This headline is a bit misleading in that a similar technique was used in the 1990’s before it was decided that we need to proceed more cautiously in mixing DNA. Currently, the technique described is not available for couples treated in the USA and is only approved for use in treating specific genetic conditions. However, this is an exciting breakthrough that may prove to be useful in areas of reproductive medicine. https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/
This news will come as no suprise to our patients as we have been demonstrating this for years. It is good to have yet another study that further supports this recommendation. The cautionary note here for patients is to check with their center on the method of freezing used in their lab–if it not the modern rapid-freeze technique called vitrification then you might be better served by a fresh transfer. http://www.latimes.com/science/sciencenow/la-sci-sn-ivf-frozen-embryos-20160809-snap-story.html
One of the most challenging problems to diagnose and treat for couples trying to conceive is the problem of recurrent early pregnancy loss (REPL). As fertility specialists, we spend a tremendous amount of time and energy making sure that we control all of the variables that might improve the chances that a pregnancy gets a healthy start. New evidence shows that women can—and should—make some simple changes in their lifestyle to also improve their chances for a successful outcome.
A study presented at the 2015 meeting of the American Society for Reproductive Medicine recently highlighted the potential impact of a chemical called phthalates on the pregnancies of women going through IVF. This was part of a study called the EARTH study; an investigation on how environmental and lifestyle can impact reproductive health. They measured phthalate levels in the urine of about 250 women going through fertility treatment and then followed these levels in nearly 300 pregnancies. What they found was that women going through fertility treatment that had higher levels of this chemical in their body had a much higher chance of miscarrying then the fertility patients with lower levels. In fact, their risk could be as much as three to four times higher—depending upon their level of exposure.
An important aspect of modern research is to pose the question of “why?” In this case, the question would be “why would phthalates increase the risk of miscarriage.” The answer to that question is by interfering with the ability of ovary to support the development of the early pregnancy. Specifically, after an egg is released from the ovary; the cells that remain at the site of the egg’s origin form a hormone producing unit called a corpus luteum (CL). The function of this CL is to help get the pregnancy off to a strong start until the placenta is large enough to take over hormone production. In 2014 a well designed study found that phthalates directly interfere with the ability of the CL to perform this critical role.
A recent multi-centered clinical study found that women pursuing Advanced Reproductive Treatments (ART) like IVF had lower levels of phthalate in their body than infertility patients pursuing other forms of treatment. The believed explanation for this finding was that patients undergoing IVF may pursue healthier lifestyle choices. For instance, it is estimated that at least 90% of the phthalates in our bodies are due to dietary intake. By reducing processed foods and decreasing consumption of animal fats, phthalate levels fall rapidly. In fact, our bodies are able to eliminate phthalates after only 6 to 12 hours. So it is only through the continued exposure that these chemicals persist in the bloodstream. So by making better choices, patients may be able to reduce their risk of miscarriage by 75%.
Here are some easy steps that you can take to begin reducing your phthalate level today:
- Only use nail polishes that are phthalate free—most add a phthalate called DBP to reduce chipping
- Don’t microwave or cook your food in plastic containers or use plastic utensils to eat hot foods—heat leaches this chemical out of the plastics and into food—the easiest pathway into your body
- Avoid plastic bottles—seek out glass or metal instead. When you must use plastic seek out bottles with the #2, #4 and #5 in the recycle triangle
- Avoid perfumes and scented products—phthalates (DEP) are used to prolong fragrances
- Don’t use air fresheners—most contain phthalates
- Avoid vinyl containing products—many products like lawn furniture, rain coats or shower curtains can not only release phthalates that can be inhaled but they can also be absorbed through the skin as well.
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.
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.
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.
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.