Technique Used for Male Infertility Climbs, but Disorder Steady

CHICAGO, July 19 -- Even when semen measurements are normal in cases of unexplained infertility, the use of intracytoplasmic sperm injection (ICSI) is increasingly common, investigators here reported.

ICSI for male-factor infertility has increased sharply in the U.S. since 1995, while rates of male infertility have remained flat, reported Tarun Jain, M.D., of the University of Illinois at Chicago, and Ruchi S. Gupta, M.D., M.P.H., of Northwestern, in the July 19 issue of the New England Journal of Medicine.

Male infertility factors can include low sperm counts, poor motility or movement of the sperm, poor sperm quality, or sperm that lack the ability to penetrate an egg.

The Chicago analysis of in-vitro fertilization trends and the use of ICSI over time revealed that even when male-factor infertility was not responsible for a couple's inability to conceive, IVF clinics were significantly more likely to use ICSI in 2005 than in 1999.

The ratio of ICSI use to male-factor infertility cases was significantly higher in states where insurance coverage of infertility services is mandated, suggesting that other, less expensive procedures were being used in larger numbers.

"Considering the remarkable success of ICSI in the treatment of male-factor infertility, many fertility centers have extended the indications for ICSI when semen measurements are normal to include cases of unexplained infertility, fertilization failure in a previous IVF cycle, and few or poor-quality oocytes available for insemination," they wrote. "Some centers have even advocated for the routine use of ICSI in all IVF cycles."

This trend is cause for concern, the authors said, because studies have shown that children conceived with ICSI are at increased risk for aberrations in sex and autosomal chromosomes, major congenital anomalies, and genomic imprinting disorders, such as Angelman's syndrome.

"However, it is unclear whether the increased risks associated with the use of ICSI are attributable to the procedure or to underlying abnormalities in persons with male-factor infertility," they wrote. "If the reported adverse pregnancy outcomes associated with ICSI are in fact attributable to this procedure, the increasing numbers of these procedures means that even small absolute risks could result in substantial numbers of adverse outcomes, with associated costs for patients and society."

In addition, the authors pointed out that a large, multicenter, randomized trial comparing clinical outcomes after ICSI or traditional IVF in couples with infertility that was not attributed to male-factor conditions, showed lower rates of implantation and pregnancy in the ICSI group.

An infertility specialist not involved in the study said that the rise in the use of ICSI in relation to the occurrence of male infertility may be in part due to an effort to increase the chances of success with each IVF cycle.

"That reflects clinics either feeling more and more comfortable with ICSI, or stated a different way, feeling more and more uncomfortable doing natural insemination or natural fertilization and risking fertilization failure," said William Schoolcraft, M.D., director of the Colorado Center for Reproductive Medicine in Englewood, in an interview.

The authors looked at data on assisted reproductive technology reported to the CDC by fertility clinics nationwide under a federal mandate. They found that the percentage of IVF cycles with ICSI increased roughly five-fold from 11% in 1995 to 57.5% in 2004, with ICSI being used in the majority of IVF cycles from 2001 on.

"In contrast, diagnoses of male-factor infertility remained steady over the time period analyzed (1999 to 2004), with a resulting increase over time in the ratio of ICSI use to diagnoses of male-factor infertility," the author wrote. "These findings suggest an increasing use of ICSI for infertility that is not attributed to male-factor conditions."

When they compared states with comprehensive mandates for coverage of infertility (Illinois, Massachusetts, and Rhode Island) with other states without mandates, they found that the percentage of IVF cycles where ICSI was used increased in states in both categories, although the percentage of total fresh-embryo IVF cycles did not vary significantly.

Beginning in 1999 and continuing through 2004, states without mandated coverage had a larger proportion of male-factor infertility cases where ICSI was used during IVF cycles, the authors found.

"This observation is consistent with the much greater use of IVF overall in states with mandated coverage," they wrote, "such that more patients in these states are likely to undergo IVF for other indications that might be treated with other, less expensive approaches in states without mandated coverage."

The authors also factored in clinic volume and found that there was no significant association between the number of cycles and the rate of ICSI use, suggesting that "insurance-related differences in ICSI use were not explained by differences in clinic volume."