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


[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

This week’s picks from the Greene Guide include a first reported case of sextuplets from the drug Letrozole as well as a new twist on the “nature vs. nurture debate” as it relates to naturally elevated testosterone levels in elite female athletes:

  • Oral Medication (Letrozole) and a case of Sextuplets—Ovulation induction is associated with a higher risk of multiple pregnancy than IVF treatment. That said, most patients and their providers often take for granted the relative safety of oral medications like Letrozole used to stimulate the ovaries. All that may change now that there is a documented case of sextuplets  using Letrozole 7.5 mg—a higher than normal dosage. Take home lesson, this may have been preventable if the patient had been monitored using ultrasound and blood tests.
  • Most Men with Borderline Testosterone Levels, More Likely to Experience Depression—New data on the hormone-brain connection suggests that a low testosterone level may trigger depressive symptoms. A recent presentation  demonstrated that not only were these men more likely to experience emotional symptoms but also to have problems with obesity and an inactive lifestyle. Further evidence that men quality of life is also linked to a healthy hormone balance.
  • US Fertility Rate Hits an All Time Low—The most recent government figures  show that the number of births has dropped below 63 per 1000 reproductive aged women (15-44 y.o.a). Whether or not this reflects a growing number of women experiencing infertility or is simply a result of people delaying their family due to recent economic downturns remains an active debate.  Most likely, it is a combination of both as well as other emerging factors.
  • Early Onset of Menopausal Hot Flashes May be a Risk Factor for Heart Disease—It is indisputable that those uncomfortable hot flashes experienced by women going through menopause are the result of changes in blood flow patterns. However there has long been debate on whether these symptoms are simply a nuisance to endure or a warning warranting treatment. Two new studies  suggest the latter. Given that there is now strong agreement that treatment of hot flashes is reasonable and safe this data offers new discussion points for patients and their healthcare providers.
  • Fertility Center  Courts Controversy: Offering non-FDA approved Treatment to Rejuvenate Eggs—The procedure involves removing a piece of a woman’s ovary in order to extract mitochondria—the power source—from immature eggs. These mitochondria are then added to mature eggs along with sperm during a subsequent IVF cycle. The company  that developed this procedure has not yet reported any live as a result of the procedure. It does however add an additional $25,000 to the cost of IVF.
  • Early Miscarriage; providing more options improves patient care AND lowers cost—About one out of every three pregnancies end in an early loss. In fact 25% of women will experience a miscarriage at some time in their life. A new study found  that providing patients with more options—beyond D&C or taking a wait-and-see approach—improves patient satisfaction as well as results in a cost savings of about $241 per case. Since about 1 million US women per year experience an early pregnancy loss the emotional and financial impact of this can be huge.
  • Testosterone Levels and Athletic Eligibility in Women—Since 2011/2012, the International Association of Athletics Federations (IAAF) and the International Olympic Committee (IOC) have implemented regulations that elite female athletes must have a blood testosterone level that is below the lower limit for men in order to compete. In reality, there is a vigorous debate  on whether there is reliable biological evidence to support this restriction. The opposing opinion  is that success in sport should be due exclusively due to talent and dedication rather than to any naturally occurring, potentially advantageous biology. Currently, the restriction stands and some women may be required to undergo hormone reducing treatment in order to compete.

[r1]Link to http://www.fertstert.org/article/S0015-0282(14)02356-5/abstract

[r2]Link to http://www.endocrine.org/news-room/current-press-releases/most-men-with-borderline-testosterone-levels-may-have-depression

[r3]Link to http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64_01.pdf

[r4]Link to http://consumer.healthday.com/cardiovascular-health-information-20/heart-attack-news-357/early-onset-hot-flashes-may-point-to-heart-disease-rosk-in-women-697085.html


[r6]Link to http://www.ovascience.com

[r7]Link to http://www.ajog.org/article/S0002-9378(14)00908-9/abstract

[r8]Link to http://press.endocrine.org/doi/abs/10.1210/jc.2014-3206

[r9]Link to http://press.endocrine.org/doi/abs/10.1210/jc.2014-3603

With more than 1.5% of the babies born in the US conceived through IVF, it’s time to review the latest data on Clinic Success Rates .

Ever since the first report issued in 1997, the Center for Disease Control (CDC) has partnered with the Society for Advanced Reproductive Technology (SART) to create the premier example of a medical specialty openly reporting the outcome of their treatment. For nearly twenty years now they have issued a joint annual account of how center’s fair individually as well as collectively in treating infertility through Advanced Reproductive Techniques. Each year this summary provides a wealth of information to track trends emerging in fertility treatment as well as set standards-for-care. This latest report is no exception.

The current summary reflects all of the babies born from ART treatment in 2013. The data reporting is delayed in order to include the pregnancy outcome from embryos transferred prior to the end of the year. Currently there are 380 SART Member Clinics included. They collectively performed nearly 175,000 IVF cycles that resulted in the birth of 63,286 babies. This reflects a substantial increase in both access to treatment as well as an increase in live births from the previous year.

