Bourn Hall Clinic, Bourn, Cambridge CB3 7TR, UK
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: embryo donation/oocyte donation/sperm donation/termination of pregnancy
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Since the report of the first pregnancy after the transfer of a donated oocyte in a patient with primary ovarian failure (Lutjen et al., 1984), older women have been increasingly seeking oocyte donation. Many studies (Serhal and Craft 1989
; Borini et al. 1991
; Antinori et al., 1993
; Sauer et al., 1995
) have shown that women in their late 50s and older, can establish successful pregnancies and live births, and that the uteri of menopausal women can respond to steroid therapy and implant embryos as efficiently as those of young women.
Limiting the number of embryos created with donated oocytes or donated embryos to two for transfer is of paramount importance because of the increased risk of high order multiple pregnancy (HFEA, 1998; Marcus et al., 1998). Both advanced age and multiple pregnancy are associated with increased obstetric risk to both mother and fetus (Antinori et al., 1993
; Sauer et al., 1995
; Report of Confidential Enquiries on Maternal Deaths, 1998). It is essential that recipients of donated oocytes and embryos should receive in-depth counselling about the implications of their decision and be made aware of the increased risk of multiple pregnancy.
We report two case histories in which the recipients of donated embryos had multiple pregnancies and subsequently requested termination of their pregnancies.
![]() |
Case 1 |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The couple were counselled by the clinician as well as by an independent infertility counsellor, not only with regard to the ethical and legal issues related to oocyte and spermatozoa donation but also to the increased maternal and fetal risks associated with multiple pregnancy and ageing. They were screened for human immunodeficiency virus (HIV), hepatitis B surface antigen and hepatitis C and signed informed consents before they were accepted onto the programme. It was decided to transfer two frozenthawed embryos in a hormone replacement cycle, as described previously (Marcus, 1999).
An oocyte donor whose physical characteristics matched those of the recipient was counselled, screened and consented, as has been described previously (Marcus and Brinsden, 1999). She underwent IVF treatment using the long gonadotrophin-releasing hormone (GnRH) agonist protocol combined with gonadotrophins (Marcus et al., 1993
). A total of 20 oocytes were collected, 16 were fertilized and 14 embryos were cryopreserved. After the oocyte donor had had a second negative HIV test 6 months later, three frozen embryos were thawed, two survived and were transferred in a hormone replacement cycle (Marcus and Brinsden, 1999
). The patient did not conceive. The case was reviewed and it was decided to transfer three embryos in the next planned cycle. The couple were fully involved in the decision and the risk of multiple pregnancy was re-emphasized.
Three frozenthawed embryos were transferred, as two 5-cell and one 4-cell embryos. The woman conceived and a pelvic ultrasound scan 5 weeks after embryo transfer diagnosed a viable triplet pregnancy. The couple were very anxious about this outcome and received advice about elective fetal reduction to a twin pregnancy. The couple was offered and declined further counselling. Thereafter the patient was referred to a clinic nearer to her home with a view to elective fetal reduction. After further discussion with two senior gynaecologists about the risks associated with fetal reduction to the mother and fetuses, as well as the benefits, they decided to terminate the entire pregnancy. They felt they could not face the possibility of bringing handicapped children into the world and they did not want to proceed with the pregnancy to the later stages and then risk losing everything. They felt that this would be too much pain after such a protracted period of infertility. Although the couple was advised against termination, their attending gynaecologist felt that he could not abandon them in their hour of need and respected their wishes. Surgical termination of pregnancy was performed. The patient made an uneventful recovery and they requested that their remaining seven frozen embryos be allowed to perish.
![]() |
Case 2 |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The couple introduced a known oocyte donor who was counselled, screened and gave informed consent. The donor underwent IVF in 1995. She was stimulated using a long GnRH agonist protocol combined with gonadotrophins, 14 oocytes were retrieved and 11 fertilized. Synchronization of both the recipient and donor treatment cycles was successful. Two 5-cell grade 1 embryos were transferred and nine embryos were cryopreserved, all at the pronucleate stage. The patient conceived and a pelvic ultrasound scan 5 weeks later indicated a singleton pregnancy. She had an uncomplicated pregnancy and safely delivered a healthy baby girl by Caesarean section in 1996. The patient returned to the clinic in 1997 to make a further attempt at frozenthawed embryo transfer. She was approaching 49 years of age. Two 4-cell frozenthawed embryos were transferred, but she did not conceive.
