Lister Fertility Clinic, Chelsea Bridge Road, London SW1W 8RH, UK
1 To whom correspondence should be addressed. e-mail: meenyau{at}hotmail.com
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Abstract |
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Key words: egg donation/egg-sharing/IVF outcome/pregnancy rate
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Introduction |
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At present, no research with large numbers of patients has been carried out in the UK to ensure that the egg-sharing programme is not detrimental to egg-sharers and/or recipients treatment outcome as compared with standard IVF/ICSI. A study by Ahuja et al. (1996) showed that there was a significantly higher pregnancy rate and live birth rate for recipients compared with egg-sharers; however, the number of patients was small (25 egg-sharers, 30 recipients) and the outcome was not compared statistically with that of standard IVF patients.
This study is a large cohort study to compare the outcome of patients participating in an egg-sharing programme with patients undergoing standard IVF treatment, therefore illustrating any deficit in positive outcomes between the groups.
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Materials and methods |
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Egg-sharing
All egg-sharers were donating their eggs anonymously and benevolently. Paid egg donation is not premitted in the UK. The criteria to be an egg-sharer are: age between 21 and 35 years, basal FSH <10 IU/l, normal blood screen (HIV, hepatitis B and C, syphilis, cytomegalovirus, cystic fibrosis and karyotype), BMI <30 kg/m2, no history of inheritable disorders and being in a stable relationship. Counselling was given to egg-sharer and recipient. The aim of the programme is for each sharer and recipient to receive at least four eggs. In the event of an egg-sharer producing less than eight eggs, she has the options of: (i) donating all the eggs to the recipient and to have a free cycle later; or (ii) to leave the egg-sharing scheme and become a standard IVF patient, keeping all the eggs that are collected with no charge. If the egg-sharer produced >12 eggs, the oocytes could be shared between two recipients as well as the donor. The donors are free to withdraw from the egg-sharing scheme at anytime before the recipient has had her embryo transfer.
Stimulation protocol for egg-sharers and standard IVF patients
Pituitary downregulation with either nafarelin or buserelin at mid-luteal phase. Ovarian stimulation was carried out with either recombinant FSH, HMG or urinary FSH. When follicles reached pre-ovulatory size (1822mm), 10 000 IU of HCG was administrated. Oocytes were aspirated using trans-vaginal ultrasound guidance 3436 h after HCG administration. All embryos were allowed to cleave and the best two or three embryos were selected for transfer. Cryopreservation was performed if more than two good quality embryos remained after transfer. Embryo transfer was performed on day 2 or day 3 using a soft catheter (Wallace, Kent, UK) with trans-abdominal ultrasound guidance. All standard IVF and egg-sharing patients started on a progesterone supplement (Cyclogest; Shire Pharmaceuticals Ltd, Andover, UK), 400 mg once a day per-vaginum (PV) or per-rectum (PR) 1 day before embryo transfer, and continued until a pregnancy test was performed. A pregnancy test was performed 2 weeks after embryo transfer.
In order to synchronize the egg-sharer cycles with recipients, the oral contraceptive pill was commenced from day 2 of pre-treatment cycle.
Hormone replacement protocol for recipients
For women with ovarian function, oral contraceptive pill was commenced from day 2 of pre-treatment cycle for synchronization with the egg-sharer. A long protocol with nafarelin or buserelin for downregulation was commenced simultaneously with the donor. A trans-vaginal ultrasound scan was performed on day 3 or 4 to check the endometrial thickness and the ovaries. If the endometrial thickness was <5 mm and no ovarian cysts were seen, patients commenced 2 mg estradiol valerate (Progynova; Schering Health Care Ltd, Welwyn Garden City, UK) three times a day or estradiol patches twice weekly. For women with no ovarian function, estradiol valerate was started when the egg-sharer commenced ovarian stimulation. All recipients were started on a progesterone supplement (Cyclogest), 400 mg twice a day PV or PR, from 4 days before embryo transfer, and continued until a pregnancy test was performed.
Information regarding a donors physical characteristics, medical history, fertility history, educational background, occupation and interests was provided for the recipient. Matching of a donor with a recipient was based on physical characteristics.
Data analysis
Data were collected in Medical System for IVF (MedicalSys, London, UK) and analysed by Statistics Package for Social Sciences (SPSS, Surrey, UK). Descriptive statistical analysis was performed initially to examine the normal distribution of all continuous variances for parametric statistical tests. The 2 cross-tabulation test was used to analyse the significant difference of pregnancy rates, miscarriage rates and live birth rates between groups. Analysis of variance (ANOVA) was then conducted to assess the duration and amount of gonadotrophin required to achieve follicular maturity, number of mature follicles, number of available embryos for transfer, number of oocytes collected and fertilization rate between groups.
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Results |
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The remaining 192 women underwent 276 egg-sharing IVF cycles; 22 of these cycles (7.9%) had extra embryos for freezing. Only those cycles with shared eggs were included in the statistics. Two hundred and forty-six recipients underwent 274 fresh embryos transfer cycles by receiving oocytes from egg-sharers. In 27 cycles, the recipients froze all the embryos created. During the same period, 718 patients with FSH <10 IU/l and BMI <30 kg/m2 underwent 1098 standard IVF cycles, 398 (36.1%) of these cycles had extra embryos for freezing.
