Setting the record straight

In a rather exquisitely written editorial in the last 2016 issue of Reproductive Biomedicine Online, (2016;33:657-8) Martin H. Johnson, one of the journal’s editors, “attempted” (and succeeded) in “setting the record straight” after what he called “some shoddy scientific journalism.” It all centered around the case, in which a New York City-based fertility specialist, John Zhang, MD, PhD, treated embryos of a Middle Eastern woman, who already had lost children to a mitochondrial disease she carried and passed onto her offspring, with a technique called meiotic metaphase II spindle cell transfer (for further detail, please refer to this VOICE‘s lead article).

Based on media reports, a child was born in a New York City hospital, and early tests suggested (though it may take years to find out for sure) that the treatment was successful in preventing transmission of this genetic disease from mother to son. Johnson notes that this case was not reported as an article in a medical journal but only as an abstract submitted to last October’s American Society for Reproductive Medicine (ASRM) and published in Fertility & Sterility as such (Zhang et al 2016;106:e375-e376), and with typical British understatement also suggested that, in this case, it represented “unfortunate form” since the same authors, over a decade earlier, also reported only in abstract form (with no full-length paper follow up for 13 years until recently) on a case, where, that time in China, a similar technique called pronuclear transfer had been used. The unfortunate adverse pregnancy outcome in this latter case was only in 2016 fully reported by the authors in the same journal (Zhang et al., Reprod Biomed Online 2016; 33:529-533).

As Johnson, however, also notes those two cases had very different purposes: while the recent case, as noted above had the purpose of replacing the mother’s genetically abnormal mitochondria, the 13-year-old case in China involved simple infertility treatment under the then vogue assumption that by exchanging “older” cytoplasm (containing older mitochondria) in eggs of older women with cytoplasm (and mitochondria) of young egg donors, eggs from “older” women would improve in their pregnancy potential. In those days, older women, thus, were believed to suffer from “ooplasmic deficiency,” which could lead to poor embryo development and implantation failure.

The techniques applied in those days (and quickly stopped by the FDA at the time) involved a much simpler and less invasive treatment, so called “ooplasmic injection” or “cytoplasmic exchange,” when only minute amounts of cytoplasm from a donor oocyte were injected into the cytoplasm of a fertility patient since in those days nobody was yet even dreaming about the possibility of performing pronuclear or spindle cell transfers, which give the recipient the donor’s almost complete cytoplasm, containing almost all of the donor’s mitochondria.

The FDA stopped these experiments, mostly conducted by investigators in New York City (NYU) and New Jersey (St. Barnabas Hospital), without citing specific reasons. But by declaring under their statutory power that such experimental treatments required an Investigational New Drug (IND) Application. This is the same kind of FDA approval process as is required for bringing a new Pharma drug to market and, therefore, makes it for financial reasons impossible for fertility centers to pursue such research since the costs end up running into the hundreds of millions of dollars per IND. The FDA in this way stopped fertility research in its tracks before it even could be started. And these same rules are still in place, still preventing fertility centers, like CHR, from responsibly exploring improvements in current IVF practices.

Johnson concludes in his editorial that a case can be made now that the current approval of use of pronuclear and spindle cell transfers for the prevention of transmission of mitochondrial diseases from mothers to offspring by UK regulatory authorities should now be extended to approval of these procedures for treating female infertility. For the Trump administration to pull even with the UK, it, therefore, appears time to allow the FDA to license appropriately qualified IVF centers to pursue pronuclear and spindle cell transfer for both indications, female infertility (mostly due to older age) and in preventing mitochondrial inheritance from mothers.

This is a part of the February 2017 VOICE.