Another attempt at frozen embryo transfer was carried out in 1998. Two 5-cell grade-1 embryos were transferred. She conceived. The couple was extremely delighted with the pregnancy until a pelvic ultrasound scan performed 5 weeks after embryo transfer showed a viable twin pregnancy. The patient then felt quite unable to cope with her twin pregnancy, felt ill and constantly sick. They were offered independent counselling and received support from the clinic staff and their family practitioner. Elective fetal reduction was discussed with the couple who initially were absolutely certain this was right for them. They were referred to a local unit with a view of elective fetal reduction to one fetus. However, after further discussion with a senior gynaecologist about the risks and benefits, they requested full termination of the pregnancy. The patient had already stopped her luteal support hoping that the pregnancy would perish, or that one fetus would be lost. They were offered independent counselling and advised against termination but ultimately her pregnancy was terminated at ~11 weeks gestation. Thereafter, the couple requested the transfer of their remaining frozen embryos to another unit.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
At Bourn Hall Clinic, all prospective oocyte donors and recipient couples receive independent infertility counselling free of charge. This includes: (i) implications counselling, which aims to help couples understand the implications of the proposed treatment for them, their family and for any children born as a result of the treatment; (ii) support counselling, which aims to give emotional support at the time of particular stress, e.g. failure of treatment; and (iii) therapeutic counselling, which aims to help couples cope with the consequences of infertility and treatment and to help them resolve any particular problems which these may cause.
In these two cases, it was their multiple pregnancies that triggered the decision to terminate the pregnancies. In the first case, three embryos were transferred and critics may argue that three embryos should not have been transferred. It would have been difficult to persuade this couple to accept only two embryos as they had had many previous failed attempts at IVF, including two failed attempts using donated oocytes and donor spermatozoa, in one of which three embryos were transferred. Should the second patient have had only one embryo transferred?
Undoubtedly the higher the number of embryos transferred, the higher the risk of multiple pregnancy and the higher the obstetric risks to both mother and babies. Moreover, multiple pregnancy has important socio-economic and psychological implications that require consideration.
The demand of patients for high success rates without the risk of multiple pregnancy cannot be satisfied until it is feasible to transfer only one embryo with high implantation potential. Even by limiting the number of embryos transferred there may still be unexpected multiple pregnancies (Marcus et al., 1996a).
A comparison of the incidence of multiple pregnancy in a unit in relation to maternal age, the number of embryos transferred, type of embryos transferred (own or donated) (Marcus et al., 1998) showed that the multiple pregnancy rates in women aged >40 years was significantly higher after oocyte or embryo donation compared with own eggs, and recommended that only two donated embryos or oocytes should be transferred. Whether or not couples will accept this recommendation, and in view of our primary obligation as clinicians not to harm our patients by putting them at increased risk, we feel that transfer of only two embryos is ethically justified because the likely benefits outweigh the potential harm.
Although both couples admitted that the only reason for requesting termination was that the pregnancies were multiple and neither admitted that their age was a factor in their decision, it is difficult to dissociate the effect of age from the multiple pregnancies. Both advanced maternal age and high order multiple gestation is associated with increased obstetric risk. Also, the effect of age alone on the ability to cope with pregnancy even if it is singleton pregnancy, remains to be answered and there is a need for such a study. Perhaps, if these women had been younger they might have coped better with their multiple pregnancies. Critics may argue that we should have not offered treatment to these two patients because of their ages, but it is our policy to treat women up to the age of 50 years. It is also possible that termination of pregnancy was an expression of ambivalent feeling against any kind of pregnancy.
Elective fetal reduction of high order multiple pregnancies has been proposed in order to reduce the number of fetuses, thereby reducing both the perinatal mortality and morbidity and protecting the mother's health and well-being and avoiding the trauma of aborting a wanted pregnancy. The procedure is usually performed by ultrasound-guided intracardiac injection of potassium chloride. The efficacy and safety of this procedure has been reported previously (Berkowitz, 1998). With the advances in assisted reproduction treatment, the demand for elective fetal reduction is rising. One group (Roest et al., 1997
) reported that 12.5% of their triplet pregnancies after IVF underwent elective fetal reduction. Another group (Evans et al., 1996
) reported that eight of their nine patients aged >45 years who underwent multifetal reduction in their programme were oocyte recipients and cited the reasons for elective fetal reduction as: parental demand, financial issues and concern about their ability to becoming parents in their 60s and 70s. While a third group (Kedhel et al., 1998
) argued that because of progress in the management of multiple pregnancy and advances in neonatal intensive care, elective fetal reduction could no longer be justified on grounds of obstetric benefit. It should however be offered to couples who may suffer from severe psychological, social or economic consequences of multiple birth.
Elective fetal reduction creates a number of ethical and medical concerns that appear to be morally acceptable to only a few patients. Both couples in our study were counselled and offered elective fetal reduction and both declined. The reasons for declining elective fetal reduction in the first couple were their inability to face the possibility of having handicapped children and because the couple did not want to proceed to the later stages of pregnancy and then possibly lose everything. They felt that it would be too much pain to bear after such a protracted period of infertility. In the second couple, the reasons for declining elective fetal reduction were more difficult to assess. Whether the time interval of <3 weeks between the diagnosis of twin pregnancy and their consultation with their gynaecologist about elective fetal reduction played a part is difficult to tell. During this time, they were seen and counselled by their fertility specialist and their general practitioner and may have needed more time for reflection and to make their decision. However, as the woman had already stopped the luteal support of the pregnancy in the few days before seeing the gynaecologist, it may be that they had already decided to terminate the pregnancy.
