Put on your lab coats and adjust that microscope to zoom in as we take a look at some of the latest research on conception & fertility methods from PGD to IVFET and embryo cloning.
In vitro fertilisation and other assisted reproductive techniques have tackled infertility and inherited disease, but advances in the technology have also raised fears of sexless societies of genetically engineered children. So where does one draw the line on such research and what more could possibly be available to us in the future as far as assisted fertility methods for conception are concerned?
Fertility Methods Currently Available
Pre-implantation Genetic Diagnosis (PGD)
Pre-implantation genetic diagnosis (PGD) screening is just one of the offerings that can motivate even fertile individuals to make conception an affair surrounded by beakers and microscopes, rather than moonlight and roses. Since its introduction 10 years ago the number of centres offering PGD has grown steadily but slowly.
PGD aims towards the transfer of unaffected embryos. It would avoid the selective termination of pregnancies after prenatal diagnosis in couples at high risk of transferring genetic diseases to their offspring. Other possible future developments related to PGD include sex determination in embryos for non-medical indications, whole genome amplification and gene therapy.
In vitro fertilisation and embryo transfer (IVFET)
While in vitro fertilisation and embryo transfer are nothing “new”, there is a lot of research being done so as to improve and further develop on these techniques.
Examples of New Fertility Research
Zona splitting – Abnormal sperm often fail to fertilise an egg because of their inability to penetrate the egg’s protective covering, the zona pellucida, therefore scientists have tried a technique known as “zona drilling” in which holes are produced in the zona pellucida to permit direct access of sperm to the oocyte plasma membrane. Thus far, this technique has not been successful, however another technique known as “zona splitting”, whereby the zona pellucida is split mechanically, has resulted in reported pregnancies. Nevertheless, basic science questions need to be answered in order to develop better markers for normal and abnormal sperm and to improve the performance of sperm in IVFET.
Cryopreservation – Freezing of in vitro fertilised embryos is another new and promising technique. If embryos are frozen for later use, the stage of their development at the time they are placed in the uterus can be matched with the stage of the uterine wall thereby increasing the likelihood of a successful pregnancy. Before cryopreservation became an option, embryos had either to be placed in the uterus or discarded and in order to avoid the ethical dilemma of what to do with excess embryos, more than the optimal number of embryos was sometimes transferred into the uterus.
By allowing the preservation of embryos for later use, the technique of cryopreservation reduces not only the chance of multiple pregnancies, but also the number of times a woman’s ovaries might be subjected to hormonal stimulation to produce oocytes for additional attempts of IVFET. More research is needed to assess the necessary parameters for successful cryopreservation and the possible deleterious effects of freezing on the embryo.
Oocyte donation – In cases of ovarian failure, failure of in vitro fertilisation, poor quality of eggs, genetic abnormality, or inaccessible ovaries, the only option available to women wanting to bear a child is to use eggs from a donor to perform in vitro fertilisation with the husband’s sperm. The donated eggs most often come from patients who have received hormonal stimulation and produced more eggs than necessary for their own use.
Sometimes, however, women who are to undergo a tubal ligation agree to ovarian stimulation before the surgery so that eggs can be harvested simultaneously. These eggs are then donated for in vitro fertilisation and transfer. Because fertilisation is more likely with mature oocytes than immature ones, research to learn how to recruit a more synchronous population of follicles is important. Alternatively, failing the recruitment of mature oocytes, research is needed to develop reliable methods of maturing oocytes in vitro.
All of these areas, if improved by increased knowledge of the cell biology of early reproductive events, should greatly increase the ability to identify couples with high probability of success and may increase the success rates of IVFET in human clinical practice.
There are a wide variety of research activities that fall under the general heading of “cloning”. Those that involve the creation and use of embryos can be divided into 2 distinct types based on the ultimate objective.
Reproductive cloning: Refers to where the objective is deliberately used to create genetically identical individuals. This technique may, theoretically, be used either to create an individual with the same genetic make-up as an existing individual (by cell nuclear replacement techniques) or to deliberately produce monozygotic twins – either by cell nuclear replacement or embryo splitting – with the primary intention of increasing the number of embryos available for transfer in an IVF cycle.
Stem cell harvesting: This second category of activities does not involve the creation of genetically identical individuals, but aims to produce an unlimited source of tissue for transplantation. It is proposed that undifferentiated embryonic stem cells, from early embryos, could be stimulated to differentiate into whatever type of tissue was needed – e.g. neural tissue for the treatment of degenerative diseases such as Parkinson’s disease, bone marrow for leukaemia sufferers, islet cells for diabetes and muscle tissue for the repair of a damaged heart or skin for treating burns victims.
A further development would be to produce tissue which was immunologically compatible to the recipient. This could be achieved by transferring the nucleus from one of the patient’s own somatic (body) cells into a donor egg (with its own nucleus removed), which would then be stimulated to begin cell-division but only to the stage needed to separate and culture the embryonic stem cells.
The use of such a technique would succeed, not only in overcoming the shortage of tissue for transplantation but also, because the cells would be generated using the patient’s own DNA, the tissue would be fully compatible so there would be no need for the use of immunosuppressive drugs.
As such, this use of cloning techniques has potentially huge implications for a vast number of people. Other future directions in human embryo research without considering their deeper ethical or legal implications, possible new developments in human embryo research may include:
Non-invasive fertility methods for more efficient selection of sperm cells, eggs or embryos which have the greatest potential for development.
Research to actively improve the quality of the embryo. This more controversial approach includes gene therapy.
Research into the production of more embryos which may be achieved by in-vitro maturation of oocytes, the use of cadavers and foetuses as a source of oocytes, the use of embryonic stem cells as a source of gametes, maturation of human gametes in living incubators, oocyte cryopreservation and embryo splitting.
New technical routes to parenthood to satisfy new patterns of parenting. Improvement of implantation by procedures on the zona pellucida or the embryo itself.
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