Cytoplasmic Transfer
by David Bruce Sable

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 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.

Causes of poor embryo development

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.

Components of cytoplasm

The cytoplasm includes several components. One component is mitochondria (remember the “powerhouse” of the cell from high school biology?) Mitochondria 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?

The journey to pregnancy via cytoplasmic transfer

This is the premise behind the development of cytoplasm transfer. 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 electricity.
The viable pregnancies (two so far) which have resulted from cytoplasm transfer used the smaller volume transfer method without the electrofusion. How important is this technique? As a step forward in the refinement of assisted reproduction it is a huge step, and my colleagues Jacques Cohen, Jacob Levron, Steen Willadsen, Tim Schimmel and Richard Scott, as well as the many other people doing related work, deserve tremendous credit for using it to bring about viable pregnancies. Presently, only a relatively small group of people will benefit from it.

Where will the research go next?

As the process of cytoplasmic transfer further refined it will help many others. Important questions need to be clarified. What I 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, I 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 I can only hope that the future is sooner rather than later