Premature ovarian failure

The major indication for use of donor oocytes is premature ovarian failure, either primary or secondary. Causes of premature ovarian failure that are potentially amenable to oocyte donation include surgical oophorectomy, irreversible gonadal damage after certain regimens of chemotherapy or radiotherapy, Turner syndrome and other chromosomal disorders causing gonadal dysgenesis. In addition, oocyte donation might be employed to avoid the risk of transmission of a genetic disorder in cases in which the carrier status of both partners is known.

Donor oocyte IVF success rates were reported to be similar in women with or without primary ovarian failure, despite recognisable differences in recipient age and degree of male factor infertility.¹⁰⁶¹ [Evidence level 2b]

Women with markedly diminished ovarian reserve should be counselled on their low chances of conception using their own gametes, even with assisted reproduction, and should be offered the options of donor oocytes or adoption.¹⁰⁶² [Evidence level 4] Egg donation is the most successful technique for producing pregnancy in perimenopausal women.¹⁰⁶³ [Evidence level 4] Early menopause due to the exhaustion of the ovarian follicles occurs in approximately 1% of women before the age of 40 years and, when there is little remaining follicular capacity, ovum donation may represent the best chance of a successful pregnancy.¹⁰⁶⁴ [Evidence level 3] While oocyte donation for women with premature menopause has become widely accepted within the UK, the use of oocyte donation to achieve pregnancy after the start of natural menopause (typically between the ages of 45 years and 55 years) remains controversial.

Turner syndrome

Spontaneous pregnancies among women with Turner syndrome are associated with a high risk of miscarriage and an inceased risk of trisomy 21 in the offspring.^{1149,1065,1066} [Evidence level 3] Oocyte donation offers women with ovarian failure due to Turner syndrome the chance of pregnancy and live birth. Pretreatment screening is essential to exclude phenotypic manifestations of the syndrome that might jeopardise successful pregnancy, including aortic dilation and cardiac lesions.¹⁰⁶⁷ An observational study (n = 29) assessing the factors influencing outcomes of oocyte donation in women with Turner syndrome reported a pregnancy rate of 41.2% per treatment cycle (n = 68 cycles; 50 fresh cycles and 18 frozen cycles) of embryo or zygote transfer (27 embryo transfer and 41 gamete intrafallopian transfer [GIFT]) The implantation rate was 17.1% per embryo transferred. The recipient’s age, chromosomal constitution and associated uterine or tubal anomaly had no influence on the treatment outcome. The implantation and pregnancy rates were significantly higher in subsequent than initial cycles (22.6% versus 9.99%; 51.3% versus 27.6%). An endometrial thickness of = 6.5 mm was an important predictor of pregnancy but the endometrial echo pattern failed to predict the outcome. The number of oocytes fertilised affected the pregnancy rate irrespective of the number of embryos transferred. The implantation and pregnancy rates were significantly higher when fresh rather than frozen-thawed embryos were transferred (20.3% versus 8.2%; 48% versus 22.2%) but the route of transfer was of no statistical importance.¹⁰⁶⁸ [Evidence level 3]. Pregnancy rates in women with Turner syndrome following oocyte donation were similar to those in women with other causes of primary ovarian failure.¹⁰⁶⁹ [Evidence level 3]. Another observational study (n = 18) reported a clinical pregnancy rate of 46% for fresh embryo transfer and implantation rate of 30% among women with Turner syndrome treated in an oocyte donation programme. This was similar to the corresponding rates among oocyte recipients with primary ovarian failure in general. However, the miscarriage rate was high, at 40%, and so was the risk of cardiovascular and other complications such as hypertension and pre-eclampsia. This suggested that a careful assessment before and during follow-up of pregnancy and transfer of one embryo at a time to avoid additional complications caused by multiple pregnancy are important considersations.¹⁰⁷⁰ [Evidence level 3]

One cohort study (n = 53) reported that women with Turner syndrome had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical pregnancy rate (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%) and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared women without Turner syndrome following oocyte donation, suggesting that those with Turner syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation.¹⁰⁷¹ [Evidence level 2b]

Ovarian failure following chemotherapy or radiotherapy

Anticancer treatment can cause ovarian failure and women face limited options for fertility preservation. Cryopreservation of oocytes has had very limited success; currently its use before chemotherapy is not a feasible option. However, cryopreservation of embryos is possible and another solution is oocyte donation followed by IVF.¹⁰⁷² Success following oocyte donation has been reported in women who had previously received chemotherapy or radiotherapy. Two cases of normal live births with embryos from donated oocytes have been reported in women (aged 36 years and 33 years) who have been treated with bone marrow transplantation following total body irradiation and cyclophosphamide for leukaemia.^1073,1074 [Evidence level 3] A successful live birth was achieved with oocyte donation in one woman following radical surgery (with uterine conservation) and chemotherapy for ovarian cancer.¹⁰⁷⁵ [Evidence level 3]

In vitro fertilisation failure

Oocyte donation has also been advocated in certain cases of repeated failure of IVF, particularly those in which oocyte quality is compromised, although unexplained failure of fertilisation has also been treated using this method.

