What’s New in Egg/Embryo Freezing: All About the TMRW Tank

Traditional Storage Tanks- Eggs/Embryos are frozen in a small vial with printed label in a designated cryotank and tracked manually or electronically through a separate system.
TMRW Tank- Eggs/Embryos are frozen in a small vial with their printed label and RFID chip in the TMRW tank, and are tracked through the integrated TMRW software system. Here is our All-star Conceptions Embryology Team with the TMRW Tank!

Egg and embryo freezing/banking have become extremely popular options over the last year. A major factor in this decision is Long Term Storage. Eggs and embryos can safely remain frozen for years until you are ready to use them. It is important to feel confident that your samples are stored at a reputable establishment in a safe, transparent, and accessible location. The TMRW tank is an evolution from our current equipment. The basic foundation is not brand new, since we have used cryotanks safely for years, but the software integration system is state of the art. It paves the way for a future where gamete and embryo data can be tracked remotely from our computers, or an app on your phone. Better still you have the assurance that your eggs and embryos are being monitored 24 hours a day every day of the year. Below is a summary of the TMRW Tank concept!

What is it?

  • TMRW Tank is the first and only automated egg/embryo storage platform
  • It links frozen egg/embryos to traceable RFID chips to completely prevent errors of identification
  • It facilitates labeling, tracking & locating samples
  • It gathers data to ensure cryogenic temperatures & egg/embryo wellness
  • It integrates all data into a software system monitored on our computers
  • It replaces old-fashioned liquid nitrogen storage tanks and manual labeling/monitoring

Why is it necessary?

  • Safer and more secure identification system- 100% digital chain of custody tracking
  • Easier monitoring in real-time with integrated software system on computer
  • Integrates embryology storage with the most up-to-date software technology

Who is using it?

  • The TMRW tank was rolled out to 30 leading fertility clinics in the US, including Conceptions
  • It was created by TMRW Life Sciences

When/where will it be in use?

  • Commercial launch was in December of 2020
  • The TMRW Tank is already at Conceptions Reproductive Associates of Colorado!

You can read more about this at https://www.tmrw.org/

Why American women are having fewer babies than ever – The Washington Post

Birth rates now are about half of what they were during the height of the “baby boom.” That’s because women are waiting to start their family until they are more settled in their careers, relationships and lifestyles. Unfortunately, this same study also found that about 40% of women between 44 and 50 years of age have had fewer children then they would have preferred. That’s why it is so important that women consider what their family buildings are and consider egg freezing during their mid thirties. Technology now offers women the best of both worlds; delayed reproduction and achieving their ideal family size!   https://www.washingtonpost.com/news/wonk/wp/2016/08/16/why-american-women-are-having-fewer-babies-than-ever/

In IVF, frozen embryos may lead to more live births than fresh embryos – LA Times

This news will come as no suprise to our patients as we have been demonstrating this for years. It is good to have yet another study that further supports this recommendation. The cautionary note here for patients is to check with their center on the method of freezing used in their lab–if it not the modern rapid-freeze technique called vitrification  then you might be better served by a fresh transfer.  http://www.latimes.com/science/sciencenow/la-sci-sn-ivf-frozen-embryos-20160809-snap-story.html

How Many EGGS do you think you have left?

You were born with every egg that you’ll ever have. Although studies suggest that there may be a process where we can create eggs; such technology is far into the future. More importantly, you’re losing eggs at a rate that far exceeds what you would guess. Current research suggests that most women will lose about 500 to 1000 eggs per month through a process of attrition called apoptosis—yet only one or two eggs each month will be capable of fertilization. A recent summary of all of the available research has shown that most women will only have about 3% of their eggs remaining by age 40.

Ovarian Reserve Curve from Conception to Menopause.png

Estimated number of remaining follicles (from birth)

Although the slope of that curve appears intimidating, the goal of this blog post is to increase your awareness and to empower you to take action. Some women are born with more eggs than others. Some women will lose their eggs at a faster rate. Most importantly, the eggs that remain in your ovaries at any given moment represent your ovarian reserve. Therefore, it is very relevant for you to consider how many eggs you have now and then plan how many (more) children you think you might someday wish to have.