Another encouraging finding was an increase in the number of Elective Single Embryo Transfers (ESET). This reflects a greater effort to reduce the number of multiple pregnancies born through ART as well as a boost in patient confidence. Best of all was that even though the number of babies born went up; the twin rate fell by 3% and the triplet rate was reduced by nearly 10%. Nearly 80% of the successful treatment cycles resulted in the birth of a single baby!

The summary data report for the nation provides many useful insights into the field of reproductive medicine. Now this data is incorporated into a patient prediction model  that allows couples to create an individualized estimate of what their anticipated pregnancy rate would be for one cycle of IVF.  This model does assume that your clinic of choice is achieving IVF conception rates that are around average. As a healthcare consumer, you can access the data base to view your clinic’s success rate  and compare it to the national average. If you find that your center is well below average, don’t make any assumptions. Instead ask questions to determine if they have made changes that you find reassuring before moving forward with treatment.

[r1]Link to https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0

[r2]Link to https://www.sartcorsonline.com/Predictor/Patient

[r3]Link to http://www.sart.org/find_frm.html

One of the ways that I hope to serve people better is to explain breaking research in a timely fashion. The following are just a handful of the hormone related studies that can impact you or someone that you care about. Stay informed and click on the link of any study that is of personal interest to you. Then discuss the findings with your healthcare provider.

  • PCOS linked to a growing risk of other health disorders—Polycystic Ovarian Syndrome (PCOS) is the most common hormone imbalance of reproductive age women affecting an estimated 5 million in the USA alone. A new study  found that in addition to the increased risk of heart disease, obesity and diabetes; women with this disorder also have an elevated risk of asthma, musculoskeletal disorders, mental health problems (i.e., depression and anxiety) as well as an increased risk of certain type of cancer. There was also a noted increase in the risk of miscarriage, ectopic pregnancy and endometriosis. Bottom line is that taking steps to correct this hormone imbalance may not only help you get pregnant but actually have a healthy pregnancy and healthier life afterwards!
  • Radioactive Iodine used to treat thyroid cancer associated with lower subsequent birthrate—A new study  found that women in their 30’s that were given radioactive iodine (RAI) to treat well differentiated thyroid cancer had about a 30% lower subsequent birthrate than their peers. It is uncertain whether or not this was a result of the treatment or the recommendation for a prolonged waiting period to conception after treatment.  Regardless of the reason, given the improved success rates associated with egg freezing; women diagnosed with thyroid cancer should be considered candidates for this fertility preserving procedure prior to RAI treatment.
  • Higher exposure to certain common chemicals associated with early onset of menopause—A new investigation  found that women that were exposed to certain cleaning products, personal care items and specific pesticides tended to begin menopause two to four years earlier than their unexposed peers. They were looking specifically at specific chemicals like PCB’s and phthalates that have been linked to ovarian toxicity in previous research studies. This should further enhance your awareness of the potential negative impact of these unnecessary hormone disruptors and promote more careful selection of what products you use on a regular basis.
  • Bisphenol-A (BPA) exposure during pregnancy may predispose to subsequent health risks after birth—There is a growing awareness that metabolic challenges during fetal development may increase health risks during adulthood. A new study  has demonstrated that BPA can cause oxidative damage during pregnancy which is considered a precursor to conditions like subsequent heart disease or diabetes during adulthood. BPA is in a large number of products including plastic water bottles, canned food liners and cash register receipts. As more manufacturers continue to phase out products that contain BPA; pregnant women may want to take steps to avoid these chemicals to reduce their child’s future health risk.
  • Drinking soda may be linked to early onset of puberty—A new study  found that over consumption of sugary beverages may be triggering earlier onset of menstrual cycles in young girls. This was a well defined observational study performed on over 5500 girls during a 5 year follow up. The risk associated with two daily sugary beverages was independent of their weight, activity level or the remainder of their diet. More reason to avoid these unnecessary hormonal calories is their impact upon developing hormone levels.
  • Corn syrup may be more toxic than table sugar—A study  performed on mice recently demonstrated that when a portion of daily calories were supplied from corn syrup rather than table sugar; the mice had a shorter life expectance and a higher rate of reproductive problems. This negative health impact seemed to greatest on the female mice for reasons that are not fully understood. Although we are uncertain if this will be true in people, its best to avoid foods that contain corn syrup until further studies are available.

