1 Infertility Clinic, The Family Federation of Finland, PO Box 849, FIN-00101, Helsinki, 2 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, PO Box 140, FIN-00029 HUCH, Finland and 3 Department of Obstetrics and Gynaecology, Karolinska Institute, Huddinge Hospital, S-14186, Sweden
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Abstract |
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Key words: embryo transfer/implantation rate/pregnancy rate/single embryo
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Introduction |
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Many investigators have presented low pregnancy rates (PR) after transfer of one single embryo (Elsner et al., 1997). These results, however, originate from transfers with only one embryo available. In a prospective setting, when the best embryo can be selected for transfer, implantation rates associated with elective single embryo transfer are likely to be higher. The following factors are known to be associated with favourable prognosis: age <36 years, first, second, or third treatment cycle and more than three embryos available for transfer (Coetsier and Dhont, 1998
).
One of the main challenges in the field of assisted reproductive technology is to avoid multiple pregnancy without significantly lowering the overall PR. The obstetric and perinatal risks as well as the impact of a multiple pregnancy on the family should be considered individually. Because we want to give objective information to the couples involved, we studied the PR during 1 year in our infertility clinics, in cases where only one embryo was transferred, and compared cycles with only one embryo available, and elective transfer of one embryo.
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Materials and methods |
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The embryos were cultured in standard media (IVF-500, Scandinavian IVF Science, Gothenburg, Sweden or IVF medium, MediCult, Copenhagen, Denmark). The cleavage rates and embryo grading were assessed 4852 h after oocyte retrieval. The embryos were graded according to the number of blastomeres and the amount of fragmentation. The following grades were used: grade 1: no fragments, grade 2: <20% fragmentation, grade 3: 2050% fragmentation and grade 4: fragmentation >50%. Cryopreservation and thawing were carried out using standard protocols with either 1,2-propanediol (PROH) (Lassalle et al., 1985) or dimethylsulphoxide (DMSO) (Van Steirteghem et al., 1987
). The frozenthawed embryos were transferred as described previously (Tiitinen et al., 1995
; Simberg et al., 1998
), during either a natural cycle after a luteinizing hormone (LH) surge measured by a home test kit (Clearplan, Unipath, Bedford, UK), or a hormone replacement cycle.
During 1997, a total of 910 embryo transfers was carried out. In 742 cases two embryos were transferred and in 168 cases a single embryo was transferred. Only one embryo was available and transferred in 94 cycles (group 1). In 74 cycles, elective one-embryo transfer was carried out (group 2), and additional embryos were cryopreserved. The three main indications for elective one-embryo transfer were: subject's wish, risk of ovarian hyperstimulation syndrome (OHSS) and various medical reasons. These included diabetes mellitus, uterine malformation, history of cervical incompetence or hysterotomy, and indication for prenatal diagnosis. The mean age of the women was 35 years (range 2442 years) in the one-embryo group and 34 years (range 2342 years) in the two-embryo transfer group.
The implantation rate and clinical PR per embryo transfer were calculated. Correlation between clinical implantation rate and embryo quality as revealed by cleavage and fragmentation status was analysed. The cumulative PR per subject after transfer of both fresh and frozenthawed embryos before 1st July 1998, as well as the outcome of pregnancies were analysed. Statistical analysis was performed using the 2 test.
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Results |
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Discussion |
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In many countries, more than three embryos are still transferred. This has led to the practice of embryo reduction in pregnancies with three or more fetuses. Embryo reductions, when carried out by experienced clinicians, still carry a 10% risk of miscarriage (Evans et al., 1998). These procedures are not without risks for the newborn (Geva et al., 1998
). They are mentally extremely stressful for the couples and many regard them as ethically problematic. Embryo reductions can be completely avoided by transferring only one embryo at a time.
When aiming for individualized transfer policy, we have to consider the probability of the embryo implanting and the subject conceiving. The quality of the embryo is probably the most important factor which predicts the outcome of transfer. One-embryo transfers offered us a unique possibility to relate embryo quality to the implantation rate. In agreement with earlier reports (Staessen et al., 1992; Giorgetti et al., 1995
; Roseboom et al., 1995
; Tasdemir et al., 1995
), embryo quality correlated with the PR. After transfer of grade 1 embryos and grade 3 embryos, the PR were 34.0 and 8.8% per embryo transfer respectively. No pregnancies followed the six grade 4 embryo transfers. Transfer of these poor quality embryos was carried out in cases where there was only one embryo available. If only grade 3 embryos are available, it would be justified to transfer two embryos at a time, and grade 45 embryos should not be transferred at all if there are better ones available. When grade 45 embryos are to be transferred, the couple should be counselled as regards the poor prognosis.
Blastocyst transfer has been suggested as a means of facilitating higher PR when the number of embryos transferred is limited (Gardner et al., 1998). The implantation rate of 35.8% achieved in our survey, when day 2 embryos at the four-cell stage were transferred, suggests that it may not be necessary to culture the embryos to the blastocyst stage in order to obtain acceptable implantation rates. It has been suggested that a delay in embryo transfer from 48 to 72 h after oocyte retrieval improves the clinical outcome in IVF (Carrillo et al., 1998
). In the few day 3 transfers carried out in our programme, we achieved an implantation rate of 45.5% with embryos at the six- to eight-cell stage. There may also be more sophisticated methods to judge embryo quality in future. Attention has to be paid, however, to the quality of the laboratory processes and culture media, to ensure the best possible outcome (Murdoch et al., 1998).
If only one embryo was available, the PR did not relate to the age of the woman in our study. Young women from whom only one embryo can be obtained appear to be a group with overall poor prognosis. In elective one-embryo transfers, the PR per embryo transfer was higher in women younger than 36 years, which is in agreement with many earlier reports (Roseboom et al., 1995; Coetsier and Dhont, 1998
). It might be considered that two embryos could be transferred in older women (Hull et al., 1996
; Adonakis et al., 1997
; Elsner et al., 1997
). In addition, the number of oocytes retrieved and the proportion of fertilized oocytes at the first attempt can be used as prognostic factors (Bouckaert et al., 1994
) when adopting guidelines on selecting subjects for elective one-embryo transfer. The chances of a live birth are related to the number of fertilized oocytes because of the greater selection of embryos available for transfer (Templeton and Morris, 1998
).
Good cryopreservation and thawing techniques are necessary when elective single embryo transfers are being carried out (Horne et al., 1997). In our clinic, we have cryopreserved all grade 13 embryos, and satisfactory pregnancy rates of 14.3% per single frozenthawed embryo transfer and 17.9% per double frozenthawed embryo transfer were obtained. After transfers of two frozenthawed embryos, two out of seven pregnancies were twin. This means that transfer of only one embryo should also be considered in selected cases after cryopreservation.
To avoid the complications of twin pregnancies in assisted reproductive technology programmes, transfer of only one embryo at a time is highly recommended, at least among younger subjects, and during the first two to three treatment cycles. A prospective randomized study would be useful to compare the outcome of elective one- and two-embryo transfers, and to identify the group of subjects suitable for elective one-embryo transfer.
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Notes |
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References |
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Submitted on February 15, 1999; accepted on May 27, 1999.