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 Greene, MD, FACOG

Conceptions Reproductive Associates of Colorado

Sleep Can Affect Male Fertility

The impact of lifestyle upon male fertility is very difficult to study and therefore rarely gets much scrutiny. In previous posts, I have referenced studies on how healthy sleep and melatonin levels impact egg quality. Now we have a new study that found that men that sleep less than 6 hours per night or more than 9 hours per night seem less fertile than those within the 6 to 9 hour time range. Although further research would be needed to confirm the validity of this study, it could be that sleep is impacting your ability to conceive with your partner.

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!!

Ectopic Pregnancy: a complication of IVF treatment with a simple prevention

Earlier this year, a comprehensive review  of advanced fertility treatments demonstrated that the risk of serious complications as a result of advanced reproductive techniques (ART) was relatively low.  Still, there is always an effort to try to reduce any adverse outcomes even further. One of the rare but more serious complications associated with successful IVF treatments is the risk of developing an ectopic pregnancy; a situation that results when the embryo migrates from where it had been placed within the patient’s uterus to another site, most commonly the fallopian tube. The frequency of ectopic pregnancy in patients that conceive through IVF is between 2% and 5%. Ironically, this is higher than the 2% to 3% incidence seen with naturally conceived pregnancies. New insights suggest what may be contributing to the elevated risk associated with ART and what steps that we can take to prevent it from happening

In order to better understand why IVF has a higher risk of ectopic pregnancy, let’s consider what we now know about implantation. The process whereby an embryo successfully establishes contact with the uterine lining is actually a coordinated event that depends upon the timing of several important factors. One major factor is development. The embryo must be develop to the blastocyst stage—where it appears as a fluid filled ball with a clump of cells concentrated at one location. It then must break out of its protective coating in a process called hatching. Another important factor is the hormonal milieu. The uterine lining must be hormonally prepared for the initial contact with the hatched blastocyst; there is typically a limited time period of about 36 hours during which the conditions are ideal for attachment (the first step towards implantation) to occur. A recent analysis   compared several variables associated with different embryo transfer strategies.

For their study, they reviewed over 3,300 embryo transfers. They compared the developmental stage of the embryos as well as whether the embryo transfers were done during the same cycle as the egg retrieval (Fresh) or whether they had been cryopreserved and transferred later (Frozen). The difference between a Fresh transfer and a Frozen transfer is two-fold. Not all embryos develop at precisely the same rate. So with Fresh transfers, some embryos are more developed than others. In fact, they separated their analysis based upon whether it was 3, 5 or 6 days after the egg retrieval. In a natural cycle, an embryo typically enters the uterus 5 or 6 days after it is released from the ovaries. With Frozen embryos, they are actually preserved when they have reached a specific stage of development chosen by the IVF center. As a result most frozen embryos are at the morula stage (day 3) of development or the blastocyst stage where they are ready to hatch. Some embryos reach this preimplantation stage on the 5th day of development and others take until the 6th. If they do not make it by day 6 it is considered an unhealthy embryo. The other distinction is that Fresh transfers tend to be associated with higher than normal hormone levels as a result of the ovaries producing multiple mature eggs instead of just one or two. By contrast, the goal of a Frozen transfer is to create a hormonally balanced environment within the uterus that more closely represents what happens in a natural physiologic conception.

In order to try to differentiate both of these factors, this study compared Day 3-Fresh and Day 5-Fresh to Day 3-Frozen, Day 5-Frozen and Day 6-Frozen, The finding in this analysis was that risk of ectopic pregnancy was lowest for Day 5-Frozen embryo transfers. In fact, the calculated risk for those patients was far less than 1% suggesting that the ideal transfer strategy is to split the ART cycle to optimize the healthy pregnancy rate while minimizing the risk of ectopic pregnancy. A previous study  also found that embryos that were judged to be of poorer quality—based upon their appearance under the microscope—also pose an elevated risk of ectopic pregnancy making the embryo grade a potential third factor to consider. There have also been two other studies  that have also found that frozen embryo transfers (FET) have lower ectopic pregnancy rates than fresh embryo transfers.

Since many centers now have advanced freezing techniques to safely preserve embryos it makes sense for more patients to separate the process of ART into two parts; the first month to create the embryos and the second month to transfer them. Although this split cycle strategy lengthens the time from start to pregnancy, there is compelling evidence that for many patients it will improve their chance of having the highest pregnancy rate with the fewest possible complications and the lowest possible risk.

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Functional Fertility Foods: eating soy foods associated with higher IVF success rates

There are few topics as emotionally driven as food choices. For most of us, our dietary choices are guided mostly by our taste preferences, familiarity (think comfort foods) and convenience. In fact, much of what passes as nutritional science in the popular media is incorrect or overstated. As a result there are often widely held misconceptions and untruths about what is a “healthy food.” A classic example is soy based food products. About 4 years ago, I wrote a column  to debunk the popular (and inaccurate) belief that some of the hormone-like chemicals—called phytoestrogens—in these healthy beans could interfere with fertility. The latest research goes one step further suggesting that these foods actually boost the pregnancy rates in women undergoing advanced reproductive techniques (ART).

