Excess IVF Oocytes

Before embryo freezing was developed, in most units a maximum of three embryos were replaced. As a consequence, some couples who had many oocytes collected were happy to donate some of their oocytes to other couples, to mitigate the risk that their embryos would potentially be wasted [11].

Historically, Monash IVF limited the number of oocytes inseminated to eight at one attempt, to avoid discarding many potentially viable embryos. Oocytes in excess could either be discarded without being inseminated, or donated to approved research, or to another couple (for the use of oocyte donation). This gave a ready supply of donated oocytes and enabled the world’s first donor egg program to be established, under the care of John Leeton [4]. However, with the development of embryo freezing, couples could utilize all their oocytes for their own use, and the supply of donated oocytes became scarce. Women who required donated oocytes then depended on altruistic oocyte donors.

Altruistic Oocyte Donors

Women who donate altruistically principally do so to help others, either friends or family who have had difficulty conceiving, or in response to stories in the media. In known donation, the recipient can use a family friend or relative directly, such as a sister donating to another sister. At times, this at can prove difficult, as ovarian insufficiency may unknowingly be unearthed in the sibling [12]. Women who donate altruistically may also provide oocytes to women they do not know in response to media campaigns promoting the need for egg donors. Whilst these donations were initially anonymous, changes in regulation in many countries (including the United Kingdom and Australia) now allow identifying information on the donor to be released to the offspring when he or she reaches adulthood.

Ethically, altruistic donors show an unselfish concern for the welfare of others, and make the donation voluntarily without payment in return, other than receipted expenses or minimal compensation. The donor’s motives are hugely relevant from the child’s perspective [13]. It could also be argued that those donating altruistically are more likely to be committed, rather than those donors who potentially donate for monetary gain, who are less likely to think about the long-term consequences. Interestingly, ‘altruistic’ donors accounted for less than half (43 per cent) of all UK donors in 2010, but, following the 2012 HFEA rule change on compensation, which allowed UK donors to be paid reasonable expenses up to the value of £750, more potential donors came forward [14].

Altruistic Donor ‘Pool’

This is a unique system where a potential recipient introduces a known donor to the pool, who is happy to donate to others, specifically to gain access to other donors in the pool in a crossover arrangement. This is applicable where the donor does not want to know the outcome, and does not want to be involved with her offspring, but is willing to help a friend or relative.

Egg Sharing

The second, and largest group of donors in the UK are those who receive ‘benefit in kind’, where they receive free or subsidized fertility treatment by donating a proportion of their gametes during their own fertility treatment. This so-called egg sharing arrangement started over 20 years ago [15]. In 2013, 533 patients registered as egg sharers [10]. These patients, who require either IVF or ICSI treatment, donate a set number of their oocytes to a recipient. Careful selection is essential to ensure that the donor will produce sufficient oocytes to make the process worthwhile for both parties. Should the donor not produce enough oocytes for her own and the recipient’s use, it is not allowed in UK law for the cycle to continue with the aim to give all the oocytes to the recipient, then for her to start a fresh cycle for her own use. This process, known as ‘egg giving’, was outlawed by the HFEA in 2003 [10]. The HFEA expects clinics to have a clear policy of whether a charge will apply to the donor under these unusual circumstances.

Egg sharers mainly consist of women not eligible for NHS-funded treatment, often as they or their partners have had children in previous relationships. Research has shown that in comparison to altruistic donors the chance of a successful outcome is similar, and that the donor and the recipient both have an equal chance of a live birth [16]. Nevertheless, there is evidence that the occasional unsuccessful egg-sharing donor feels regret in the knowledge that another couple may become the parents of a child genetically related to her [17]. In many countries the concept of ‘egg sharing’ does not exist as it is considered commercialization of human tissues.

Commercial Oocyte Donation

Those countries that perform the majority of egg donation in Europe pay their donors a financial incentive to donate. Recent data from the Spanish Fertility Society demonstrate that in Spain (the largest exponent with around 50 per cent of all egg donation activity), approximately one-third of all their ART cycles are oocyte donation. Other countries within Europe performing a large number of oocyte donation cycles include Czech Republic 2365, Russia 2147, the UK 1891 and Belgium 1412. There are potential concerns about paid oocyte donation, as there is a risk that where money is involved donors may be encouraged to donate several times, which may ultimately have an impact on their own health and fertility [18].

In 2007 the American Society of Reproductive Medicine recommended a limit on the payment to donors to US$5000, and no more than US$10 000 could be justified as financial compensation of oocyte donors [19].

A recent survey of agencies and clinics offering egg donor matching and donation in the US demonstrated that these guidelines are being flouted. Furthermore, many of these agencies and clinics are paying additional amounts for certain characteristics [20]. There is evidence that the community does not have concerns about oocyte donors being rewarded, although they undervalue the effort and inconvenience associated with the process. A recent Australian community opinion poll carried out by GTK [21] found two-thirds of respondents supported the payment of egg donors. However, oocyte donation was grossly undervalued with 21 per cent of those surveyed suggested less than US$500 per donation, with 13 per cent suggesting A$500–1000.

‘Cross-Border’ Oocyte Donation

Recruitment of donors overseas is variable, and some countries like Sweden manage almost entirely on altruistic donation. However, because of the shortfall of egg donors in the UK with long waiting lists many patients now choose to travel overseas. In other countries, such as Turkey, where egg donation is not permitted on religious grounds, services have developed across the borders in neighbouring states or provinces where the rules permit, such as Northern Cyprus, which now has a flourishing egg donation program. Across the globe in North America egg donation programs are well developed, with payment of donors an established practice.

