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    Use of ICSI on rise, but are outcomes better?


    Commentary by Contemporary OB/GYN Tech Editors Brian Levine, MD, MS, and Dan Goldschlag, MD, FACOG:

    An initial review of this article suggests that intracytoplasmic sperm injection (ICSI), a type of assisted reproductive technology (ART) that requires a tremendous amount of skill and resources, is being over-utilized. A crucial argument not addressed in this paper but that may explain the “rise” in ICSI use is simple economic pressure, that is, supply and demand for in vitro fertilization (IVF).

    With the dramatic increase in use of ART in the past 20 years, access to IVF has become more common, resulting in better technology and a drop in the costs of the requisite tools (and training). With that said, it is evident in both Figures 1 and 2 that the greatest increase in ICSI use was upon its introduction. In the last chronological quartile of the study, there appears to be little change in the relative frequency of ICSI.

    As part of the ICSI procedure, the operator must select the best-appearing sperm, immobilize it, and then gently inject it into the egg. This selection process allows the operator to inject what may appear to be the best sperm into the eggs. Some may feel that this is “unnatural,” but embryologists and ICSI operators strive to identify the best gametes, which may ultimately make the best embryos, furthering what everyone would agree is the goal of IVF: creation of the healthiest pregnancy possible for both mother and baby. Discussing “natural selection” in the context of ART, thus, is awkward.

    Boulet and colleagues do not ad- dress the relative importance of egg freezing in the armamentarium of tools that reproductive endocrinologists can offer their patients. With the advent and adoption of oocyte cryopreservation, many women are choosing to freeze their eggs for a multitude of reasons. That being said, cryopreserved eggs that are subsequently thawed must undergo ICSI for efficient fertilization because of the steps involved for proper freezing/ thawing. Therefore, as more women thaw and fertilize their eggs, use of ICSI is likely to increase.

    Read: Should all women freeze their eggs?

    Similarly, trophectoderm (Day 5) biopsies for preimplantation genetic diagnosis (PGD) can only be done on an embryo that has been fertilized by ICSI because excess sperm surrounding the embryo would skew the genetic results, potentially generating a false diagnosis. Increased use of ICSI in patients undergoing PGD—a population that is growing—is an indicator that practitioners are offering better genetic testing modalities (Day 5 instead of Day 3) to these women.

    The authors of this article incorrectly focus on post-fertilization outcomes: specifically, rates of implantation, live birth, and multiple live births. It is possible that ICSI was associated with lower post-fertilization metrics in couples for whom male-factor infertility was not considered a primary diagnosis and instead, the male may have been subfertile but did not meet the threshold for being called infertile.

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    As such, some of the non-male-factor cases in which ICSI was used may, in fact, be some of the most complicated cases in the series and not cases “without any indication,” as the authors describe them. For example, the etiology of infertility may not have been labeled as male factor for a patient with a history of recurrent miscarriage and low ovarian reserve whose partner had low sperm motility.

    Taking all of this information together, it is important to understand that, while this article has academic merit, it does not address the emergence of new technologies and the effects of market pressures and technological development on increased access to care. It is “good” that the cycles using ICSI had more Day 5 transfers and more embryos cryopreserved because we should try to avoid multiple gestations whenever possible.

    This paper indirectly shows that IVF is becoming potentially safer and more available. However, given that this is a large retrospective study, all of the findings are worth discussing, but it is also important to understand that it suffers from the limitations of analyzing large registry-derived data. The hardest task would be designing and implementing a prospective study to address the authors’ concerns about the current state of IVF in America.

    Brian A. Levine, MD, MS, FACOG
    Dr. Levine is Practice Director at the Colorado Center for Reproductive Medicine, New York, New York.
    Dan Goldschlag, MD, FACOG
    Dr. Goldschlag is an assistant professor of Clinical Obstetrics and Gynecology and Assistant Professor of Clinical Reproductive Medicine ...


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