Assisted Reproductive Technology And Genetic Testing Biology Essay

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Complex legal, moral and social issues arise when considering the flow of genetic information between parties to gamete and embryo donation, and are the basis of this thesis. However, before these issues can be discussed in subsequent chapters, it is necessary to explore the use of assisted reproductive technologies (ART), how the parties may come to possess genetic information about each other, and the relevance of that genetic information.

This Chapter will provide an overview of assisted reproductive technologies, including the role of gamete and embryo donation, a simple description of how genetic information is inherited, and the role of genetic testing in assisted reproductive technology. Together, this will set the scene for subsequent legal and ethical discussion by explaining how and why gamete donors and recipients are brought together, and how and why they may come to possess genetic information relevant to the other.

Subsequent chapters will focus on the legal and ethical relationship between parties to gamete and embryo donation, and whether and how they should share relevant genetic information.

Assited reproductive technology

And when Rachel saw that she bare Jacob no children, Rachel envied her sister; and said unto Jacob, Give me children or else I die.

Although many couples are able to conceive children without difficulty, around one in six Australian couples experience infertility while trying to conceive naturally. While remaining childless is an acceptable outcome for some couples, others are prepared to expend a great deal of effort into overcoming their infertility to have children. In addition to the pressure they may place on themselves, infertile couples can face community and family pressure or even stigmatisation resulting from their inability to reproduce

Until recently, infertile couples that desired children had limited means of realising their desire; they were limited to either using donated sperm to achieve a pregnancy, adopting genetically unrelated children, or very occasionally relying upon a surrogate to be inseminated with the male partner's sperm, carry a pregnancy to term and relinquish the baby to the couple. Although these methods are still in use, a new frontier in treatment for infertility opened in 1978, following the birth of Louise Brown in Manchester, who was the first baby born after being conceived through in vitro fertilisation (IVF){Steptoe, 1978 #65}.

While the first IVF baby was born in England, Australian researchers had been the first to report an IVF pregnancy two years previously {Steptoe, 1976 #66}, and Melbourne-based researchers had been involved in the development of assisted reproductive technologies throughout the late 1960's and 1970's. Not long after Louise Brown's birth, the Queen Victoria Medical Centre offered a clinical In Vitro Fertilisation program (later renamed Monash IVF), and the first Australian IVF baby (the third in the world) was delivered in Melbourne on 23 June 1980.

Although assisted reproduction was not new, IVF was an entirely novel way of treating infertility and achieving pregnancy {Singer, 1984 #69}. Prior to IVF, pregnancy could only be achieved by a healthy female oocyte being produced, and fertilised by healthy male sperm, in-vivo (inside the female body). IVF instead allowed a female oocyte to be fertilised by male sperm in-vitro, the resulting cell cultured until it reached embryo (~ 3-days post-fertilisation) or blastocyst (~5 days post-fertilisation) stage, and then implanted directly into the woman's uterus.

Initial attempts at IVF were not often successful, for two main reasons: Firstly, successful IVF requires a large number of oocytes, which were not readily available given that women generally produce a single viable oocyte each ovulation cycle. Secondly, implantation of the fertilised egg into the woman's uterus needed to be perfectly timed to the woman's natural ovulation cycle, which was extremely difficult to predict, and furthermore required that the woman have a regular ovulation cycle, which many IVF candidates do not.

However, during 1979-1980 Australian researchers investigated the use of artificial hormones to control the ovulation cycle of women using IVF treatment, and noted a significantly higher rate of pregnancy when using what is now known as the Fertility Drug Schedule{Buttery,1983 #67}. In addition to controlling timing for embryo implantation, the Fertility Drug Schedule is used to invoke ovarian hyperstimulation to increase the number of oocytes available for collection and fertilisation. From the mid-1980's, success rates for IVF treatment have been fairly constant, at around 25% live births per cycle, until the age of 34 years, when there is steep decline{Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine, 1998 #68 393, 395}, probably due to reduced oocyte quality in older women.

Several alternative techniques to classic in vitro fertilization (whereby the embryo is transferred directly into the uterus) have been introduced over time. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are among the most popular. In these techniques, oocytes and spermatozoa or fertilized oocytes are transferred into the fallopian tube, respectively. However, these techniques do not appear to demonstrate any benefit over classic IVF.

Today, Assisted Reproductive Technology, including IVF, is widely available in Australia and New Zealand and, despite opposition from some feminist and religious groups, infertile couples are increasingly turning to fertility service providers to assist them to become pregnant. This increased uptake of fertility services is partially attributable to decreasing cost of treatment (particularly in Australia where the Medicare safety-net extends to cover the cost of fertility treatment), but is chiefly driven by a social trend towards delayed childbearing in women.

