CSI Has Benefits in Unexplained Infertility: Meta-Analysis

June 28, 2013

By Megan Brooks

NEW YORK (Reuters Health) Jun 28 - For couples with well-defined unexplained infertility, the routine use of intracytoplasmic sperm injection (ICSI) for some or all oocytes offers several benefits, a meta-analysis indicates.

Compared with conventional insemination, ICSI improves the overall likelihood of fertilization and decreases the risk of total fertilization failure (TFF) in couples with unexplained infertility, the reviewers found.

"Although the use of ICSI does not completely prevent TFF, the substantial reduction in risk supports its routine recommendation," say Dr. Lauren Johnson from Reproductive Endocrinology and Infertility, University of Pennsylvania in Philadelphia and colleagues.

Still, they say, the impact of ICSI on clinical pregnancy and live birth rates needs more study.

Up to 30% of couples seeking fertility treatment are ultimately diagnosed with unexplained infertility, the investigators say in an article online June 17 in Fertility & Sterility. It's thought that a fertilization defect, either due to occult sperm abnormalities not revealed during semen analysis or abnormalities in the oocyte, such as hardening of the zona pellucida or meiotic errors, may be to blame.

And while in vitro fertilization (IVF) can be an "expeditious and cost-effective" option for these couples, in up to 25% of IVF cycles performed for unexplained infertility, no fertilization of the oocyte occurs with the use of conventional insemination, Dr. Johnson and colleagues point out.

Several small studies have shown that ICSI improves fertilization rates and decreases the likelihood of TFF. It's not routinely recommended, however, first because a benefit has not been demonstrated in all studies and second because pregnancy outcome data are lacking, the reviewers note. Also, ICSI increases the cost of IVF, and in male factor infertility it has been associated with an increased prevalence of sex chromosome abnormalities in offspring compared with conventional IVF.

Because it is difficult to predict which couples with unexplained infertility may benefit from ICSI, some IVF clinics have adopted the practice of inseminating one half of the retrieved oocytes conventionally and the other half with ICSI, the authors point out.

To get a better handle on the value of ICSI in unexplained infertility, Dr. Johnson and colleagues searched Medline and Embase from 1992 to 2012 for studies of couples with well-defined unexplained infertility undergoing IVF in which sibling oocytes were randomly split between conventional insemination and ICSI.

They included in their meta-analysis 11 studies with a total of 901 couples with 11,767 sibling oocytes from women between 30 and 35 years old.

Nine studies reported fertilization rates per injected and inseminated oocyte. The overall fertilization rate per oocyte that underwent ICSI was 67.5%, compared with 47.8% for oocytes allocated to conventional insemination. The pooled relative risk (RR) of a mature oocyte fertilizing was significantly higher with the use of ICSI (RR 1.49, p<0.001).

There was significant heterogeneity within studies. Only five of the 11 studies reported the total number of oocytes retrieved; the remaining six studies reported only the number of mature oocytes. Nonetheless, the pooled RR of fertilization per allocated oocyte in these five studies remained higher with ICSI than with conventional insemination (RR 1.27, p=0.031).

The pooled RR of TFF was also significantly higher with conventional insemination than with ICSI (RR 8.22). The number of subjects needed to treat with ICSI to prevent one case of TFF was five.

The authors could not do a meta-analysis of pregnancy outcomes. Ten of the 11 studies reported pregnancy outcomes but only four studies reported outcomes by insemination method. However, each of these four studies used different criteria for selection of embryos for transfer and the patient groups undergoing transfer were small and not comparable between studies.

This analysis shows several benefits to using ICSI for unexplained infertility, the authors say.

"Randomizing oocytes between conventional insemination and ICSI potentially allows for both diagnosis of the cause of infertility and treatment within the same cycle," they explain. "Additionally, improved fertilization rates with ICSI may provide better selection of embryos for transfer or more embryos available for cryopreservation, thus improving the cumulative pregnancy rates. TFF can be an emotionally and financially devastating outcome, and the use of ICSI significantly reduces these risks, preventing one case of TFF for every five patients with unexplained infertility treated with ICSI."

Dr. Johnson and colleagues say couples will need to be counseled regarding the potential risks of ICSI. They note that some studies have suggested an increased risk of congenital anomalies among children conceived with IVF and additionally with ICSI.

Also, studies examining outcomes in couples undergoing ICSI for non-male factor indications, including preimplantation genetic diagnosis, low oocyte yield, and oocyte cryopreservation, are lacking. Furthermore, the impact of epigenetic changes associated with IVF and ICSI is not known.

"Therefore, the decision to perform ICSI for non-male factor indications such as unexplained infertility must include discussion of the potential benefits and risks, both financial risk and the possible risk of gamete manipulation," the authors write.

In summary, Dr. Johnson told Reuters Health, "Our meta-analysis suggests that couples with unexplained infertility may benefit from the routine use of ICSI. Given the financial and emotional consequences of failed fertilization, the routine use of ICSI in couples with unexplained infertility offers significant benefit. Couples with unexplained infertility should be offered the option of using ICSI for some or all of their oocytes. Ultimately, the decision to perform ICSI for non-male factor indications such as unexplained infertility must include discussion of the potential benefits as well as the potential risks, including the possible risk of gamete manipulation."

The authors made no relevant disclosures.

SOURCE: https://bit.ly/13a9PPx

Fertil Steril 2013.


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