This diagram shows the various stages of egg development summarized in a single ovary.

Ovary demonstrating egg development.png

It takes an egg several months to develop from its status as a primordial follicle to that of a mature fertilizable oocyte. It is only when they reach that stage that the ovary releases the egg through a process called ovulation. Fewer than 300 of your eggs are likely to ever complete this journey. In other posts on this blog, we focus on various steps you can take to optimize the health of your developing eggs; but for now let’s focus on the future of your fertility in the months and years to come.

At least 99% of your remaining eggs are dormant—alive but not metabolically active. They have been in this resting state since you were a newborn. The eggs that are in these intermediate stages of development—which represents your fertility—can be estimated by a simple well timed blood test. Consider having your ovarian reserve tested today. Then think about how many children you envision yourself having. Consider when you will be ready to start or expand your family. By doing so, you can better estimate whether or not egg freezing or embryo banking (creating and storing embryos for future use) are steps you should be considering to assist you in creating your future family.

Zika Virus for Fertility Patients: here’s what you need to know

We’re all frightened by what we don’t understand. Many infectious diseases feed in to that fear. Consider for example the recent media frenzy over Ebola Virus; then again over Bird Flu and then more recently over Chikungunya—all of which have died down without the nightmare scenarios coming to fruition. Now we’re focusing on Zika virus.  This is admittedly scary due to its possible link to birth defects in babies born in Brazil. So let’s review what we know, what we don’t know AND what we can do in the meantime.

Recently the Society of Maternal-Fetal-Medicine held a special session to review this important topic and provide updated advice and guidance for women’s healthcare specialists in the USA. Zika is a virus transmitted by mosquitos. Those developing a symptomatic infection during pregnancy may be at high risk of having a child with a birth defect known as microcephaly. Although this link has not yet been definitively established it is recommended that we provide very close surveillance of any suspected cases while additional information is gathered. Although this sounds scary here are some of the key facts to keep in mind:

  • Only 1 in 5 people bitten by an infected mosquito is likely to develop an infection
  • Those infected have pretty specific symptoms including sore joints, a rash and conjunctivitis (red, swollen areas around the eyes)
  • The infection will appear within one or two weeks of the mosquito bite
  • The current test available is nonspecific and can create concerns due to false-positive results (a positive test due to a related virus that has not been linked with birth defects)
  • The Center for Disease Control and Prevention is monitoring places in the world known to have active Zika transmission for travelers and advising those that are pregnant or planning pregnancy to avoid traveling to those locations
  • Meanwhile, alternate causes of the fetal malformations are being investigated including a possible link to an insecticide widely used to control mosquitos in the area of Brazil most heavily effected by fetal microcephaly

Clearly we need to learn more about the Zika virus. In the meantime, here is some practical advice for patients that want to become pregnant:

  • If possible avoid traveling to areas effected by Zika for at least one month prior to starting fertility treatment
  • During mosquito season (as well as while traveling to effected areas) consider the following protective steps
    • Wear long sleeves when possible and stay in air conditioned facilities (rather than using open windows for cooling
    • Use insect repellants to reduce the risk of mosquito bites. Here are two that are among the safest (and least toxic) for women trying to conceive:
    • If you live in an area with a high rate of Zika virus exposure, consider undergoing fertility treatment and freezing the embryos for delayed embryo transfer–a process known as embryo banking.
    • If you develop the symptoms of rash, joint pain and red eyes, contact your healthcare provider to discussed current recommendations on testing.
    • Stay informed. If you subscribe to this blog, I will do my best to remain current on this topic.

