The best donor

Adrian Shulman1, Yael Frenkel, Jehoshua Dor, David Levran, Eyal Shiff and Shlomo Maschiach

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


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Oocyte donation has become a common treatment modality for a large spectrum of infertility conditions. The purpose of this study was to assess the success rate of a shared egg donation programme, and to define the profile of a successful `donor–recipient' couple in view of the limitations imposed by the shared programme. The results of all consecutive cycles of egg donation from 1st January 1995 to 31st December 1996 were analysed. A total of 383 donor cycles were matched with 946 recipient cycles; clinical pregnancy rates were 23.5 and 16.7% respectively. With the exception of endometriosis, which significantly reduced the pregnancy rate in both groups, similar pregnancy rates were obtained in both groups for all the other infertility aetiologies of the donors. The donor's age had no impact on pregnancy rate of the recipient, but pregnancy rate was significantly decreased in donors >35 years. Recipients >50 years had significantly reduced pregnancy rates and those >45 years a significantly increased abortion rate. Recipients with severe male factor infertility, who had intracytoplasmic sperm injection treatment, showed pregnancy rates equivalent to those recipients who had regular in-vitro fertilization. We conclude that in a shared egg donation programme, the recipients' pregnancy rate and outcome are dependent only on the donors' infertility aetiologies and on recipients' ages.

Key words: infertility aetiology/oocyte donation


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Oocyte donation, originally performed in patients with premature ovarian failure or surgical castration, is now commonly used in menopausal patients, despite their advanced chronological ages. In countries like Israel, where a paid donor is prohibited by law, the paucity of available eggs is a major problem. The donors are infertile, anonymous patients who volunteer to donate a proportion of their eggs in return for subsidized in-vitro fertilization (IVF) treatment (shared egg donation). Egg sharing raises several ethical and medical concerns. An interesting positive profile of egg share donors emerges from a comprehensive survey conducted in the UK which addressed the emotional and practical benefits as well as the problems of donation and egg sharing for the patients involved (Ahuja et al., 1997Go).

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.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
We analysed all the egg donation cycles between 1st January 1995 and 31st December 1996. Each recipient received oocytes donated by only one individual, although donors supplied oocytes to one or more recipients. According to the regulations of the Israeli Ministry of Health, oocytes may be donated anonymously only by patients undergoing IVF themselves. Therefore, our egg source was infertile, healthy women undergoing IVF, who willingly consented to donate excess oocytes.

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 Tay–Sachs 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 5–7 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, {chi}2 test, and Fisher's exact test when appropriate.

Statistically significant differences were determined at P < 0.05.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
A total of 383 donor cycles were reviewed and 90 clinical pregnancies were reported. The mean (± SD) donor age was 29.0 ± 3.95 years (range 18–39); 12.1 ± 6.99 eggs per cycle were donated and 14.1 ± 6.4 were used by the donors themselves.

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 IGo). 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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Table I. Donor's pregnancy rates according to the infertility aetiology
 
We reviewed 946 recipient cycles; 158 (16.7%) clinical pregnancies were reported. A mean (± SD) of 4.4 ± 0.7 eggs was received by each recipient, resulting in a mean of 2.9 ± 1.2 embryos/cycle. The number of embryos transferred to the recipients was significantly lower than the number of embryos transferred to the donors (P < 0.05). The recipients' cycle characteristics are presented in Table IIGo. The donor's age had no impact on the recipient pregnancy rate (Table IIIGo).


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Table II. The recipient's cycle characteristics
 

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Table III. Donor's and recipients pregnancy rates according to the donor age group
 
The pregnancy rate in the donors was 23.5% per cycle. A mean ± SD of 5.1 ± 0.1 embryos was transferred per cycle in the donors. The previous obstetric history had no impact on donor pregnancy rate, but donors >35 years had a statistically significant reduced pregnancy rate compared with younger groups (Table IIIGo). Overall, the pregnancy rate in the recipients was significantly lower (P < 0.05) than in the donors.

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 IVGo). 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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Table IV. Recipient's pregnancy rates according to aetiology of donor's infertility
 
The age of the recipients did not influence the pregnancy rates, with the exception of recipients >50 years, in whom there was a significant fall in pregnancy rate (Table VGo). The abortion rate was also significantly increased in recipients >45 years old in comparison with the patients <34 years old (Figure 1Go).


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Table V. Recipient's pregnancy rates according to recipient's age group
 


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Figure 1. Recipients' pregnancy outcome according to recipients' age group. Y = years.

 
Severe male factor was found in 163 recipient couples. They had 273 cycles with ICSI. Forty-seven clinical conceptions were achieved in these patients, with a mean of 17.2% pregnancies per cycle. No statistical differences were noted in pregnancy rates among the recipients when ICSI cycles were compared with regular IVF cycles and classified according to the recipient's age (Table VIGo).


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Table VI. Comparison of pregnancy rate between intracytoplasmic sperm injection (ICSI) cycles and regular in-vitro fertilization (IVF) cycles according to the recipient's age
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Since a successful oocyte donation was first reported 16 years ago (Trounson et al., 1983Go), the procedure has spread around the world, although fewer patients are treated in this way compared with sperm donation or IVF techniques. Although the number of potential recipients is continuously increasing, the shortage of donors is the main limiting factor. A comprehensive survey on the motivation of egg-share donors and on the perceived moral issues was recently conducted in the UK (Ahuja et al., 1998Go). It was concluded that in a regulated environment the egg-share donation is an appropriate treatment for both donors and recipients.

