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
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