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.

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.

AMH: an accurate, reproducible test for ovarian reserve

Unlike men—who continue to produce sperm throughout their lives—women are born with every egg that they’re ever going to have. As a result, women do experience a decrease in their fertility over time. Some women start with more eggs (called oocytes) then others. Additionally, some women have a more rapid decline in their fertility then others. That’s why age alone is only a rough estimate for a woman’s fertility.

Over the years, there have been various tests proposed to estimate a woman’s ovarian reserve. Some were better estimates than others but they all had their limitations. Over the last several years however there has been one test that has emerged as the most consistent and predictive of a woman’s fertility; a test called AntiMüllerian Hormone or AMH. Until recently, this test has been widely used around the world, it has had more limited exposure within the USA.

AMH is a hormone that is directly released by immature eggs into a woman’s bloodstream. Better still, it remains stable from day-to-day with minimal fluctuation over subsequent months. That means that the test can be performed on any day in a woman’s monthly fertility cycle and the results are considered to be predictive for months to follow. Other tests proposed to measure ovarian reserve actually tend to be more representative of the specific month that they were performed. AMH is also predictive of how a woman will respond to fertility treatment and can be helpful in diagnosing problems like polycystic ovarian syndrome as well.  It is reasonably priced and now easily accessible.

I have been recommending the AMH test to women for several years. Oftentimes, the response that I hear back is that “my doctor isn’t familiar with this test” or worse “my doctor doesn’t believe in this test.” Enough research has now been completed and this test is widely available so those complaints should no longer be acceptable. If you’d like to download a recent article written about this test to initiate a discussion with your doctor then please check out the September 2009 issue of Contemporary OB/GYN.