Human Reproduction, Vol. 17, No. 10, 2626-2631,
October 2002
© 2002 European Society of Human Reproduction and Embryology
Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme
Center for Reproductive Medicine, Middelheim Hospital, Lindendreef 1, 2020 Antwerp, Belgium
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Abstract |
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BACKGROUND: Data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. METHODS AND RESULTS: A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. CONCLUSIONS: Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.
Key words: elective single embryo transfer/twin pregnancy prevention
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Introduction |
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It has been recognized that multiple pregnancy and its obstetric, neonatal, developmental and financial consequences represent the main iatrogenic complication of IVF and ICSI (Dhont et al., 1999
; Keith and Oleszcuk, 1999; Bergh et al., 2000; Elster, 2000) and that urgent action should be taken in order to limit this unwanted state of affairs (ESHRE Capri Workshop, 2000). Several authors have shown that reducing the number of embryos transferred from a standard number of three to two, in patients who have several early cleaving stage embryos to choose from, is not followed by a decrease of the overall ongoing pregnancy rate. It eliminates most triplets but does not diminish the rate of twin pregnancies (Nijs et al., 1993; Staessen et al., 1993; Fujii et al., 1998; Hu et al., 1998; Templeton and Morris, 1998; Milki et al., 1999; Dean et al., 2000). The extremely high incidence of twin pregnancies, varying between 25 and 40%, constitutes the foremost challenge, although in some countries the incidence of triplets remains alarmingly high (Martin et al., 1999).
Some authors have tried to identify factors that could predict the chance of birth and of multiple birth on the basis of some key characteristics belonging to the background of the patient, to the cycle and to the embryos available for transfer. In most cases the underlying assumption has been to assess in which patients the transfer of two embryos would lead to a twin and in which patients to a singleton pregnancy (Templeton and Morris, 1996; Bassil et al., 1997; Commenges-Ducos et al., 1998; Croucher et al., 1998; Minaretzis et al., 1998; Schieve et al., 1999; Terriou et al., 2001; Tur et al., 2001). Few authors have done this type of multivariate analysis with the clear intention to identify patients suitable for single embryo transfer (Strandell et al., 2000).
Others have developed mathematical models to try to understand the interrelationship of the chance of pregnancy, multiple pregnancy or no conception as a function of the number and the (theoretical) implantation potential of embryos (Martin and Welch, 1998; Trimarchi, 2001; Hunault et al., 2002).
Both of these approaches are interesting since by explaining in retrospect why the observed results are what they are, they might, could and should be useful in actually applying elective single embryo transfer (eSET). They are in that sense preparatory steps to identify clinical and laboratory prerequisites prior to introducing eSET in an ongoing IVF/ICSI programme.
Still others have used just single embryo transfers in a clinical programme and have analysed the results. A retrospective analysis reported on 957 compulsory single embryo transfers (Giorgetti et al., 1995). The first report of a straightforward application of single embryo transfer mainly concerned a group of women with a medical contraindication for twin pregnancy (Vilska et al., 1999); in this study no particular efforts were made to identify the embryo that had the best chance of implantation prior to the introduction of single embryo transfer. Our own approach consisted of the preliminary identification and validation of strict top quality embryo characteristics prior to eSET (Van Royen et al., 1999), followed by a prospective randomized comparison between one versus two top quality embryos in twin-prone patients (Gerris et al., 1999). Other authors have reported their experience with single versus double embryo transfer, using standard but not strict embryo criteria (De Sutter et al., 2000; Martikainen et al., 2001) and have reported on the additional benefit of cryopreservation in the context of eSET (Tiitinen et al., 2000).
In this retrospective analysis, we report the effect of the gradual introduction of single embryo transfer and its impact on the overall ongoing pregnancy rate and the multiple pregnancy rate over a 4 year period.
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Materials and methods |
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Patients
We studied an uninterrupted series of 1559 IVF/ICSI cycles over a period of 4 years (1998–2001). Patients were treated for all accepted indications for IVF/ICSI, including microscopical epididymal sperm aspiration (MESA) (n = 75) and testicular sperm extraction (TESE) (n = 54) in cases of obstructive and non-obstructive azoospermia respectively. Mean age of the female partner was 32.4 ± 4.4 years. Treatment cycle rank varied between the first (n = 802) and the 13th (n = 1).
