assisted reproduction
assisted reproduction Although techniques like donor insemination and induction of ovulation (stimulation of the ovary to produce eggs) have been used for many years, it was the birth of Louise Brown (the first ‘test-tube baby’) in 1978 that marked the beginning of new methods of assisted reproduction. The success of in vitro fertilization (IVF) showed that eggs and sperm could be manipulated in the laboratory to produce embryos which, when implanted into the uterus, could result in successful pregnancies. The success of IVF opened new horizons in the alleviation of infertility and in the science of embryology. It is now possible to observe the very earliest stages of human development, and with these discoveries came the hope of identifying defects at this very early stage and making it possible to remedy these defects. However, there was unease at the apparent uncontrolled advance of science and the new possibilities for manipulating the early stages of human development. Society was worried.
Because of this concern the UK government set up, in 1982, the Committee of Inquiry into Human Fertilisation and Embryology under the chairmanship of Lady Warnock — it is now commonly known as the Warnock Committee. This committee considered all aspects of assisted reproduction available at the time and made some 63 recommendations. One of the most important of these was that the government should set up a new statutory licensing authority to regulate both research and those infertility services which the committee recommended should be subject to control. Certain activities were to be made a criminal offence, such as the placing of a human embryo in the uterus of another species. The UK government did not act until 1990 when the Human Fertilisation and Embryology Act was passed. This Act set up the Human Fertilisation and Embryology Authority (HFEA), and the main recommendations of the Warnock Committee were incorporated into the Act, which now regulates the use of assisted reproduction in the UK.
In the period between 1984, when the Warnock Committee reported, and the 1990 Act, the Medical Research Council of Great Britain and the Royal College of Obstetricians and Gynaecologists set up a Voluntary Licensing Authority (VLA). This body had no statutory authority but great moral authority and all the centres in the UK using the new techniques were licensed by the Authority after inspection. The VLA set the pattern for the later HFEA, and much of the methodology used by the HFEA derives from the work and experience of the VLA. Unfortunately not all other countries have followed this example. For example, in the USA there is no Federal law relating to embryo research or IVF, and rules tend to be established on a case by case basis. Some other countries have legislated, but what is required is some international agreement to control developments in this area.
IVF was initially instituted to bypass blockage of the Fallopian tubes, but it is now utilized in the treatment of infertility from various causes — male, female, combined or unexplained; also when donor insemination or ovulation induction (see below) have failed.
IVF is carried out in many centres in the UK and elsewhere. The UK centres have all been licensed by the HFEA after inspection by a team from that body. Many centres have evolved specific criteria for inclusion in their programmes. Each couple has to be carefully assessed. Factors like female age and sperm dysfunction affect the success rate considerably. These couples have usually undergone a series of tests before being accepted as suitable for IVF, and this frequently puts a strain on their marriage, so counselling is an important aspect of decision making. IVF treatment should not be used as a panacea for marital or psychosexual disorders but to fulfill the wishes of a well-adjusted couple to have a baby.
In recent years, however, some rather unorthodox requests have been made for IVF. For example a number of lesbian couples have requested IVF using the egg from one of the partners and sperm from a donor. Also, male homosexual couples have requested the use of a donated egg to be fertilized by the sperm from one of them, the resulting embryo to be implanted into the uterus of a woman who would be a surrogate and hand over the baby, when born, to the homosexual male couple. These developments have caused concern to society, as has the use of IVF to enable women past the menopause to have babies. The oldest of such women to date had a successful pregnancy at the age of 63. These new developments require to be reviewed and society must decide what is appropriate and what is not acceptable.
