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In Vitro Fertilisation and Embryo Research

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In Vitro Fertilisation and Embryo Research Briefing Note INFORMATION FOR MEMBERS FROM THE 6 Parliamentary Office of Science and Technology November 1989 Figure 1.. Conceptus after 15 days In Vitro Fertilisation and Embryo Research Actual size Following the Warnock Report of 1984 and the 1987 White Paper, the Government has introduced the Human Fertilisation and Embryology Bill con­ taining provisions on research involving human embryos. Parliament is asked to decide between two options set out in Section 11 of the Bill which determine whether the Human Fertilisation and Embryology Authority(HFEA) is empowered to grant licences for research involving human embryos less than 14 days old. This question involves substantial ethical and religious considerations. An understanding of scientific aspects of human fertilisation and embryology may assist Parliamentarians to come to grips with these considerations. Some of the relevant science and technology is de­ scribed in this note. it is argued that this should not be such as to prevent the benefits to others which research may provide. THE STATUS OF THE EARLY EMBRYO Science alone cannot resolve this question, but a clearer understanding of the early developmental process of An important issue relates to the status afforded the the fertilised egg may provide illumination to allow in­ fertilised egg and the early (pre-14 day) embryo or dividuals to reach their own decision. conceptus1. Some argue that these should have the status of a human being from the moment of fertilisa­ Early Human Development tion, since the fusion of egg and sperm produces a unique genetic combination which, if it develops nor­ After the egg has been fertilised, it divides into two mally, will develop into a child. Others point out that it cells, then four, eight and so on. The conceptus (the total is not possible to establish with certainty whether an product of the fertilized egg) initially remains unat­ early embryo will become a child; neither is it capable tached, passing down the Fallopian tube into the uterus. of any continued existence independent of the mother. Around the 6th or 7th day, it starts to implant into the Thus, while some legal protection should be provided, wall of the uterus - a process which takes about a week. At this stage, most of the conceptus consists of cells 1. There has been some ambiguity in terminology in previous discus­ which develop into the life support structures of the sions. Medical/scientific debate often uses the terms: Conceptus - the whole of the developing egg, which includes placenta, the umbilical cord, and the amniotic sac. the surrounding membranes and tissues (Figure 1 and 2) Embryo - the developing baby within the conceptus (Figure 2) The first cells whose specialised function is to form the Pre-embryo - the pre-14 day conceptus The Bill uses the term 'embryo' in the wider context as the product of fetus (or fetuses), develop separately at around the conception from the completion of fertilisation. Except for Figure 2, beginning of the third week. These cells organise them­ which illustrates the more specific use of the word, embryo is used selves along a line in the conceptus and are called the here in the same context as the Bill - i. e. embryo and conceptus have the same meaning. "primitive streak" (Figure 1). From this point, growth P.O.S.T. BRIEFING NOTE 6 NOVEMBER 1989 of all tissues in the conceptus continues; Figure 2 shows its development at the end of the third week. By the end TABLE 1 Success rates in IVF in the U. K. (1987) of the fourth week (Figure 3), the embryo alone (exclud­ Treatment Egg Embryos Pregn- Live ing the surrounding support tissues) is a few mm long. cycles collections transferred nancies births' At this stage, a little tail is visible, tiny buds mark the Number 8899 6983 14941 980 760 places where the arms will grow, and the future posi­ tion of the head is marked by a bulge. Overall success 11.0 8. 5 rate(%) * The Success Rate of Human Reproduction •per treatment cycle "Subsequent neonatal deaths 21 Human reproduction has a low success rate relative to other mammals. The exact rate is difficult to determine, IN VITRO FERTILISATION TECHNOLOGY but most work suggests that between 25 and 75% of fertilised eggs proceed through pregnancy to a live Most embryo research to date has been with the objec­ birth. Most losses appear to be through failure of the tive of improving IVF techniques. An understanding of conceptus to implant during the first fourteen days current IVF technology is thus relevant. after fertilisation. IVF to produce "test-tube babies" was first successfully Some argue that this uncertainty over whether a fertil­ applied over 10 years ago to overcome a range of causes ised egg will or will not succeed in developing into a for infertility2 which affect some 10-15% of married child bom live, has