During this period, transfer of a single top quality embryo was gradually introduced. Before 1998, the standard transfer procedure consisted of the transfer of the two ‘best looking’ embryos, defined according to traditional criteria. At the end of this period, strict embryo criteria had been defined and reported in previous papers (Van Royen et al., 1999, 2001). The essential characteristics of a top quality embryo are: 4 or 5 blastomeres on day 2 and 
7 blastomeres on day 3; 
20% fragmentation and total absence of multinucleated blastomeres both on day 2 and day 3.
From 1998 onwards, transfer of a single day 3 top quality embryo was applied in two subsequent clinical trials. The first trial was a single-centre prospective randomized comparison in women <34 years of age in their first IVF/ICSI cycle and who agreed with randomization between the transfer of one top quality embryo versus two top quality embryos and has been reported previously (Gerris et al., 1999). The second trial, immediately following the first, is a multi-centre health–economic impact study in women <38 years of age in their first IVF/ICSI cycle ever or after a previous successful IVF/ICSI pregnancy, who could choose between one or two embryos. The primary endpoint of this study is a comparison between the total costs (of the IVF/ICSI treatment, the pregnancy, the delivery and the neonatal care up to 3 months after delivery) of ongoing pregnancies after the transfer of one embryo versus the transfer of two embryos. Although the final health-economic results of this study are not yet available, the intermediate clinical results for our centre are fully known, since the intake ended on December 31, 2001. In this study, patients who chose to receive only one embryo did so on the condition that it was a top quality embryo, as strictly defined. If not, they received the two best embryos, unless of course, there was only one (non-top quality) embryo to transfer.
In addition, transfer of a single day 3 top quality embryo was also performed in women who did not fulfil the inclusion criteria of either study but nevertheless wanted only one embryo, either a top quality embryo or not, to be replaced; some of them were >38 years of age.
In summary, three categories of patients received a single embryo: those participating in the first study, those participating in the second study and those spontaneously requesting the transfer of only one embryo. All these patients are considered retrospectively together on the basis of what they have actually received at the time of transfer. Of a total of 1559 oocyte retrievals, 1464 transfers resulted; 385 of a single embryo (26.3%): 299 (20.4%) of a single top quality embryo and 86 (5.9%) of a single non-top quality embryo.
Ovarian stimulation protocol
Patients were treated with the long GnRH agonist desensitization protocol, starting in the mid-luteal phase with 6x100 µg of buserelin (Suprefact; Hoechst, Germany) intranasally for a period of 3 weeks. Gonadotrophin stimulation (Metrodin HP or Gonal-F; Serono, Geneva, Switzerland) was initiated if basal vaginal sonography showed a thin endometrium and no ovarian cysts. Stimulation was initiated with 150 IU of Metrodin HP or Gonal-F, i.m. or s.c., except in patients with known poor response, where 225 IU was used. The criterion for hCG administration was the presence of at least three mature follicles at sonography with a diameter of 18x18 mm. hCG (Profasi, Serono, Geneva, Switzerland) 10 000 IU i.m. was given exactly 37 h before oocyte retrieval.
IVF/ICSI procedure
Motile sperm were isolated from fresh semen in a two-step protocol. First the sperm were pretreated by gradient centrifugation consisting of three discontinuous layers of Percoll (55–70–90%). The 90% fraction was washed with Universal IVF medium (Medi-Cult, Copenhagen, Denmark), and the resulting sperm pellet was resuspended and subsequently pipetted into the ring of a migration–sedimentation tube. After an incubation period of 1–4 h at 37°C, a suspension containing 
90% motile sperm was used for standard IVF insemination or ICSI. The MESA and TESE procedures are described elsewhere (Silber, 1997; Tournaye, 1997). In all cases of MESA/TESE, frozen–thawed aspirates or biopsies were used.
Oocyte retrieval was performed vaginally under ultrasound guidance. Cumulus–oocyte complexes were isolated from the follicular aspirates and washed in Medi-Cult medium. Each was placed individually in a 25 µl microdrop of Ménézo B2 medium (C.C.D., Paris, France) under mineral oil (Sigma, St Louis, MO, USA) and incubated at 37°C in a humidified atmosphere of 5% CO2 in air. For standard IVF, 3–5 h after retrieval every oocyte was inseminated with 20 000 motile sperm and incubated overnight. The ICSI standard procedure was performed.