[r1]Link to http://consumer.healthday.com/diseases-and-conditions-information-37/misc-diseases-and-conditions-news-203/female-hormone-disorder-linked-to-numerous-other-conditions-695830.html

[r2]Link to http://www.medscape.com/viewarticle/838775

[r3]Link to http://consumer.healthday.com/women-s-health-information-34/menopause-and-postmenopause-news-472/pesticides-plastics-chemicals-tied-to-earlier-menopause-in-women-695892.html

[r4]Link to http://www.medscape.com/viewarticle/838387?src=emailthis

[r5]Link to http://consumer.healthday.com/kids-health-information-23/adolescents-and-teen-health-news-719/sodas-may-prompt-early-puberty-in-girls-study-suggests-695871.html

[r6]Link to http://www.reuters.com/article/2015/01/06/us-usa-health-cornsyrup-idUSKBN0KF03820150106

It feels great to be blogging again. I figured the best was to re-start this blog was to provide an update and summary on how these remarkable techniques have grown and developed as well as summarizing their current success and limitations. The technique of In Vitro Fertilization (IVF) has become the gold-standard of fertility treatment both for its diagnostic value as well as its high success rates compared to other treatment options. It is currently estimated that over 5,000,000 people have been born using IVF since the first reported success in 1978. In 2012 about 1% of all births in the USA —a total of 65,160 babies—were conceived and born through IVF. So let’s first consider the safety of this technology.

A recent report  summarized the safety of Assisted Reproductive Technology in the US by reviewing all of the available data from 2000 to 2011. This analysis included 1.14 million IVF cycles in order to determine the incidence of medical complications within 12 weeks of the procedure. They were looking for complications like infection, bleeding, adverse reaction to medications, anesthetic complications and Ovarian Hyperstimulation Syndrome (OHSS). OHSS was the most common complication and occurred in about 1.54% (154 times in 10,000 cycles). Even this It was rare for any complications to require hospitalization which occurred in 0.35% (35 times in 10,000 cycles). Best of all, the incidence of complications—including adverse medical reactions—declined throughout the time period analyzed.

Importantly, as the pregnancy rates have increased; ART treatment is also resulting in the birth of healthier babies. For instance a 20 year review  of cycles performed in the Scandinavian countries of Norway, Sweden, Finland and Denmark demonstrated a remarkable decline in the incidence of preterm birth or with low birth rate. They also found a similar reduction in still birth and infant mortality. The most important contributing factor to this remarkable success is that these countries have a national policy of transferring only one embryo at a time. The practice of elective single embryo transfer (ESET) is rapidly becoming the norm in the US as well. Another reassuring finding  was that the risk of Autism Spectrum Disorder (ASD) was not increased in children born through IVF; a fear that many had theorized before the data was available to review.

Finally, a recent report  on the increased use of Intracytoplasmic Sperm Injection (ICSI) as a technique to fertilize eggs was recently misinterpreted—in my opinion—rather cynically by the popular critics. ICSI was a treatment first used in 1992 to overcome severe male factor infertility. This report revealed that the use of ICSI has doubled during the last two decades even though the incidence of male factor infertility has remained steady.  Their reports suggested it was being used unnecessarily. As a clinician however I know that many couples have multiple factors contributing to their infertility challenge. Even with a normal sperm count, the sperm may not be able to penetrate the egg; either because the sperm is too weak or because the egg shell (zona) is too tough. Either way, this technique overcomes either challenge. In fact, this recent study found that the rate of “failed fertilization” was markedly reduced by the wider use of ICSI. Another important benefit of using ICSI routinely is that it makes it possible to minimize the risk of a good egg being fertilized by an abnormal sperm. The end result is that ART becomes increasingly safer and more effective and ICSI is one aspect that has contributed to that success.

If you’d like to estimate your own unique chance of a achieving a successful pregnancy through IVF, check out the following link to the Society for Assisted Reproductive Technology: https://www.sartcorsonline.com/Predictor/Patient . There you can answer a few short questions about your current situation and you’ll be given your own personalized IVF cycle prognosis using the statistics from the SART National Database (2006-2012). The results from your center may vary but this should give you an excellent reference point to have further discussions with your reproductive healthcare provider.

[r1]Link to http://jama.jamanetwork.com/article.aspx?articleid=2088842

[r2]Link to http://humrep.oxfordjournals.org/content/early/2015/01/16/humrep.deu345.abstract?sid=ab6c68c3-4f95-40cb-9b74-c9367305e75a

[r3]Link to http://jama.jamanetwork.com/article.aspx?articleid=1707721&resultClick=3

[r4]Link to http://jama.jamanetwork.com/article.aspx?articleid=2091303&resultClick=3

Here is a link to this free blog post:

I so enjoy writing and having this venue to share emerging evidence-based research in the field of reproductive medicine. In order to more efficiently balance my responsibilities to my patients as well as my readers, I will continue to reach out in this fashion. Starting this month however, I will be posting a title and excerpt in this blog with a link to the full post. That link will take you to the remainder of the post (free service that we offer to our patients– http://cnyfertility.com/blogs ). I truly hope you don’t find this to be inconvenient and I look forward to sharing more useful and practical information with you.
Best thoughts,

Robert Greene, MD, FACOG
CNY Fertility Center


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