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

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.

IVF with hGH: time to reconsider an under-used treatment option

One of the greatest challenges that we face in treating couples with infertility, is what options to offer beyond the typical treatment protocols. Clearly, most of our patients are well served with the basic ovarian stimulation methods but in some patients that may exacerbate or simply ignore an underlying hormone imbalance that’s compromising success rates. Therefore, one of the greatest challenges is to figure out how and when to tweak the typical combination of meds in order to shift the hormone balance back to a more favorable outcome. This is the reason that we should now reconsider the use of human growth hormone (hGH) for patients that have failed previous IVF treatment.

I trained under Dr. David Meldrum at UCLA-Harbor Medical Center in Los Angeles. Back in the early 1990’s he was advocating the consideration of adding hGH to the protocol of certain patients. His reasoning was good. First of all, we know from previous research [u1] that healthy developing eggs produce a growth hormone analogue known as IGF-2.  Better still, other studies [u2] have demonstrated that hGH could possibly increase the ability of eggs to repair damaged DNA. Finally, several studies have found that growth hormone can improve the response of the ovaries to stimulation during an IVF cycle. Given that all of this information has been available for quite some time, it may be surprising to a patient that there hasn’t been wider use of hGH during IVF treatment. Recently, Dr. Meldrum and several other experts [u3] suggested that this was because there remained too much confusion amongst specialists on which patients would benefit from the use of this somewhat expensive but also possibly game-changing hormone.

The good news is that recent studies [u4] have more carefully defined the characteristics of the patients that were receiving hGH. As a result, we have some new data to better guide us as to which women may be most likely to benefit from hGH. Here is a summary of what they found:

  • In women >40 years of age, they found a higher implantation rate and better on-going pregnancy rate in women treated with hGH during ovarian stimulation.
  • In women that are poor responders to ovarian stimulation—defined as three or fewer eggs produced per IVF cycle—there was a marked improvement in pregnancy rate with growth hormone supplementation. They also found an improved outcome in FET cycles from embryos created during these cycles.
  • In women that have poor embryo quality and low pregnancy rate in otherwise encouraging ART cycles, there is not be a clear benefit of using growth hormone. Instead, other causes of poor embryo quality should be explored. Once those have all been addressed, reconsideration of hGH is worthwhile.

Robert Greene, MD, FACOG

CNY Fertility Center

e-mail me at rgreene@cnyfertility.com

Call our toll-free number at 800.539.9870 or request a consult here.

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.