Embryo quality assessment
Approximately 16–19 h after insemination/injection, normal fertilization was checked. All oocytes containing two clearly visible pronuclei were placed together in one fresh 10 µl microdrop of Ménézo B2 medium (maximum 10 oocytes/drop) and cultured for another 24 h. The next day (40–43 h after insemination/injection) the embryos were separated and each transferred to a 10 µl drop of Medi-Cult M3 Medium for further culture of 24 h. Every embryo was scored for the total number of cells, the presence of anuclear fragments as well as multinucleated blastomeres. From the moment day 2 embryo criteria were recorded, embryos were cultured separately.
On day 3 (64–67 h after insemination/injection), embryo quality was evaluated again. Selection for embryo replacement was made according to the top quality embryo selection criteria, defined above. Supernumerary embryos were frozen.
Embryo transfer technique
All transfers were performed on an outpatient basis using a Wallace embryo transfer catheter (Sims Portex Ltd, Hythe, Kent, UK), consisting of an inner catheter and an outer catheter showing a calibration in centimetres. The outer catheter was introduced first using a guidewire, which allows the outer catheter to be bent if necessary, in order to facilitate its passage through the cervical channel. Care was taken to limit the introduction of the outer catheter to a maximum of 4 cm into the cervix, in order to minimize potential microtrauma of the uterine cavity. The inner catheter was then passed through the outer catheter, passing the external ostium by a distance of 6 cm. The embryo(s) were then gently deposited into the cavity in a volume <30 µl of Medi-Cult M3 medium. After removal, the catheter was checked under the microscope to ascertain that the embryos had been placed in the uterine cavity. Strict care was taken that all clinicians followed the instructions for embryo transfer in a similar way, as it has been shown that pregnancy rates are highly dependent on the embryo transfer technique (Karande et al., 1999; Hearns-Stokes et al., 2000).
Luteal phase
In all cycles, luteal phase was supported with 3x200 mg of micronized natural progesterone (Utrogestan; Laboratoires Piette International, Belgium), administered vaginally. Blood samples were taken on days 8 and 12 after embryo transfer, for analysis of serum estradiol, progesterone and hCG concentrations.
A cycle was considered a conception cycle when at least two subsequently rising hCG values of >5 mIU/ml were obtained on the 12th day after transfer and any day thereafter, suggesting at least one hatched blastocyst and the beginning of implantation. A clinical miscarriage was defined as a conception cycle leading to at least one amniotic sac at ultrasonography, or a clinical extrauterine pregnancy necessitating surgical intervention. An ongoing pregnancy was defined as a conception cycle with at least one fetal sac with a positive heartbeat reaching beyond 12 weeks of amenorrhoea. For the calculation of the implantation rate, biochemical conceptions were not included, while a clinical miscarriage or a clinical extrauterine pregnancy count for one implantation.
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Results |
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Table I
shows the proportion of transfers of a single, two, three and more than three embryos in a total series of 1559 IVF/ICSI cycles over a 4 year period (1998–2001).
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Table II
illustrates the evolution of the proportion of single embryo transfers, the mean number of embryos transferred, the ongoing pregnancy rate, the ongoing implantation rate, the twin pregnancy rate and the total multiple pregnancy rate over these years during which single embryo transfer was gradually applied. The total multiple pregnancy rate fell from 33.6% in 1998 to 18.6% in 2001. The incidence of twins over the same period fell from 29.5% in 1998 to 16.3% in 2001. The progressive effect of an increasing proportion of single embryo transfers over the years is reflected in a steady decrease of the average number of embryos transferred in the programme and a parallel decrease in the multiple pregnancy rate (Figure 1). The evolution of the ongoing pregnancy rate, the ongoing implantation rate and the multiple pregnancy rate before (1995–1998) and after (1998–2001) the introduction of single embryo transfer is shown in Figure 2. Although a small decrease in ongoing pregnancies could be observed in 1999, probably due to a provider effect, the overall 
2-test showed no significant difference between the different years, neither per oocyte retrieval nor per embryo transfer.
