Elective single embryo transfer yields good delivery rates in oocyte donation

Viveca Söderström-Anttila1,3, Sirpa Vilska1, Sirpa Mäkinen1, Tuija Foudila2 and Anne-Maria Suikkari1

1 The Family Federation of Finland, Infertility Clinic, PO Box 849, FIN-00101 Helsinki and 2 Department of Obstetrics and Gynaecology, University Central Hospital of Helsinki, FIN-00290 Helsinki, Finland

3 To whom correspondence should be addressed. e-mail: viveca.soderstrom-anttila{at}vaestoliitto.fi


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
BACKGROUND: High pregnancy rates have been noted after oocyte donation (OD). Multiple pregnancies should be avoided, because oocyte recipients have an increased risk of obstetric complications. METHODS: We analysed our OD results from 2000–2001 when elective single embryo transfer (eSET) was introduced as a recommended policy for all recipients if at least one good quality embryo was available. The results were compared with those achieved in 1998–1999, when usually two embryos were transferred (double embryo transfer, DET). Between 1998 and 2001, 100 healthy women donated oocytes and 135 fresh embryo transfers were carried out. The mean age of the donors was 31 years and that of the recipient women was 35 years. RESULTS: The proportion of eSET of all OD transfers was 17.1% in 1998–1999 and 61.0% in 2000–2001. There was no statistically significant difference in clinical pregnancy (36.8 versus 45.8%) and delivery rates (31.6 versus 33.9%) per embryo transfer between the two time periods. The proportion of twins declined from 29% (1998–1999) to 10% (2000–2001). The delivery rate was similar after eSET and DET (32.6 versus 32.1% respectively). CONCLUSIONS: By increasing the proportion of eSETs it is possible to reduce the number of twins without affecting delivery rates in oocyte recipients.

Key words: multiples/oocyte donation/pregnancy rate/recipients/single embryo


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
High pregnancy rates have repeatedly been reported in oocyte donation (OD) programmes. Successful results have been thought to depend on the quality of the oocytes from which the embryo is derived, in combination with a receptive endometrium in oocyte recipients (Navot et al., 1991Go; Edwards, 1992Go; Simón et al., 1995Go; Cohen et al., 1999Go). High implantation rates predispose recipients to multiple pregnancies if more than one embryo is transferred. In OD programmes the rate of multiple pregnancies has been reported to be between 15 and 45% (Pados et al., 1994Go; Applegarth et al., 1995Go; Abdalla et al., 1998Go; Söderström-Anttila et al., 1998Go; Yaron et al., 1998Go; Schoolcraft and Gardner, 2000Go; Toner et al., 2002Go). Increased risks of obstetric complications have been demonstrated after OD, even in singleton pregnancies (Söderström-Anttila et al., 1998Go; Sheffer-Mimouni et al., 2002Go). A high incidence of multiple pregnancies further increases the risks of obstetric complications, preterm delivery and adverse perinatal outcome (Bergh et al., 1999Go).

In the European Society of Human Reproduction and Embryology (ESHRE) there is general agreement that twin pregnancy is the most severe complication of IVF/ICSI, resulting in considerable medical risks for the mother and offspring, as well as excess obstetric and neonatal costs (ESHRE Campus Course Report, 2001Go). Recommendations for elective single embryo transfer (eSET) in certain groups of subjects with top-quality embryos have been presented (ESHRE Campus Course Report, 2001Go). The recommendations are based on experience with eSET in conventional IVF/ICSI cycles (Gerris et al., 1999Go; Van Royen et al., 1999Go; Vilska et al., 1999Go; Martikainen et al., 2001Go; Tiitinen et al., 2001Go). Thus far, there have been no corresponding recommendations for women receiving oocytes from donors and, to our knowledge, no reports of eSET in recipients of donated oocytes.