important implications for the couples. Over 2000 children have been born in the UK degree of protection that should be afforded the fertil­ as a result of this technique. IVF involves removal of ised egg and ensuing conceptus under law. Others eggs from the woman, fertilisation with the partner's argue that the same unique genetic combination is sperm in a test-tube or glass laboratory dish, cultivation present at all stages, and that to attempt to distinguish in a nutrient mixture for the first few days as a growing between any one stage of development and the next is conceptus, and return to the woman's uterus in the an artificial exercise. hope that the conceptus will implant and develop via a normal pregnancy. The Significance of 14 Days and the Primitive Streak This is a simple procedure in principle, but has a relatively low success rate. Returns to the Interim Li­ The option allowing licensing of research places an censing Authority which oversees all IVF facilities, are absolute upper limit of 14 days' development after the summarised in Table 1 which show that treatment start of fertilisation, or the appearance of the “primitive succeeds in giving rise to a live birth only around one in streak" - which generally coincides with the completion ten attempts. This low rate arises from difficulties in of implantation. As described above, this comprises the several key steps in the procedure including first differentiation of cells which develop into the fetus, and is taken by some as marking the onset of a discrete - ovarian stimulation may produce eggs which are human existence. In most cases, only one primitive immature and not as readily fertilised streak will form which can go on to develop into a single - difficulties in getting efficient fertilisation in vitro child. In rare cases, two streaks may form which can without causing fertilisation by more than one sperm develop into identical twins. In other cases, the concep­ - problems in determining the optimum growth me­ tus fails to develop fetal cells at all. This "blighted dium for the conceptus ovum" usually fails to implant properly and is lost, but - low rates of implantation on return to the woman after very occasionally it may develop into an abnormal culture growth which has to be surgically removed. - slightly lower rates of success for conceptuses im­ planted after freezing. The 14 day or primitive streak limitation would there­ fore restrict research to the conceptus before the fetal For these reasons, clinics collect several eggs at once. cells start to develop separately. There is no possibility Eggs suitable for fertilisation cannot be stored at pres­ of the embryo having any consciousness because the ent, so are all fertilised. Two or three of these are development of the central nervous system does not returned to the mother to compensate for the low begin until late in the third or early in the fourth week. 2. The main causes of infertility found in a study in Bristol were: Sperm defects /deficiency 24% Ovulatory failure 21% At the current state of technology, the 14-day option Blocked Tubes 14% Endometriosis 6% would be hypothetical because no conceptus has suc­ Unexplained 28% Mucus defects 3% cessfully developed in vitro for more than 8-9 days. Other male infertility 2% Coital failure 6% Other causes 11% P.O .S.T. BRIEFING NOTE 6 NOVEMBER 1989 implantation rate - a practice which gives rise to a multiple pregnancy rate of over 20% (compared with TABLE 2 Research Involving Human Embryos Approved by the ILA 1985-9 the normal rate of only around 2%). Excess fertilised eggs can be frozen to provide reserves in the event of the Subject Objectives Number of first set not implanting successfully Projects IVF Improve efficiency of 41 -egg and sperm collection Much research has already gone into developing the -fertilisation -culture of fertilised eggs existing techniques used for IVF. This has inevitably -embryo storage involved fertilisation using eggs and sperm from con­ -embryo implantation senting donors, culture, and study of the resulting -tests for embryo viability conceptuses in order to define and develop procedures Diagnosis Embryo biopsy 11 which have a better success rate. genetic Tests for x-linked disorders genetic diseases (inc. Lesch-Nyhan’s disease) IVF has clearly brought benefits to those it has helped have children. However, some have criticised it as Contraception Vaccine development 1 technologically and emotionally demanding, expen­ sive and inefficient, as well as introducing the ethical difficulties associated with the creation of excess em­ projects are related to the diagnosis of genetic defects, bryos. Critics suggest increased emphasis on the devel­ and one to the development of a contraceptive vaccine. opment of more "natural" techniques, for instance by . transferring the egg to the woman's uterus for fertilisa­ In considering applications, the ILA applies criteria tion through sexual intercourse.
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