Injecting Sperm More Popular but Does Not Improve Outcomes

Diedtra Henderson

January 21, 2015

Intracytoplasmic sperm injection (ICSI), a relatively new technique that by 2012 had soared to represent 76.2% of so-called fresh in vitro fertilization (IVF) cycles, was not associated with improved reproductive outcomes, according to a retrospective cohort study.

Sheree L. Boulet, DrPH, MPH, from the Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues report their findings in an article published in the January 20 issue of JAMA.

According to the American Society for Reproductive Medicine, in traditional IVF, thousands of swimming sperm are placed next to the egg; when one sperm enters the egg's cytoplasm, fertilization occurs. ICSI employs a micropipette to inject one sperm directly into the egg's center, according to the society.

Since its introduction in 1992, increased use of ICSI has allowed men previously unable to father children, such as men with nonobstructive azoospermia or no measurable sperm count, to experience paternity, according to Dr Boulet and coauthors. But the expensive technique, which bypasses natural barriers to fertilization, is associated with 1.5 to 4 times increased incidence of autism, birth defects, chromosomal abnormalities, and intellectual disabilities when compared with pregnancies that result from conventional IVF, according to the authors.

Per federal mandate, assisted reproductive technology cycles performed in the United States are recorded in the National Assisted Reproductive Technology Surveillance System. The researchers examined the database to analyze "fresh" IVF and ICSI cycles, or those in which embryos had been transferred without being frozen, from 1996 to 2012.

The national database captured 1,395,634 fresh IVF cycles: 65.1% used ICSI, and 34.9% used conventional IVF. Despite clinical practice guidance cautioning against using ICSI in patients without male factor infertility, in 64.2% of cycles, no male factor diagnosis was reported. Overall, ICSI was performed in 90.0% of cycles in which male factor infertility was diagnosed and in 51.2% of cycles without male factor infertility.

From 2008 to 2012, a period during which assisted reproductive technology advanced, there were 494,907 fresh IVF cycles; ICSI was used in 74.6% of them, but male factor infertility was identified in just 35.7% of the cycles. ICSI was performed in 92.9% of cycles in which male factor infertility was diagnosed and in 64.5% of cycles without male factor infertility.

In couples in which male factor infertility was not identified, the woman was more likely to be older than 40 years, to have diminished ovarian reserve, and to have had at least one previous assisted reproductive technology attempt, according to the authors.

"The use of ICSI doubled during the study period, from 36.4% to 76.2% of all fresh IVF cycles, with the greatest increase occurring in cycles without male factor infertility," Dr Boulet and colleagues write. "When male factor infertility was present, reproductive outcomes — including pregnancy, miscarriage, and live birth rates — were comparable for cycles that used ICSI vs conventional IVF after adjustment for maternal factors."

Although the rate of ICSI use is increasing, the diagnosis of male factor infertility is stable, leading the authors to postulate that "unmeasured factors" underlie its rising popularity.

The largest relative increase was noted among cycles with no diagnosis of male factor infertility, the authors conclude. "Compared with conventional IVF, use of ICSI was not associated with improved reproductive outcomes irrespective of male factor infertility diagnosis."

Financial support for the study was provided by the National Institutes of Health. The authors have disclosed no relevant financial relationships.

JAMA. 2015;313:255-263. Full text

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