During the last 10 years, at the Infertility Clinic of the Family Federation of Finland, Helsinki, Finland, we have made an effort to decrease the frequency of multiple births by reducing the number of embryos transferred at any one time. Since 1993, no more than two embryos at a time have been transferred in our OD programme. Supernumerary embryos have been cryopreserved for later use. However, even with this strategy the number of twin pregnancies remained high. From the beginning of 1996 we began to transfer only one embryo at a time in recipients with a medical contraindication for twin pregnancy, as in patients with diabetes, Turner’s syndrome, previous hysterotomy or a uterine malformation. Good pregnancy results, together with experience of eSET in conventional IVF (Vilska et al., 1999Go) inspired us to change the embryo transfer policy one step further.

From the beginning of 2000, we started to recommend SET to all our recipients, independent of their age or number of treatment cycles, if there was at least one good quality embryo available. For example, if the couple had two good-quality embryos, one embryo was transferred and the other was cryopreserved for later use. If the quality of the embryos was poor and they could not be cryopreserved, double embryo transfer (DET) was recommended. The recipients received extensive counselling about the risks involved in multiple pregnancy. The final decision on SET or DET was made in conditions of mutual understanding between the clinician and the couple, taking into account the medical situation and the wishes of the couple.

The primary purpose of this work is to report our OD results from 2000–2001, when eSET was introduced as a recommended policy for all oocyte recipients if one good-quality embryo was available for transfer. The results are compared with those in 1998–1999, when usually two embryos were transferred at a time. The preliminary cumulative pregnancy rates, including those resulting from frozen–thawed embryo transfer, are presented.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Donors
Between January 1998 and December 2001, a total of 100 healthy women donated oocytes in our OD programme. Twenty of these donors had a known recipient. In all other cases the donation was carried out anonymously. The entry criteria for oocyte donors have been described previously (Söderström-Anttila et al., 1996Go). The upper age limit was 35 years for anonymous donors and 37 years if the donor was known to the recipient. The characteristics of the donors are presented in Table I.


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Table I. Data on oocyte donors (values are means ± SD)
 
All donors underwent ovarian stimulation after pituitary down-regulation with a GnRH agonist, according to a well established protocol. In 1998–1999, ovarian stimulation was performed using recombinant FSH (rFSH) in 40 donors and hMG in 16 donors. In 2000–2001, 32 donors received rFSH and 12 donors hMG for ovarian stimulation.

Recipients
The oocytes obtained from a single anonymous donor were allocated to two recipients if the number of collected oocytes was at least 10, and to one recipient if fewer than 10 oocytes were retrieved. In 1998–1999, 76 recipient couples received donated oocytes, and in 2000–2001, 59 couples received oocytes. The mean age of the recipient women was 35 years. At our clinic the upper age limit for a recipient woman who wants to have anonymously donated oocytes is 42 years. If she is older, the couple has to arrange their own donor. In 1998–1999, the oldest recipient woman was 48 years, and in 2000–2001, 47 years. During both time periods, approximately half of the OD treatments (49 and 51% respectively) were carried out because of primary or secondary ovarian failure, and in the other cases, the indication for treatment was poor response to ovarian stimulation, repeated failures in earlier IVF treatments, suspicion of oocyte abnormality or because the woman was a carrier of a genetic disease. The recipients were going through their first OD–embryo transfer in 72% of the treatments in 1998–1999, and in 69% in 2000–2001 (not significant). The number of treatment cycles with ICSI was 10 (13.2%) in 1998–1999, and five (8.5%) in 2000–2001 (not significant). In 2001, one embryo transfer was carried out via a transmyometrial route because of congenital absence of the cervix.

Priming of the endometrium in oocyte recipients has been described previously (Söderström-Anttila et al., 1996Go). Briefly, women with ovarian failure used estradiol valerate, 4–6 mg/day, for 12–16 days before embryo transfer. Vaginally administered micronized progesterone (Lugesteron®; Leiras, Turku, Finland), 600 mg/day, was started on the day of donor oocyte collection. Women with functioning ovaries underwent pituitary down-regulation with a GnRH agonist and thereafter they used the same HRT as those with ovarian failure. If pregnancy was achieved, estrogen therapy was continued until 10–11 weeks of gestation and progesterone replacement until 12 weeks gestation. A similar HRT protocol was carried out in cases of frozen–thawed embryo transfer cycles.

