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Injecting Sperm into Egg Doesn’t Guarantee Pregnancy

  • - Urology / Nephrology News
  • Jan 23, 2015
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The use of the new IVF procedure has doubled in prevalence over the past decade without evidence of reproductive outcome

The use of intracytoplasmic sperm injection (ICSI) was not associated with improved reproductive outcome compared to conventional in vitro fertilization (IVF), researchers reported.

A retrospective analysis looked at the data on fresh IVF and ICSI cycles reported to the U.S. National Assisted Reproductive Technology Surveillance System during 1996-2012 and found that while the use of ICSI had doubled between the study period, ICSI use was associated with small but statistically significant decreases in implantation, pregnancy, live birth, multiple birth, and low birth weight rates compared with conventional IVF, Sheree L. Boulet, DrPH, MPH, of Centers for Disease Control and Prevention in Atlanta reported online in the Journal of the American Medical Association.

Intracytoplasmic sperm injection was an IVF technique first introduced in 1992 that help treat couples with male factor infertility (infertility due to abnormal semen characteristics, abnormal sperm function, or surgical sterilization). This technique directly injects a single sperm into an egg, thus bypassing many of the natural barriers to fertilization.

However, such technique is not without its own problems. In addition to the tremendous increase in cost, pregnancies resulting from the use of ICSI have been associated 1.5 to 4 times increased incidences of chromosomal abnormalities, imprinting disorders, autism, intellectual, disabilities, and birth defects compared with pregnancies resulting from conventional IVF.

In 2012, Practice Committees of the American Society for Reproductive Medicine and Society for Assisted Reproductive Technology concluded that “there are no data to support the routine use of ICSI for non-male factor infertility.” However, such practice continued to become more pervasive over the years.

“The higher reimbursement associated with ICSI has been postulated as one possible reason for the increasing use of this technology,” the authors wrote.

“ICSI adds approximately $1,500 to the cost of an IVF cycle. The average cost of an IVF cycle in the U.S. is $12,400. The total cost to have a baby varies depending on how many cycles of IVF are needed to achieve a live birth.”

The retrospective cohort study identified 1,395,634 fresh IVF cycles during this period, and 908,767 (65.1%) used ICSI and 486,867 cycles (34.9%) used conventional IVF. The proportion of fresh IVF cycles using ICSI increased from 36.4% (15,073/41,450) in 1996 to 76.2% (74,512/97,756) in 2012. Among cycles with a diagnosis of male factor infertility, ICSI use increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506).

To account for improvement in technology, researchers also specifically looked between 2008-2012 when evaluating for the efficacy of ICSI compared to conventional IVF. During this period, male factor infertility was reported for 35.7% (176,911/494,907) of fresh cycles. Among those cycles, ICSI use was associated with a lower multiple birth rate compared with conventional IVF (30.9% vs 34.2%; adjusted relative risk [RR], 0.87; 95%CI, 0.83-0.91). Among cycles without male factor infertility (n = 317 996), ICSI use was associated with lower rates of implantation (23.0%vs 25.2%; adjusted RR, 0.93; 95%CI, 0.91-0.95), live birth (36.5%vs 39.2%; adjusted RR, 0.95; 95%CI, 0.93-0.97), and multiple live birth (30.1%vs 31.0%; adjusted RR, 0.93; 95%CI, 0.91-0.95) vs conventional IVF.

With the above finding, researchers concluded that ICSI use was not associated with improved post-fertilization reproductive outcomes, irrespective of male factor infertility diagnosis.

“Although such differences may be a function of the large sample size and thus not clinically relevant, our findings suggest that use of ICSI may improve fertilization rates but not implantation or pregnancy rates in the setting of unexplained infertility, advanced maternal age, and low oocyte [a cell from which an egg develops] yield,” the authors wrote.

“IVF practitioners may be surprised by the four-fold increase in the use of ICSI over time for cycles without a diagnosis of male factor infertility. Given that we found no improvement in reproductive outcomes regardless of whether male factor infertility was present, practitioners may decide to more thoroughly discuss the potential risks and benefits of using ICSI with their patients.”

However, not all experts agreed with the above finding. Jim Toner, MD, President of the Society for Assisted Reproductive Technologies, commented that “data used for this analysis are insufficient to provide anything close to a clear answer.”

“In this dataset, there is no fixed definition of ‘male factor’ (each clinic defined this group for themselves); no certainty that all those with ‘male factor” were tagged in the system as such; no information on fertilization rate; no information on embryo quality; no information on whether the transferred embryos in the ICSI group were subjected to ICSI (many clinics do ICSI for some but not all eggs in cases of unexplained infertility), and no information about differential rates of cryopreservation.”

“The strongest effect of ICSI on outcomes, in both the male factor and non-male factor groups, was the reduction in cycle cancellation (50% for male factor, and 12% for non-male factor). Fewer canceled cycles is a very important benefit of ICSI. Had the authors reported pregnancy rates per cycle start, or per egg retrieval, instead of per embryo transfer, the benefit of reduced cancellations on the ultimate outcome would be obvious.”

Lastly, Toner said, “I don’t think most practitioners will alter their practice based on this study, because of the limitations cited above. More research in needed. We don’t want to risk more failed cycles by abandoning ICSI unless the risks outweigh the benefits.”

All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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  Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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