Gluten and Fertility; the facts vs. the fad

Whole Grains

Writing about nutritional choices is tricky. One author recently compared our dietary choices as being like our own personalized religion. We’re all born into certain dietary patterns. Then as we grow, we either accept or modify these choices based upon our own belief as well as our own personal preference. Unfortunately today, many of the fad diets are like dietary cults—people not only want to make their own choice but they encourage others to embrace their decision as well. Unfortunately, most of these popularized diets are based upon scientific rhetoric. They often use encouraging language and small bits of science (often taken out of context) to try to create a compelling message. They want you to join them. As a scientist and a as a physician, I find this troubling because it often has a negative impact upon the care of my patients. For example, let’s consider gluten.

 

Gluten is a combination of proteins found in wheat, barley, rye, oats and various other grains. It has become a very prominent part of our diet because these proteins help dough to rise and retain their shape in baked goods. Although gluten has been vilified by some recent nutritional gurus; many foods that contain these proteins have major health benefits. These whole grain foods are attributed with a lower risk of developing obesity, diabetes, heart disease and various types of cancer. It is estimated that about 1-2% of us may have a true allergy or autoimmune disease (Celiac disease) as a reaction to these proteins. So let’s consider the possible health benefit for the other 98% of the population.

 

Gluten is also a prebiotic. Prebiotics are the nutrients necessary to help the healthy bacteria thrive within your body. A common reason that many people today are taking probiotics is because their diet is not providing these healthy bacteria the nutrients that they need to survive. However, taking a probiotic is not sustainable without feeding these healthy bacteria so they can thrive. There is also evidence that gluten can be an immune booster.

 

Natural Killer cells (NK cells) are part of your body’s immune system. Despite their ominous sounding name, they serve a sort of security role. They are responsible for identifying and eliminating dangerous invaders like virus infected cells and potential tumor cells—they keep you healthy. Ironically, they also serve a critical role in promoting pregnancy. When functioning properly, they enhance the ability of an embryo to implant and thrive. New studies are now demonstrating that gluten can actually facilitate healthy NK cell activity. Whatever the reason, there is convincing evidence that gluten containing whole grains are associated with higher pregnancy rates in patients that are trying to conceive.

 

Patients undergoing IVF provide a unique opportunity to study interventions in a closely monitored setting. Recently, the impact of eating whole grains was investigated at Harvard University as part of the Environment and Reproductive Health (EARTH) study. In this study they were tracking whole grain content by following the diets of women going through IVF treatment. They found that women that were eating more whole grains had a higher pregnancy rate and a higher live birth rate (53% vs. 35%) than those eating little or no whole grains. In fact, at least one serving per day of a whole grain food was able to boost the odds of success by about 33%. Another recent study that was looking at comprehensive dietary patterns and success during Advanced Reproductive Treatment (ART) found that women eating whole grain cereals had about a 30% greater chance of fertilization and early embryo development and an almost a 60% greater chance of becoming pregnant. Finally when researchers measured the urine for a marker of whole grain food consumption in a healthy population of fertile women they found that those eating more gluten containing foods took fewer months to conceive naturally. Taken together, it seems that we should encourage women that are not truly allergic to gluten to eat more whole grain as part of their fertility boosting diet.

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.

Omega-3 Fatty Acids: another tool for ovarian rejuvenation

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!!

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.

EGG QUALITY 3.0: “ovarian priming” can be another useful strategy for women with diminished ovarian reserve

Finding at least one high quality egg is the most important factor in achieving a successful pregnancy. In previous blog posts, I have outlined various strategies to achieve that goal. But what about women whose ovaries do not respond well to standard ovarian stimulation protocols? For them treatment can sometimes seem frustrating or even futile. New data supports that “ovarian priming” may help women with diminished ovarian reserve (DOR) achieve that goal even if they have a history of poor response to IVF treatment.

The common theme of Advanced Reproductive Treatments (ART) is to produce a group of mature healthy eggs in order to create at least one or more healthy embryos. In 2011 a large consensus  meeting agreed upon the definition of a ‘poor response’ to ovarian stimulation and described it as three or fewer oocytes recovered with a conventional IVF protocol. Pregnancies do occur when even one egg is recovered. However, success rates are markedly lower in patients with DOR. The goal of creating this definition was to encourage research on how we can better serve women with this biological challenge.

The most common reason for DOR is a simple depletion in the number of eggs secondary to aging. However new information now suggests that the quality of the remaining eggs is also impacting their ability to respond to the hormonal signals and thus limiting the ability of the ovaries to produce multiple follicles. The goal of preparing or “priming” the potential population of eggs prior to IVF is to optimize the ability of the ovaries to respond prior to starting the hormonal stimulation. Several strategies for priming have been used for the last several years with much debate about which (if any) is best. The FOLLPRIM study  was designed to compare them in patients with an established history of DOR.

The FOLLPRIM study was a randomized prospective study intended to minimize the risk of bias based upon protocol selection. Patients that had failed an IVF attempt were randomly assigned to one of three priming protocols prior to their next IVF attempt. They were either given estradiol (to simulate the cycle of young fertile women), an oral contraceptive (to synchronize follicle development) or testosterone (which serves as a precursor to estradiol as well as to help promote the earlier stages of egg development). The patients then repeated their IVF cycle with a comparison of number of eggs recovered after priming compared to their initial response without priming. The results were very encouraging.

They found that all three strategies increased the number of mature eggs that were recovered through IVF compared to the unprimed cycle. In fact, they averaged two to three more eggs per patient. Although it was uncertain which priming protocol had the highest pregnancy rate, the data suggested that the testosterone priming might be the best. Further research will be needed to determine if this is true. In fact, another technique (not tested in this study) to boost testosterone levels is to give women the supplement DHEA for one to three months prior to IVF. Many centers have adopted this strategy as well.

What’s most important about this research is that women with DOR are being given choices rather than simply discouraged or re-directed to egg donors. Ovarian priming prior to IVF is one option that should be considered. Combined with other tools like anti-oxidants and CoQ10, more women are overcoming this biological challenge of DOR and having healthy babies.

[r1]Link to http://humrep.oxfordjournals.org/content/26/7/1616.full.pdf+html

[r2]Link to http://www.pubfacts.com/detail/25955224/Antral-follicle-priming-FOLLPRIM-prior-to-ICSI-in-previously-diagnosed-low-responders-A-randomized-c

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

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