It was recently reported in the journal "Human Reproduction" that cytoplasmic transfer could be used to transfer healthy mitochondria (small structures that power the cell) into certain infertile women's eggs. This has resulted in 30 healthy children that were "born from three parents". This pioneering work into fertility treatment was conducted at Institute for Reproductive Medicine and Science of St Barnabas, in New Jersey. The 30 children born were actually the first human babies ever whose genetic makeup has been artificially altered. Even though the babies were born healthy (and without this novel technique would not have existed at all), the cytoplasmic transfer technique was condemned as unethical by some opponents, who said it amounted to human cloning (BBC). However, cytoplasmic transfer and nuclear transfer are NOT the same thing, and the genetic makeup of mitochondria does not govern key aspects of the child's development, like intelligence, personality or physical form. These things are predominately determined by nuclear genes, and these genes were not altered in the children. Cytoplasmic transfer is certainly not cloning, as has been suggested, but it is a useful fertility technology for certain women affected with mitochondrial diseases. Cytoplasmic transfer is a logical extension of assisted reproduction, a procedure that represents a hybrid between in vitro fertilization in its traditional form and IVF using donated oocytes. As the IVF procedure has improved, several groups of patients continue to pose huge challenges. One such group is characterized by normal FSH levels and normal responses to stimulation. Patients have lots of follicles when stimulated and high estradiol levels, but poor subsequent embryo development. For years these women, after numerous failed cycles, had no alternative but to discontinue treatment. Oocyte donation, now a common procedure, offered these women a viable procedure, one with a high pregnancy rate. Unfortunately, oocyte donation includes the disadvantage of losing the mother's genetic link to the child, as the genes of the donor are passed on to the child born through the procedure.
Two potential reasons account for poor embryo development. Studies of the genetic component of many of the eggs in women with persistent poor embryo development showed that eggs with abnormal chromosomes often made poor embryos. However, this was not always true. Many eggs with normal chromosomes also developed poorly. Logically, the reason may lie in the cytoplasm, the area within the shell of the egg that lies outside of the nucleus, outside of the region that contains the genetic material or DNA. The cytoplasm includes several components. One component is mitochondria which provide energy to the cell, fuel for many of its functions including, presumably, cell division. In theory, a deficiency in mitochondria may leave a cell without the necessary fuel to power its own division after fertilization, resulting in abnormal division. This abnormal division then results in an accumulation of fragments from the dividing cells and a poor chance of further development after embryo transfer.
Another important component of the cytoplasm is the spindle apparatus, a sort of railroad track within the cell, along which the chromosomes separate. The steps in cell division include the duplication of the chromosomes and the subsequent distribution of the genes equally between the two daughter cells. If an egg contained normal chromosomes but had inadequate mitochondria to power cell division or a defective railroad track system for the chromosomes to divide, would this not result in poor embryo formation? And if the cause of the egg problem was in the cytoplasm, then why not replace just the cytoplasm instead of the whole egg, thus keeping the mother's own genetic contribution to the pregnancy? This is the premise behind the development of cytoplasm transfer by Jacques Cohen & his group from St. Barnabas, New Jersey, USA. But the journey from good idea to actual pregnancies has been long and complex. As in many of the procedures in assisted reproduction, much of the initial research came from our colleagues in veterinary medicine. Two methods of cytoplasm transfer were developed, one which transfers a small amount of cytoplasm by tiny needle from the donor to the recipient egg, the other transfers a larger amount of cytoplasm which is then fused to the recipient cytoplasm with electrical impulses.
As a step forward in the refinement of assisted reproduction it is a huge step, and presently, only a relatively small group of people will benefit from it. As the process of cytoplasmic transfer is further refined it will help many others. Important questions need to be clarified. What we most want to know is how will this technique work with the poorer responders? Can cytoplasm transfer affect the poor results we consistently see in patients with elevated FSH levels? And what exactly is in the cytoplasm that might make the eggs "better?" Can we someday hope to find a source of that substance that does not
require the expensive and cumbersome process of using a donor's eggs? For now, we can only give the unsatisfying answer that we'll have these answers sometime in the future. For those of us struggling with the frustrations of infertility now , we can only hope that the future is sooner rather than later.