It is important to counsel couples who achieve multiple pregnancies about the possibility that one or more of the fetuses may vanish, as this may influence their decision. The obstetric outcome of 232 ovum donation pregnancies was studied (Abdalla et al., 1998) and it was found that of 47 patients with initial finding of twin gestation sacs, 11 ended in singleton deliveries (23%) and 32 twin deliveries (68%). In the seven cases with triplet sacs, there were no singleton deliveries, three twin deliveries and three triplet deliveries. Another study (Manzur et al., 1995
) reported that after seeing three fetal heart beats on day 28 after embryo transfer, 70% ended in triplet delivery and the remainder ended in either singleton or twin delivery.
An analysis of the frequency of vanishing fetuses in 253 multiple pregnancies (210 sets of viable twin pregnancies and 43 sets of viable triplets pregnancies; Marcus et al., 1996b) after IVF and embryo transfer showed an overall incidence of 12% of vanishing fetuses and that the frequency increased with maternal age. Embryo resorptions were observed mainly during the first trimesters of the pregnancies (Manzur et al., 1995; Marcus et al., 1996b
).
In summary, these two reported cases show that, even after successful treatment with donor oocytes and donor spermatozoa and appropriate counselling, some couples will demand termination of their pregnancies. It is possible that our counselling may not be sufficient in some older women to understand their unconscious wishes for a child.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Antinori, S., Versaci, C., Hossein Gholami, G. et al. (1993) Oocyte donation in menopausal women. Hum. Reprod., 8, 14871490.[Abstract]
Berkowitz, R.L. (1998). Ethical issues involving multifetal pregnancies. Mt Sinai J. Med., 65, 185190.[ISI][Medline]
Borini, A., Bafaro, G., Violini, F. et al. (1991) Pregnancies in postmenpausal women over 50 years old in an oocyte donation program. Fertil. Steril., 63, 258261.
Evans, M.I., Johnson, M.P., Quintero, R.A. et al. (1996) Ethical issues surrounding multifetal pregnancy reduction and selective termination. Clin. Perinatol., 23, 437451.[ISI][Medline]
Human Fertilization and Embryology Authority (1998) Annual Report for the year 1996. HFEA, London, UK.
Kedhel, P., Olivennes, F., Fernandez, H. et al. (1998) Are there still obstetric and perinatal benefits for selective embryo reduction of triplet pregnancies? Hum. Reprod., 13, 35553559.[Abstract]
Lutjen, P.J., Trounson, A.O., Leeton, F.J. et al. (1984) The establishment and maintenance of pregnancy using in vitro fertilisation and embryo transfer in a patient with primary ovarian failure. Nature, 307, 174176.[ISI][Medline]
Marcus, S.F. (1999) Embryo donation. In Brinsden, P.R. (ed.), A Textbook of In Vitro Fertilization and Assisted Reproduction. 2nd edn. Parthenon, Carnforth and New Jersey, pp. 222333.
Marcus, S.F. and Brinsden, P.R. (1999). Oocyte donation. In Brinsden, P.R. (ed.), A Textbook of In Vitro Fertilization and Assisted Reproduction. 2nd edn. Parthenon, Carnforth and New Jersey, pp. 222333.
Marcus, S.F., Brinsden, P.R., Macnamee, M.C. et al. (1993) Comparative trial between an ultra-short and long protocol of luteinizing hormone releasing hormone agonist for ovarian stimulation in in-vitro fertilization. Hum. Reprod., 8, 228243.
Marcus, S.F., Marcus, N.K. and Brinsden, P.R. (1996a) Astonishing fertility from a single oocyte recovery. Hum. Reprod., 11, 21362137.[Abstract]
Marcus, S.F., Marcus, N.K., Williams, G. et al. (1996b) Does the frequency of vanishing fetuses after IVF and embryo transfer increases with rise of maternal age. [Abstr. no. 148] Hum. Reprod., 11 (Abstract Book 1), 69.
Marcus, S.F, Abusheikha, N., Marcus, N.K et al. (1998) How many embryos to transfer in women aged >40 years? [Abstr. no. R-039] Hum. Reprod., 13 (Abstract Book 1), 286.
Manzur, A., Goldsman, S.C., Stone, S.C. et al. (1995) Outcome of triplet pregnancies after assisted reproductive techniques: how frequent are the vanishing embryos? Fertil. Steril., 63, 252257.[ISI][Medline]
Roest, J., Van Heusden, A.M., Verhoeff, A. et al. (1997) A triple pregnancy after in vitro fertilization is a procedure-related complication that should be prevented by replacement of two embryos only. Fertil. Steril., 67, 290295.[ISI][Medline]
Report of Confidential Enquiries on Maternal Deaths in the United Kingdom 19941996 (1998) HMSO Publications, London
Sauer, M., Paulson, R. and Lobo, R. (1995) Pregnancy in women 50 or more years: outcome of 22 consecutive established pregnancies from oocyte donation. Fertil. Steril., 64, 111115.[ISI][Medline]
Serhal, P. and Craft, I. (1989) Oocyte donation in 61 patients. Lancet, 11851187.
Submitted on August 20, 1999; accepted on November 25, 1999.