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Table III
shows the clinical outcome variables of 385 (26.3%) single embryo transfers compared with 1079 transfers of two (n = 853) or more than two (n = 226) embryos. Table IV shows the outcome of the 853 double embryo transfers separately, broken down into three groups: two, one and no top quality embryos. The ongoing implantation rate was 35.1% for (top quality) embryos transferred in the group who received a single top quality embryo and 36.5% in the group that received two top quality embryos. For the group with one top and one non-top quality embryo, the ongoing implantation rate was still high (26.8%), whereas in the two non-top quality embryo group, it was only 11.8%. Dizygotic triplets (n = 5) occurred only in patients who received two top quality embryos, four in women <38 years of age and one in a woman of 39 years. The seven other triplets occurred in patients who received three embryos because they were in a high-rank IVF/ICSI trial.
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Discussion |
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Prevention has been focused until now mainly on high-order multiple pregnancies, leaving twins largely unaffected. Reducing the number of embryos from a standard of three to two in the whole population results in a sharp decrease in the incidence of triplets without affecting the overall (ongoing) pregnancy rate and the twin pregnancy rate (Staessen et al., 1993
; Templeton and Morris, 1998). It has been suggested and theoretically calculated (Coetsier and Dhont, 1998; Strandell et al., 2000) that a substantial proportion of twins could easily be avoided without much of a drop in the overall pregnancy rate by the application of single embryo transfer in good-prognosis patients. The data reported here reveal stable, high ongoing implantation and pregnancy rates per oocyte retrieval, although the number of transferred embryos decreased, and a steadily declining multiple pregnancy rate was observed. A decrease in the number of embryos transferred from two to one is feasible in at least one-third of the population of patients, reducing the twin incidence to approximately half of its original incidence, and maintaining a high overall ongoing pregnancy rate. The group receiving one top quality embryo had the same overall ongoing pregnancy rate as the group receiving more than one embryo, supporting our criteria for both embryo and patient selection.
We can calculate the effect of single embryo transfer on this programme from the values in Table IV: in the group of 853 double transfers, all patients who produced at least one top quality embryo (n = 322 + 209 = 531) would have received only this embryo. Assuming an ongoing implantation rate of 35.1%, 531x35.1% = 186 ongoing pregnancies would have been obtained, instead of the actually obtained number of 160 + 84 = 244; i.e. 58 fewer pregnancies, but all would have been singletons. There would have been only eleven twins (those occurring in the two non-top quality double embryo transfer group) in a total of 186 + 65 = 251 ongoing pregnancies, i.e. 4.4% twins, instead of what we obtained in reality: 109 twins (including five dizygotic triplets) in 309 ongoing pregnancies (35.3%). We would have had 109 – 11 = 98 fewer twins (–90%) for a mere 309 – 251 = 58, i.e. 58/309 = 18.8% fewer pregnancies, not taking into account a potential effect of cryopreservation.
The group of patients suitable for single embryo transfer may be smaller in other programmes with patients who are older on average. It could also be larger if higher-rank treatment cycles with top quality embryos are also included. The most suitable group of patients are young women in their first IVF/ICSI cycle. Combining validated strict growth criteria of early cleaving embryos with a clinical profile of the twin prone patient, as described by some authors (Strandell et al., 2000) results in an acceptably high and stable ongoing pregnancy rate of 33.5% per started cycle (Table II
). Single top quality embryo transfer can be considered the standard of care in these patients. The role of cryopreservation is likely to become increasingly important as eSET finds its way into the clinic, as demonstrated by others (Strandell et al., 2000; Tiitinen et al., 2000; Martikainen et al., 2001).
In order to avoid a decrease of the overall ongoing pregnancy rate in the programme, we introduced single top quality embryo transfer in a gradual way and in distinct clinical phases. At the present time, the introduction of eSET could perhaps be more prompt.