IVF involves the removal of an egg from the ovary and the fertilization of the egg by the partner's sperm in the laboratory. The embryo thus formed is then placed in the woman's uterus, where it will, hopefully, implant resulting in a pregnancy. The incidence of live births resulting from this procedure is on average 20%. Before the egg is removed the ovary is stimulated with drugs (gonadotropins). This results in a number of eggs — maybe 10 or more — being available instead of the usual natural single one. All of them are removed and fertilized, and usually 3 are implanted in the uterus at one time. This number is stipulated as a maximum by the HFEA. This gives a higher pregnancy rate than if only one egg is implanted, but if more than 3 eggs are implanted there is obviously a greater risk of triplets or more. Even when only 3 embryos are implanted the multiple births, usually twins, account for 30% of outcomes, so some centres now replace only 2 embryos to try to avoid this situation, as the loss rate with twins is greater than in single pregnancies. The ‘spare embryos’, as they are called, are frozen and used if the first attempt is not successful. Should a high multiple pregnancy (triplets or above) become evident (and this can be diagnosed early in pregnancy by ultrasound scan) the question of ‘fetal reduction’ has to be considered. The higher the multiple the greater is the risk of miscarriage or preterm birth of a small baby which may be handicapped. Fetal reduction means the injection, under ultrasound control, of a lethal substance into one or more fetuses to reduce the number from, say, four to two. This gives a much greater chance of survival for the remaining two babies. This method has also caused concern to society but it should be discussed with the couple involved and they should be offered this procedure if they so wish. It follows that with all IVF methods the couple must be well informed of the details of the procedures and the possible outcomes. The message is that, with careful evaluation, persistance in IVF can lead to a successful outcome in a large proportion of cases.
Other techniques which can be used include GIFT (gamete intra fallopian transfer) and ZIFT (zygote intra fallopian transfer). In GIFT eggs and sperm are transferred to the fallopian tube where fertilization occurs naturally. This seems to be particularly effective in unexplained infertility. In the case of ZIFT the egg is fertilized in the laboratory and then placed in the fallopian tube, where it passes down the tube in the natural way.
A newer technique that is very successful is called ICSI (intracellular sperm injection). In this method a single sperm is injected into the egg, which is thus fertilized. The advantage of this method is that the doctor can select and use a single sperm that looks normal and is active. This can be done using sperm from men with very low counts and has therefore greatly improved the results and has given hope to many couples when this is the problem
What are the results for the babies born as a result of these methods? The incidence of preterm delivery is high and there is a 4-fold increase in the number of babies of low birth weight. The reason for this is not clear. The rates of perinatal (around birth) and infant deaths are about twice the national average. This is mainly due to the number of multiple births and the age of the mother — IVF mothers are usually older. There is no greater incidence of congenital abnormalities.
Other forms of assisted reproduction include donor insemination (DI) and ovulation induction. In DI the sperm from a donor is used to inseminate the wife of an infertile man. Provided the husband agrees to his wife being inseminated in this manner he is considered in the UK to be the legal father of the child. However, the birth certificate is false because it says that the husband is the father when he is not. While this is of benefit to the child, ethicists are worried about this falsehood.
Sperm can be frozen and stored and now, to avoid the possible transmission of the AIDS virus, donors have to be tested for the virus at the time of donation and again 180 days later. If the tests are negative on both occasions the sperm which has then been frozen for 180 days can be used. Eggs cannot be frozen at the present time so they have to be fertilized at once, forming embryos which can be frozen and stored. The stored embryos come under the same storage regulations as sperm. The storage of sperm and embryos have sometimes caused difficulties when the partners have separated or one or both has died. Therefore when sperm or embryos are frozen and stored the donors of the gametes now have to record what should happen in such eventualities.
Ovulation induction is a method of assistance for women who are not producing eggs. Drugs (gonadotropins) which stimulate the ovary to produce eggs are used. The dose is care-fully monitored by ultrasound scanning of the ovary and the measurement of hormones in the blood.
There are many ethical dilemmas arising out of assisted reproductive methods and the developments therefrom, many of which were not foreseen. Society has to consider which advances are acceptable and which are not. The latest to date is the possibility of ‘cloning’ human beings by taking cells from a human embryo and forming identical human beings. This has been done with animals and it seems likely that it will be done in the human, probably in a country with no restrictions on such a procedure. Assisted reproduction has enabled many couples to have children who would not otherwise have been able to do so. As long as these methods and the developments from them are kept under control they can be of great benefit to mankind.