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., 1997Go). 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., 1993Go), 20% per embryo transfer (Pados et al., 1994Go) and recently 22.2% (Yaron et al., 1998Go). Although pregnancy rates of 56% (Navot et al., 1991Go) and 67% (Paulson et al., 1990Go) 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., 1996Go) 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., 1995bGo) 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., 1998Go), 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., 1991Go), using a mathematical model. Senescence has been suggested to affect both the ovary and the uterus (Pellicer et al., 1995aGo). Several explanations for the reduced pregnancy rates in elderly recipients have been proposed; impaired uterine perfusion (Goswamy et al., 1988Go), depletion in the number of oestradiol receptors (Han et al., 1989Go), or a reduced number of stromal cells in the endometrium (Craig and Jollie, 1985Go).

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., 1998Go) 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., 1996Go) 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.


    Notes
 
1 To whom correspondence should be addressed Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Ahuja, K.K., Mostyn, B.J. and Simons, E.G. (1997) Egg sharing and egg donation: attitudes of British egg donors and recipients. Hum. Reprod., 12, 2845–2852.[Abstract]

Ahuja, K.K., Simons, E.G., Mostyn, B.J. and Bowen-Simpkins, P. (1998) An assessment of the motives and morals of egg share donors: policy of `payments' to egg donors requires a fair review. Hum. Reprod., 13, 2671–2678.[Free Full Text]

Antinori, S., Versaci, C., Hossein Gholami, G. et al. (1993) Oocyte donation in menopausal women. Hum. Reprod., 8, 1487–1490.[Abstract]

Arici, A., Oral, E., Bukulmez, O. et al. (1996) The effect of endometriosis on implantation: results from the Yale University in vitro fertilization and embryo transfer program. Fertil. Steril., 65, 603–607.[ISI][Medline]

Borini, A., Bafaro, M.G., Bianchi, L. et al. (1996) Oocyte donation programme: results obtained with intracytoplasmic sperm injection in cases of severe male factor infertility or previous failed fertilization. Hum. Reprod., 12, 2843–2852.

Chetkowski, R.J., Rode, R.A., Burruel, V. and Nass T.E. (1991) The effect of pituitary suppression and the women's age on embryo viability and uterine receptivity. Fertil. Steril., 56, 1095–1103.[ISI][Medline]

Craig, S.S. and Jollie, W.P. (1985) Age changes in density of endometrial stromal cells of the rat. Exp. Gerontol., 20, 93–97.[ISI][Medline]

Faber, B.M., Mercan, R., Hamacher, P. et al. (1997) The impact of an egg donor's age and her prior fertility on recipient pregnancy outcome. Fertil. Steril., 68, 370–372.[ISI][Medline]

Goswamy, R.K., Williams, G. and Steptoe, P.C. (1988) Decreased uterine perfusion: a cause of infertility. Hum. Reprod., 3, 955–959.[Abstract]

Han, Z., Kokkonen, G.C. and Roth, G.S. (1989) Effect of aging on populations of estrogen receptor-containing cells in the rat uterus. Exp. Cell. Res., 180, 234–242.[ISI][Medline]

Navot, D., Bergh, P.A., Williams, M.A. et al. (1991) Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility. Lancet, 357, 1375–1377.

Pados, G., Camus, M., Van Steirteghem, A. et al. (1994) The evolution and outcome of pregnancies from oocyte donation. Hum. Reprod., 9, 538–542.[Abstract]

Paulson, R.J., Hatch, I.E., Lobo, R.A. and Sauer, M.V. (1990) Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. Fertil Steril, 53, 870–874[ISI][Medline]

Pellicer, A., Simon, C. and Remohí, J. (1995a) Effects of aging on the female reproductive system. In Simon, C. and Pellicer, A. (eds), Regulators of Human Implantation. Hum. Reprod., 10 (Suppl.1), 77–83.

Pellicer, A., Oliveira, N., Ruiz, A. et al. (1995b) Exploring the mechanisms of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction. In Simon, C. and Pellicer, A. (eds), Regulators of Human Implantation. Hum. Reprod., 10 (Suppl.1), 91–97.

Shulman, A., Frenkel, Y., Dor, J. et al. (1998) The outcome of in-vitro fertilization treatment by egg donation and intracytoplasmic sperm injection for severe male factor infertility: a preliminary report. Hum. Reprod., 13, 2158–2160.[Abstract]

Trounson, A., Leeton, J., Besako, M. et al. (1983) Pregnancy established in an infertile patient after transfer of a donated embryo fertilized in vitro. Br. Med. J., 286, 835–838.[ISI][Medline]

Yaron, Y., Ochshorn, Y., Amit, A. et al. (1998) Oocyte donation in Israel: a study of 1001 initiated treatment cycles. Hum. Reprod., 13, 1819–1824.[Abstract]

Submitted on March 26, 1999; accepted on June 28, 1999.