State of the A.R.T (Advanced Reproductive Techniques) 2015

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

Boosting Pregnancy Rates for “poor responders” to IVF—new hope by applying existing technology

One of the greatest challenges in reproductive medicine is trying to figure out ways to improve pregnancy rates for women that produce a limited number of eggs. Other posts on this blog[u1]  address various steps to try to optimize/improve egg quality[u2] . But new data suggests that the use of intracytoplasmic sperm injection (ICSI) can improve embryo formation and more importantly increase a woman’s chance of becoming pregnant. Traditionally, ICSI has been used to overcome male factor infertility. Over the last several years, some centers have included it in all of their treatment cycles as a means of maximizing fertilization. Some experts criticized this practice since it was based upon a theory rather than clinical proof of an improved outcome. In fact, the American Society for Reproductive Medicine has a Patient Fact Sheet [u3] that describes the guidelines for the use of ICSI (last revised in 2008). Recently a large study attempted to settle this debate on whether or not ICSI should be used in women considered to be “poor responders” to fertility therapy.

One of the limitations of previous studies on “diminished ovarian reserve (DOR)” was the lack of an agreed upon definition of how to diagnose this condition. In 2011 an international meeting was held to form a consensus [u4] on the identification of “poor response to ovarian stimulation.” Their goal was to improve the design of future studies and provide practical guidelines as well as assist doctors in the diagnosis of this condition. To meet diagnostic criteria it was agreed that a woman must have at least two of the following:

  • 40+ years of age or any other risk factor for poor ovarian response
  • A previous cycle producing  3 (or fewer) eggs with a conventional protocol (excludes Mini IVF)
  • An abnormal ovarian reserve test (i.e., AMH [u5] below the age- related norms)

The recent study [u6] referred to in this blog post followed over 1000 IVF patients that had failed on a previous cycle and met the new criteria for “poor responders.” These patient/couples completed nearly 3000 total cycles of IVF with ICSI. They found that including ICSI—despite a normal sperm count—improved the ongoing pregnancy rate by 40%. Another noteworthy fact is that this study was performed in Israel where IVF is a fully covered health benefit for all citizens. This made it possible for patients to continue treatment without concern of cost thereby removing a “selection bias.” The potential benefit of ICSI—in the absence of a male factor—does make sense. Some studies show that women with DOR have a thicker coating on the egg making it more difficult for a healthy sperm to enter. Selecting a sperm for use in ICSI may also reduce the possibility of an abnormal sperm fertilizing an otherwise limited number of healthy eggs. Whatever the reason, most women with a poor response to fertilization are immediately directed to use donor eggs. However, this study found that ~35% of these “poor responders” achieved a successful pregnancy within 5 to 7 IVF attempts. The bottom line is that couples that would otherwise have been discouraged from completing a second attempt went on to have a baby at least 1/3 of the time.

So discuss with your doctor whether or not you may benefit from including ICSI in your next IVF cycle. In doing so, be careful to ask if there is an additional charge for this service. At CNY Fertility[r7]  Center, we are pleased to offer this augmented fertilization technique to all of our patients as part of the standard IVF cycle (included in the standard fee). Now we have more data supporting this recommendation.

Robert Greene, MD, FACOG

CNY Fertility Center

e-mail me at rgreene@cnyfertility.com

Call our toll-free number at 800.539.9870 or request a consult here.