Embryology
The embryos were cultured in standard media (IVF-Universal; MediCult, Copenhagen, Denmark). Cleavage rates and embryo grading were assessed 48–52 h after ovum retrieval, and in the case of day-3 transfer, 72 h after ovum retrieval. The embryos were scored as regards the number and regularity of blastomeres, the amount of fragmentation and the presence of multinucleated blastomeres (Scott et al., 1991Go). The following grades were used: grade 1, no fragments and even-sized blastomeres; grade 2, <20% fragmentation; grade 3, 20–50% fragmentation; and grade 4, >50% fragmentation. A good-quality embryo was defined as follows: an embryo in the 2- to 5-cell stage on day 2 and at least in the 5-cell stage on day 3 after ovum retrieval, with mononuclear blastomeres and fragmentation not more than 20%. Supernumerary good-quality embryos were cryopreserved by using 1,2-propanediol (Lassale et al., 1985Go).

Statistics
Student’s t-test was used to compare the characteristics of the donors and the recipients, and the weight of the infants. In the other comparisons the {chi}2-test was employed.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
During the two time periods (1998–1999 and 2000–2001) there were no differences in the number of follicles aspirated and the number of oocytes collected in the donor treatment cycles (Table I). Each recipient was allocated a mean of 10.2 oocytes (range 1–16) in 1998–1999 and a mean of 9.7 (range 1–13) oocytes in 2000–2001. The embryological efficacy data are shown in Table II.


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Table II. Embryological efficacy data (mean ± SD)
 
The proportion of eSET of all transfers was 17.1% in 1998–1999 and 61.0% in 2000–2001 (P < 0.001). There was no statistically significant difference in clinical pregnancy rate per embryo transfer or in delivery rate per embryo transfer during the two time periods (Table III). The proportion of twins declined from 29% (1998–1999) to 10% (2000–2001). This is reflected in the mean birth weight of the infants born (Table III). The mean (± SD) birth weight of all singletons (n = 34) was 3280 ± 927 g (range 630–4420) and that of the twins (n = 18) was 2520 ± 411 g (range 1700–3225) (P = 0.0018).


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Table III. Outcome of fresh embryo transfers in the oocyte donation programme
 
During the whole time period (1998–2001), the pregnancy and delivery rates per embryo transfer were similar in recipients who had only one embryo available and in those with eSET and DET (Table IV). The clinical pregnancy rate per embryo transfer was similar regardless of whether embryo transfer was carried out on day 2 (n = 100; 40.0%) or day 3 (n = 35; 42.9%) after donor oocyte collection. The miscarriage rate of all clinical pregnancies was 20% (11 out of 55). The pregnancy results after SET, analysed according to the cell cleavage stage and grade of the embryos, are shown in Table V. No statistically significant difference was found between the groups.


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Table IV. Outcome of fresh embryo transfers in the oocyte donation programme 1998–2001
 

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Table V. Implantation and delivery rates according to embryo quality after SET (n = 57)
 
The pregnancy rate with frozen–thawed embryos and the cumulative delivery rate per started cycle are shown in Table VI. There are still couples without delivery who have embryos remaining in the freezer. Therefore, the cumulative delivery rate may yet increase in both groups. A significantly smaller number of embryos have been transferred among embryos cryopreserved in 2000–2001 compared with those cryopreserved in 1998–1999 (Table VI). Two women who delivered in 2001 are pregnant again after frozen–thawed embryo transfer (not included in the cumulative delivery rate). Among the 21 ongoing pregnancies resulting from frozen–thawed embryo transfer cycles, there are 19 singletons, one pair of twins and one set of triplets, which includes a pair of monoamniotic twins.