Donor gametes and embryos

While ) can assist heterosexual couples to overcome sub-fertility and some physical conditions that prevent otherwise "natural" conception (generally blockages in the male and/or female reproductive tract and female hormonal imbalance), it also provides a means of introducing donor reproductive material to replace missing or damaged reproductive material from the couple or individual seeking treatment.

In this way, IVF treatment can use donor sperm, oocytes and embryos to achieve pregnancy by "artificial" means in females who can not produce (or do not wish to use) their own oocytes, by using donor oocytes, and couples who can not (or do not wish to) use their own sperm and/or oocytes, by using donor sperm or embryos. Additionally, IVF treatments using donor oocytes, sperm, and embryos are associated with higher pregnancy and live birth rates than treatments using individuals' own gametes.

IVF and associated reproductive technologies have therefore created a new and strong demand for donor oocytes and embryos, as well as a wider scope of use for donor sperm.

Donor Spermatozoa

In cases of male infertility, fertilization itself is the major bottleneck to achieving pregnancy, and this can usually be easily and quickly identified when couples seek treatment or advice for infertility.

Although the cause of infertility may be readily ascribed to the male partner, identifying the cause and providing efficacious treatment is not always straight forward. Because many men suffer either idiopathic infertility or from conditions for which treatment outcomes are poor, few (less than 20%) men with reproductive failure have identifiable conditions for which a proven effective treatment is available. Monash IVF Australia states that one in eight couples seeking assistance for infertility require sperm donation to achieve pregnancy.

Donor sperm is required to achieve pregnancy in a number of circumstances: where the male partner's infertility cannot be overcome or treated, he does not wish to use his own sperm for fertilisation, or where there is no male partner. The donor may be either recruited by the fertility clinic or known to the recipients. The ready availability of donor sperm and the relative ease of artificial insemination have, for many years, enabled couples with male infertility to achieve successful pregnancy.

Today, donor sperm may be used either for vaginal or intrauterine insemination (IUI), conventional IVF (with or without donor oocytes) or intracytoplasmic sperm injection (ICSI) in conjunction with IVF.

In Australia and New Zealand, donor semen is analysed for sperm quality, both before and after freezing. And the donor's blood is tested for blood type, Rhesus factor, and karyotype, as well as a number of infectious and genetic diseases, including hepatitis, human immunodeficiency virus (HIV), syphilis, cystic fibrosis, and thalassemia. The donor's urine is also tested for several sexually transmitted infections, including chlamydia and gonorrhea. If the donor's sperm is of a high quality and free from disease, it is frozen for six months (180 days) in quarantine, so that further blood testing can confirm Hepatitis and HIV-free status. Although pregnancy rates using frozen sperm are lower than those with fresh sperm, use of unquarantined sperm is not acceptable clinical practice in Australia or New Zealand.

Australian and New Zealand sperm donors who are recruited through fertility clinics are compensated for their time and inconvenience, but payments are modest considering the significant commitment to undergo medical and psychological testing, make the donations, submit details to the relevant register, and update this information indefinitely.

Oocyte donation

Oocyte donation is a relatively new method for overcoming infertility, and demand is exclusively tied to the use of donor oocytes in IVF and, more recently, GIFT. Donor oocytes are used when the female partner is unable to produce oocytes, or her oocytes are unsuitable for fertilisation. Older women, in particular, benefit from the use of donor oocytes from a younger woman to overcome age-related secondary infertility.

Oocyte donation as a treatment for infertility was first reported in 1984. Originally egg donations were made by infertile women undergoing IVF treatment themselves, who donated excess eggs. However, this practice has significantly declined due to the widespread availability of embryo freezing. Although many infertility clinics operate oocyte donor recruitment programmes, the procedure required to obtain oocytes is far more complex and invasive than that to obtain sperm, and recruitment levels are low. Australian and New Zealand couples and women waiting for donor oocytes may experience long delays in undergoing fertility treatment, and many clinics close waiting lists from time to time, to guard against unrealistic expectations that donor oocytes will become available. Many couples undergoing fertility treatment with donated oocytes rely upon a known and fertile donor, such as a sister or close friend, who is willing to donate altruistically

Oocyte donors are generally between the ages of 21 and 34 years. Proven fertility is desirable, but not necessary. As with sperm donors, all oocyte donors undergo thorough psychological and physical assessment before donating. Oocyte donors' blood and urine are tested for the same genetic and infectious diseases as sperm donors.

