that may find abnormalities not readily detected using traditional screening approaches. Such abnormalities include sex chromosome aneuploidy, microdeletions, trisomy 9, and trisomy 16.

Approximately 1.3 million in vitro fertilization (IVF) procedures are performed globally each year; however, only 25% of the procedures meet with success. The low success rate is usually attributed to complicating factors associated with advanced maternal age and chromosomal aneuploidy in the embryo.

“The aim of PGS in the IVF setting is to select chromosomally balanced embryos during the IVF process and ensure that only euploid embryos—those with a normal number of chromosomes—are implanted during IVF procedures,” explained Dr. Jones. He added that PGS has been shown to improve implantation success rates and reduce the number of high-risk pregnancies associated with multiple egg transfers.

In Illumina’s VeriSeq™ PGS platform, genomic DNA from a single cell is amplified and sequenced to provide a genome-wide view of the copy number state of the embryo. The protocol takes less than a day and allows multiplexing of up to 24 samples per sequencing run, translating to an increased likelihood of identifying a viable embryo and decreasing the time between biopsy and an answer. “The broad dynamic range derived from the sequencing data makes interpretation clear with a high degree of confidence,” Dr. Jones asserted.

Testing for Minimal Residual Disease

“The overarching theme in the NGS molecular diagnostics space is that robust clinical validation is a must,” said Martin Moorhead, Ph.D., vp of computational biology and software development at Sequenta. The company’s LymphoSIGHT platform is an NGS-based immune repertoire analytical solution that combines multiplex PCR assays and informatics algorithms to interrogate rearranged immunoglobulin and T cell receptor genes.

“Our PCR process targets the CDR3 region and the immediate surrounding sequence, yielding amplicons that are typically around 150 base pairs in length, which is ideal for NGS analysis,” Dr. Moorhead pointed out. In the assay, sequencing of rearranged B or T cell receptor gene amplicons from patient lymphocyte samples allows for an absolute quantification of the number of each clonotype—cells all sharing the same rearranged receptor sequence in the original sample.

“The first clinical product we developed using the LymphoSIGHT platform is the ClonoSIGHT test for measuring minimal residual disease (MRD) in patients with blood cancers, including diffuse large B cell lymphoma, multiple myeloma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, and mantle cell lymphoma,” stated Dr. Moorhead. MRD refers to cancer cells that may remain in the body of a person with lymphoid cancer after treatment, and is the leading cause of relapse in this condition.

Testing for MRD can help determine whether treatment has been successful, provide important information about patient prognosis, and help guide additional treatment decisions. At its essence, the ClonoSIGHT assay compares cancer cell DNA sequences generated using the LymphoSIGHT platform in a diagnostic sample with those in follow-up samples to determine the presence of residual cancer cells.

“ClonoSIGHT test results, which are generated in seven days using our CLIA-certified, CAP-accredited laboratory, are provided in a simple, actionable report,” added Dr. Moorhead. “[The report] shows a patient’s MRD status and level as well as MRD trends over time.”

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Data source: Stork Fertility Center 2013 data
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6 Ways to Boost Your Odds of IVF Success

Original Source:

by Laura Tedesco

As the rate of first-time moms over age 35 rises—it’s up to 15 percent in the U.S. now—so does the country’s reliance on in-vitro fertilization. In fact, what was once a last-resort procedure has become increasingly routine: In 2012, U.S. doctors performed 165,172 fertility procedures—more than 99 percent of which were IVF, according to the most recent data from the Society for Assisted Reproductive Technology, reflecting a 7 percent increase over 2011.

And how many of those procedures actually lead to deliveries? Among women younger than 35, the data shows that 46 percent of the embryo transfers resulted in live births. That number drops to 38 percent for women ages 35 to 37, and 28 percent for women ages 38 to 40.

Although those stats may sound discouraging, consider this: Only 55 percent of “chromosomally normal” embryos successfully become a baby, “whether you make them at home in bed, or whether you make them in a lab,” Jamie Grifo, M.D., program director of the NYU Fertility Center, told Yahoo Health. “It’s mostly not under your control. It’s about the luck of getting a good embryo.”

But that doesn’t mean the only way to boost your chances of success is to cross your fingers and hope for the best. “There are things the patients can do themselves to actually improve the odds of IVF,” A. Musa Zamah, M.D., an infertility expert at the University of Illinois at Chicago, told Yahoo Health. “And I don’t think those things are always fully utilized.”

