New IVF technique

Behind the Headlines

Monday July 7 2008

The new technique involved choosing the healthiest sperm before fertilising the egg

“Science thinks big for better IVF” is the headline in The Times. A new technique called intra-cytoplasmic morphologically-selected sperm injection (IMSI) can double the chances of a successful pregnancy, the newspaper says. IMSI involves “examining sperm under a high-magnification microscope, about five times more powerful than standard laboratory equipment, to select those with a shape and size that indicates good genetic quality”, the newspaper explains. The best-looking sperm are then injected into eggs.

The newspaper story is based on a trial which showed an overall pregnancy rate in the IMSI group of 39.2% compared to 26.5% in the conventional care group. This new technique appears promising and may offer the hope of improving the rates of pregnancy for some infertile couples. Reports of the long-term outcomes from this study, including the healthy baby rate, will be needed, as well as an assessment of the cost and reproducibility of the technique in other countries. The researchers report that IMSI is about twice as expensive as conventional treatment, and requires special equipment and training.

Where did the story come from?

Dr Monica Antinori and colleagues from the International Associated Research Institute for Human Reproduction in Rome carried out this research. The authors report no financial or commercial conflicts of interest. It was published in the peer-reviewed medical journal: Reproductive BioMedicine Online.

What kind of scientific study was this?

This was a randomised controlled trial in which the researchers enrolled 446 couples who met four criteria, between January 2006 and June 2007. The women had to be 35 years or younger, and have an undetected female factor to their infertility. The couple had to have been trying for a baby for at least three years, and the men had to have been diagnosed at least twice by semen examination for the condition known as severe oligoasthenoteratozoospermia (OAT). This condition is the most common cause of male sub-fertility, and it includes three abnormalities: a low sperm count, poor sperm movement and abnormal sperm shape.

"Patients with two or more previous failed attempts benefited the most from IMSI in terms of pregnancy"

Monica Antinori, lead author

In this study, the researchers randomised the participants so that they were unaware of the groups to which they were assigned. 219 were assigned to intracytoplasmic sperm injection (ICSI) – the traditional treatment – and 227 to the new intra-cytoplasmic morphologically-selected sperm injection (IMSI) treatment. Following randomisation, three sub-groups were identified, which would allow for analysis according to the number of previous failed attempts using ICSI, providing a measure of severity for the condition. The three sub-groups were divided according to those couples with no previous failed IVF attempts, those with one previous failed attempt and those with two or more failed attempts.

Eggs were harvested from the participating women using standard methods of ovarian stimulation and induction of ovulation. Three of the recovered eggs were transferred to culture media to be used for IVF.

For those randomised to IMSI, the researchers divided the fresh sperm into droplets of about 4 microlitres in size, and examined them using a high-powered microscope. They placed the best, healthy looking sperm into a selection droplet under microscopic control. Then, using a very narrow tube, they selected only two of the best sperm from this droplet for each of the three eggs to be inseminated. It took anywhere from two to three and a half hours for the researchers to find the best-quality sperm under the microscope. Standard ICSI techniques were used to inject the sperm into the eggs that had been retrieved from the woman, and a maximum of three eggs were placed back in the uterus – the maximum allowed by Italian law.

The researchers recorded the number of eggs that successfully implanted, the number of miscarriages and the number of successful pregnancies.

What were the results of the study?

The women were on average 32 years of age and each had the same average number of embryos implanted (2.4 per patient).

The researchers say that by comparing the two randomised groups, “IMSI pregnancy and implantation rates appear to be significantly higher than those for ICSI”. The pregnancy rate for IMSI was 39.2% versus 26.5%, and the implantation rate for IMSI was 17.3% versus 11.3%. Both these differences were statistically significant.

The researchers also compared the pre-determined subgroups and found that the pregnancy rate was statistically different between IMSI and ICSI in the couples that had been through two or more unsuccessful IVF attempts before, compared with those who had been through one (12.9% versus 29.9%, P=0.017). There was no statistical difference in pregnancy or miscarriage rates in the other subgroups. However, the researchers comment that the clinical outcome was still clearly in favour of the IMSI method.

What interpretations did the researchers draw from these results?

The researchers conclude that, to the best of their knowledge, “this paper is so far the only prospective randomised study showing that IMSI is significantly more beneficial than ICSI on all patients with severe oligoasthenoteratozoospermia, regardless of the number of previous IVF failures”.

They add that “in the near future… IMSI could be recommended as a routine IVF technique to solve complicated male infertility cases from their first attempt.”

What does the NHS Knowledge Service make of this study?

This study has been carefully designed, with all patients analysed and followed up according to a well-defined, pre-determined protocol. There are a few features to the study that deserve comment:

  • Other measures of infertility can be important to infertile couples such as the number of babies that proceed to normal delivery. Because the study is still ongoing, the researchers are only able to report that up to the publication of the trial, the IMSI procedure has resulted in 27 deliveries of a total of 35 healthy babies, 47 ongoing pregnancies and 15 miscarriages. As for the ICSI group, 25 healthy babies were born, 14 miscarriages occurred and 20 pregnancies are still ongoing. The significance of these differences is not reported.
  • The number of twin pregnancies is also an outcome of interest to clinicians and women. The researchers report that there were eight twin pregnancies among the 97 successful implantations in the IMSI group and only one among the 59 successful ICSI implantations. The researchers do not comment on any statistical significance or attempt to explain the reasons for this difference.

This new technique appears promising and may offer the hope of improving the rates of pregnancy for selected infertile couples. Reports of the long-term outcomes from this study, including the healthy baby rate, will be needed, as well as an assessment of the cost and reproducibility of the technique in other countries.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Science thinks big for better IVF. The Times, July 7 2008

Success after sperm 'close-ups'. BBC News, July 7 2008

Links to the science

Antinori M, Licata E, Dani G, et al. Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. Reprod Biomed Online 2008; 16:835–841

Further reading

van Rumste MME, Evers JLH, Farquhar CM. Intra-cytoplasmic sperm injection versus conventional techniques for oocyte insemination during in vitro fertilisation in patients with non-male subfertility. Cochrane Database Syst Rev 2003, Issue 2

Pandian Z, Bhattacharya S, Ozturk O, et al. Number of embryos for transfer following in-vitro fertilisation or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev 2004, Issue 4


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