Two aspects are important. First, each centre should decide on how to select the best embryo for implantation. Some centres may prefer extended culture to blastocysts (Gardner et al., 1998, 2000); others may (have to) focus on day 1 embryos (Scott and Smith, 1998; Ludwig et al., 2000); but most will stick to day 2 and/or day 3 embryos. Local customs or regulations, legal constraints (e.g. Germany) as well as insurance policies, may play a disproportionately important role in this decision process. The present authors prefer to transfer day 3 embryos because a prospectively randomized trial comparing the transfer of two day 3 embryos with two blastocysts did not show blastocyst culture to be superior in an unselected population (Coskun et al., 2000). In addition we obtain a conception rate of 207/322 = 64.3% and an ongoing pregnancy rate of 160/322 = 49.7% after transfer of two top quality day 3 embryos (Table II), which is similar to published results for the transfer of two blastocysts. The present authors think it is important to adhere to strict embryo criteria, especially with respect to the presence of multinucleation, because these embryos are often aneuploid. We also think that many programmes do not use day 3 criteria optimally, resulting in suboptimal implantation rates. Second, the centre should undertake judicious patient selection. The application of eSET will, and probably should, always remain a matter of sound clinical judgement and common sense rather than of compelling mathematics.
The main risk to be avoided is an undiscriminating legislation that would make single embryo transfer compulsory, irrespective of strict embryo quality considerations or irrespective of the clinical profile of the patient.
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Notes |
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1 To whom correspondence should be addressed. E-mail: jan.gerris{at}ocmw.antwerpen.be
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References |
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Submitted on February 25, 2002; resubmitted on May 14, 2002; accepted on June 20, 2002.
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  S. Bechoua, K. Astruc, S. Thouvenot, S. Girod, A. Chiron, C. Jimenez, and P. Sagot How to demonstrate that eSET does not compromise the likelihood of having a baby? Hum. Reprod., December 1, 2009; 24(12): 3073 - 3081. [Abstract] [Full Text] [PDF]
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T. El-Toukhy, A. Kamal, E. Wharf, J. Grace, V. Bolton, Y. Khalaf, and P. Braude Reduction of the multiple pregnancy rate in a preimplantation genetic diagnosis programme after introduction of single blastocyst transfer and cryopreservation of blastocysts biopsied on Day 3 Hum. Reprod., October 1, 2009; 24(10): 2642 - 2648. [Abstract] [Full Text] [PDF]
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A.M. van Peperstraten, R.P.M.G. Hermens, W.L.D.M. Nelen, P.F.M. Stalmeier, G.J. Scheffer, R.P.T.M. Grol, and J.A.M. Kremer Perceived barriers to elective single embryo transfer among IVF professionals: a national survey Hum. Reprod., December 1, 2008; 23(12): 2718 - 2723. [Abstract] [Full Text] [PDF]
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 A. Bettegowda, O. V. Patel, K.-B. Lee, K.-E. Park, M. Salem, J. Yao, J. J. Ireland, and G. W. Smith Identification of Novel Bovine Cumulus Cell Molecular Markers Predictive of Oocyte Competence: Functional and Diagnostic Implications Biol Reprod, August 1, 2008; 79(2): 301 - 309. [Abstract] [Full Text] [PDF]
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 I. Kosmas, J. Van der Elst, P. Devroey, and H. Tournaye Elective single embryo transfer Obstet Gynaecol (Lond), July 1, 2008; 10(3): 163 - 169. [Abstract] [Full Text] [PDF]
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G. M. Chambers, M. G. Chapman, N. Grayson, M. Shanahan, and E. A. Sullivan Babies born after ART treatment cost more than non-ART babies: a cost analysis of inpatient birth-admission costs of singleton and multiple gestation pregnancies Hum. Reprod., December 1, 2007; 22(12): 3108 - 3115. [Abstract] [Full Text] [PDF]
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P.O. Karlstrom and C. Bergh Reducing the number of embryos transferred in Sweden-impact on delivery and multiple birth rates Hum. Reprod., August 1, 2007; 22(8): 2202 - 2207. [Abstract] [Full Text] [PDF]
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 R. J. Stillman A 47-Year-Old Woman With Fertility Problems Who Desires a Multiple Pregnancy JAMA, February 28, 2007; 297(8): 858 - 867. [Abstract] [Full Text] [PDF]
