Human Reproduction, Vol. 16, No. 6, 1140-1144,
June 2001
© 2001 European Society of Human Reproduction and Embryology
Elective single embryo transfer: the value of cryopreservation
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, PO Box 140, 00029 HUS, Finland
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Abstract |
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In-vitro fertilization is associated with a high rate of multiple pregnancies, a consequence of the number of embryos transferred. There is a challenge in avoiding even twin pregnancies in assisted reproduction, and this can be accomplished with elective single embryo transfer and a good cryopreservation programme. In our follow-up study, we analysed all our elective single embryo transfers during 1998–1999. In all these cycles at least one embryo was frozen. A total of 127 elective single embryo transfers were performed with a clinical pregnancy rate of 38.6%. The highest implantation rate was obtained with four-cell embryos with <10% fragmentation (39.8%). Thirty-four patients have delivered (26.8%), one of these being a monozygotic pregnancy. In total 129 frozen–thawed cycles have been achieved in 83 patients. One frozen–thawed embryo has been transferred in 46 cycles with a clinical pregnancy rate of 17.4%, and two embryos have been transferred in 83 cycles, with a clinical pregnancy rate of 37.3%. Up until now, 66 of 125 patients in our single embryo transfer programme have delivered or have on-going pregnancies, and 77 still have embryos frozen. The cumulative delivery rate per oocyte retrieval is 52.8% and the twin rate 7.6%. We conclude that elective single embryo transfer with a good cryopreservation programme results in very acceptable pregnancy rates with a low risk of twins. This is a cost-effective practice that substantially reduces all risks associated with multiple pregnancies and lowers the cost per delivery.
Key words: cryopreservation/embryo transfer/in-vitro fertilization
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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A new strategy is needed to improve the quality of assisted reproductive techniques. The main reason for adverse treatment outcome in assisted reproductive techniques is the high rate of multiple pregnancies, including twins (Bergh et al., 1999
). To avoid triplet pregnancies, many European IVF centres have accepted the policy of transferring only two embryos (Coetsier and Dhont, 1998), and nowadays an overall pregnancy rate of 30–40% per cycle is obtained in many assisted reproductive technique programmes. However, the number of twin pregnancies after transfer of two embryos is still high (Templeton and Morris, 1998), increasing the health-care costs for delivery and the newborn by 5.4 times (Gissler et al., 1995). One of the main challenges is to avoid twin pregnancies without significantly lowering the overall pregnancy rates. This can be done if the best embryo can be selected for transfer and if the freezing and thawing techniques can be improved.
Cryopreservation of embryos following IVF/intracytoplasmic sperm injection (ICSI) provides further possibilities of pregnancy in addition to those achieved from the fresh cycle. The contribution of embryo cryopreservation to the results of assisted reproductive techniques over a long period of time is not usually reported. The efficacy of IVF, which is more important for the infertile couple, as well as for the health administrators, is the cumulative birth rate after completion of the IVF cycle. The contribution of cryopreservation to pregnancy has been reported to increase the take-home baby rate by 5.2% (Kahn et al., 1993), to 11% (Wang et al., 1994) or even 19% (Bergh et al., 1995).
The objective of our follow-up study was to analyse data from our elective single embryo transfer programme and to expand the findings by combining the results from frozen–thawed cycles. In an attempt to establish quality criteria for embryos, we examined the characteristics of the embryos that resulted in ongoing implantation both in fresh and frozen–thawed transfers.
