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BARCELONA: STEM CELLS

No improved ICSI outcome with mitochondria from 'egg precursor cells'

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Energising eggs with a patient's own mitochondria offers no benefit, after controversial procedure is tested in first randomised trial

A controversial technique of energising eggs to improve their quality has been shown in an experimental randomised trial to offer no benefit in terms of pregnancy or live birth rate. The study was performed at the IVI centre in Spain in 59 infertile patients aged 42 or less with a past record of unsuccessful IVF and now having embryo screening in a subsequent attempt; the patients were described as "difficult to treat", and thus representing those previously proposed as likely to benefit from the enhanced egg quality procedure.

The technique, which has attracted much controversial publicity in the past few years, requires the micro-injection of isolated mitochondria resident in "egg precursor cells" (found in ovarian tissue) into the egg of the infertile patient with a partner sperm during the ICSI procedure. The technology, a proprietary process since 2014, has been claimed in previous reports of non-randomised studies in Canada and the Emirates, to improve egg and embryo quality and increase the success rate of ICSI.

Results of the study, which were presented in Barcelona by Dr Elena Labarta of IVI Valencia, showed that live birth rate per blastocyst transfer was 41% in the mitochondria injection group and 39% in the control group, suggesting at least that any "energising" effect of the mitochondria made no difference to outcome. It was also found that the number of euploid blastocysts in the mitochondria groups was significantly less than in the control group. Labarta said that IVI has now abandoned the procedure as a study subject.

The science behind the procedure has been dogged by controversy since first reported in mice more than a decade ago. Later, in 2012, the US biologist Jonathan Tilly described the discovery of human egg-producing stem cells, dubbed "bona fide" egg precursor cells, harvested from the ovaries of six young women, which the investigators were confident would go on to make "baby-making eggs". The controversy, of course, was implicit in the biology - that eggs could now be grown from egg precursor stem cells and need not be drawn only from a fixed store which declines to zero at the menopause.

At the level of fertility treatment the belief was that these egg precursor stem cells would invigorate eggs with a patient's own mitochondria. Results of this randomised trial, however, now suggest that this does not happen, with no differences found in live birth rates in either of the two embryo cohorts.

So do egg precursor cells really exist? Did the IVI trial identify and isolate mitochondria from these ovarian stem cells? Unfortunately, this study cannot provide the answer. "The isolation of egg precursor cells and mitochondrial extraction were processes performed by the external company," explained Labarta. "Our embryologists received the mitochondrial solution and injected it with the sperm at the time of ICSI. Thus, our team could never see the egg precursor cells, but worked with a solution presumably containing the isolated mitochondria from them."

So the questions remain, and raised at this congress yet again when, in a precongress course, the New York specialist Kutluk Oktay described his results in an earlier series of ten previously unsuccessful IVF patients all given the energising mitichondrial treatment. Only one was reported to have had a live birth, and Oktay himself - from his own work at least - was unable to confirm the existence of these oogonial stem cells.