Egg Quality: new insights into why human eggs don’t age well

It has long been accepted that the primary reason that human eggs don’t age well is due to a dysfunction in when and how the chromosomes separate. This reduced chance of becoming pregnant associated with aging as well as the increased miscarriage rates. A new paper has now demonstrated that it’s not just the DNA separation that declines with time but also how the chromosomes are actually sorted and divided.

Within each egg are cable-like structures called microtubules. These microtubules not only help the egg maintain its shape but also are integral in sorting/separating the DNA. They are also in charge of cell division after fertilization is complete. In fact, some of the most powerful cancer fighting drugs are used to deliberately damage microtubules in order to prevent cancers from growing. This new information provides us with further insight into another important aspect of egg quality.

Although we don’t currently have any specific recommendations on what we can do to improve microtubule function; this information does provide us with more diagnostic information for patients that are going through In Vitro Fertilization (IVF). IVF is not only the treatment that provides patients with the highest pregnancy rates but when performed in a high quality setting; it also provides important diagnostic information. There is no accurate test for egg quality except to put a healthy sperm inside and see if/how well the process of fertilization and development takes place. We routinely use this information in discussing treatment options for patients that do not successfully conceive in their first IVF cycle at our center.

Fertile thoughts,

~Robert

Robert Greene, MD, FACOG

Conceptions Reproductive Associates

Daylight Savings Time May Lower Chances of IVF Success for Some: Study

At our center, we have long held that your circadian rhythm–how your biology responds to the day-night cycle–impacts your fertility. This is one of the many reasons we focus on optimizing vitamin D levels, melatonin (when necessary) and paying careful attention to our embryo transfer schedules. In case your fertility center hasn’t figured out how important that this is, check out the following recent study on miscarriage risk associated with time shifts.  https://consumer.healthday.com/infertility-information-22/infertility-news-412/daylight-savings-time-may-lower-chances-of-ivf-success-for-some-study-719514.html

The kids are all right: Children with 3-way DNA are healthy

One of the emerging therapies in advanced reproductive techniques involves combining the parts of a healthy egg donor to rejuvenate or correct deficiencies in a woman’s own egg. When a sperm is then added, the resulting person can actually contain the DNA of three people rather than two. Although this technology is currently not available for use in the USA–the first babies have been born in England through this technique. Interestingly, there were 17 babies born in the USA using this technique more than a decade and a half ago. This procedure was then banned due to potential health concerns in the children that resulted. We now have a follow up report on these original children who are now teenagers. Most importantly, this update is reassuring that although caution is recommended, this procedure does seem safe and reasonable for continued investigation.

https://www.statnews.com/2016/10/26/children-3-way-dna/

Exclusive: World’s first baby born with new “3 parent” technique | New Scientist

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/

In IVF, frozen embryos may lead to more live births than fresh embryos – LA Times

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

Early Pregnancy Loss; simple changes to reduce your risk

 

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.

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.