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Materials and methods |
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We analysed all cycles with single fresh embryo transfer performed during the years 1998–1999 at the Infertility Clinic of Helsinki University Central Hospital. All patients were treated with the long protocol for ovarian stimulation. Briefly, long luteal phase down-regulation with nafarelin (Synarela; Syntex Nordica AB, Södertälje, Sweden) was used and, after 2 weeks, suppression was confirmed by transvaginal sonography (TVS). Ovarian stimulation was commenced with recombinant follicle-stimulating hormone (recFSH; Gonal-F; Laboratories Serono, Aubonne, Switzerland, or Puregon; Organon, Oss, The Netherlands). When two or more follicles reached a size of
17 mm in diameter in TVS, human chorionic gonadotrophin (HCG; Pregnyl; Organon, or Profasi; Laboratories Serono) was administered. Transvaginal oocyte retrieval was performed 36 h later. Embryo transfer was performed 2 days after oocyte retrieval. Micronized vaginal progesterone (Lugesteron, Leiras, Tampere, Finland) was used for luteal support. Serum HCG levels were measured 12 days after embryo transfer and, if positive, micronized progesterone was continued for 1 week. Clinical pregnancy was confirmed by TVS 5 weeks after embryo transfer. The oocytes and embryos were cultured in microdrops under oil (Ovoil; Scandinavian IVF Science, Gothenburg, Sweden) in IVF-500 medium (Scandinavian IVF Science,) or Sydney IVF fertilization medium and Sydney IVF cleavage medium (Cook IVF, Brisbane, Australia). The spermatozoa were prepared using both density gradient centrifugation (PureSperm; NidaCon, Gothenburg, Sweden) and swim-up. Insemination was carried out 4–5 h after oocyte retrieval with 25 000–75 000 progressively motile spermatozoa. If ICSI was performed, denudation of oocytes was carried out with hyaluronidase (HYASE-10X; Scandinavian IVF Science). ICSI was done with PVP (ICSI; Scandinavian IVF Science). On the next day, 17 h after the insemination, oocytes were examined for the appearance of pronuclei. Unfertilized oocytes and oocytes containing only one pronucleus were examined again 4–5 h later. The embryo grading and cleavage rate was assessed 24 h later at x400 magnification. The embryos were graded according to the number of blastomeres, the degree of fragmentation, regularity of blastomeres and mono-/multinuclearity in the blastomeres. Embryos were suitable for transfer or cryopreservation if they had <50% fragmentation and, if nuclei were visible, only one nucleus per blastomere. The best embryo was selected for fresh transfer. Elective transfer of one embryo was performed only if there was at least one four-cell embryo on day 2 after oocyte retrieval.
Freezing and thawing were carried out using the standard protocol (Testart et al., 1986) with 1,2-propanediol (PROH), modified according to the manual of the media provider (Freeze-kit1 and Thaw-kit1; Scandinavian IVF Science) in vials. Usually two or three embryos were frozen in the same vial for practical reasons and to ensure the possibility for transfer after thawing. Two-cell embryos were thawed and cultured overnight and transferred only if they cleaved (Van der Elst et al., 1997). Four-cell embryos were thawed and transferred on the same day. One embryo was always transferred if there was a medical reason. Two-embryo transfer was allowed after careful counselling of the couple, if two good quality embryos in the same vial were alive after thawing. The frozen–thawed embryos were transferred during a natural cycle, if possible, 3 days after a luteinizing hormone (LH) surge measured by a home test kit (Clearplan; Unipath, Bedford, UK). Micronized vaginal progesterone was administered for 2 weeks after embryo transfer. In cases of anovulatory cycles, hormone replacement with oestradiol valerate (Progynova, Schering) and micronized progesterone was used.
During the years 1998–1999, we performed 708 IVF or ICSI cycles with embryo transfer. In 487 cases, two embryos were transferred and in 221 cases one embryo was transferred. In 127 cycles, a single embryo was transferred and at least one embryo was cryopreserved, whereas in 94 cycles only one embryo was available.
The main indication for elective single embryo transfer was the couple's wish to avoid twins, and in some cases various medical reasons, which include diabetes mellitus, uterine malformation, a history of cervical incompetence and indication for prenatal diagnosis. The mean age of the women in this group was 31.3 years (range 20–40 years), and 57 (44.9%) had primary infertility. Eighty-nine (70.0%) cycles were first attempts at IVF. The implantation rate and pregnancy rate per transfer and cumulative pregnancy rate per oocyte retrieval was calculated. The correlation between clinical implantation rate and embryo quality as revealed by cleavage and fragmentation status was analysed.