An observational study (n = 32 couples, 119 cycles) reported a pregnancy rate of 24.5% per cycle following oocyte donation in women with previously failed IVF treatment. Variables found to have an effect on oocyte donation outcome included the number of previous natural conceptions and live births, and the IVF fertilisation rate. However, increasing female age did not affect outcome.¹⁰⁷⁶ [Evidence level 3] Pregnancy rates of 33.3% per started cycle and 38.4% per embryo transfer were reported in another study (n = 15 couples, 15 cycles) in women following oocyte donation by ICSI in women with previous failed IVF.¹⁰⁷⁷ [Evidence level 3]

Genetic disorders

Heritable genetic diseases can be avoided with the use of donor oocytes. A case series study used donor oocytes from anonymous, matched, fertile donors in four women with heritable genetic disorders and found that use of donor oocytes was a practical, successful, and currently available technique for the prevention of genetic disorders.¹⁰⁷⁸ [Evidence level 3]

Recommendations

Recommendations

Oocyte donation

‘Shared’ oocyte donation can be an efficient use of precious resource of human oocytes. In a retrospective analysis of a programme using ‘shared’ anonymous oocyte donation (n = 249 donor cycles, 241 retrievals), the efficacy of ‘shared’ oocyte donation between two phenotypically matched recipients has been shown to provide a high delivery rates per donor retrieval (95.4%).¹⁰⁸⁶ [Evidence level 3] However, the number of treatment cycles undertaken in the UK using donated oocytes remains small, due to the practical difficulty of recruiting volunteer donors willing to undergo the time consuming and painful processes of pituitary downregulation, superovulation and transvaginal oocyte collection. Volunteers must undergo adequate counselling concerning the possible risks of the procedures, including the surgical risk of oocyte retrieval and the putative link between superovulation with gonadotrophins and the risk of ovarian cancer in later life.

The professional counselling of prospective donors with respect to the results of tests and the implications of test results with respect to their future medical and reproductive health are important parts of providing good care. In one study, 1087 only 50% of women wishing to participate in oocyte donation were considered suitable candidates; 50% of these women were scheduled an entry interview on completion of the formal medical, genetic and psychological screening process and 18% of those actually interviewed were denied entry. [Evidence level 3]

Concerns about complications and logistic factors such as travel and time commitment involved were major reasons for non-donation in a survey of women on anonymous oocyte donation.¹⁰⁸⁸ [Evidence level 3] A survey of UK licensed centres reported that nearly all have experienced difficulty in obtaining a sufficient supply of donated oocytes. Seventy-five percent of potential donors changed their mind about donating after receiving information on the procedures involved. There is also a shortage of both oocyte and semen donors from specific ethnic groups.¹⁰⁸⁹ [Evidence level 3]

For many volunteer donors, guaranteeing anonymous oocyte donation plays a crucial role in their decision to donate.¹⁰⁹⁰ In the UK, nonidentifying information on the donor is recorded by statute in assisted reproduction with gamete donation. This may be made available eventually to the resulting children. One study analysed forms from the HFEA completed by all donors at one IVF unit and found that 94% of oocyte donors did not respond to the question asking for a brief description of themselves, leaving only profession and interests as information to be given to the child in the future. There was a significant difference between the known and anonymous responders.¹⁰⁹¹ [Evidence level 3]

A survey of a sample of couples in Canada undergoing oocyte donation with known donors found that anonymity was a primary concern for recipients and donors: 80% of the sample had not confided in anyone at the time of the study and 70% did not intend to disclose any information at any time; 80% did not plan to inform the child.¹⁰⁹² [Evidence level 3]

In a follow-up study of the first 30 Finnish volunteer oocyte donors, most donors were very satisfied with the experience at 12–18 months after donation. The adverse effects of the treatment had been slight and tolerable. A majority of the respondents reported that they had thought about the possibility of a child from their donation (89%) and would have liked to have known whether pregnancy had been achieved in the recipient (67%). A majority thought the offspring should be told about their origin (59%). However, some 42% of the respondents preferred to receive no information concerning either the child or the recipient couple and 33% thought the child should be given identifying information about the donor. About 50% of the others would agree to the release of nonidentifying information. All donations had been carried out anonymously and without payment and no one regretted their donation.¹⁰⁹³ [Evidence level 3]

The attitudes of anonymous couples undergoing IVF toward sperm and oocyte donation were explored in a UK survey (n = 234). A high proportion of couples found the use of donor sperm acceptable for therapeutic, diagnostic and treatment purposes and 72%, 84% and 90%, respectively, were willing to donate oocytes for these purposes. Of potential oocyte donors, 41% would agree to non-anonymous donation, 12% would wish to meet the recipient couple and although only 4% wanted to choose the recipient, 25% of the couples would prefer a relative or friend as the recipient. Provision of nonidentifying information about the donor to the recipient couple was acceptable to almost 70%, whereas 40% found giving the same information to the child acceptable.¹⁰⁹⁴ Another UK survey (n = 399) compared the attitudes towards egg and sperm donation in four groups of subjects: women receiving egg donation, women receiving sperm donation, potential egg donors and a general population control group. Egg donation appeared to be as acceptable as sperm donation but subjects overall were more in favour of donor anonymity for sperm donation than for egg donation and the sperm recipients were more in favour of donor anonymity than egg recipients. Subjects demonstrated uncertainty on the issue of giving information to children conceived by gamete donation but held positive attitudes towards the counselling of both donors and recipients.¹⁰⁹⁵ [Evidence level 3]

