The IVF Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer (affiliated with Sackler Faculty of Medicine, Tel Aviv University), Israel
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Abstract |
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Key words: infertility aetiology/oocyte donation
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Introduction |
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A `shared' egg donation programme is limited by the number of eggs available for donation and the egg quality, which depends largely on the donor's age and her infertility aetiology.
A major question is how the donors' age and infertility influence the cycle outcome of the recipients, and if the recipients' age has any impact on these results. In this study, we analysed the cycle outcomes for a `shared' egg donation programme in an attempt to answer these controversial questions.
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Materials and methods |
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Donors
Oocyte donors were patients undergoing assisted reproductive treatment cycles, who agreed to donate oocytes anonymously. All the patients denied having chronic and genetic diseases, with no genetic familial disease. A preliminary blood test for count, chemistry, hepatic and renal functions was performed, as well as blood tests for hepatitis A, B and C, human immunodeficiency virus (HIV) and TPHA. Due to the relatively high incidence of the TaySachs gene among the Israeli population, every patient underwent screening for this gene. Only patients with normal follicle stimulating hormone (FSH) concentrations (8 IU/l on day 3 of the menstrual cycle) were accepted as donors. If only a few eggs were retrieved (fewer than seven), the patients were advised not to donate, but they were still exempt from treatment fees. After this first cycle, they were not accepted (enrolled) for further treatment cycles as egg donors. The criteria for the allocation of eggs between donors and recipients were based mainly on physical features. Both egg donors and egg recipients had to sign a detailed informed consent. This was in addition to our regular informed consent for IVF, and was designed with special emphasis on the ethical aspects of egg donation. Agreement on a similar informed consent was mandatory also from the patients' partners. The consent form stipulated that a patient would donate only if this did not affect her treatment cycle. Patients who had agreed to donate, but did not produce sufficient eggs were suitable for financial subsidy in the respective cycle and special care was taken before re-enrolment in a subsequent cycle. The anonymity of donors and recipients was strictly observed, with the obligation to reveal any possible consanguineous relationship between the future progeny at the time of their marriage.
Patient preparation
Following initial pituitary suppression with a gonadotrophin-releasing hormone agonist, ovarian stimulation was achieved by administration of human menopausal gonadotrophins (HMG). According to sonographic data (leading follicle size >18 mm diameter) and hormonal criteria (oestradiol concentration), oocyte maturation was induced by administration of human chorionic gonadotrophin (HCG) (10 000 IU), and oocytes were collected under vaginal ultrasound-guided puncture 36 h later.
Recipients
A total of 521 couples with ovarian failure were treated. Only couples in whom at least one embryo was transferred were included. All patients had a preliminary work-up to evaluate their general health status. A hysterosalpingography and/or hysteroscopy were performed before the treatment to confirm the presence of an adequate uterine cavity. During the transfer cycle, women first received oestradiol valerate (Progyluton; Schering AG, Berlin, Germany) in a fixed dose of 6 mg over a period varying between 12 and 35 days, depending on the patient. Natural micronized progesterone (Endometrin; Sloris Co. Ltd, Gush Seger, Israel; via the vaginal route) 300 mg divided into three daily doses was started once oocytes were available. Donor and recipients were always synchronized in such a manner that the day of ovum retrieval for the donor was the first day of progesterone administration for the recipient.
At 12 days after the embryo transfer, a blood test for ß-HCG assessment was performed and if positive was repeated 2 days later. Clinical pregnancy was considered only when a gestational sac was visualized by ultrasonography. Once a ß-HCG was found to be positive, the replacement therapy was continued for the next 57 weeks.
The final outcome of the pregnancy was obtained through a personal (face-to-face) or telephone interview.
Statistical analysis
All data were analysed by the SPSS program. Statistical significance was tested using Student's t-test, 2 test, and Fisher's exact test when appropriate.
Statistically significant differences were determined at P < 0.05.
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Results |
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Although there were no differences in the mean number of embryos transferred per cycle to the donor with respect to infertility aetiology, the pregnancy rate was significantly lower in patients with endometriosis than in patients with unexplained or ovulatory infertility (Table I). The embryo implantation rates were lowest in donors with endometriosis (3%), and similar for the other groups: mechanical infertility 8.5%, unexplained infertility 6%, male factor infertility 6.3%.
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As in the donors, the pregnancy rates in recipients were lower when endometriosis was the donor's aetiology of infertility and this was statistically significant when compared with mechanical infertility (Table IV). Furthermore, embryo implantation rates in recipients were significantly lower for embryos originating from endometriotic patients (2.5%) than for those from donors with mechanical (7.8%), unexplained (6.4%) or male infertility (6%; P < 0.005).