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Results |
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The overall clinical pregnancy rate per transfer in unselected patients during the same time period was 38% and the mean number of embryos transferred was 1.7. Of these pregnancies, 24.5% were twins. Only one embryo was available and transferred in 94 cycles, with a pregnancy rate of 18.1% (Table I
).
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Altogether, 127 elective single embryo transfers were performed on 125 patients (Tables I and II
). These resulted in 49 clinical pregnancies (38.6%). Pregnancy rate was 38.5% (42/109) in women <35 years of age and 38.9% (7/18) in those >35 years. Table III shows the implantation rates according to fragmentation stage. The highest implantation rates were obtained when four-cell embryos with <10% fragmentation were transferred on day 2 after oocyte retrieval (39,8%). Fifteen out of 49 pregnancies (30.6%) in the elective single-embryo transfer group resulted in spontaneous abortion or extrauterine pregnancy, while the others have delivered (26.8% per embryo transfer). One was a monozygotic pregnancy (Table II).
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A total of 932 embryos were frozen, a mean of seven embryos per cycle (range 1–21). Up to March 31, 2000, thawing had been performed in 83 patients (147 thawings). A total of 437 embryos have been thawed, 335 being alive (76.6%). The criteria were at least 50% of the blastomeres alive, with <50% fragmentation and normal zona pellucida. Two hundred and twelve embryos have been transferred in 129 cycles. The embryos were eligible for transfer if two-cell embryos cleaved during overnight culture (van der Elst et al., 1997
), and the embryos had only one nucleus per blastomere. After thawing, one embryo was transferred in 46 cycles, resulting in eight clinical pregnancies (pregnancy rate 17.4%), of these, five have delivered or are on-going (delivery rate per embryo transfer 10.9%). Two embryos were transferred in 83 cycles, resulting in 31 pregnancies (pregnancy rate 37.3%), of these, 27 have delivered or are on-going (delivery rate per embryo transfer 32.5%). Table IV shows the implantation rates according to survival and cleavage and fragmentation stage. Two embryo transfers were included in the calculations only when two identical embryos were transferred.
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Up to now, 66 of 125 patients in our single embryo transfer programme have delivered, which gives us a cumulative on-going pregnancy rate per oocyte retrieval of 52.8% (Table II
). The twin rate is 7.6%. Seventy-seven patients still have embryos frozen. |
Discussion |
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Our clinical data show that elective single embryo transfer with a good cryopreservation programme results in very acceptable pregnancy rates with a low risk for twins in a selected patient group. More than half the patients have delivered after a single ovarian stimulation and oocyte retrieval. We have already reported acceptable pregnancy rates with single embryo transfer in selected patient groups (Vilska et al., 1999
). In women aged 
35 years, the clinical pregnancy rate per elective one-embryo transfer was 32.8%. The implantation rates were highest when the embryos were at the four-cell stage on day 2 and had <20% fragmentation. If strict criteria for selecting top quality embryos are utilized, and one embryo is transferred in a highly selected patient group (age <34 years, first IVF/ICSI cycle, at least two top quality embryos available), even higher ongoing pregnancy rates of 38.5% can be achieved (Gerris et al., 1999).
The ultimate goal of assisted reproductive techniques is to get the woman pregnant with a singleton pregnancy (Coetsier and Dhont, 1998; Hazekamp et al., 2000). The increased efficiency of IVF and ICSI programmes in many centres has produced overall pregnancy rates of 30–40% per cycle, with multiple rates of 25–35%. The need for a high success rate conflicts with a low complication rate. It is essential to give objective information to the couples concerned. In aiming for an individualized transfer policy, we have to consider the probability of the embryo implanting and the subject conceiving. The obstetric and perinatal risks should also be considered, as well as the long-term social and psychological impact on the whole family. Competition between the centres should not result in multiple embryo transfers and thus multiple pregnancies.