To obtain oocytes for donation, the donor takes hormonal medication to induce controlled ovarian hyperstimulation, as with conventional IVF. If hyperovulation is successful, and a sufficient number of oocytes have been produced by the donor, a minor operation (ultrasound-guided transvaginal oocyte recovery) is performed with intravenous sedation and analgesia. The donor oocytes are then inseminated in vitro with the sperm of the partner of the recipient (or donor sperm), and the fertilized ova are either transferred to the hormonally synchronized recipient within 48-72 hours or cryopreserved for transfer at a later date.

Oocyte donors may be required to commit to several months of monitoring, strict medication compliance (including likely unpleasant and potentially dangerous side-effects) and invasive procedures before their role is fulfilled. In addition, they must submit their details to a donor register and be available for contact by the recipients and any resulting child(ren). Although recruited donors are reimbursed for travel expenses, the compensation is disproportionate to the process endured, and Oocyte donors are clearly driven by altruistic motivation.

Embryo donation

The demand for, and availability of, donor embryos is relatively new and exclusively tied to their use in IVF and ZIFT treatments. Donated embryos can be used to overcome male, female or combined male/female infertility where the female partner is otherwise capable of maintaining a pregnancy. The three main indications for using donor embryos are; women with an infertile or same-sex partner who do not wish to, or cannot, use their own gametes; recurrent IVF failure; or carriers of genetic disease or chromosomal abnormalities who do not wish to use their own gametes.

Presently, there are two ways in which embryos are made available for donation. Most commonly, unused cryopreserved embryos can be designated for donation by couples that have undergone IVF and completed their families, as an alternative to destroying their surplus embryos. Far less commonly, embryos can be created for the specific purpose of donation using donor sperm and donor ova.

Most major fertility service providers in Australia and New Zealand maintain waiting lists for couples requiring donor embryos for IVF treatment, although there are often strict requirements to enter and remain on the lists, and waiting times can exceed 12 months. Some couples may attempt to recruit their own donor embryos, usually from friends or family members who have excess embryos after completing their families through IVF.

Embryo donors are required to undergo thorough psychological and physical assessment before donating. Blood and urine samples are taken and tested for the same genetic and infectious diseases as gamete donors.

Generally, embryo donors are not reimbursed for their donation, and most choose to donate their surplus embryos as an alternative to destruction/disposal, and out of a feeling of compassion for other couples struggling with infertility. the majority of couples and individuals with surplus embryos choose to destroy, rather than donate, their embryos.


Modern methods of ART can assist couples and individuals to overcome previously insurmountable obstacles to achieving pregnancy. In particular, patients who have missing or damaged gametes can now make use of donated sperm, oocytes or embryos to replace what is lacking, and achieve pregnancy.

Donors receive poor financial compensated for their efforts, which include not only the donation process, but also a willingness to share their medical history and personal details, be contacted by recipients and resulting children in future, and a moral obligation to update their contact and personal details indefinitely. Donors can elect to be notified of the birth and gender of children resulting from their donation, but do not have a right to any other information.

Recipients of donor gametes and embryos are, for social and legal purposes, the owners of the donated material and parents of the resulting child(ren) and are not required to commence or continue a personal relationship with the donor, nor are they legally required to have further contact with, or provide any further information to, the donor or fertility services provider.

Nevertheless, although the link between the donor, his donated material and resulting child(ren) may be socially and legally severed, they are inextricably linked by a genetic bond. This link becomes especially salient when genetic disease is involved.

GENETIC disease

The focus of this thesis is the flow of genetic information between donors and recipients of oocytes, sperm and embryos. In particular this thesis will focus on the flow of such information in the context of genetic disease or disorder. Genetic information is likely to be very relevant where a genetic disease or disorder is identified. A discussion of the relevance of genetic information, and means of obtaining such information, is necessary to set the context of any subsequent legal analysis.

Inheritance of genetic disorder and disease

Genetic disorder and disease is not rare; around 3% of infants are born with a significant genetic disorder or disease. In a Canadian screening study of one million consecutive live births, where 1 million consecutive live births were screened and a population-based register was evaluated, it was found that 5.3% of live-born individuals could be expected to develop diseases with an important genetic component before the age of twenty five.

Although some genetic diseases are the result of spontaneous mutation of the gametes, and so appear for the first time in the resulting child, many are directly inherited along biological family lines and affect not only the resulting child, but the gamete provider and his/her past, present, and future biological family line. Information about directly inherited disease is clearly relevant to both gamete donors and resulting children, who may be affected themselves, have affected family members, or go on to produce other affected children. Genetic disease resulting from spontaneous mutation is obviously relevant to the affected child (and their future biological family line), but may also be relevant to the gamete donor because the mutation may not be random. That is to say, that the mutation may occur in all, or some, of the donor's gametes and may affect future children too.