For the latest updated information from the CDC on this emerging problem, check out the following link: http://www.cdc.gov/zika/

Latest Update 02/29/2016: “It’s entirely possible there’s something else going on in Brazil — something unique to the population or environment in which transmission takes place.”  – Dr. Anthony Fauci, Direct of National Institute for Allergy and Infectious disease 

http://www.latimes.com/science/sciencenow/la-sci-sn-zika-microcephaly-link-20160226-story.html 

 

EGG FREEZING: the latest twist on “family planning”

For decades, “family planning” was synonymous with contraception. The Guttmacher Institute—a prominent reproductive health think tank—stated that “controlling family timing and size can be a key to unlocking opportunities for economic success, education and equality” for women. In fact, their most recent analysis concluded that effective contraception has contributed to increasing women’s earning power and narrowing the gender pay gap. Whether it’s for these reasons or not, studies have consistently demonstrated that many women are choosing to delay childbearing. The age at first birth for women is now approaching 28 year of age and the birth rate in the USA is at an all time low. As more women choose to delay (or extend) their reproductive years, it is important that more women become aware of the potential benefit of oocyte freezing. In a recent study called “Baby Budgeting” one research group described this technique of freezing/storing eggs as a “technologic bridge” from a woman’s reproductive prime to (her) preferred conception age.

Today egg freezing has made it possible for women to truly “plan their family” by storing eggs for later use. The first successful pregnancy from frozen eggs was reported in 1986. But for decades the process remained very inefficient; requiring about 100 eggs for each successful pregnancy. Therefore the procedure was considered experimental and primarily offered to women that were faced with chemotherapy, radiation or other fertility-robbing treatments used to treat serious illnesses. But with the development of more effective techniques for freezing eggs; success rates in many centers using frozen eggs is as good as it is with using fresh eggs. As a result of this improvement in pregnancy rates, the American Society of Reproductive Medicine lifted the “experimental” label from egg freezing and began supporting its use for social (rather than medical) reasons. Recently, two different studies determined that the most common reason for women to seek egg freezing as a means of protecting their fertility was the “lack of a current partner.”  That said, Facebook and Apple have made egg freezing available to their employees and many predict other companies to follow this trend as well. As more women consider this option of preserving their fertility, there are several questions that they should think about in order to create an individualized plan.

For practical reasons, the process of creating a fertility plan should be tailored to a woman’s current age, how many children she would like to have and her current ovarian reserve. Existing guidelines suggest that if a woman is in good health, less than 31 years old and with a normal ovarian reserve—she should wait and reevaluate her situation every one to three years. On the other end of the spectrum, if a woman is over 38 years of age she should consult with a board certified reproductive endocrinologist to discuss her options. So the women that are typically the most suitable candidates for egg freezing are women between 31 and 38 years of age that are seeking to delay pregnancy for at least 2 years. The “Baby Budgeting” study found these are the patients for whom the procedure is most cost-effective. A similar study found that based upon successful pregnancy rates women should ideally freeze their eggs by 35 to 37. Testing a woman’s ovarian reserve however is the critical factor in customizing these recommendations.

Ovarian reserve represents the best estimate of how fertile a woman is compared to other women of the same age. It is usually tested by means of a blood test and/or a properly timed ultrasound examination of her ovaries. Sometimes, this test reveals that a young healthy woman may have a fewer number of fertile eggs remaining than would be otherwise expected. That’s why this test is so important. It can inexpensively identify if someone should consider egg freezing prior to the 32-38 year old age range. This test is also predictive of how many eggs a woman is likely to produce in a single egg-freezing cycle. The current recommendation is that women should try to have 15 to 20 eggs available for each one or two pregnancies that she hopes to have. Many women will produce this number in a single egg-freezing cycle whereas others may need to go through the process two or three times in order to bank this many eggs. Once properly frozen, the eggs are generally considered as fertile on the day that they are thawed as they were on the day that they were frozen—effectively prolonging fertility for 10 years or longer.

Each egg frozen is estimated to have a 2 to 12% chance of producing a live birth. That’s the reason that it is recommended that women store a larger number of eggs than the number of children that she hopes to have. Doing so improves the odds of having several that are of good quality. Since a woman’s age serves as an estimate of her egg quality, online databases can provide estimates of a successful live birth based on a few simple questions. So now it is a lot easier for women that aren’t quite ready to become pregnant to create a proactive family plan that fits in with the rest of her personal and professional goals.