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Table VI. Outcome after frozen–thawed embryo transfers in the OD programme 1998–2001
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In this retrospective analysis of our OD programme we report a good clinical outcome after introduction of a new embryo replacement policy. The study includes every OD treatment cycle carried out during the last 4 years. The pregnancy and delivery rates (36.8 and 31.6% in 1998–1999 versus 45.8 and 33.9% in 2000–2001) remained unchanged, while the proportion of eSETs increased from 17 to 61%. As a result, the multiple pregnancy rate markedly decreased, from 29 to 10%. A tendency of better overall implantation rate (IR) was noted in 2000–2001 compared with 1998–1999 (37.7 versus 27.2%), but this difference was not statistically significant. Furthermore, the IR after eSET was similar between the two time periods (38.5 versus 41.7%). The overall clinical IR of all IVF and ICSI cycles performed at our clinic (ovum donation excluded) was 22.5% in 1998–1999 and 23.2% in 2000–2001 (not significant). Thus, the overall IR has not changed, and possible differences in IR among oocyte recipients cannot be explained by differences in IVF technology conditions. Because of the retrospective nature of the study there may, of course, be some aspects of oocyte quality that could not be controlled for in comparing the two time periods. However, the mean age of the donors, the ovarian stimulation protocol, the number of oocytes allocated to the recipients, HRT in the recipients and the laboratory techniques used were the same during these years.

Most centres involved in OD report a clinical pregnancy rate of 20–60% per embryo transfer (Paulson et al., 1997Go; Remohí et al., 1997Go; Yaron et al., 1997Go; Toner et al., 2002Go). Mostly, at least two to three embryos are transferred at a time, but it is not unusual that up to five embryos are transferred at one time. Yaron et al. (1997)Go stated that the success rate increases with increasing number of transferred embryos. They concluded that limiting the number of transferred embryos to two would give a very low pregnancy rate, of only 16.4% per embryo transfer. If five embryos were transferred, the pregnancy rate would be 36.7%, with a 44.4% risk of multiple pregnancy. Another group has stated that among recipients who had supernumerary embryos cryopreserved, transferring more than two embryos increased the multiple pregnancy risk, with no corresponding increase in the chance of a live birth (Reynolds et al., 2001Go). Increased pregnancy rates have been noted after extended culture and blastocyst transfer. A pregnancy rate of 88% per embryo transfer was found when an average of 2.1 blastocysts were transferred (Schoolcraft and Gardner, 2000Go). Of these pregnancies, 44% were multiples, and the authors recommended single blastocyst transfer in OD programmes.

Recently, statements have been made regarding the situations in which eSET should be carried out in conventional IVF cycles in order to reduce the number of multiple pregnancies (ESHRE Campus Course Report, 2001Go). Oocyte recipients differ in many aspects from standard IVF subjects and these differences must be taken into consideration when the embryo transfer policy is planned. The success rate after OD is independent of the age of the recipient woman, at least up to the age of 45 years (Legro et al., 1995Go; Toner et al., 2002Go). In contrast to standard IVF subjects, advanced age of the recipient does not reduce the risk of multiple birth (Reynolds et al., 2001Go). Oocyte donation has also mostly been associated with similar prognosis regardless of the indication for treatment (Paulson et al., 1997Go; Remohí et al., 1997Go). The most important factors determining the success rate of OD are the age of the donor and the quality of the oocytes, in combination with a well-prepared endometrium (Navot et al., 1991Go; Edwards, 1992Go; Cohen et al., 1999Go). Support for this theory can perhaps be seen in our study, as we found no difference in the pregnancy and delivery rates in cycles with only one embryo available compared with those with eSET and with DET. This is in contrast to earlier results among women undergoing conventional IVF (Vilska et al., 1999Go). This difference is not unexpected, as the donated oocytes originated from healthy women of normal ovarian status. Thus, the outcome of OD is more a reflection of embryo quality than the number of embryos.

