2. Reproductive biology

2.1 Introduction
Certain areas of research in reproductive biology may give rise to complex ethical problems, particularly because various moral, cultural, religious, family and personal factors are involved.^10,11

Research is essential in order to improve knowledge but it should not cause moral dilemmas or be harmful to the patient. The balance between these two extremes can be achieved only by in-depth discussion of the research protocol and by ensuring that all protocols are submitted to the institution's Research Ethics Committee for approval.

Because of the diversity of reproductive biology research programmes, ethics guidelines should not be too rigid. Only basic issues in the various areas of reproductive research will be addressed here.

2.2 Research on pre-embryos
A pre-embryo is defined as the product of gamete union from the time of fertilisation to the appearance of the embryonic axis. The pre-embryonic stage is considered to last for 14 days. The pre-embryo should be treated with the utmost respect because it is a genetically unique, viable human entity. If pre-embryo transfer to the uterus is envisaged, special care should be taken to ensure the welfare of the potential fetus. The production of excess embryos for the sole purpose of research should be discouraged.

2.3 In vitro fertilisation (IVF)

Probably no medical procedure has been examined as carefully from a moral and ethical point of view as in vitro fertilisation. About 85 reports from various official bodies in 20 countries have been published, 15 of them more than 50 pages in length.¹² There is consensus that there is no moral problem intrinsic in using this technique in cases where gametes from the husband and wife are used.¹³

Since 10-15% of married couples are affected by some or other form of infertility, investigation and treatment of these couples involve a substantial part of gynaecological practice.

Also since IVF, as applied today, is effective in only about 15-20% of cases, more research is necessary to improve results.

2.4 Gamete intrafallopian transfer (GIFT)
The ethics considerations in GIFT and other methods of artificial reproduction are similar to those applicable to IVF. Research to improve the efficacy of GIFT is therefore ethically acceptable.

2.5 Artificial insemination - husband
The use of the husband's sperm for artificial insemination has been practised for many years, and this technique is ethically acceptable. However, more structured studies are needed to assess the efficacy of insemination in the clinic. Research is also needed to improve techniques for cryo-preservation of sperm in sperm banks because there are cases where surgery, radiotherapy or chemotherapy may permanently impair gonadal function.

2.6 Artificial insemination - donor (AID)
The main indication for the use of donor sperm is infertility in couples where abnormal semen findings exist in the male, but the female partner is potentially fertile.

The primary reservation concerning AID is the uncertainty that arises with the introduction of third-party gametes into the marital unit. These concerns are mainly due to potential psychological problems, the risk of transmitting serious genetic disorders and the danger of transmitting infectious diseases, especially AIDS.

The MRC recommends that research methods in AID should be limited to the essential, and that adequate consent should be obtained from all people involved in the donation or reception of gametes.

Artificial insemination procedures should be performed in full compliance with the regulations promulgated in terms of the Human Tissue Act, No. 65 of 1983, Section 37. These regulations are embodied in Government Notice R1182 of 20 June 1986.

2.7 Donor sperm
Treatment of male infertility is one of the main aims of IVF and GIFT. In cases of severe subfertility, the use of donor sperm is the only method of treatment. Although the ethical considerations of using donor sperm and thus introducing a third party into the fertilisation process must be considered as controversial, careful counselling and informed consent by all persons involved should help to resolve many of the dilemmas.

2.8 Donor eggs
Use of donor eggs remains controversial. This, again, is due to general concern about the involvement of a third party. Provided the donor receives no compensation for donating the egg, the MRC finds the use of donor eggs ethically acceptable. However, attempts to extend child-bearing beyond the menopause have many medical, familial and sociological disadvantages, and research in this field is usually ethically unacceptable.

2.9 Pre-embryo from IVF for donation
Since the failure rate of IVF is high, three or four pre-embryos are usually transferred. To obtain this number of embryos, superovulation needs to be induced. All oocytes are fertilised in vitro. The transfer of more than four embryos may occasionally lead to multiple pregnancies of a grand order, and is therefore not recommended. In this way supernumerary pre-embryos, which are not going to be used immediately, are sometimes obtained. These are immediately cryopreserved. If not required any longer by the couple (after successful IVF, for instance), the pre-embryos become available for donation. Since these pre-embryos may be used in couples who might otherwise not produce a pregnancy, research in this field is ethically acceptable.

2.10 Uterine lavage for pre-embryo transfer
Uterine lavage for pre-embryo transfer carries the risk that some of the pre-embryos may be retained in the uterus. Research using this procedure is legal in countries where abortion on demand is provided for by law. This is the case in South Africa where the Choice on Termination of Pregnancy Act, No. 92 of 1996, provides for abortion on demand during the first 12 weeks of pregnancy. The husband's consent is not needed for a lawful abortion, and no age limit is set by the Act for the woman seeking an abortion.

2.11 Consent
Written consent to use gametes or pre-embryos should be obtained from the donor(s) as well as from their spouses.

2.12 Zygote intrafallopian transfer
Primary use of this technique is in candidates for GIFT, in whom evidence of the fertilising capacity of gametes is also desired. Main indications are usually in patients with low or abnormal sperm counts, or in patients with unexplained infertility who have had unsuccessful GIFT procedures. Research in this field should therefore not be restricted.

2.13 Peritoneal ovum and sperm transfer
Transvaginal and transabdominal peritoneal ovum and sperm transfer have been described as alternatives to GIFT. The technique is still regarded as experimental. No specific ethics dilemmas are foreseen.

2.14 In vitro maintenance of embryos
Maintenance of embryos in vitro beyond the gestational age of 2 weeks is not ethically justifiable.

2.15 Contraception research
Many new methods of fertility control are being investigated, but their efficacy in the human is still uncertain. This research is allowed in South Africa, where non- therapeutic abortion on demand is legal during the first 12 weeks of pregnancy.

2.16 Research on selecting fetal sex
Research into the selection of the fetal sex may be inappropriate if it may result in a request for an abortion because the sex of the fetus is unacceptable to the parents. On the other hand, gender selection may be beneficial in sex-linked genetic diseases and may be justified under exceptional circumstances.

2.17 Pre-embryo manipulation and research
Pre-embryo manipulation and research may yield valuable medical information. However, it can be regarded as ethical only if the embryos are not specifically produced for the purpose of research. In addition, the embryos should not be transferred to the uterus unless there is reasonable certainty that the manipulation carries no potential risks for the fetus.

2.18 Embryo research
At this stage, a great deal of the work concerned with embryos is developmental. Work involving animal embryos is subject to the guidelines on the use of animals in biomedical research (see Book 3). Work concerned with human embryos is subject to the guidelines on ethics for the use of human embryos in research (see 2.1-2.16). The use of recombinant technology in selecting fetal sex is subject to the guidelines on human embryos, and is currently regarded as not ethical.

However, gender testing in connection with sex-linked genetic diseases and aimed at therapeutic abortion, may be considered as ethical, subject to the broader guidelines on ethics in human biology and subject to the laws of South Africa (see the Choice on Termination of Pregnancy Act, No. 92 of 1996). Equally, testing of human embryo or other extra-embryonic tissue, aimed at determining genetic diseases which are not sex-linked, is subject to the same guidelines.