Kick stress to the curb

Don’t stress too much about de-stressing — just devote a few minutes every day to unwinding without totally checking out from your daily routine. “Just because you’re stressed doesn’t mean you can’t get pregnant,” Grifo said. “If that were true, nobody in New York would have a baby.” In fact, he said, eliminating every source of anxiety — say, by quitting your job — may just leave you without a distraction, tempting you to fret 24/7 about getting pregnant (which is, in and of itself, a serious stressor).

That said, mental tension definitely doesn’t do your fertility any favors, since being in chronic fight-or-flight mode can compromise the quality of your eggs, Grifo said. Plus, the stress hormone cortisol may interfere with implantation, while also blocking estrogen action in your endometrium, said Sarah Berga, M.D., the chair of obstetrics and gynecology at Wake Forest University.

Easing stress, on the other hand, may actually help speed things along: In a 2011 Fertility & Sterility study, women who watched a clown perform magic tricks for about 15 minutes after undergoing IVF were nearly three times more likely to become pregnant than the control group. So figure out what works for you — knitting, yoga, watching funny cat videos, whatever — and commit to doing it daily.

Resist the urge to over-exercise

Being fit equals higher fertility, so constantly hitting the gym is a step in the right direction, right? Not necessarily. Exercise is a form of physiological stress, which means too much of it could hurt your pregnancy odds, noted Grifo. “If you’re running 60 miles a week or training for a marathon, that’s not a good thing,” he said. “If you’re doing an hour of cardio, seven days a week, that’s not a good thing.”

You should be especially cautious about high-intensity workouts during the actual stimulation phase of IVF, when you’re receiving hormone injections, said Zamah. “You don’t want to risk the ovaries twisting,” he explained. So what’s a reasonable workout regimen? Grifo recommended 30 to 40 minutes of cardio three times a week, with yoga or light weightlifting on the days in between.

Load up on vitamin D

It’s not just folic acid you should be popping: Consider taking a dose of D, too. “Vitamin D has long been thought to be primarily important for bone health,” said Zamah. “But it can really affect all aspects of health, including reproduction.” In fact, a 2014 study in the journal Human Reproduction found that D-deficient women who underwent IVF had a 39 percent lower chance of pregnancy than ladies with normal levels of the vitamin. Although the reverse isn’t yet proven — that taking D boosts your pregnancy odds — supplementing with 400 to 800 IUs of vitamin D per day could be “potentially beneficial,” Zamah said.

Establish a healthy weight — before attempting IVF

Don’t wait until you’re ready to start trying for a child to worry about the number you see on the scale. “Doctors might be reluctant to bring this up with patients, but weight can impact the success of IVF,” Zamah said. Specifically, being overweight has been linked to poor IVF outcomes, including decreased pregnancy rate, lower live birth rate, and increased risk of miscarriage. The likely explanation? “Obesity appears to hurt the eggs and maybe the endometrium,” said Berga.

So before you start IVF, aim to get your weight into the “normal” BMI range, or as close to it as possible. “Even if you’re not fully in the ‘normal’ range, a 5 to 10 percent reduction in body weight can really be beneficial for IVF outcomes,” Berga told Yahoo Health. Just don’t go too far — being underweight can have a similarly negative effect on pregnancy success.

Consider a DHEA supplement

A third of all IVF centers across the globe now use DHEA, a hormonal supplement shown to boost pregnancy chances in women with a shortage of viable eggs, according to a recent study review in Reproductive Biology and Endocrinology.How does it work? “DHEA might help the ovary respond to the fertility medications,” particularly in patients with a low number of eggs, explained Zhama. The suggested dose: 25 milligrams, three times a day.

Get the guy involved

Your body carries the baby, but his sperm also plays a role in your IVF odds. “The male partner needs some attention, too,” said Berga. In addition to him limiting his stress and watching his weight, your partner (or donor) can also try a more targeted approach to boosting the health of his swimmers: by popping multivitamins, plus an antioxidant supplement. “Nobody has shown one antioxidant blend to be superior to another for sperm,” Zamah said. “But there are multiple studies showing at least a potential benefit on sperm parameters.”
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India's Supratech Micropath Developing NGS-based Tests for PGS, Newborn Dx, Cancer

India's Supratech Micropath Developing NGS-based Tests for PGS, Newborn Dx, Cancer

by Monica Hedger

Original resource:

NEW YORK (GenomeWeb) – Supratech Micropath, a reference and diagnostic lab in the state of Gujarat, India, is developing next-generation sequencing-based tests for preimplantation genetic screening and diagnosis, newborn diagnosis, and cancer.