There are also other important considerations in planning an optimal embryo transfer strategy for oocyte recipients. A high risk of obstetric complications has been demonstrated in OD pregnancies, even singleton ones (Pados et al., 1994Go; Söderström-Anttila et al., 1998Go; Sheffer-Mimouni et al., 2002Go). One of the most frequently observed obstetric complications is pregnancy-induced hypertension, which occurs in 23–38% of recipients (Pados et al., 1994Go; Abdalla et al., 1998Go; Söderström-Anttila et al., 1998Go; Yaron et al., 1998Go; Salha et al., 1999Go; Sheffer-Mimouni et al., 2002Go). These pregnancies are also complicated by a high incidence of gestational diabetes, as well as first and second trimester vaginal bleeding (Sheffer-Mimouni et al., 2002Go). In general, 15–45% of all OD pregnancies are reported to be multiples (Pados et al., 1994Go; Applegarth et al., 1995Go; Abdalla et al., 1998Go; Yaron et al., 1998Go; Schoolcraft and Gardner, 2000Go; Toner et al., 2002Go). Multiple pregnancy will further increase the risks of obstetric complications and health problems for the children involved (Bergh et al., 1999Go). There are good reasons why multiples should be avoided, and the only way to achieve this goal is to transfer only one embryo at a time. In this study the reduction of multiples to 10% did not reach statistical significance because of the small sample size, but the tendency was obvious and undeniable.

Very often, couples are not greatly aware of the increased health risks and the added psychosocial burden involved in multiple pregnancy. They need thorough counselling about these facts, as well as information about prognosis with various transfer policies. At our clinic the practice of transferring only one embryo has not been forced on the couples but rather presented as a safer option. We have informed the recipients that if two good-quality embryos are transferred, the risk of having twins will be about 30% if pregnancy is achieved. After counselling it has often been the wish of the couples that only one embryo is transferred at a time. Mostly, however, the couples leave the final decision to be made by the doctor, in regard to the quality of the embryos. We try to achieve a situation in which the recipients feel comfortable with the decision. If the recipient couple, after counselling, expresses a strong wish for DET independent of embryo quality, and there is no medical contraindication for twins, we support them and share the responsibility for this decision. The recipients have also been informed that, thus far, we cannot predict individual embryos likely to implant.

Our present results show that it is possible to achieve a delivery rate of 33.3% after SET carried out on day 2 or 3 after ovum retrieval. It is worth pointing out that 42% (24 out of 57) of these embryos were not classified as top-quality according to criteria recently presented in the literature (Gerris et al., 1999Go; Van Royen et al., 1999Go). In subjects undergoing conventional IVF/ICSI, late cleaving embryos have been linked to lower implantation rates compared with those showing early cleavage (Bos-Mikich et al., 2001Go; Lundin et al., 2001Go). In contrast to some other investigators, we included 2- and 3-cell stage embryos in the definition of good embryos. This group was analysed separately from the 4-cell cleavage stage embryos on day 2 (Table V). We found good implantation rates in the 2- and 3-cell embryos with no more than 20% fragmentation. These embryos resulted in pregnancy at a rate of 55.6% per embryo transfer and may be recommended for eSET. However, the number of embryos analysed was too small to draw firm conclusions on their implantation potential. Nevertheless, it is interesting to speculate that there may be differences in endometrial receptivity in relation to embryo cleavage stage between women undergoing conventional IVF and oocyte recipients, depending on the different hormonal treatment regimens. Consistent with earlier findings (Ziebe et al., 1997Go; Vilska et al., 1999Go), we noted higher implantation rates among embryos with low fragmentation, although the results did not reach statistical significance because of the small sample size (Table V).

Centres in which eSET is carried out need a well-functioning cryopreservation system. During the last 2 years we have mostly transferred only one embryo at a time in frozen–thawed embryo transfer cycles, and the results are reassuring. At this point, of the 59 recipients treated in 2000–2001, 20 women have given birth after fresh embryo transfer and 10 after frozen–thawed embryo transfer, i.e. at least one-third of all the infants originated from frozen–thawed embryos. Using primarily single embryo transfers we have achieved a 50% cumulative delivery rate per recipient cycle.

In conclusion, oocyte recipients constitute a special group of subjects. They have excellent pregnancy results but also high risks of obstetric complications. Multiple pregnancies further increase the risks for mother and offspring and should therefore be particularly avoided in this group of women. We have shown that by increasing the proportion of eSETs it is possible to reduce the number of twins without affecting pregnancy and delivery rates. Based on our experience, we recommend eSET to oocyte recipients.