Here’s brief segment on Egg Freezing from Colorado & Co

Women Getting Pregnant Later AND Aging at a Slower Rate; a review of the data

Most women are aware that their fertility declines more rapidly than other—often more visible—signs of aging. In fact, the ovaries have very unique properties. They begin a prolonged hibernation-like state from infancy until the start of puberty. During this ten to fourteen year period, the ovaries remain inactive; producing neither hormones nor mature eggs. However, there are still biological signs of aging taking place within the resting ovary but at a much slower pace than after the menstrual cycles begin. Then throughout the reproductive years a group of eggs is lost each month. In some women—depending on their diet and lifestyle—eggs may be lost at a faster pace. This happens for instance in women that use tobacco products. As I’ve written about previously, the blood test for the hormone AntiMullerian Hormone (AMH) is considered by most fertility specialists today to be the most reliable assessment of a woman’s ovarian reserve (the approximate number of immature eggs that she has available at any given time). Now there are also new ways to actually measure how we age physiologically as well.

One study recently demonstrated that people do age at variable rates. They quantified the aging process by measuring various physiologic and genetic markers over a 12 year period in 954 individuals beginning at age 26. They correlated their findings with each test subject’s appearance and their quality of life. They found that those that appeared to be aging faster also had measureable changes in their physiology, cognition and physical complaints consistent with their appearance. The researchers also analyzed their DNA. Their analysis supported that some individuals were aging faster than others and that diet and lifestyle seemed to be a major influence on the rate of aging. In fact, some people seemed to age 3 years for each 1 year that passed on the calendar while others didn’t seem to be aging at all during the 12 years of the project. So taking steps to improve your health and wellness may in fact slow your rate of aging. However, there are still some changes taking place that can’t be delayed indefinitely.

In most species, females are able to conceive throughout their natural lifespan. Humans are unique from most other mammals in that women typically live about half of their life after their fertility has ceased. It has also been reported that women that conceive later in life tend to live longer. Efforts to look at the genetic relationship have found that there are 17 genetic markers that explain about 30% of the occurrence of premature ovarian failure. That means that most ovarian aging is related to other factors including damage to the egg’s DNA (telomere length) that naturally occurs over time. There are also changes that occur in the egg’s power house, the mitochondria. Each egg has 20,000 to 800,000 of these important power units. Each mitochondrion has its own small strand of DNA. We inherit all of our mitochondria from our mother. As women age, the DNA of mitochondria within the eggs becomes damaged. This damage cannot be repaired. As a result, the mitochondria are intimately linked to egg quality. They not only impact the chance that an egg will fertilize and grow successfully but also the health of the child that results. There are also other ways that delaying pregnancy may influence the child’s health but in a more positive way. There is considerable evidence that children born to older mothers may have more positive cognitive and behavioral outcomes.

There is a growing trend for women to delay childbearing. Doing so is associated with higher socioeconomic status, increased educational achievement, higher income level and smaller family size. It may be due to any or all of these reasons or it may be due to greater readiness for pregnancy or more that children of older mothers tend to fair better when it comes to cognitive and behavioral measures. Others feel that it may due to a more mature mother-child interaction. Whatever the reason the benefits are present without any elevated risks in psychiatric problems.  So even though cause and effect cannot be established in the available studies, advanced maternal age seems to have a protective effect upon the psychological and cognitive development of children. Now there is also evidence that carrying a pregnancy may in turn have healthy implications on the aging of the mother as well.

A new series of investigations is finding that a healthy pregnancy may slow aging process. In animal studies, it has been a consistent finding that pregnancy has a rejuvenating effect upon mother through a process called parabiosis (connecting the circulation between the young and the old). In humans, studies have found measureable benefits including improved liver functioning, improved reparative abilities within the central nervous system and protective effects upon the heart following a healthy pregnancy. There is also data suggesting that unhealthy pregnancies can identify women at risk of age-related conditions like diabetes, stroke and heart disease—possibly identifying those at risk so that preventive measures can be initiated. So it seems that healthy women have a longer opportunity to conceive and that when women in their later years get pregnant that they remain healthier longer.