A follow-up study (n = 23) of donor satisfaction in the USA found a high satisfaction rate with the experience (91%) and 74% would donate for another cycle given the chance. The transient adverse psychological symptoms reported by two donors were resolved with medical or psychological treatment.¹⁰⁹⁶ [Evidence level 3] A survey in the USA (n = 25) assessed the psychological characteristics and post-donation satisfaction of anonymous oocyte donors. Following oocyte donation, 80% of women stated that they would be willing to donate again. Post-donation satisfaction was high. Although monetary compensation for donation was provided, altruism was reported as the most salient motivating factor. A significant negative correlation was found between predonation financial motivation and post-donation satisfaction and between pre-donation ambivalence and post-donation satisfaction, suggesting that careful screening and counselling of donors with high levels of pre-donation financial motivation or ambivalence might be prudent.¹⁰⁹⁷ The increasing demand for young and healthy donors and the recent escalation of payment to oocyte donors in the USA have raised concerns in the attitudes of young donors who may not be able to adequately weigh the risks of ovarian hyperstimulation and oocyte retrieval against the benefit of large monetary reward.¹⁰⁹⁸ [Evidence level 3]

A review of the methodological adequacy of the psychosocial literature on information access when donated gametes and embryos are used to identified ten major flaws which may preclude any conclusion either way about the wisdom of promoting information disclosure and access to all parties concerned.¹⁰⁹⁹ [Evidence level 3]

Generally, oocyte donation is acceptable with oocyte donors having a high satisfaction rate. Counselling from someone who is independent of the treatment unit could contribute to this, as well as to the understanding of the potential risks and complications associated with this process.

Some 2000 children are born each year in the UK as a result of the use of donated gametes. Recent debates have focused on the issues surrounding privacy and disclosure among donor gamete recipients.¹¹⁰⁰ In 2002, the Department of Health held a public consultation on the amount of information that should be given to donor offspring and parents of those who donated gametes. The HFEA recommended that there should be a move toward the removal of donor anonymity and that stronger guidelines should be developed on the counselling needs of those considering treatment with donor gametes and donor offspring seeking information on donors. A two-track system that allows some donors to be identified and others to preserve their anonymity should be rejected.⁷⁴³ [Evidence level 4]

‘Egg sharing’

A possible solution to the imbalance between the large number of potential recipients and the currently small number of donors is the practice of egg sharing. ‘Egg sharing’ enables two or more infertile couples to benefit from a single IVF cycle.

A pilot study (n = 55, 25 donors and 30 recipients, 73 fresh and frozen cycles) to establish the place of ‘egg sharing’ in an assisted reproduction programme was undertaken. This study followed HFEA guidelines on medical screening of patients, counselling, age and rigid anonymity between the donor and recipient. Although the recipients were older than the donors (41.4 ± 0.9 years versus 31.6 ± 0.5 years), there were no differences in the number of eggs allocated, fertilisation rates or the mean number of embryos transferred. There were more births per woman among recipients than among donors (30% versus 20%), although the groups were too small to determine if this was statistically significant or not. This suggested that providing the donors are selected carefully, the ‘egg-sharing’ scheme whereby a subfertile donor helps a subfertile recipient is a constructive way of solving the problem of shortage of eggs for donation.¹¹⁰¹ A cohort study which compared the use of fresh embryos in donor cycles (n = 135) and standard IVF cycles (n = 474) confirmed similar pregnancy rates (17.5% and 18.7%) and implantation rates (7.5% and 7.2%) in the two groups.¹¹⁰² Careful patient selection and counselling from someone who is independent of the treatment unit for both the donors and recipients and their partners is clearly essential. [Evidence level 3]

A survey of attitudes of egg donors and recipients in the UK (n = 217) found that: donating or ‘sharing’ eggs is a social issue, with 94% of respondents having discussed it with partners, family or friends; 86% of ‘egg share’ donors and 79% of ‘egg share’ donor enquirers felt that helping the childless was as important as having a chance of IVF themselves. The treatment procedure caused the most anxiety for egg donors. However, 65% of respondents with prior experience of ‘egg sharing’ would do it again (63% of donors, 72% of recipients). Counselling was highly valued, with 84% of respondents agreeing that patients, donors and recipients should have time to talk over egg donation issues with a counsellor.¹¹⁰³ [Evidence level 3]

‘Egg sharing’ is a new area of practice that has developed in response to a shortage of donor gametes. As yet, there has been little research to evaluate the effectiveness of counselling in relation to oocyte donation and egg sharing, and research to evaluate the effectiveness of counselling in terms of long-term psychological and social implications of these practices is needed.

Recommendations