How is an embryo with high implantation potential selected? This is mainly accomplished by looking at two parameters: cleavage speed and fragmentation. The implantation rate increases with better quality embryos in cycles where only one embryo is available (Giorgetti et al., 1995; Ziebe et al., 1997). Van Royen et al. describe the implantation potential of a well-defined embryo in their retrospective analysis: the top quality embryo has no multinucleated blastomeres, four or five blastomeres on day 2 and <20% fragmentation (Van Royen et al., 1999). Using these embryos, they achieved an implantation rate of 49% (Van Royen et al., 1999) and 45% in a prospective randomized study (Gerris et al., 1999). In our earlier retrospective study (Vilska et al., 1999), the highest implantation rates were obtained when four- to five-cell embryos with fragmentation <20% were transferred on day 2 (36%) or when six- to eight-cell stage embryos were transferred on day 3 (45%) or embryos with no fragmentation irrespective of cleavage stage were transferred (34%). The implantation rate in the present study was 39.8% with the same criteria as applied in the Belgian study.
The scoring of the embryos could be improved even more (Edwards and Beard, 1999). Besides the commonly used morphological criteria, polarity of the pronuclei (Scott and Smith, 1998; Garello et al., 1999), or variations in the thickness of zona pellucida (Palmstierna et al., 1998) might be applicable. Tesarik et al. have shown implantation rates of 30.2% in embryos judged normal at the pronuclear stage (Tesarik et al., 2000). Until now, we have not used this criterion for selection of the embryo for transfer. Careful evaluation of all blastomeres in four-cell embryos is also essential. It has been demonstrated that embryos displaying multinuclearity have impaired implantation potential (Pickering et al., 1995; Pelinck et al., 1998). In our practice, embryos with multinuclear blastomeres are not used for transfer unless they are the only embryos available.
In our previous study (Vilska et al., 1999) the selection criteria for patients for single embryo transfer were not as strict as in the Belgian study (Gerris et al., 1999), which produced an ongoing pregnancy rate of 40%; we had a pregnancy rate of 30%. In the present study, the criteria for elective single embryo transfer were even more liberal. We cautiously counsel our patients who come for the first IVF/ICSI treatment cycle and who are under 38 years of age, to accept only one embryo for fresh transfer, in order to avoid multiple pregnancies. In cases where good embryos are not produced, transfer of two embryos is allowed. This means that a change in attitude is necessary both in patients but, more importantly, in doctors (Gerris et al., 1999). We have not performed any three-embryo transfers during the last 5 years, because we think that triplets should not be allowed in a responsible fertility centre. During 1998–1999, 31% of our fresh transfers were single embryo transfers. This year our aim is to perform at least 50% of all cycles as single embryo transfers.
Whether the laborious blastocyst culture will result in a high pregnancy rate while lowering the number of twins has to be studied in a prospective setting, in which transfer of the best embryo on day 2 is compared with the transfer of one blastocyst, and cumulative pregnancy rates per oocyte retrieval with frozen–thawed embryos are analysed. Until now, there has been no evidence that single blastocyst transfer is a cost-effective method of avoiding twins. Moreover, the cryopreservation of blastocysts is difficult.
The ability of embryo cryopreservation to enhance the cumulative pregnancy potential after oocyte retrieval is somewhat underappreciated (Damario et al., 2000). Good cryopreservation and thawing techniques are necessary in elective single embryo transfers (Horne et al., 1997; Vilska et al., 1999). Many variables may influence the outcome of embryo cryopreservation and frozen embryo transfer. Multicell embryonic survival of cryopreservation and thawing with all blastomeres intact might identify embryos with superior implantation potential (Burns et al., 1999). In our study, we had similar implantation rates irrespective of the fragmentation stage of the embryo or whether it had all blastomeres intact. We transferred two embryos to selected patients, achieving an on-going pregnancy rate of 32.5%, of which 14.8% were twins. This means that we have to consider single embryo transfer in frozen–thawed cycles as well. In order to do this, the selection criteria for embryos to be frozen should be optimized, preferably only one top quality embryo, possibly accompanied by a lower grade embryo in the same vial.
More than half of our 125 patients have delivered, and 18 non-pregnant couples still have frozen embryos. It can be speculated that if the implantation rate is the same with these cryopreserved embryos, ultimately 57% of the couples will have a live birth after single oocyte retrieval cycle. However, we can already state that embryo cryopreservation is effective in increasing the pregnancy rate per oocyte recovery and thus lowering the ultimate cost per delivery. This information should be used when counselling patients and formulating health care policy (Van Voorhis et al., 1995). IVF results should be presented as `birth per embryo transferred' and this term should be given the status of `the criterion of assisted reproductive techniques excellence' (Hazekamp et al., 2000).