See also infertility; pregnancy.
Because of this concern the UK government set up, in 1982, the Committee of Inquiry into Human Fertilisation and Embryology under the chairmanship of Lady Warnock — it is now commonly known as the Warnock Committee. This committee considered all aspects of assisted reproduction available at the time and made some 63 recommendations. One of the most important of these was that the government should set up a new statutory licensing authority to regulate both research and those infertility services which the committee recommended should be subject to control. Certain activities were to be made a criminal offence, such as the placing of a human embryo in the uterus of another species. The UK government did not act until 1990 when the Human Fertilisation and Embryology Act was passed. This Act set up the Human Fertilisation and Embryology Authority (HFEA), and the main recommendations of the Warnock Committee were incorporated into the Act, which now regulates the use of assisted reproduction in the UK.
In the period between 1984, when the Warnock Committee reported, and the 1990 Act, the Medical Research Council of Great Britain and the Royal College of Obstetricians and Gynaecologists set up a Voluntary Licensing Authority (VLA). This body had no statutory authority but great moral authority and all the centres in the UK using the new techniques were licensed by the Authority after inspection. The VLA set the pattern for the later HFEA, and much of the methodology used by the HFEA derives from the work and experience of the VLA. Unfortunately not all other countries have followed this example. For example, in the USA there is no Federal law relating to embryo research or IVF, and rules tend to be established on a case by case basis. Some other countries have legislated, but what is required is some international agreement to control developments in this area.
IVF was initially instituted to bypass blockage of the Fallopian tubes, but it is now utilized in the treatment of infertility from various causes — male, female, combined or unexplained; also when donor insemination or ovulation induction (see below) have failed.
IVF is carried out in many centres in the UK and elsewhere. The UK centres have all been licensed by the HFEA after inspection by a team from that body. Many centres have evolved specific criteria for inclusion in their programmes. Each couple has to be carefully assessed. Factors like female age and sperm dysfunction affect the success rate considerably. These couples have usually undergone a series of tests before being accepted as suitable for IVF, and this frequently puts a strain on their marriage, so counselling is an important aspect of decision making. IVF treatment should not be used as a panacea for marital or psychosexual disorders but to fulfill the wishes of a well-adjusted couple to have a baby.
In recent years, however, some rather unorthodox requests have been made for IVF. For example a number of lesbian couples have requested IVF using the egg from one of the partners and sperm from a donor. Also, male homosexual couples have requested the use of a donated egg to be fertilized by the sperm from one of them, the resulting embryo to be implanted into the uterus of a woman who would be a surrogate and hand over the baby, when born, to the homosexual male couple. These developments have caused concern to society, as has the use of IVF to enable women past the menopause to have babies. The oldest of such women to date had a successful pregnancy at the age of 63. These new developments require to be reviewed and society must decide what is appropriate and what is not acceptable.
IVF involves the removal of an egg from the ovary and the fertilization of the egg by the partner's sperm in the laboratory. The embryo thus formed is then placed in the woman's uterus, where it will, hopefully, implant resulting in a pregnancy. The incidence of live births resulting from this procedure is on average 20%. Before the egg is removed the ovary is stimulated with drugs (gonadotropins). This results in a number of eggs — maybe 10 or more — being available instead of the usual natural single one. All of them are removed and fertilized, and usually 3 are implanted in the uterus at one time. This number is stipulated as a maximum by the HFEA. This gives a higher pregnancy rate than if only one egg is implanted, but if more than 3 eggs are implanted there is obviously a greater risk of triplets or more. Even when only 3 embryos are implanted the multiple births, usually twins, account for 30% of outcomes, so some centres now replace only 2 embryos to try to avoid this situation, as the loss rate with twins is greater than in single pregnancies. The ‘spare embryos’, as they are called, are frozen and used if the first attempt is not successful. Should a high multiple pregnancy (triplets or above) become evident (and this can be diagnosed early in pregnancy by ultrasound scan) the question of ‘fetal reduction’ has to be considered. The higher the multiple the greater is the risk of miscarriage or preterm birth of a small baby which may be handicapped. Fetal reduction means the injection, under ultrasound control, of a lethal substance into one or more fetuses to reduce the number from, say, four to two. This gives a much greater chance of survival for the remaining two babies. This method has also caused concern to society but it should be discussed with the couple involved and they should be offered this procedure if they so wish. It follows that with all IVF methods the couple must be well informed of the details of the procedures and the possible outcomes. The message is that, with careful evaluation, persistance in IVF can lead to a successful outcome in a large proportion of cases.