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 A.A.A. Fiddelers, J.L. Severens, C.D. Dirksen, J.C.M. Dumoulin, J.A. Land, and J.L.H. Evers Economic evaluations of single- versus double-embryo transfer in IVF Hum. Reprod. Update, January 1, 2007; 13(1): 5 - 13. [Abstract] [Full Text] [PDF]
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A. P.A. van Montfoort, J. L.H. Evers, and J. C.M. Dumoulin Reply: In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared to double embryo transfer. Hum. Reprod., August 1, 2006; 21(8): 2195 - 2196. [Full Text] [PDF]
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N. Gleicher and D. Barad The relative myth of elective single embryo transfer Hum. Reprod., June 1, 2006; 21(6): 1337 - 1344. [Abstract] [Full Text] [PDF]
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D. De Neubourg and J. Gerris What about the remaining twins since single-embryo transfer? How far can (should) we go? Hum. Reprod., April 1, 2006; 21(4): 843 - 846. [Abstract] [Full Text] [PDF]
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A. P.A. van Montfoort, A. A.A. Fiddelers, J.M. Janssen, J. G. Derhaag, C. D. Dirksen, G. A.J. Dunselman, J. A. Land, J. P.M. Geraedts, J. L.H. Evers, and J. C.M. Dumoulin In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial Hum. Reprod., February 1, 2006; 21(2): 338 - 343. [Abstract] [Full Text] [PDF]
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R. Matorras, F. Matorras, R. Mendoza, M. Rodriguez, J. Remohi, F. J. Rodriguez-Escudero, and C. Simon The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates Hum. Reprod., October 1, 2005; 20(10): 2923 - 2931. [Abstract] [Full Text] [PDF]
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M. Porter, and S. Bhattacharya Investigation of staff and patients' opinions of a proposed trial of elective single embryo transfer Hum. Reprod., September 1, 2005; 20(9): 2523 - 2530. [Abstract] [Full Text] [PDF]
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M.J. Pelinck, N.E.A. Vogel, A. Hoek, E.G.J.M. Arts, A.H.M. Simons, and M.J. Heineman Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: a pilot study Hum. Reprod., March 1, 2005; 20(3): 642 - 648. [Abstract] [Full Text] [PDF]
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H.G.M. Lukassen, D. D.Braat, A. M.M. Wetzels, G. A. Zielhuis, E. M.M. Adang, E. Scheenjes, and J. A.M. Kremer Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial Hum. Reprod., March 1, 2005; 20(3): 702 - 708. [Abstract] [Full Text] [PDF]
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A. P.A. van Montfoort, J. C.M. Dumoulin, J. A. Land, E. Coonen, J. G. Derhaag, and J. L.H. Evers Elective single embryo transfer (eSET) policy in the first three IVF/ICSI treatment cycles Hum. Reprod., February 1, 2005; 20(2): 433 - 436. [Abstract] [Full Text] [PDF]
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C. Bergh Single embryo transfer: a mini-review Hum. Reprod., February 1, 2005; 20(2): 323 - 327. [Abstract] [Full Text] [PDF]
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P. Saldeen and P. Sundstrom Would legislation imposing single embryo transfer be a feasible way to reduce the rate of multiple pregnancies after IVF treatment? Hum. Reprod., January 1, 2005; 20(1): 4 - 8. [Abstract] [Full Text] [PDF]
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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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M. Germond, F. Urner, A. Chanson, M.-P. Primi, D. Wirthner, and A. Senn What is the most relevant standard of success in assisted reproduction?: The cumulated singleton/twin delivery rates per oocyte pick-up: the CUSIDERA and CUTWIDERA Hum. Reprod., November 1, 2004; 19(11): 2442 - 2444. [Abstract] [Full Text] [PDF]
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A. P.A. Van Montfoort, J. C.M. Dumoulin, A. D.M. Kester, and J. L.H. Evers Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers Hum. Reprod., September 1, 2004; 19(9): 2103 - 2108. [Abstract] [Full Text] [PDF]
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J. A. Land and J. L.H. Evers What is the most relevant standard of success in assisted reproduction?: Defining outcome in ART: a Gordian knot of safety, efficacy and quality Hum. Reprod., May 1, 2004; 19(5): 1046 - 1048. [Abstract] [Full Text] [PDF]
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W. Buckett and S. L. Tan What is the most relevant standard of success in assisted reproduction?: The importance of informed choice Hum. Reprod., May 1, 2004; 19(5): 1043 - 1045. [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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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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