Metformin and Fertility Treatment: the expanding uses for an age-old drug

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.

Galego officianalis

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.

Atypical PCOS: new insights for patients with fertility problems that don’t have other symptoms

Women with Polycystic Ovarian Syndrome (PCOS) can have a variety of symptoms including irregular/infrequent menstrual cycles, skin problems and weight gain. This creates a diagnostic challenge as many healthcare providers rely heavily upon these symptoms to make their diagnosis. New discoveries over the last two decades have demonstrated that PCOS is not a simple cluster of findings.  Instead it is a spectrum of conditions with a variety of presentations. New information has provided greater understanding why some PCOS patients may present primarily with infertility alone and none of the other commonly associated symptoms.

 

PCOS is essentially a hormone imbalance. One of the most important hormones that is typically involved is one called Anti-Müllerian Hormone (AMH). What’s disappointing is that some physicians either don’t measure this hormone or don’t understand its implications. Many women with PCOS have very high levels of AMH. Having too much of this hormone may be their greatest obstacle to becoming pregnant.

 

A new study shows that AMH (referred to as Müllerian Inhibiting Substance or MIS in this article) can inhibit the maturation of eggs. In fact, it can be so potent that it may someday be used as a contraceptive. But most importantly, having a high AMH level can make a woman’s ovaries behave like a woman that has PCOS; even if she does not have any of the other common symptoms. Regardless of what we call this hormone imbalance; women with a high AMH often benefit from similar treatment recommendations as women with PCOS.

 

Stay informed,

~Robert

 

Robert Greene, MD, FACOG

Conceptions Reproductive Associates of Colorado

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!!

Do your hormones feel out of balance?

Hormones represent an integral communication system. They are chemical messages that are made in one part of your body and sent through your blood stream to coordinate everything from digestion to ovulation. They even make it possible for you to sleep. They are essential to your health and wellness. Yet most people don’t realize that they also impact how you feel. Your energy level, your hunger even your physical attractions are profoundly impacted by what is happening in your body hormonally. Although we may not think of this delicate balance when we’re at our peak of fitness; people often have a strong sense of “imbalance” they’re not doing well. Yet these symptoms are often overlooked when they can actually provide tremendous insights into what’s going wrong as well as provide strategies to improved health and quality-of-life. By paying attention to your symptoms, you can feel better while boosting your chances of conceiving as well as improve the health of your baby. Here’s how it works.

There are over 200 hormones that can be circulating through your blood stream at any given time and new ones are being discovered every month. I like to think of these hormones in groups according to their function. Most people have heard of the fight-or-flight hormones associated with the stress response. The other groups to consider are tend-and-befriend, rest-and-digest, mate-and-relate. Think of them as if they are different elements on a mobile in a dynamic state of equilibrium; an imbalance in one group can cause an imbalance in another.  If you have too much stress hormone for instance, it can cause digestive problems, difficulty with sleep and infertility problems.

Some of the most exciting research in this field is shedding light on the dual role some hormones can play. For instance, one study recently demonstrated that the same hormone—called oxytocin—which is responsible for promoting feelings of love and affection can also contribute to jealousy and envy. Some imbalances can be ominous. For instance, another recent study demonstrated that women with even slightly reduced levels of thyroid hormone during pregnancy are associated with blood pressure problems during pregnancy.  That’s why I feel it is so important to consider how hormones interact with one another.

I’ve spent a decade and a half now studying symptoms and how they relate to hormone balance. In my books, I’ve tried to use questionnaires in order to help people gain insight into their own hormone milieu as well as provide practical tips on how they can restore harmony when problems occur. I encourage you to check out PERFECT HORMONE BALANCE FOR FERTILITY and PERFECT HORMONE BALANCE FOR PREGNANCY in order to learn more about how you can optimize how you feel as well as maximize your chance of success. And please check back here as I update this blog with the latest research in this exciting field.

What should “he” be doing to boost our pregnancy rate?

Although most fertility treatment focuses on women; at least 1/3 of couples have a male factor contributing to infertility. Newer studies even show that subtle changes in sperm quality—that aren’t detectable by standard testing—can contribute to poor fertilization, abnormal embryo development and even recurrent early pregnancy loss.  That’s because the sperm contributes half of the genetic material to the developing embryo as well as factors that contribute to normal fertilization and early development. But they are easily damaged.

Sperm are particularly susceptible to free radical damage—the charged particles that are a normal byproduct of oxygen metabolism. They are so compact, that they contain very low concentrations of the scavengers that neutralize these damaging little sparks of energy. When a free radical encounter DNA—which the mature sperm is loaded with and ready to contribute to the awaiting egg—the genetic material can be damaged; a process called “fragmentation.” Sperm lack the ability to repair this damage when it occurs. As a result, seemingly healthy looking sperm can prevent a pregnancy from getting off to a healthy start.

The good news is that there are steps that men can take to minimize the naturally occurring damage to sperm and markedly improve your chance of having a baby together. Here’s what he can do:

  • Avoid exposure to tobacco and other products that promote free radical formation (more about this in future posts).
  • Eat foods rich in the following antioxidants:
    • β-carotene (i.e., spinach, carrots, tomatoes, cherries, melons, peaches)
    • Vitamin C (i.e., citrus fruits, tomatoes, broccoli, cabbage, berries, mangos, pineapples)
    • Vitamin E (i.e., peanuts, almonds, soy, olive oil, wheat germ, cereals)
    • Zinc (i.e., asparagus, eggs, potatoes, fish)
  • Consider a “preconception supplement.”

A recent study confirmed that making these healthy changes can improve pregnancy rate while also reducing the risk of miscarriage. I know when my wife and I were going through fertility treatment; I took the product called Conception XR despite my healthy diet and normal semen analysis. Not only did I feel it was the least I could do but I do believe that it helped us to conceive our daughter.

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.