We all get excited about new things. But most people remain skeptical when you suggest that something old may be better. In fact, what if something VERY old may be one of the hottest developments in a high tech field like fertility treatment? That’s what has been quietly happening with the medication known as metformin.
Metformin has been used since the time of the pharaohs (around 1500 B.C.E.) but it was extracted from the plant Galega officinalis (see image). From then until the discovery of insulin; this was the primary treatment for diabetes. Unfortunately, like many plant extracts there were many other compounds present as well—some with serious and/or troubling side effects. The modern synthesized version of metformin has been purified making it safer and easier to study.
The best known use of metformin in reproductive medicine is in the treatment of women with polycystic ovarian syndrome (PCOS). But we’re now learning that there are many other ways that his modern version of an herbal remedy can help improve the outcome of fertility treatment. Although I’m not a fan of lists, the complexity of this treatment is beyond a simple blog post. So here is what you may want to consider when planning your treatment with your doctor:
In summary, pregnancy is a very multifaceted process. Sometimes, we still have a lot to learn about something that has been around for a long time.
It has long been accepted that the primary reason that human eggs don’t age well is due to a dysfunction in when and how the chromosomes separate. This reduced chance of becoming pregnant associated with aging as well as the increased miscarriage rates. A new paper has now demonstrated that it’s not just the DNA separation that declines with time but also how the chromosomes are actually sorted and divided.
Within each egg are cable-like structures called microtubules. These microtubules not only help the egg maintain its shape but also are integral in sorting/separating the DNA. They are also in charge of cell division after fertilization is complete. In fact, some of the most powerful cancer fighting drugs are used to deliberately damage microtubules in order to prevent cancers from growing. This new information provides us with further insight into another important aspect of egg quality.
Although we don’t currently have any specific recommendations on what we can do to improve microtubule function; this information does provide us with more diagnostic information for patients that are going through In Vitro Fertilization (IVF). IVF is not only the treatment that provides patients with the highest pregnancy rates but when performed in a high quality setting; it also provides important diagnostic information. There is no accurate test for egg quality except to put a healthy sperm inside and see if/how well the process of fertilization and development takes place. We routinely use this information in discussing treatment options for patients that do not successfully conceive in their first IVF cycle at our center.
Robert Greene, MD, FACOG
Conceptions Reproductive Associates
This headline is a bit misleading in that a similar technique was used in the 1990’s before it was decided that we need to proceed more cautiously in mixing DNA. Currently, the technique described is not available for couples treated in the USA and is only approved for use in treating specific genetic conditions. However, this is an exciting breakthrough that may prove to be useful in areas of reproductive medicine. https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/
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.
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.
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.
One of the most frustrating questions for women trying to conceive is “what can I do to improve my chances?” Given that women are born with every egg that they will ever have, there are a limited number of ways to optimize the health of the remaining eggs. But for those that are motivated, I have described steps like the use of Acai berry extract and CoQ10 as well as improved sleep and Vitamin D. Now for the first time, there is evidence that some women may be able to improve the responsiveness of their ovaries in as little as one month!
The typical diet of people living in the USA has changed dramatically over the last century. One glaring example has been in the type of fats that we consume on a daily basis. Essential dietary fats—those that we must get from foods because our bodies can’t make them—are typically classified as Omega-6 and as Omega-3 and serve many important physiologic functions. The ideal ratio of Omega-6 to Omega-3 is 1-to-1. However, the typical Western diet—popular amongst most Americans—has a ratio as high as 25-to-1. The result of this unhealthy shift is that many people are eating foods that promote inflammation. This unhealthy shift is associated with a higher risk of heart disease, diabetes, cancer and infertility.
Given that it’s not easy to encourage people to make lasting dietary changes, a recent study looked at the effects of starting a high potency omega-3 fatty acid supplement upon ovarian function and hormone balance. For this study, they put 27 women on a 4 gram supplement and measured their FSH levels before and 30 days after starting this program. Even within this short time frame—effectively one menstrual cycle—they found a dramatic improvement in the omega-6 to omega-3 ratio. Their inflammatory markers improved and their FSH levels dropped. Given that FSH level is considered a marker of ovarian sensitivity; this result is interpreted to mean that their ovaries were more sensitive and thus more fertile.
A cautionary note; they did not find an improved ovarian sensitivity in the women in the study that were obese. It is possible that with longer time and with weight loss, obese women might also experience improved fertility. Obesity has been linked to worsening infertility as well as resistance to some of the treatments offered to normal weight women. It is theorized that obesity itself produces inflammatory chemicals in the body which in turn trigger a state of hormone imbalance. In act, it was discovered that all of the women in the study—including the women that were obese—had improved markers of glucose metabolism. That suggests that the omega-3 fatty acids could help reduce the risk of diabetes and maybe make it easier to lose weight as well.
Another important benefit of omega-3 fatty acids is that they can reduce oxidative stress. That means that consuming these healthy dietary fats can reduce the risk of DNA damage to a woman’s eggs—another important fertility promoting benefit. So although this was a small study and needs to be confirmed in a longer time period, you don’t need to wait. Make this health promoting change in your fertility promoting plan now. Here are a few practical suggestions:
- Switch to a low-fat diet plan taking care to avoid animal fats when possible
- Use products at home that include healthy omega-3 fatty acids instead of butter
- Incorporate more olive oil, Flax seeds and tree nuts into your daily diet
- Start taking a daily supplement—preferably a plant based one (rather than fish oil) like those made by Life’s DHA
- IMPORTANT NOTE TO MEN: Emerging evidence suggests that increasing your omega-3 fatty acid consumption can improve sperm shape (teratospermia) as well!!
Within days of writing about the modern benefits of egg freezing a new study was published in JAMA based upon old data. They looked at national data from 2013 and concluded that pregnancy rates from egg donors were lower if the eggs had been frozen than if they were fresh. That was probably true back then. But technology is advancing at an exponential rate. Reproductive medicine is arguably one of the most technology dependent fields of medicine. So applying 2013 results to current decision making is flawed from the very onset. Having said that, let’s consider what this publication may be able to teach us and how we should more accurately interpret it today.
This study looked at the 2013 Annual Report of the pregnancy rates from fertility centers in the USA which were collected by the Society for Assisted Reproductive Technology. The science and experience of most centers using this technology has advanced considerably since then. In fact, it was in late 2013 that the Practice Committee for the American Society for Reproductive Medicine published the guidelines for oocyte cryopreservation. In their review they pointed out the fact that much of the data that they analyzed was from Europe as few clinics in the USA had published their experience with egg freezing at that time. They also clarified how the difference in techniques used to freeze/thaw the eggs had progressed rapidly resulting in dramatic improvements in success rates. As a result, the removed the “experimental label” from the procedure because of these advances. However one of their most important ultimate conclusions was that “success rates may not be generalizable, and clinic-specific success rates should be used to counsel patients whenever possible.” Despite that clearly stated recommendation, this latest research paper lumped together all of the clinic data and created the latest public misinformation campaign.
Today, many more centers have experience in freezing/thawing eggs using the most modern technique of vitrification. As a result, more patients that need donor eggs are able to benefit from the lower cost and greater convenience of frozen eggs and still enjoy the very best in success rates. Better still, many egg banks offer special guarantees so that if a specific donor’s eggs do not perform well: they will have access to replacement eggs without additional cost. So the best message for patients in need of donor eggs today is to be a wise consumer. Patients should ask their clinical very candidly about their unique experience with frozen donor eggs. I think that they will find greater reassurance in today’s science than in yesterday’s news.
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