Tag: ovarian reserve

How Many EGGS do you think you have left?

by Robert Greene, M.D., posted in Age, egg freezing, egg quality, embryo banking, Female Fertility Tests, fertility planning, Fertility Preservation, ovarian reserve, Uncategorized, vitrification

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.

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

by Robert Greene, M.D., posted in aging, egg quality, Fertility, Fertility Preservation, Food and Diet, Lifestyle, ovarian reserve

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.

Egg Quality and Antioxidants; why Acai berries may provide another key to achieve a successful pregnancy in women with a history of poor egg quality

by Robert Greene, M.D., posted in Uncategorized

An important aspect of “lifestyle medicine” is helping our patients take control of the factors of their daily routine that may tip them towards a higher pregnancy rate. Toward that end, one of important determining factors of egg quality has to do with whether not the egg has been damaged prior to fertilization. So let’s consider what causes egg damage and what we can do to prevent it.

Each egg that you have has been waiting since you were an infant for the opportunity to grow and develop. During the years that the eggs remain dormant, they are very susceptible to adverse conditions. For instance, small charged particles called free radicals can damage the proteins, membranes and the DNA within the eggs. These free radicals are formed normally as a result of physiologic processes like digestion and ovulation. However, there are lifestyle situations like tobacco use or over-eating that can promote free radical formation.  Additionally, conditions like endometriosis are believed to impair fertility at least partially due to the increase in the production of free radicals. A recent review  detailed how eggs that have been damaged by free radicals have a lower capacity to produce a successful pregnancy.

Your body makes chemicals called antioxidants whose purpose is to be there to capture and neutralize free radicals when they are formed. Since free radicals only exist for an instant, it is important that these antioxidants are always around. Unfortunately, most of us don’t make enough of these little protectors. That’s why foods that contain antioxidants are believed to be so healthful. Not only can they provide us with these chemicals that we need but they can do so when they would be most useful—during digestion. There is evidence that berries of the Acai—a palm tree grown primarily in northern Brazil—may be able to tip the delicate balance in your favor and therefore protect your ovaries from damage.

Studies suggest that Acai berries may contain more antioxidants than blueberries, raspberries or any other potent natural antioxidants. Additionally, the juice contains healthy omega-3 fatty acids suggesting that this may be another means by which it may provide health benefits. To date, one on-going study suggested that women that had failed IVF due to poor egg quality; had an improved outcome after taking an Acai supplement prior to their next attempt. The two to three months prior to an egg’s release represent the time when it is most susceptible to harm. Therefore if you have a low ovarian reserve and/or a history of poor egg quality; you should consider taking an Acai Supplement. A convenient dosing schedule is 1000 mg taken twice each day. There are various supplements available or you can try consuming Acai products two to three times each day as part of a healthy diet. I find the Sambazon products (http://www.sambazon.com/products ) to be diverse and very appealing because they are organic and sustainably harvested.

[r1]Link to http://www.fertstert.org/article/S0015-0282(14)02371-1/fulltext

Egg Quality: here is the reason that your medications matter

by Robert Greene, M.D., posted in Fertility

A reader of this blog recently requested that I explain why I utilize certain medications for my IVF/fertility patients and caution against the use of others. It all comes down to their effect upon egg quality. Although there is still much to be learned, most fertility specialists agree that what is going on hormonally in a woman’s body will impact the success of her cycle. That’s why I feel that it’s so important to optimize their hormone balance and individualize the protocol to suit each woman’s unique situation. Here’s what we know.

Prior to the month that an egg is going to have its opportunity to ovulate, the DNA within it remains inactive. It has been in this state of rest since birth. Whether or not egg develops in an environment that is balanced more toward estrogen or testosterone is the key factor which will determine whether it will mature normally. Eggs that are “estrogenized” are more likely to mature earlier, fertilize normally and develop into healthy embryos. “Androgenized” eggs are more likely to become atrophic, fertilize abnormally or become a first trimester miscarriage.

Typically, a woman’s fertility begins to drop dramatically about 13 years before she’s going to enter menopause; typically their mid to late thirties. This drop is associated with a shift toward a higher level of testosterone within the ovary and not surprisingly a drop in egg quality. What triggers this hormone shift within the ovary is that as women age they produce a more potent form of the hormone LH as well as develop a tendency to have greater sensitivity to this hormone. Therefore, when designing a protocol for a fertility treatment cycle, I feel it is important that we shift the balance toward a higher level of FSH relative to LH in order create a more favorable setting for egg maturation. Creating such protocols has been among the great accomplishments of my friends and colleagues Drs. Geoffrey Sher and Jeff Fisch when they demonstrated in their landmark paper that pregnancy rates can be substantially improved in women with a history of previous fertility treatment failure. The trick is to stimulate the ovaries with an FSH dominant signal early in their development and then add in a low level of LH late in maturation to optimize the quality of as many eggs as possible. From a practical standpoint, that means being able to control FSH and LH levels independently.

Many centers use simplified preparations of FSH and LH for their ease or lower cost. But I describe this as being similar to mixing your salt and pepper together in the same shaker. It may work in some situations but most patients need varying degrees of adjustment get “more salt” or “less pepper.” What makes this approach even more problematic is that these mixed preparations—called urinary derived gonadotropins—are made from the urine of the least fertile population, women in menopause. In effect, that “makes the pepper even spicier” as these women produce a far more potent form of LH. All too often, this results in a disappointing outcome. It is true that the lower cost, pre-combined products work well enough when given to the most fertile patients. I believe that’s what keeps the market for them alive. In addition to their impact upon egg quality however, I am also concerned about the impurities that they contain.

A recent analysis of both the standard and more highly purified urinary preparations found them to be 95 to 99% free of contamination. These contaminating proteins can not only impact the how a woman’s ovaries respond to them, they can also initiate an allergic reaction. Even more problematic, they carry a very low but real risk of transmitting infection which recently resulted in their use being banned in England and the rest of the United Kingdom.

In summary, the use of the latest technology has made it possible for companies to manufacture untainted FSH and LH in separate preparations so that their dosing can be uniquely adjusted to each patient’s individual needs. Better still, these are BioIdentical products that are exact replicas of the hormones produced by fertile women. Additionally, they are 100% pure and therefore free from the risk of allergic reaction or infection. For all of these reasons, I believe that these products are most suited toward meeting the needs of the patients that I see in my practice.