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Discussion |
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In countries like Israel where donors are patients undergoing oocyte retrieval for their own needs and consent to donate some oocytes to an anonymous recipient, the definition of a `good donor' is highly pertinent. This study attempts to define the profile of a good donor.
No difference has been observed regarding pregnancy rates in recipients of eggs from donors with proven or unproven fertility (Faber et al., 1997). In our study, we also saw no difference between nulligravid and gravid donors.
The reported pregnancy rates for egg recipients vary between 39% (Antinori et al., 1993), 20% per embryo transfer (Pados et al., 1994
) and recently 22.2% (Yaron et al., 1998
). Although pregnancy rates of 56% (Navot et al., 1991
) and 67% (Paulson et al., 1990
) were previously reported, the patient series involved were relatively small, and included predominantly young amenorrhoeic patients. Our overall results concur with the above more recent studies. The embryo implantation rate was similar in the donor and recipient groups for a given infertility diagnosis of the donor. However, the pregnancy rate was significantly higher (P < 0.05) for the donors than the recipients (most probably due to a higher number of replaced embryos).
The lower pregnancy rates of the donors as well as of the recipients whenever the donor infertility cause was endometriosis is noteworthy.
Furthermore, the embryo implantation potential was significantly lower in both groups for embryos obtained from endometriotic patients. This concurs with a study from Yale University (Arici et al., 1996) which reported on reduced pregnancy rates in endometriotic patients: the pregnancy rate per transfer was 14.8% in patients with endometriosis compared with 25.7% in patients with tubal infertility and 23.3% in patients with unexplained infertility. Their implantation rate of an embryo from an endometriotic patient was significantly reduced (3.9%) when compared with embryos from patients with tubal (8.1%) and unexplained (7.2%) infertility. In addition, a significant decrease has been reported in implantation rates (Pellicer et al., 1995b
) for embryos originating from endometriotic patients when transferred to recipients from an egg-donation programme. As expected, mechanical infertility had a lesser impact on donor pregnancy rates.
In our study, donors <35 years had higher pregnancy rates than those 35 years, but the recipients' pregnancy rate was not influenced by the donor age.
As in previous studies (Yaron et al., 1998), we found a significant decline in pregnancy rate with increasing age of recipients. Reduced pregnancy rates in patients >50 years, and the increased miscarriage rates in patients >45 years old can be explained by a uterine factor in elderly patients. A significant age-related drop in both embryo quality and uterine receptivity has been demonstrated (Chetkowski et al., 1991
), using a mathematical model. Senescence has been suggested to affect both the ovary and the uterus (Pellicer et al., 1995a
). Several explanations for the reduced pregnancy rates in elderly recipients have been proposed; impaired uterine perfusion (Goswamy et al., 1988
), depletion in the number of oestradiol receptors (Han et al., 1989
), or a reduced number of stromal cells in the endometrium (Craig and Jollie, 1985
).
The lack of statistical difference in pregnancy rates among recipients of the same age, irrespective of the assisted reproduction procedure (regular IVF insemination versus ICSI) emphasizes the feasibility of ICSI when applied to a very limited number of eggs. In a previous paper (Shulman et al., 1998) we found no statistical difference in pregnancy rate between recipients treated with ICSI micromanipulation (due to severe male factor) and the donors when classified according to the recipients' age. Our results are in agreement with previous findings (Borini et al., 1996
) and support the concept of ICSI treatment in egg donation cycles even when only a few eggs are available.
In conclusion, despite initial optimistic reports on very high pregnancy rates after egg donation, we found that in our model, due to a lower number of transferred embryos in the recipients, the pregnancy rate was lower than for donors. The pregnancy rate is also very dependent on both donors' and recipients' characteristics. According to our results, it seems inappropriate to counsel patients on success rate in general; rather we suggest a more accurate prognosis based on variables such as donor age and infertility aetiology as well as recipient age. Young women (<30 years), diagnosed with mechanical, male or unexplained causes of infertility achieve the higher pregnancy rates as donors, and are more likely to achieve success in an egg donation programme than older patients or patients with endometriosis.
Furthermore, our results encourage earlier enrolment and treatment of recipient couples in the egg donation programme with the best results in terms of pregnancy rates and pregnancy outcome occurring in women up to 45 years old. Male factor infertility does not adversely affect the treatment outcome.
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Notes |
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References |
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Submitted on March 26, 1999; accepted on June 28, 1999.