The laboratory is CAP accredited and certified by India's National Accreditation Board for Testing and Calibration Laboratories. It has been offering molecular testing five years ago using PCR, Sanger sequencing, FISH, and other technologies. This year it began offering NGS tests that it markets as research-use only, and is aiming to market them for clinical use in 2015.

Parth Shah, a research scientist at Supratech Micropath, told Clinical Sequencing News that the lab has developed preimplantation tests and cancer panels on Thermo Fisher's Ion Torrent PGM. The lab currently has one PGM machine and runs around 20 to 30 tests per month, he said.

Shah said that the lab decided to go with the PGM over an Illumina system because of the cost and also because an Illumina system would have had too much throughput for the lab's needs. "In India, people are much happier with small panels," he said. And with the higher throughput of the Illumina system, the lab would need many more samples in order to fill the machine, which would have made turnaround times prohibitively long. Additionally, Shah said that Thermo Fisher has more clinical support available in India.

Thus far, he said that the lab has experienced some issues in calling variants in homopolymeric regions, but added that chemistry improvements are helping to resolve those issues. In addition, he said that the lab can now readily identify those errors, so the overall sensitivity of the assays is still very high.

The first NGS test the lab developed was a preimplantation aneuploidy test, which uses low-coverage whole-genome sequencing of single cells to look for chromosomal aneuploidies in embryos before they are implanted, Shah said. The group plans to publish its method in a journal this year.

Currently, most insurance plans in India do not cover these tests, Shah said, so patients pay out of pocket. The PGS test cost varies depending on how many embryos are screened, but is around $250 per embryo when eight are screened. The lab returns information about chromosomal aneuploidies, but will not give sex chromosome information unless there is an abnormality.

Supratech is also developing preimplantation genetic diagnostic tests for blood disorders like hemophilia and beta thalassemia, as well as for glycogen storage disorders, urea cycle disorders, muscular dystrophy, neuromuscular disorders, and lysosomal disorders.

These panels include between 20 and 30 genes each, said Shah, and can be used for both preimplantaion or newborn diagnoses.

In the realm of cancer, Shah said that the lab is offering a comprehensive AmpliSeq panel of around 400 genes, a 50-gene hotspot AmpliSeq panel, and smaller panels of fewer than 10 genes for specific types of cancer like lung or colon.

For the comprehensive and hotspot panels, the lab started with the Ion AmpliSeq kits and then "customized them for our own purposes," Shah said, adding or subtracting genes as necessary. "Where we find that the AmpliSeq panels are not sufficient, we develop our own amplicons and make them a part of those panels in order to expand them," he added.

In addition, in order to cater to oncologists in India that are not familiar with broad genomic testing and want to just analyze a few genes, Supratech offers a targeted lung cancer panel and a targeted colon cancer panel that each have only a handful of genes — fewer than 10 — but are sequenced to 1,000-fold coverage. Prices for the cancer panels also vary, but Supratech charges around 20,000 rupees ($328) for the hotspot panel, Shah said.

Thus far, Shah said the majority of tests run have been for inherited diseases and PGS. For cancer, the benefits are less obvious, and the test results more difficult for the clinician to interpret. In addition, a Sanger-based EGFR test will cost around $120, Shah said, so although a 50-gene panel test is more efficient from a cost-per-gene standpoint, physicians are not as interested in those other genes.

However, Shah said, he expects that cancer test volumes will pick up as more data accrues around the actionability of cancer genes and as physicians become more comfortable with the data.

In the future, the lab plans to develop assays to detect pathogens from body fluids, Shah said. He added that scientists from Supratech are working to validate a protocol established by a group at the University of California, Los Angeles on pathogen detection. In addition, he said the lab is working to develop a cancer panel for fusion transcripts. Currently, the lab has several PCR-based assays for gene fusions in cancer, but would like to incorporate all of those into an NGS assay.

NGS (next generation sequencing)-based preimplantation genetic screening has become another powerful platform in IVF realm. 
Array based
Sequencing based
It provides   vastly improved resolution and detection capability and more consistent results compared to traditional karyotyping, the American College of Medical Genetics (ACMG) recommends microarrays as the first approach for postnatal cytogenomic screening.
NGS offers complimentary chromosome aberration testing that can add additional mutational and higher-resolution data beyond the CNV (copy number variation) and AOH (absence of heterozygosity) capabilities of microarrays. With higher levels of functional resolution, NGS is ideal for measuring chromosome inversions, balanced translocations, and disease-associated point mutations.
(reference: Illumina. inc)
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