Ovarian stimulation characteristics and cycle outcomes of all three cohorts are shown in Table I. The average number of days taking FSH for ovarian stimulation and the average amount of gonadotrophin used for stimulation were not significantly different between all groups receiving stimulation, and in fact was less in group A. The average number of mature follicles and the average number of oocytes collected in group A (egg-sharers) and group B (standard IVF patients) were not statistically significantly different. There was no significant difference in fertilization rate, average number of embryos transferred and implantation rate between all three cohorts. In group A the average number of embryos available for transfer was significantly less than group B; however, this was expected, as group A subjects were sharing their eggs. Nevertheless, there was no significant difference in pregnancy rate and live birth rate per cycle started compared with group B. The pregnancy rate and live birth rate per egg retrieval, including frozen embryo transfer if pregnancy did not occur on fresh embryo transfer, were lower in egg-sharers, but this difference was not statistically significant. However, this was expected, as egg-sharers have fewer embryos available for cryopreservation. The mean number of eggs allocated to each patient was not statistically different between group A (egg-sharers) and C (recipients).
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Discussion |
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In our unit, all egg-sharers are offered counselling to ensure their commitment to and understanding of egg-sharing. Egg-sharers have the right to withdraw from the egg-sharing programme at any time before the recipient has her embryo transfer. In the event of an egg-sharer not producing enough eggs to share, she has the options of donating all the eggs to the recipient and to have a free cycle later, or to leave the egg-sharing programme and become a standard IVF patient, keeping all the eggs that are collected with no charge. Since the egg-sharing programme was commenced in 1998, only six patients have withdrawn from the programme after a treatment cycle has started and claimed a free IVF treatment cycle. This reflects the commitment and understanding of these patients to the act of donation. On the other hand, 43 patients donated all the eggs collected in the initial treatment cycle. This was because there were not enough eggs to share. These women subsequently had a free treatment cycle where they kept all the eggs collected. From those 43 patients, 15 pregnancies (35%) and 13 live births (30.2%) were achieved.
There are concerns (Blyth, 2002) that bias occurs during oocyte allocation toward egg-sharers or recipients. This study demonstrates that the mean number of oocytes allocated, fertilization rate, number of available embryos for transfer and pregnancy rates were not statistically different between egg-sharers (group A) and recipients (group C). Oocyte quality cannot be determined very accurately at the time of oocyte aspiration; therefore, oocytes were allocated randomly at the time of collection with maximum benefit to both parties.
Blyth (2002) speculated that an egg-sharer may reduce her own chances of success by giving away a proportion of her eggs. Such a view is largely speculative, and was proved to be incorrect by our study. Although the number of available embryos for transfer was less in group A and group C compared with group B, the pregnancy and live birth rates were not significantly different. The mean duration of infertility was significantly longer in the standard IVF patients. In both groups, however, the average duration of infertility was <4 years. Templeton et al. (1996)
demonstrated that infertility duration up to 4 years has no significant adverse effect on IVF treatment outcome.
Other studies have demonstrated a lower pregnancy rate and live birth rate in egg-sharers compared with recipients (Check et al., 1992; 1995
; Ahuja et al., 1996
). They suggested that this might have been linked to ovarian stimulation affecting the endometrium (Check et al., 1999
). However, in our study both pregnancy rate and live birth rate were similar in all three groups.
Although the evidence provided in this study promotes a very positive outcome for those patients participating in an egg-sharing programme, standard IVF patients may have a potentially better overall outcome because they have more embryos to freeze than egg-sharing donors. The live birth rate for fresh and frozen combined from the same egg collection was higher in the standard IVF group, but it was not statistically significant.
It is also important not to ignore the psychological and ethical aspects of such a treatment programme. It has been discussed elsewhere that the egg-sharers autonomy may not be fully respected in an egg-sharing programme, and that the egg-sharers may not reveal their true feelings (Johnson, 1999; Blyth, 2002
). It has also been suggested that it could be emotionally traumatic for an egg-sharer, desperate for a child, to consider that although her treatment has been unsuccessful, recipients could be pregnant with her eggs. All the egg-sharers and recipients attend counselling sessions prior to embarking on treatment, and counselling is available during and after treatment has finished at no cost to our patients. Moreover, donors can withdraw their consent at anytime prior to embryo transfer. One can speculate regarding the attitude of both donors and recipients if one is successful and the other is not. Currently, however, in the UK the Human Fertilisation and Embryology Authority code of practice prohibits information regarding the outcome of the egg donation to be given to the donor and vice versa. It is also necessary to obtain the medical, psychological and social background of the egg-sharers and recipients from their general practitioner. However, these issues require further study in order to fully evaluate egg-sharing treatment programmes, and a more detailed study of the psychological and emotional impact of participating in an egg-sharing treatment programme is currently in progress.
Conclusions
In conclusion, egg-sharing conducted in the above manner is a constructive way of solving the problem of the shortage of eggs. Those patients participating in an egg-sharing programme are providing a valuable resource of donor eggs while not compromising their own treatment outcome or putting themselves at any additional risk of complications. With efficient co-ordination, an egg-sharing programme will help to increase the limited resource of donor eggs, which is desperately required, while simultaneously providing a chance of treatment to those women limited by financial restraints. We support shared oocyte donation as the most efficient use of the precious resource of human oocytes. The most imperative conclusion is that participating in an egg-sharing program does not compromise the chance of achieving a pregnancy or live birth for the egg-sharer or the recipient compared with standard IVF/ICSI patients.
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References |
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Submitted on May 27, 2003; accepted on August 1, 2003.