Recipients of donor gametes, resulting children and gamete donors therefore may have an interest in being informed of the discovery of genetic disease or disorder affecting the other. But what types of disease and disorder are we talking about, and how can they be identified ¾ sometimes even before the donor gametes are implanted into the recipient?

Inherited genetic disorders and disease can be classified into one of three major categories: chromosomal, single-gene defects, and multi-factorial disease.

Chromosomal defects:

Normal individuals have 44 autosomal chromosomes (22 pairs), and two sex chromosomes (one pair). Generally speaking, autosomal chromosomes determine the individual's bodily appearance and function, while sex chromosomes determine whether the individual is male or female. Sometimes, however, an individual may have an unusual number of chromosomes (whole chromosomes are deleted or added) or parts of a chromosome may be missing or added.

Although chromosomal genetic defects can be inherited, they are usually the result of a spontaneous addition or deletion of entire chromosomes (aneuploidy). Because whole chromosomes are affected, the manifestation of chromosomal defects in surviving infants can be severe and seriously reduce both length and quality of life.

Although significant chromosomal defects occur in only around 1% of all live births, it has been estimated that around 25% of conceptions suffer from major chromosome problems; the vast majority are spontaneously aborted. Because of the very obvious nature of chromosomal defects, they are especially suited to pre-implantation screening, whereby affected embryos are discarded before implantation. Many chromosomal abnormalities are also identified during prenatal screening (particularly Trisomy 21, during routine nuchal translucency scan at 12 weeks gestation), and couples will usually be offered the option of terminating an affected pregnancy.

Although most chromosomal abnormalities result from spontaneous mutation of the gametes, and donors will likely know if there is an inherited pattern of chromosomal defect in their family, chromosomal abnormalities are strongly linked to increased maternal age and decreasing fertility. So, these results are not only of interest to the recipient couple who request the testing and receive the results, but the information may be of great interest to the donor, if they intend to donate again or have more children of their own.

Single-gene defects:

Disorders resulting from inheritance of a single mutant gene can have a large effect on an affected person's health. This type of inherited disease is not uncommon; over 4000 disorders are now known to result from single-gene inheritance, and a recent study demonstrated that around 8.5% of paediatric hospital admissions are the result of single-gene inherited disorders.

Single-gene disorders are usually inherited, but occasionally occur as the result of a new mutation. Inherited single-gene disorders show one of three simple (Mendelian) generational inheritance patterns:

Autosomal dominant; or

Autosomal recessive; or

Sex chromosome linked.

In order to understand the above inheritance patterns, one must have a basic understanding of what genes are and how they affect our genetic make-up and physical characteristics:

Genes are located at fixed points (loci) along the arms of chromosomes, and each gene has an allele at the same location on the other member of the chromosome pair (see figure 1.1). If the two alleles are identical, the individual is described as homozygous for the particular gene. If the alleles are different, the individual is heterozygous. The term 'genotype' refers to the genetic make-up of an individual, while the term 'phenotype' refers to the physical expression of the genotype ¾ the observed effect of the genotype and environment interacting.

Figure 1.1: Chromosome pair with homozygous alleles (left) and heterozygous alleles (right)

In some cases, only a single gene is required to create an effect on the individual. That is, the expression of one gene will supersede the expression of its allele. In this case, the expression is said to be dominant. Hence, all individuals with the gene will have an affected phenotype, and may be genetically heterozygous or homozygous for the gene to be expressed. In other cases, two identical genes are required before there will be an effect on the individual. Here, the expression is said to be recessive. The individual must be homozygous for both genes before the gene is expressed and his phenotype is affected.

If the relevant gene is located on one, or a pair of, the individual's 44 autosomal (non-sex) chromosomes, inheritance is referred to as autosomal. When the relevant gene is located on the individual's sex chromosomes, inheritance is referred to as sex-linked.

The distinction between autosomal and sex-linked inheritance is especially important to males, who have XY sex chromosomes, rather than the female XX pair. The X sex chromosome is particularly large, containing approximately 6% of an individual's total DNA. Because the Y chromosome in males is significantly smaller, several genes on the paired X chromosome will not have an allele, so even recessive genes will be expressed (affected males are said to be hemizygous). This means that recessive sex-linked genetic defects show a far higher rate of expression in males than recessive autosomal defects in the general population.