In summary, the links between fertility and healthy aging are far more complicated than previously believed. We can reassure women that taking steps during their younger years to live a healthy lifestyle should optimize their opportunities for pregnancy. We can not only track a woman’s fertility status through ovarian reserve testing but now we can also freeze/store eggs to extend their reproductive years. Then, by taking steps to optimize a women’s health during pregnancy, women may both have a healthier child as well as slow their own aging.

HORMONE HAPPENINGS: Greene Guide’s News Recap

Let’s take a few moments to review some of the latest findings in reproductive medicine. This month there is another first in reproductive medicine as well as new evidence that hormone problems may be passed to spouses. Check out the following:

Ovarian Stimulation for IVF does not increase the risk of cancer: The largest review of the data available provides more reassuring news to women undergoing advanced reproductive treatment. Included in their review was the information obtained from nearly 180,000 women that had undergone IVF therapy. They found that there was no increased risk of ovarian cancer, endometrial cancer, cervical cancer or breast cancer. Although a few isolated studies raised concerns in the past; this new information should further reassure patients and egg donors of that ovarian stimulation will not create future health risks.

First successful birth after woman receives her own ovarian tissue frozen during her childhood: In a new report, it has been proven that ovarian tissue from a child can be removed, frozen and replaced later in her life to restore lost fertility. Previously there have been about 3 dozen cases of women freezing ovarian tissue prior to receiving life-saving chemotherapy. However this was the first report a 14 year old having her fertility preserved through removing an ovary prior to the onset puberty and before receiving chemotherapy. Now at age 27—and two years after a piece of her ovary was transplanted back into her body—she conceived and delivered a healthy child naturally. This proof-of-concept should make fertility preservation a more tangible option for children faced with the need for chemotherapy.

Diet and lifestyle impact embryo quality: A research group recently looked at the quality of 2659 embryos produced by 269 patients. They had data on the diet and some of the social habits of the women that were undergoing treatment as well. They found that eating fruit, vegetables and fish was associated with higher embryo quality. By contrast consumption of red meat, smoking and alcohol reduced the chances that an embryo would develop to the blastocyst stage—the last stage before it hatches. They also found that women that consumed red meat have a lower chance for implantation as well. This is only one study so patients shouldn’t feel compelled to make dramatic dietary changes. However, it should encourage women trying to conceive to pay greater attention to their diet and lifestyle.

Fathers at risk of diabetes after their partners experience Gestational Diabetes: As we continue to seek to prevent new cases of diabetes, an emerging risk factor may be having a partner with a history of gestational diabetes. A study from Canada followed nearly 72,000 male partners after the delivery of their child. They found that the risk of developing diabetes was 33% higher following a pregnancy complicated by gestational diabetes vs. normal controls. The authors theorized that this increased risk may be likely due to shared diet/lifestyle as well as ethnocultural risks. If confirmed however it could provide support that counseling the entire family to prevent later risk may be in order.

Sunshine boosts IVF success: Many studies have looked at seasonal variations on pregnancy rates and tried to explain their fluctuations. But a new study from Belgium has taken their analysis a step further. They looked at a group of almost 11,500 women undergoing IVF at the same center between 2007 and 2013. They then analyzed what the weather was like the month prior to their cycle. Although they did not find a clear seasonal pattern; they did find that women exposed to more sunlight the month prior to their IVF cycle had a higher pregnancy rate. This boost in success translated to about a one third higher chance of conceiving. The authors theorized that the boost might be related to higher melatonin and vitamin D production. The strongest correlation was actually with live birth rate.

Men with low-normal testosterone levels have high rate of depressive symptoms: There has been a recent trend to check testosterone levels in men; most likely due to media attention and advertising. This prompted a group of researchers to study whether or not there was a higher rate of depression and/or depressive symptoms in people requesting such testing. They screened 200 men with an average age of 48 (range 20 to 77) with a validated symptom questionnaire. They found 56% screened positive. In fact, the risk that a man experienced depressive symptoms seemed highest for the younger men with low-normal testosterone levels. Follow up studies are needed to determine if testosterone replacement—instead of traditional antidepressants—would relieve these symptoms.

Robert Greene, MD, is a reproductive endocrinologist with Conceptions Reproductive Associates in Denver.