We conclude that even better results can be achieved if the embryo culture and freezing techniques can be improved. Single embryo transfer combined with freezing of extra embryos is highly effective and lowers the ultimate costs per delivery.
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Notes |
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1 To whom correspondence should be addressed: E-mail: aila.tiitinen{at}hus.fi
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References |
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Bergh, T., Ericson, A., Hillensjö, T. et al. 1999) Deliveries and children born after in-vitro fertilisation in Sweden 1982–95: a retrospective cohort study. Lancet, 354, 1579–1585.[Web of Science][Medline]
Bergh, C., Josefsson, B., Nilsson, L. and Hamberger, L. (1995) The success rate in a Swedish in-vitro fertilization unit: a cohort study. Acta Obstet. Gynecol. Scand., 74, 446–450.[Web of Science][Medline]
Burns, W.N., Gaudet, T.W., Martin, M.B. et al. (1999) Survival of cryopreservation and thawing with all blastomeres intact identifies multicell embryos with superior frozen embryo transfer outcome. Fertil. Steril., 72, 527–532.[Web of Science][Medline]
Coetsier, T. and Dhont, M. (1998) Avoiding multiple pregnancies in in-vitro-fertilization: who's afraid of single embryo transfer? Hum. Reprod., 13, 2663–2664.
Damario, M.A., Hammitt, D.G., Session, D.R. and Dumesic, D.A. (2000) Embryo cryopreservation at the pronuclear stage and efficient embryo use optimizes the chance for a liveborn infant from a single oocyte retrieval. Fertil. Steril., 73, 767–773.[Web of Science][Medline]
Edwards, R.G. and Beard, H.K. (1999) Is the success of human IVF more a matter of genetics and evolution than growing blastocyst? Hum. Reprod., 14, 1–4.
Garello, C., Baker, H., Rai, J. et al. (1999) Pronuclear orientation, polar body placement, and embryo quality after intracytoplasmic sperm injection and in-vitro fertilization: further evidence for polarity in human oocytes? Hum. Reprod., 14, 2588–2595.
Gerris, J., De Neuborg, D., Mangelschots, K. et al. (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.
Giorgetti, C., Terriou, P., Auquier, P. et al. (1995) Embryo score to predict implantation after in-vitro-fertilization: based on 957 single embryo transfers. Hum. Reprod., 10, 2427–2431.
Gissler, M., Malin Silverio, M. and Hemminki, E. (1995) In-vitro fertilization pregnancies and perinatal health in Finland 1991–1993. Hum. Reprod., 10, 1856–1861.
Hazekamp, J., Bergh, C., Wennerholm, U.-B. et al. (2000) Avoiding multiple pregnancies in assisted reproductive techniques. Consideration of new strategies. Hum. Reprod., 15, 1217–1219.
Horne, G., Critchlow, J.D., Newman, M.C. et al. (1997) A prospective evaluation of cryopreservation strategies in a two-embryo transfer. Hum. Reprod., 12, 542–547.
Kahn, J., von During, V., Sunde, A. et al. (1993) The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study. Hum. Reprod., 8, 247–252.
Palmstierna, M., Murkes, D., Csemiczky, G. et al. (1998) Zona pellucida thickness variation and occurrence of visible mononucleated blastomeres in preembryos are associated with a high pregnancy rate in IVF treatment. J. Assist. Reprod. Genet., 15, 70–75.[Web of Science][Medline]
Pelinck, M.J., De Vos, M., Debens, M. et al. (1998) Embryos cultured in vitro with multinucleated blastomeres have poor implantation potential in human in-vitro fertilization and intracytoplasmic sperm injection. Hum. Reprod., 13, 960–963.
Pickering, S.J., Taylor, A., Johnson, M.H. and Braude, P.R. (1995) An analysis of multinucleated blastomere formation in human embryos. Mol. Hum. Reprod., 1, see Hum. Reprod., 10, 1912–1922.
