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.

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.

Successful Fertility Treatment; it’s about much more than what happens in the office

Whenever someone asks me “what else can we do to boost our chances?” it represents one of the most exciting and challenging moments of our interaction. It’s exciting because it shows a willingness to make changes in their current diet and/or lifestyle. It’s challenging because there are no simple answers and most of the data is rather loosely supportive of the recommendations. Fortunately better studies are coming out all the time.

The January 2015 Issue of the journal Fertility & Sterility put this topic front and center. The journal opened with a commentary  that pointed out the fact that each egg–even those from fertile egg donors–has no more than a 40% chance of becoming a successful pregnancy. Therefore, we need to look beyond what we do with the sperm and eggs and also direct our attention toward what else can impact their quality. A “global medicine approach” proposes  that we look at the nutritional status, environment and lifestyle for additional answers and better outcomes. The journal went on to present three papers to bring us closer to that goal.

The first study  looked at infant birthweight and the risk–several decades later–of male factor infertility. Specifically, they were looking at the theory that some male infertility begins in the womb prior to birth. Other studies have found results suggesting this happens for women; that low birthweight may increase the risk of longer time to conception and a higher risk of diminished ovarian reserve. That prompted this research to determine if the same might be true in men. It was. They found that men that were born with a birthweight less than 2,500 gm (normal is 2,500 to 3,500 gm at term) were at a higher risk of having a low sperm count and their sperm was more likely to have damaged DNA. They also tended to be overweight or obese which is also associated with male factor infertility. So nutrition during pregnancy can have lasting implications for the children that are born.

A second article  summarized the concept of “ecofertlility;” environmental toxins that may alter fertility. The examples that they focused on were those that were most common and most easily controlled, tobacco and marijuana since there is typically a choice to use or not use these substances. The authors reviewed a variety of studies that consistently demonstrate that women that are cigarette smokers tend to take about a year longer to conceive, have a higher rate of infertility and are more likely to have a diminished ovarian reserve than nonsmokers. Men were impacted similarly. Male smokers had a higher risk of abnormal semen analysis as well as a higher rate of erectile dysfunction. The authors also presented evidence that various substances produced by tobacco smoke appear in the fluid that surrounds the eggs and then have a very toxic impact. These substances may actually result in a higher rate of failed fertilization. This may explain why smokers have about a 40% lower pregnancy rate when undergoing IVF than nonsmokers. Even with sperm injection (ICSI) directly into the egg; the rate of “fertilization failure” is about three times higher in smokers. The impact of marijuana was more difficult to quantify. In men it has been linked to a higher risk of sperm abnormalities, as well as various hormonal dysfunctions including gynecomastia (increase in breast size), low libido and problems with erectile dysfunction. There is less data on women as exposure is difficult to accurately assess and monitor and correlate with egg function since exposure now may impact an egg many months (or even years) later.

Finally, in a third paper  they reviewed the potential impact of one of the most widely studied chemicals that we’re all exposed to called bisphenol-A (BPA). This chemical was first produced in 1891. It was identified to have estrogen-like activity as far back as 1936. Unfortunately, that did not stop its production and distribution. Today it is recognized as one of the most ubiquitous hormone disrupting chemicals. About 20% of the BPA produced—nearly 3.4 million tons per year—is used to line various food containers. From there, it has clearly been shown to leech into the food that we eat and then contribute to various health problems like diabetes, obesity, heart disease, lung problems, kidney disorders as well as various reproductive problems. The data on its toxicity has been alarming enough to prompt Canada from banning its use in baby bottles (2008). More recently the European Union went a step further and banned its use entirely in 2011. Here in the US, there is just now legislation  proposed to require clear labeling on food containers that contain BPA.  The study authors went on to provide a further note of caution by providing evidence that two chemicals that have been proposed to replace it—BPS and BPF—may have similar negative effects based upon animal data. Human studies are pending. The bottom line is that we need to pay more attention to the chemicals that we use to package our food in as they may actually taint our food supply as well as reduce our health and fertility.

As a reproductive health specialist, I don’t want to alarm my patients but I also don’t want to marginalize the potential impact of our choices upon our ability to initiate a healthy pregnancy. Although walking the line between concern and unnecessarily upsetting people may be a delicate one; I do feel compelled to empower those that are willing to listen. Success is not just about what happens in the clinic—it begins at home.

[r1]Link to http://www.fertstert.org/article/S0015-0282(14)02274-2/abstract

[r2]Link to http://www.fertstert.org/article/S0015-0282(14)02383-8/abstract

[r3]Link to http://www.fertstert.org/article/S0015-0282(14)02354-1/abstract

[r4]http://www.fertstert.org/article/S0015-0282(14)02351-6/abstract

[r5]Link to http://www.endocrine.org/membership/email-newsletters/endocrine-insider/2015/march-19-2015/endocrine-society-endorses-bpa-in-food-packaging-right-to-know-act

Take charge of your fertility treatment; steps you can take optimize your success

One of the most frustrating aspects of trying unsuccessfully to have a baby is the sense that you’re not in control of your own destiny. Most of us take for granted that our health will accurately reflect our fertility. Therefore, why shouldn’t we be able to conceive whenever we decide the timing is right? At least that’s the common perception. The repeated success of friends and family often makes it even more exasperating. I know this. Not only do I treat couples trying to become pregnant on a daily basis but my wife and I went through fertility treatment on our own. During our treatment, we were repeatedly annoyed by the lack of individualization of our treatment protocol by my colleagues whom we’d entrusted our care to. Worse still was the way our input was disregarded even though we’re as fully informed of the science behind the treatment as they were.

My wife and I chose to redirect our approach to treatment; both personally and professionally. After all, I didn’t want my patients to experience the same frustrations that we endured. The results or our action was dramatic; we now have a daughter and we manage a fertility treatment center that empowers patients. We remain fully committed to helping other couples take control of their fertility treatment as well regardless of where they go for treatment. Here’s what we recommend:

  • Get informed—Although it is important that expose yourself to as much information as possible, it is best to consider the source as well as how old the material is that you’re reading. In other words, not everything you read is accurate. Some is outdated and much of it may be true but not apply to you. Seek information that is verifiable. Look for reputable sources and references to specific research studies.
  • Ask questions—Once you feel comfortable with your knowledge base, write down questions. Don’t be shy about asking your doctor very specific reasons why the do or do not recommend a specific course of action if it is appealing to you. It’s best for your doctor to earn your trust through such encounters rather than expect it based upon their title or reputation.
  • Create a fertility plan—This is a unique concept that I don’t think enough people do for themselves. Take the time to consider your options and periodically re-evaluate your goals. Just like writing a business plan or creating an itinerary for a planned vacation plan your course of action. There is nothing that can be more empowering than to actually be in control. If you need some assistance with this, check out pp, 127-129 and pp 285-287 in my book PERFECT HORMONE BALANCE FOR FERTILITY.
  • Analyze your diet and lifestyle—Consider the steps that you and your partner can take outside of the doctor’s office to boost your chance of pregnancy. This can involve matters like losing weight, taking a prenatal vitamin or evidence-based supplement or finding ways to lower your stress level. Bottom line is that success begins at home.
  • Consider a second opinion—If you’re not comfortable with the plan proposed to you, consider meeting with another board certified reproductive endocrinologist. There is typically more than way to achieve success. You should be able to form a partnership with your doctor that you’re both comfortable with. Therefore you shouldn’t feel committed to seeking treatment that you’re not comfortable with since there are other options.