Oocyte/Embryo Banking

If there was a way of predicting whether a girl or woman will undergo POI (Chapter 3) it would be possible for these individuals to consider fertility preservation. This could be achieved by either collecting and cryopreserving oocytes, or if they have a life partner, creating embryos to be cryopreserved. In prepubertal girls, ovarian cortical ovarian tissue containing immature oocytes could potentially be harvested laparoscopically and cryopreserved for subsequent grafting. Unfortunately, in the majority of situations currently POI cannot be predicted, and once diagnosed, none of these techniques are applicable.

Screening of Oocyte Donors

Egg donors in the UK have to be under the age of 36, unless there are exceptional documented reasons to use older women, such as a known donation. Donors are encouraged to allow the clinic to verify their medical and psychological history with their general practitioner. When selecting donors, clinics need to take into account the implications of the donation for the donor’s family and her future fertility.

Assessment of donors includes a very careful medical and social history with specific reference to any current or past physical conditions that may have a bearing on a future child. People with a known gene, chromosomal or mitochondrial abnormality that may cause serious physical or mental disability, and those who have a personal history of a transmissible infection are excluded. Clearly lifestyle issues such as diet, weight and smoking are important in those considering donating. A thorough psychological assessment, with implications counselling, is essential, and considered mandatory in the UK. Only those who successfully complete this phase of the assessment are then subject to laboratory testing.

Laboratory testing focuses on three aspects: the donor’s natural fertility, a transmissible infection screen and a simple genetic screen. The latter will be modified according to their ethnicity. In some countries, a more extensive genetic screening test is offered screening for up to 600 genetic diseases [22]. The infection screen is performed contemporaneously with the time the donor will donate and will be repeated should the donation process happen on more than one occasion. When a fresh embryo transfer takes place there is a small but largely hypothetical risk of a donor being infected with HIV despite screening negative for HIV antibody (if they are still in the immune window period). However, modern fourth-generation tests, which test for both the antibody and antigen, minimize this potential issue [23].

Counselling

Although donors in the UK can put conditions on the use and storage of their gametes, these need to be compatible with the Equality Act 2010. Both donors and potential recipients need to be aware that the donors can withdraw their consent to the use of their gametes and to the use of embryos created from their gametes at any stage in the treatment process. It is therefore mandatory that all gamete donors and recipients are provided with the opportunity to receive appropriate implications counselling. In the UK, couples are encouraged to reveal to their donor-conceived child their genetic origins. The emphasis placed on telling the child following egg donation comes from the extensive psychological literature outlining the experiences of adopted children and their perceived need to find out about their genetic origins. However, we need to understand that like sperm donation, egg donation cannot be equated to adoption, and the same conclusions cannot be drawn.

Regulation

The regulations governing egg donation vary substantially around the world. In the UK, where IVF treatment has been closely regulated by the HFEA since 1991, information on donors, including a description of themselves, their ethnic group, marital status, the number and gender of their current children, their physical characteristics, details of screening tests and medical history as well as a ‘goodwill message’ for potential children, is held by the HFEA. A change in the HFEA Act saw anonymity removed from all gamete donations from 1 April 2005. Since that time, at the age of 18 a child can contact the HFEA and be provided with identifying information about their genetic origins including contact information. The HFEA will inform the donor that a request has been received, prior to releasing information.

This loss of anonymity did not receive uniform approval, and there was a decline in those coming forward as egg donors in 2006, although this has now recovered almost completely. Furthermore, in a recent survey up to a 34 per cent of recipients travel overseas for egg donation, mainly to avoid the rules about identifying information being recorded [24]. Donors who donated prior to 2005 can apply to the HFEA to add their identifying information to the records. However, no donor has the legal right to contact their donor-conceived child, although they can find out how many children were born as a result of their donation.

Donor Matching

When donor gametes are employed, most couples are keen to have a donor that matches their physical characteristics and their ethnicity. Physical features such as height, build, hair, skin and eye colour of both partners are recorded. Blood group is often matched such that the conceived child’s blood group could have arisen from the parents, to preserve the desire for anonymity, though with current regulations and the availability of relatively cheap genetic testing this is becoming less relevant. In the UK, where most clinics offering egg donation perform less than 100 cycles per annum, the choice is extremely limited, particularly for certain ethnic groups.

The advent of successful oocyte cryopreservation using vitrification techniques has led to the development of egg donor banks, which potentially offer greater choice of matching for prospective donors, similar to sperm banking, which has been available for 50 years. These include some large egg donation programs in Southern Europe and the commercial North American egg banks. The World Egg Bank (TWEB) is the first and largest international frozen egg bank. Located in Phoenix, Arizona, TWEB is unique because it does everything from recruitment, to retrieval, to shipping all under one roof.

Recipients are carefully screened for common transmissible infections, similar to the donor infection screening. Cytomegalovirus is a relatively common infection that can cause a mild flu-like illness in an adult, but if a woman is infected in early pregnancy, it can cause a similar spectrum of fetal abnormalities to rubella infection. Recipients found to be CMV negative are generally matched with donors that are CMV negative. However, the risk of reactivation of a CMV infection using donor eggs is theoretical only, and where all other parameters match, an informed couple may select to use a CMV-positive donor.