Scott, L.A. and Smith, S. (1998) The successful use of pronuclear transfers the day following oocyte retrieval. Hum. Reprod., 13, 1003–1013.
Templeton, A. and Morris J. (1998) Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N. Engl. J. Med., 339, 573–577.
Tesarik, J., Junca, A.M., Hazout, A. et al. (2000) Embryos with high implantation potential after intracytoplasmic sperm injection can be recognized by a simple, non-invasive examination of pronuclear morphology. Hum. Reprod., 15, 1396–1399.
Testart, J., Lassalle, B., Belaisch-Allart, J. et al. (1986) High pregnancy rate after early human embryo freezing. Fertil. Steril., 46, 268–272.[Web of Science][Medline]
Van der Elst, J., Van den Abdeel, E., Vitrier, S. et al. (1997) Selective transfer of cryopreserved human embryos with further cleavage after thawing increases delivery and implantation rates. Hum. Reprod., 12, 1513–1521.
Van Royen, E., Mangelschots, K., De Neubourg, D. et al. (1999) Characterization of a top quality embryo, a step towards single-embryo transfer. Hum. Reprod., 14, 2345–2349.
Van Voorhis, B.J., Syrop, C.H., Allen, B.D. et al. (1995) The efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques. Fertil. Steril., 64, 647–650.[Web of Science][Medline]
Vilska, S., Tiitinen, A., Hyden-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.
Wang, X.J., Ledger, W., Payne, D. et al. (1994) The contribution of embryo cryopreservation to in-vitro fertilization/gamete intra-Fallopian transfer: 8 years' experience. Hum. Reprod., 9, 103–109.
Ziebe, S., Petersen, K., Lindenberg, S. et al. (1997) Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. Hum. Reprod., 12, 1545–1549.
Submitted on November 13, 2000; accepted on February 20, 2001.
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 A. Thurin, J. Hausken, T. Hillensjo, B. Jablonowska, A. Pinborg, A. Strandell, and C. Bergh Elective Single-Embryo Transfer versus Double-Embryo Transfer in in Vitro Fertilization N. Engl. J. Med., December 2, 2004; 351(23): 2392 - 2402. [Abstract] [Full Text] [PDF]
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A. Tiitinen, C. Hyden-Granskog, and M. Gissler What is the most relevant standard of success in assisted reproduction?: The value of cryopreservation on cumulative pregnancy rates per single oocyte retrieval should not be forgotten Hum. Reprod., November 1, 2004; 19(11): 2439 - 2441. [Abstract] [Full Text] [PDF]
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S. Bhattacharya and A. Templeton What is the most relevant standard of success in assisted reproduction?: Redefining success in the context of elective single embryo transfer: evidence, intuition and financial reality Hum. Reprod., September 1, 2004; 19(9): 1939 - 1942. [Abstract] [Full Text] [PDF]
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U.B. Wennerholm and C. Bergh What is the most relevant standard of success in assisted reproduction?: Singleton live births should also include preterm births Hum. Reprod., September 1, 2004; 19(9): 1943 - 1945. [Abstract] [Full Text] [PDF]
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H. Martikainen, M. Orava, J. Lakkakorpi, and L. Tuomivaara Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles Hum. Reprod., June 1, 2004; 19(6): 1364 - 1366. [Abstract] [Full Text] [PDF]
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S. Murray, A. Shetty, A. Rattray, V. Taylor, and S. Bhattacharya A randomized comparison of alternative methods of information provision on the acceptability of elective single embryo transfer Hum. Reprod., April 1, 2004; 19(4): 911 - 916. [Abstract] [Full Text] [PDF]
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J. Gerris, P. De Sutter, D. De Neubourg, E. Van Royen, J. Vander Elst, K. Mangelschots, M. Vercruyssen, P. Kok, M. Elseviers, L. Annemans, et al. A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles Hum. Reprod., April 1, 2004; 19(4): 917 - 923. [Abstract] [Full Text] [PDF]