Additionally, because heterozygous females are largely unaffected by the deleterious gene, they can act as carriers and allow very severe sex-linked diseases to continue to be inherited and expressed in male offspring, whereas similarly severe autosomal dominant disorders tend to kill or disable both female and male carriers before they can pass on the deleterious gene.

Gamete donors in Australia and New Zealand are generally tested for a number of single-gene defects, including thalassemia and cystic fibrosis, before their donation is accepted. Recipients may also request further genetic testing of embryos before implantation or prenatal screening once a pregnancy is established. However, it is neither practical nor possible to test every embryo for every possible single-gene disorder, and some genetic disease will only be diagnosed after an affected child has been born. For donors, identification as a carrier of genetic disease may assist them to plan their own reproduction, or assist diagnosis of ill family members.

Multifactorial inheritance

Many inherited disorders are not simply the result of a single deleterious gene, and the pattern of inheritance cannot be explained by a Mendelian analysis.

These disorders may be the result of a combination of altered or missing genes (such disorders are said to be polygenic), and/or a single gene may create a weakness that only manifests as a disorder/disease under certain environmental conditions (this type of disorder is said to be multifactorial).

Polygenic genes are quantitative in nature, and generally appear in a binomial (bell-shaped) distribution within the general population. In terms of polygenic disorders, once the number of genes for a deleterious trait reaches a threshold, the disorder will be expressed (affected phenotype). Expression may be strong or weak, depending on how far over the threshold the individual lays.

Certain families may experience a higher than expected incidence of polygenic disease. Within these families, greater numbers of genes for the deleterious trait are inherited. Most family members will remain unaffected (phenotypically normal) but, because even unaffected individuals carry a high number of deleterious genes, liability for genetic disease is high. High incidence of polygenic disorder is one of the major sanctions against consanguinity.

Screening for genetic disease

Genetic diseases are chronic in nature with no cure, and represent a significant health care and psychosocial burden for the patient, their family, the health care system and the community as a whole. Testing for an ever-expanding range of genetic disease is now a reality, and can provide a valuable addition to assisted reproductive technology techniques.

All couples can, theoretically at least, undergo testing to determine whether they are carriers for genetic disease before conception.

But pre-conception tests will not necessarily provide conclusive information about whether a child will be affected by, or will carry the genes for, a genetic disease. Antenatal tests, such as amniocentesis and choronic villus sampling are available to answer these questions after conception, but may leave couples in an unenviable position ¾ deciding whether to terminate, or continue, an affected pregnancy.

Couples who are concerned about the possibility of genetic disease prefer to know the genetic status of their child before a pregnancy is established. When the couple is relying upon assisted reproductive technology to achieve pregnancy, the opportunity arises to test oocytes, sperm and/or embryos for genetic disease before a pregnancy is established. In this way, genetically diseased gametes and embryos may be discarded before fertilization or implantation, and a wide range of genetic diseases eliminated.

Preimplantation Genetic Diagnosis (PIGD) is available in Australia and New Zealand to couples who have had, or are at risk of having, a child affected by severe genetic disease. The PIGD procedure requires the couple to undergo standard IVF, except all embryos are tested for specific genetic disease and affected embryos discarded, prior to implantation{see generally: Franklin, 2006 #64}. Gamete and embryo donors in Australia and New Zealand are required to consent to tests for a few common genetic diseases (usually thalassemia and cystic fibrosis) before their donation is accepted, and recipients of donor gametes and embryos may request some further genetic testing of embryos prior to implantation.

Although the purpose of genetic testing (both pre- and post-implantation) in the context of assisted reproductive technology is to improve the health of resulting children, the repercussions of this technology may be far wider. Genetic testing of donors, embryos and resulting children lays bare their genetic status, and places that genetic information in the hands of third parties - the donation recipients and health care providers involved in the testing. While these third parties may have an interest in knowing the genetic status of the donor, embryo or child, it is the donor or child who stands to receive direct benefit, harm, or both, from having their genetic information available.

Genetic information may also have far-reaching implications beyond the original donor-recipient-resulting child dyad, especially where the information identifies a genetic defect. In that case, the donor's family may have a legitimate interest, or even a right, to access the results of ART-related genetic testing.

Finally, donors themselves may become aware, after donating, of genetic information that is relevant to recipients of their gametes or embryos and any resulting child(ren). The recipients of the donation and any resulting child(ren) may have an interest, or right, to access the donor's genetic test results, or even those of his/her family.


The remaining chapters of this thesis will consider the legal, ethical and moral implications of genetic testing of gamete and embryo donors, donor reproductive material and resulting children, how genetic information ought to be disseminated between relevant parties, and who the relevant parties are..