Researchers from Emory University and the Centers for Disease Control and Prevention (CDC) say use of intracytoplasmic sperm injection (ICSI) for the treatment of infertile couples has more than doubled in the last two decades, primarily among couples without male factor infertility, and without clear evidence of benefit over conventional in vitro fertilization (IVF). They also report ICSI did not improve reproductive outcomes, and may even worsen outcomes, when used in cases with non-male factor infertility. The results were published in the Journal of the American Medical Association (JAMA) on Jan. 20, 2015.

Introduced to the reproductive medicine field in 1992, ICSI revolutionized the treatment of couples with male factor infertility and made fathering a child possible for a large proportion of men with very low or non-measurable sperm counts. ICSI is an assisted reproductive technology (ART) procedure in which a single sperm is injected directly into an egg in the lab.

"ICSI is indicated for couples with severe male factor infertility, after first attempting medically or surgically correctible ways to improve fertility," says Akanksha Mehta, MD, senior associate in the Department of Urology at Emory University School of Medicine, a specialist in male reproductive medicine.

"We found more doctors are using this technology for indications other than male factor infertility, without any clear evidence of benefit." Mehta sees male patients at Emory’s Reproductive Center at Emory University Hospital Midtown, at the Emory Clinic (Clifton Road), and at Emory Saint Joseph’s Hospital.

In contrast to conventional IVF, ICSI bypasses all natural barriers to fertilization, thereby increasing the possibility of transmission of genetic defects from one generation to the next. Previous research shows that pregnancies resulting from the use of ICSI have been associated with an increased incidence of chromosomal abnormalities, imprinting disorders, autism, intellectual disabilities and birth defects compared to natural conception. These increased risks may be related to the effects of underlying male or female sub-fertility, other medical factors present in couples that are candidates for ICSI or the ICSI procedure itself.

Of the 1,395,634 fresh ART cycles performed between 1996 and 2012, 908,767 (65.1 percent) used ICSI and 499,135 (35.8 percent) reported male factor infertility. Among cycles with male factor infertility, ICSI use increased from 76.3 percent to 93.3 percent during 1996-2012. For those without male factor infertility, ICSI use increased from 15.4 percent to 66.9 percent during the same time period.

Among cycles without male factor infertility, ICSI use was associated with lower rates of implantation and likely contributed to the lower rates of live births and multiple live births, as well as low birth weight rates, when compared with conventional IVF.

"We found that pregnancy and birth rates are no better with ICSI when used in cases without male factor infertility, and may even be worse," says Mehta. "ICSI is also about $5,000 more than a regular IVF cycle. For patients, this means greater risks and more money spent, many times out of pocket, for no additional gain."

Mehta goes on to say, "While this is a great tool for the right population, we caution doctors and patients to carefully consider the use of this technology if male factor infertility is not present."

Other Emory School of Medicine researchers include: Jennifer Kawwass, MD, assistant professor, Dmitry Kissin, MD, MPH, adjunct assistant professor and Denise Jamieson, MD, adjunct professor, all in the Department of Gynecology and Obstetrics.