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J. K. Min, S. A. Breheny, V. MacLachlan, and D. L. Healy What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction Hum. Reprod., January 1, 2004; 19(1): 3 - 7. [Abstract] [Full Text] [PDF]
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P. Devroey and A. Van Steirteghem A review of ten years experience of ICSI Hum. Reprod. Update, January 1, 2004; 10(1): 19 - 28. [Abstract] [Full Text] [PDF]
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V. Soderstrom-Anttila, S. Vilska, S. Makinen, T. Foudila, and A.-M. Suikkari Elective single embryo transfer yields good delivery rates in oocyte donation Hum. Reprod., September 1, 2003; 18(9): 1858 - 1863. [Abstract] [Full Text] [PDF]
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A. Salumets, T. Tuuri, S. Makinen, S. Vilska, L. Husu, R. Tainio, and A.-M. Suikkari Effect of developmental stage of embryo at freezing on pregnancy outcome of frozen-thawed embryo transfer Hum. Reprod., September 1, 2003; 18(9): 1890 - 1895. [Abstract] [Full Text] [PDF]
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A. Vahratian, L. A. Schieve, M. A. Reynolds, and G. Jeng Live-birth rates and multiple-birth risk of assisted reproductive technology pregnancies conceived using thawed embryos, USA 1999-2000 Hum. Reprod., July 1, 2003; 18(7): 1442 - 1448. [Abstract] [Full Text] [PDF]
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A. Tiitinen, L. Unkila-Kallio, M. Halttunen, and C. Hyden-Granskog Impact of elective single embryo transfer on the twin pregnancy rate Hum. Reprod., July 1, 2003; 18(7): 1449 - 1453. [Abstract] [Full Text] [PDF]
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T. El-Toukhy, Y. Khalaf, K. Al-Darazi, F. O'Mahony, E. Wharf, A. Taylor, and P. Braude Cryo-thawed embryos obtained from conception cycles have double the implantation and pregnancy potential of those from unsuccessful cycles Hum. Reprod., June 1, 2003; 18(6): 1313 - 1318. [Abstract] [Full Text] [PDF]
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A. Salumets, C. Hyden-Granskog, S. Makinen, A.-M. Suikkari, A. Tiitinen, and T. Tuuri Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures Hum. Reprod., April 1, 2003; 18(4): 821 - 825. [Abstract] [Full Text] [PDF]
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R. D. Lambert Safety issues in assisted reproduction technology: The children of assisted reproduction confront the responsible conduct of assisted reproductive technologies Hum. Reprod., December 1, 2002; 17(12): 3011 - 3015. [Abstract] [Full Text] [PDF]
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D.D. Neubourg, K. Mangelschots, E. Van Royen, M. Vercruyssen, G. Ryckaert, M. Valkenburg, J. Barudy-Vasquez, and J. Gerris Impact of patients' choice for single embryo transfer of a top quality embryo versus double embryo transfer in the first IVF/ICSI cycle Hum. Reprod., October 1, 2002; 17(10): 2621 - 2625. [Abstract] [Full Text] [PDF]
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J. Gerris, D. De Neubourg, K. Mangelschots, E. Van Royen, M. Vercruyssen, J. Barudy-Vasquez, M. Valkenburg, and G. Ryckaert Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme Hum. Reprod., October 1, 2002; 17(10): 2626 - 2631. [Abstract] [Full Text] [PDF]
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R. Isaksson, M. Gissler, and A. Tiitinen Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study Hum. Reprod., July 1, 2002; 17(7): 1755 - 1761. [Abstract] [Full Text] [PDF]
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P. Poikkeus, V. Hiilesmaa, and A. Tiitinen Serum HCG 12 days after embryo transfer in predicting pregnancy outcome Hum. Reprod., July 1, 2002; 17(7): 1901 - 1905. [Abstract] [Full Text] [PDF]
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L. Engmann, N. Maconochie, S. L. Tan, and J. Bekir Trends in the incidence of births and multiple births and the factors that determine the probability of multiple birth after IVF treatment Hum. Reprod., December 1, 2001; 16(12): 2598 - 2605. [Abstract] [Full Text] [PDF]
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