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.
One of the greatest challenges that we face in treating couples with infertility, is what options to offer beyond the typical treatment protocols. Clearly, most of our patients are well served with the basic ovarian stimulation methods but in some patients that may exacerbate or simply ignore an underlying hormone imbalance that’s compromising success rates. Therefore, one of the greatest challenges is to figure out how and when to tweak the typical combination of meds in order to shift the hormone balance back to a more favorable outcome. This is the reason that we should now reconsider the use of human growth hormone (hGH) for patients that have failed previous IVF treatment.
I trained under Dr. David Meldrum at UCLA-Harbor Medical Center in Los Angeles. Back in the early 1990’s he was advocating the consideration of adding hGH to the protocol of certain patients. His reasoning was good. First of all, we know from previous research [u1] that healthy developing eggs produce a growth hormone analogue known as IGF-2. Better still, other studies [u2] have demonstrated that hGH could possibly increase the ability of eggs to repair damaged DNA. Finally, several studies have found that growth hormone can improve the response of the ovaries to stimulation during an IVF cycle. Given that all of this information has been available for quite some time, it may be surprising to a patient that there hasn’t been wider use of hGH during IVF treatment. Recently, Dr. Meldrum and several other experts [u3] suggested that this was because there remained too much confusion amongst specialists on which patients would benefit from the use of this somewhat expensive but also possibly game-changing hormone.
The good news is that recent studies [u4] have more carefully defined the characteristics of the patients that were receiving hGH. As a result, we have some new data to better guide us as to which women may be most likely to benefit from hGH. Here is a summary of what they found:
- In women >40 years of age, they found a higher implantation rate and better on-going pregnancy rate in women treated with hGH during ovarian stimulation.
- In women that are poor responders to ovarian stimulation—defined as three or fewer eggs produced per IVF cycle—there was a marked improvement in pregnancy rate with growth hormone supplementation. They also found an improved outcome in FET cycles from embryos created during these cycles.
- In women that have poor embryo quality and low pregnancy rate in otherwise encouraging ART cycles, there is not be a clear benefit of using growth hormone. Instead, other causes of poor embryo quality should be explored. Once those have all been addressed, reconsideration of hGH is worthwhile.
Robert Greene, MD, FACOG
Few disorders can be more difficult to diagnose or more frustrating to treat then recurrent early pregnancy loss (REPL). Traditional diagnostic criteria call for at least three pregnancy losses prior to evaluation and treatment of this vexing problem. With more women choosing to delay pregnancy until their thirties or even their forties, REPL can create an additional burden on their already limited opportunities to achieve a successful pregnancy. Ironically, as women age they are more likely to experience a miscarriage when/if they do become pregnant. A new technique called comparative genomic hybridization (CGH) offers couples some reassurance.
Studies show that most pregnancy losses (50-70%) are due to genetic abnormalities. In fact, the earlier that miscarriage occurs the more likely it is to be due to abnormal changes in the DNA. These are not typically abnormalities that are detected by testing the parents but rather spontaneous mutations that occur during early development. Moreover, they often go undetected by the most commonly used technique for genetic assessment, called G-banded karyotype analysis. That’s because karyotype analysis has limited resolution. It is only able to detect the addition or deletion of relatively large portions of the genetic code. By contrast however, CGH is able to detect genetic changes that are far smaller. In fact, this technique has been reported to identify genetic causes for unexplained mental retardation in about 10% of patients that had previously had a “normal” conventional genetic karyotype. Moreover, a study in the current issue of the journal Obstetrics & Gynecology found that CGH was able to identify genetic abnormalities in 13% of miscarriages that were missed using conventional genetic testing. More exciting still is the potential of CGH to detect certain abnormalities before birth.
Maybe the best use of this technique however is when testing is performed on embryos prior to becoming pregnant. Combining CGH with in vitro fertilization (IVF) allows us to perform a biopsy upon an embryo for genetic analysis prior to transfer into a woman’s uterus. Early data using IVF with CGH has been very reassuring. We’re finding that by identifying and transferring only the embryos that are determined to be genetically competent—meaning without identifiable deletions or additions to the genetic code—we may be able to double or even triple the chance of a healthy live birth. Since this technique is still relatively new, more studies are needed before it is widely accepted but it is already revolutionizing the diagnosis and treatment of couples seeking fertility treatment.
Although we still recommend prenatal screening once pregnancy is established, CGH can dramatically reduce the anxiety of couples during those critical weeks of the first trimester; especially those with a history of recurrent early pregnancy loss. Remembering when my wife and I conceived—both of us are in our forties—I know that we would have had fewer sleepless nights early in our pregnancy had we been able to have CGH as part of our fertility treatment. There is certainly an additional therapeutic benefit of that stress reduction as well!