It’s been well established that adding soy based foods can lead to small changes in the hormone balance  of people that eat them. But for too long, people that wanted to promote unhealthy dietary choices successfully created concerns among fertility patients. Then two clinical studies came along that demonstrated women taking soy supplements during either ovulation induction  treatment or IVF cycles  had higher pregnancy rates. The problem with these studies however was that the supplements that were used boosted the level of phytoestrogens to levels that are over 10 times higher than people eating a traditional Asian diet. New research has provided more practical insights into the health benefits achieved by simply switching to easily obtained soy based foods.

This latest study  was very practical because they looked at the dietary choices in a group of 315 women that ultimately completed 520 ART cycles in 2013. Better still, they followed them prospectively to minimize the risk of obtaining biased results. They then looked at various results from their IVF cycles. They found that the eggs from women that were eating foods that contained soy had a higher fertilization rate. More specifically, they found that the clinical pregnancy rate was 11% and live birth rate was 13% when they compared women that were eating soy to age-matched women that were not. In fact, women that were consuming the most amount of soy had a nearly 80% higher chance of success. Bottom line was that soy containing foods seem to be very beneficial to women undergoing fertility treatment without making huge dietary changes.

An important step towards validating any finding is to then try to establish a theory of how the intervention may have resulted in the finding. The previous studies on soy supplements and IVF outcome suggested that the isoflavones—these are the estrogen-like chemicals in soybeans—resulted in a healthier uterine lining and thereby improved the ability of embryos to implant. They based this assumption on the fact that the ultrasound imaging of the lining appeared different. This recent study did not find any such changes. Instead, they hypothesized that the benefit are demonstrated by the fertilization rate of the eggs from the women eating soy vs. those that weren’t The fact that it was higher in the soy group suggests that eating soy may improve egg quality. Regardless of the mechanism, all of the research agrees that dietary soy is associated with higher pregnancy rate and greater chance at a live birth.

Maybe the most important aspect of clinical research is guiding and motivating patients on how and when to implement changes. Given the large number of products that now contain soy as well as the various “meat substitutes” (ie, veggie patties, soy milk, soy yogurt, soy butter) it makes sense to encourage women going through IVF to try to make some conscious changes to select these products or to eat soybeans. Another potential advantage of reducing meat, chicken and fish consumption is that plant based proteins contain far less of the unhealthy aspects of our modern diet like; hormone disrupting chemicals, pesticides and antibiotics. The end result is not only a higher chance of conceiving but also having a healthier pregnancy and giving your child the very best start possible.

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HORMONE HAPPENINGS—Greene Guide’s News Recap

It’s time to review the latest findings in Reproductive Medicine. This month there are new insights into why more boys are born in the US than girls as well as a new strategy for women undergoing fertility treatment to reduce the risk of having a child with autism. As always, I have included links to the studies for you check them out for yourself:

  • More Boys are Born than Girls; here’s why—about 51% of all of the babies born are male. This observation has been consistent for several hundred years.  A new study  has provided the most comprehensive data to explain why we don’t see an equal number of boys and girls in the delivery room. It turns out that the explanation is based upon what happens during pregnancy; not prior to fertilization as previously assumed. The researchers found that although a higher number of male are lost during the first trimester; female fetuses are more likely to miscarry later in pregnancy. The end result is that a slightly higher number of males survive until birth than females.
  • Supplementing Estrogen Does Not Improve Pregnancy Outcome—there has long been debate amongst fertility centers as to whether or not additional estrogen is beneficial to pregnancy rates. New data  shows that levels higher than the normal physiologic ones are not helpful. Other studies have suggested the extra estrogen may even boost the risk of blood pressure problems later in pregnancy. Combined these findings support the ongoing trend to create a hormonally balanced environment rather than simply adding more.
  • Genetic Testing improves Live Birth Rate in Women over 40—using pre-implantation genetic screening (PGS) to identify the healthiest embryos for transfer is an effective tool according to new information . They demonstrated a live birth rate that was three times higher using this technique then using standard IVF alone for women over 40. This means that identifying healthy embryos prior to transfer is a highly effective strategy to achieve a successful birth.
  • Single Embryo Transfer associated with Lower Risk of Autism—previous data has suggested that there may be a higher risk of Autism Spectrum Disorder (ASD) associated with advanced reproductive techniques (ART). Other studies have shown that this is more likely age related or that it might be due to the population of patients seeking fertility treatment. This new study  found that when only singleton pregnancies result following IVF; the observed risk disappears. This is another good reason to consider elective single embryo transfer (ESET).
  • Vitamin D Deficiency associated with Lower Pregnancy Rate in IVF—a comprehensive review  of 34 published trials has found that women with lower than normal vitamin D levels have less success when undergoing IVF treatment. There is not yet proof that supplementing with vitamin D reverses this trend. However, given the other health benefits and the low cost of this “sunshine hormone” it sure makes sense to consider vitamin D supplementation for women whose level is lower than normal.
  • Smoking during Pregnancy can have Lasting Effects Upon your Child—it has long been recognized that women that were smokers had lower fertility rates, higher miscarriage rates and earlier onset of menopause than nonsmokers. New information  now suggests that at least some of these negative reproductive effects can be passed on their children as well. Specifically, they found girls born to women that smoked had an earlier onset of puberty than those born to nonsmokers. Noted by the investigators was that early onset of puberty is also linked to a higher risk of certain types of cancer including breast cancer.

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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.

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