    Acknowledgements
 
The authors want to thank Nicholas Bolton for revising the language and Helena Korpelainen for statistical assistance. This study was supported by a grant from the Medical Society in Finland.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Abdalla, H.I., Billett, A., Kan, A.K.S., Baig, S., Wren, M., Korea, L. and Studd, J.W.W. (1998) Obstetric outcome in 232 ovum donation pregnancies. Br. J. Obstet. Gynecol., 105, 332–337.[ISI][Medline]

Applegarth, L., Goldberg, N.C., Cholst, I., McGoff, N., Fantini, D., Zellers, N., Black, A. and Rosenwaks, Z. (1995) Families created through ovum donation: A preliminary investigation of obstetrical outcome and psychosocial adjustment. J. Assist. Reprod. Genet., 12, 574–580.[ISI][Medline]

Bergh, T., Ericson, A., Hillensjö, T., Nygren K.G. and Wennerholm, U.B. (1999) Deliveries and children born after in-vitro fertilisation in Sweden 1982–1995: a retrospective cohort study. Lancet, 354, 1579–1585.[CrossRef][ISI][Medline]

Bos-Mikich, A., Mattos, A.L.G. and Ferrari, A.N. (2001) Early cleavage of human embryos: an effective method for predicting successful IVF/ICSI outcome. Hum. Reprod., 16, 2658–2661.[Abstract/Free Full Text]

Cohen, M.A., Lindheim, S.R. and Sauer, M.V. (1999) Donor age is paramount to success in oocyte donation. Hum. Reprod., 14, 2755–2758.[Abstract/Free Full Text]

Edwards, R.G. (1992) Why are agonadal and post-amenorrhoeic women so fertile after oocyte donation? Hum. Reprod., 7, 773–774.

ESHRE Campus Course Report (2001) Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. Hum. Reprod., 16, 790–800.[Abstract/Free Full Text]

Gerris, J., Neubourg, D., Mangelschots, K., Van Royen, E., Van de Meerssche, M. and Valkenburg, M. (1999) Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. Hum. Reprod., 14, 2581–2587.[Abstract/Free Full Text]

Lassale, B., Testart, J. and Renad, J.P. (1985) Human embryo features that influence the success of cryopreservation with the use of 1,2 propanediol. Fertil. Steril., 44, 645–651.[ISI][Medline]

Legro, R.S., Wong, I.L., Paulson, R.J., Lobo, R.A. and Sauer, M.V. (1995) Recipient’s age does not adversely affect pregnancy outcome after oocyte donation. Am. J. Obstet. Gynecol., 172, 96–100.[CrossRef][ISI][Medline]

Lundin, K., Bergh, C. and Hardarson, T. (2001) Early embryo cleavage is a strong indicator of embryo quality in human IVF. Hum. Reprod., 16, 2652–2657.[Abstract/Free Full Text]

Martikainen, H., Tiitinen, A., Tomás, C., Tapanainen, J., Orava, M., Tuomivaara, L., Vilska, S., Hydén-Granskog, C., Hovatta, O. and the Finnish ET Study Group (2001) One versus two embryo transfer after IVF and ICSI: a randomized study. Hum. Reprod., 16, 1900–1903.[Abstract/Free Full Text]

Navot, D., Bergh, P.A., Williams, M., Garrisi, G.J., Guzman, I., Sandler, B., Fox, J., Schreiner-Engel, P., Hofmann, G.E. and Grunfeld, L. (1991) An insight into early reproductive processes through the in vivo model of ovum donation. J. Clin. Endocrinol. Metab., 72, 408–414.[Abstract]

Pados, G., Camus, M., Van Steirteghem, A., Bonduelle, M. and Devroey, P. (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. (1997) Cumulative conception and live birth rates after oocyte donation: implications regarding endometrial receptivity. Hum. Reprod., 12, 835–839.[Abstract]

Remohí, J., Gartner, B., Gallardo, E., Yalil, S., Simón, C. and Pellicer, A. (1997) Pregnancy and birth rates after oocyte donation. Fertil. Steril., 67, 717–723.[CrossRef][ISI][Medline]