Other techniques which can be used include GIFT (gamete intra fallopian transfer) and ZIFT (zygote intra fallopian transfer). In GIFT eggs and sperm are transferred to the fallopian tube where fertilization occurs naturally. This seems to be particularly effective in unexplained infertility. In the case of ZIFT the egg is fertilized in the laboratory and then placed in the fallopian tube, where it passes down the tube in the natural way.
A newer technique that is very successful is called ICSI (intracellular sperm injection). In this method a single sperm is injected into the egg, which is thus fertilized. The advantage of this method is that the doctor can select and use a single sperm that looks normal and is active. This can be done using sperm from men with very low counts and has therefore greatly improved the results and has given hope to many couples when this is the problem
What are the results for the babies born as a result of these methods? The incidence of preterm delivery is high and there is a 4-fold increase in the number of babies of low birth weight. The reason for this is not clear. The rates of perinatal (around birth) and infant deaths are about twice the national average. This is mainly due to the number of multiple births and the age of the mother — IVF mothers are usually older. There is no greater incidence of congenital abnormalities.
Other forms of assisted reproduction include donor insemination (DI) and ovulation induction. In DI the sperm from a donor is used to inseminate the wife of an infertile man. Provided the husband agrees to his wife being inseminated in this manner he is considered in the UK to be the legal father of the child. However, the birth certificate is false because it says that the husband is the father when he is not. While this is of benefit to the child, ethicists are worried about this falsehood.
Sperm can be frozen and stored and now, to avoid the possible transmission of the AIDS virus, donors have to be tested for the virus at the time of donation and again 180 days later. If the tests are negative on both occasions the sperm which has then been frozen for 180 days can be used. Eggs cannot be frozen at the present time so they have to be fertilized at once, forming embryos which can be frozen and stored. The stored embryos come under the same storage regulations as sperm. The storage of sperm and embryos have sometimes caused difficulties when the partners have separated or one or both has died. Therefore when sperm or embryos are frozen and stored the donors of the gametes now have to record what should happen in such eventualities.
Ovulation induction is a method of assistance for women who are not producing eggs. Drugs (gonadotropins) which stimulate the ovary to produce eggs are used. The dose is care-fully monitored by ultrasound scanning of the ovary and the measurement of hormones in the blood.
There are many ethical dilemmas arising out of assisted reproductive methods and the developments therefrom, many of which were not foreseen. Society has to consider which advances are acceptable and which are not. The latest to date is the possibility of ‘cloning’ human beings by taking cells from a human embryo and forming identical human beings. This has been done with animals and it seems likely that it will be done in the human, probably in a country with no restrictions on such a procedure. Assisted reproduction has enabled many couples to have children who would not otherwise have been able to do so. As long as these methods and the developments from them are kept under control they can be of great benefit to mankind.
Malcolm Macnaughton
Bibliography
Harris, J. and Holm, S. (eds) (1998). The future of human reproduction. Clarendon Press, Oxford.
Houghton, D. and and Houghton, P. (1994). Coping with childlessness. George Allen & Unwin, London.
Bellar, F. K. and Weir, R. F. (eds) (1994). The beginning of human life. Kluwer Academic Publishers.
See also infertility; pregnancy.
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