Reynolds, M.A., Schieve, L.A., Jeng, G., Peterson, H.B. and Wilcox, L.S. (2001) Risk of multiple birth associated with in vitro fertilization using donor eggs. Am. J. Epidemiol., 154, 1043–1050.[Abstract/Free Full Text]

Salha, O., Sharma, V., Dada, T., Nugent, D., Rutherford, A.J., Tomlinson, A.J., Philips, S., Allgar, V. and Walker, J.J. (1999) The influence of donated gametes on the incidence of hypertensive disorders of pregnancy. Hum. Reprod., 14, 2268–2273.[Abstract/Free Full Text]

Schoolcraft, W.B. and Gardner, D.K. (2000) Blastocyst culture and transfer increases the efficiency of oocyte donation. Fertil. Steril., 74, 482–486.[CrossRef][ISI][Medline]

Scott, R.T., Hofmann, G.E., Veeck, L.L., Jones, H. W. and Muasher, S.J. (1991) Embryo quality and pregnancy rates in patients attempting pregnancy through in vitro fertilization. Fertil. Steril., 55, 426–428.[ISI][Medline]

Sheffer-Mimouni, G., Mashiach, S., Dor, J., Levran, D. and Seidman, D.S. (2002) Factors influencing the obstetric and perinatal outcome after oocyte donation. Hum. Reprod., 17, 2636–2640.[Abstract/Free Full Text]

Simón, C., Cano, F., Valbuena, D., Remohí, J. and Pellicer, A. (1995) Clinical evidence for a detrimental effect on uterine receptivity of high serum estradiol levels in high and normal responder patients. Hum. Reprod., 10, 2432–2437.[Abstract]

Söderström-Anttila, V., Foudila, T. and Hovatta, O. (1996) A randomized comparative study of highly purified follicle stimulating hormone and human menopausal gonadotrophin for ovarian hyperstimulation in an oocyte donation programme. Hum. Reprod., 11, 1864–1870.[Abstract]

Söderström-Anttila, V., Tiitinen, A., Foudila, T. and Hovatta, O. (1998) Obstetric and perinatal outcome after oocyte donation – comparison with in vitro fertilization pregnancies. Hum. Reprod., 13, 483–490.[CrossRef][ISI][Medline]

Tiitinen, A., Halttunen, M., Härkki, P., Vuoristo, P. and Hydén-Granskog, C. (2001) Elective single embryo transfer: the value of cryopreservation. Hum. Reprod., 16, 1140–1144.[Abstract/Free Full Text]

Toner, J.P., Grainger, D.A. and Frazier, L.M. (2002) Clinical outcomes among recipients of donated eggs: an analysis of the U.S. national experience, 1996–1998. Fertil. Steril., 78, 1038–1045.[CrossRef][ISI][Medline]

Van Royen, E., Mangelschots, K., De Neubourg, D., Valkenburg, M., Van de Meerssche, M., Ryckaert, G., Eestermans, W. and Gerris, J. (1999) Characterization of a top quality embryo, a step towards single-embryo transfer. Hum. Reprod., 14, 2345–2349.[Abstract/Free Full Text]

Vilska, S., Tiitinen, A., Hydén-Granskog, C. and Hovatta, O. (1999) Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth. Hum. Reprod., 14, 2392–2395.[Abstract/Free Full Text]

Yaron, Y., Amit, A., Kogosowski, A., Peyser, M.R., David, M.P. and Lessing, J.B. (1997) The optimal number of embryos to be transferred in shared oocyte donation: walking the thin line between low pregnancy rates and multiple pregnancies. Hum. Reprod., 12, 699–702.[Abstract]

Yaron, Y., Ochshorn, Y., Amit, A., Kogosowski, A., Yovel, I. and Lessing, J.B. (1998) Oocyte donation in Israel: a study of 1001 initiated treatment cycles. Hum. Reprod., 13, 1819–1824.[Abstract]

Ziebe, S., Petersen, K., Lindenberg, S., Andersen, A.-G., Gabrielsen, A. and Nyboe Andersen, A. (1997) Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. Hum. Reprod., 12, 1545–1549.[Abstract]

Submitted on April 14, 2003; accepted on June 3, 2003.