Hum. Reprod. Advance Access originally published online on January 20, 2006
Human Reproduction 2006 21(4):1041-1046; doi:10.1093/humrep/dei424
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The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies
1 Centre for Reproductive Medicine, Middelheim Hospital, Lindendreef, Antwerp and 2 Faculty of Medicine, University of Antwerp, Universiteitsplein, Wilrijk, Belgium
3 To whom correspondence should be addressed at: Centre for Reproductive Medicine, Middelheim Hospital, Lindendreef 1, 2020 Antwerp, Belgium. E-mail: diane.de.neubourg{at}skynet.be
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Abstract |
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BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI. Because the population of patients receiving single-embryo transfer (SET) resulting in singleton pregnancies is different from the one that would have become pregnant (with a singleton) before SET was introduced, we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons. METHODS: The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was prospectively collected and analyzed. RESULTS: Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59 535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology. The mean birthweight of the singletons after SET was 3322 g (±538 SD) versus 3330 g (±531 SD) for the spontaneously conceived singletons (P = 0.82). The mean gestational age was 38.7 weeks (±1.9 SD) for SET and 38.9 weeks (±1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous singletons (P = 0.03). However, mean birthweight of very preterm, preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group. Stillbirth was 0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in whom SET is applied, do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons.
Key words: obstetrical and neonatal outcome/single-embryo transfer/singletons after ART
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Introduction |
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To reduce the epidemic of multiple and twin pregnancies, initially double-embryo transfer (DET) (Templeton and Morris, 1998
) and later on single-embryo transfer (SET) was introduced (Gerris et al., 1999; Vilska et al., 1999; Thurin et al., 2004).
We progressively introduced SET into daily practice after the population of women at risk for twin pregnancy was identified (Gerris et al., 2002). During 1998–2002, the percentage of SETs increased from 13 to 39% (De Neubourg and Gerris, 2003). This resulted in a decrease of twin (and multiple) pregnancy rate from 33.6 to 11.7%. We performed a real-life prospective health economic analysis over a 2-year period (2000–2001) and showed that if treatment and outcome variables until 3 months after delivery were taken into account, SET of a top-quality embryo was equally effective but substantially cheaper than DET in women <38 years in their first IVF/ICSI cycle (Gerris et al., 2004).
The subsequent logical step is to know how this evolution would affect the clinical outcome of children born after IVF/ICSI. There are still a lot of questions with regard to the obstetrical and neonatal outcome of children born after IVF/ICSI. Higher morbidity and mortality for IVF/ICSI babies can at least in part be attributed to the high incidence of multiples in most programs (Bergh et al., 1999). In most studies, the comparison between the obstetrical and neonatal outcome of spontaneous and IVF/ICSI twins yielded a similar outcome. A systematic review of controlled studies by Helmerhorst et al. (2004) came to the same conclusion. However, when zygosity is taken into account and corrected for, obstetric outcome for induced dizygotic twin pregnancy is less optimal than in natural dizygotic twin pregnancy (Lambalk and van Hooff, 2001). In contrast to the twin pregnancies, the same review by Helmerhorst et al. (2004) as well as by other recent publications indicates that singletons after IVF/ICSI have a worse obstetrical and neonatal outcome when compared to spontaneous singletons or to the general population (Schieve et al., 2002, 2004; Ochsenkuhn et al., 2003; Jackson et al., 2004). They report an increased incidence of very low birthweight, low birthweight, preterm delivery, small for gestational age and perinatal mortality. This raises the question whether the IVF/ICSI treatment per se is detrimental to obstetrical and neonatal outcome. The suggestion is often made that the infertile population in itself carries an increased risk of adverse outcome of the IVF/ICSI pregnancy (Pandian et al., 2001). Draper et al. (1999) described that having a history of infertility irrespective of treatment gives the pregnancy an increased risk for perinatal death.
A lot of questions are still pending concerning a potential relationship between morphological and other embryo characteristics and obstetrical and neonatal outcome. As we have previously shown, embryo quality is an important factor in the prediction of the chance of conception itself (Van Royen et al., 1999, 2001). We also showed that embryo quality on the day of transfer did not predict first trimester pregnancy loss (De Neubourg et al., 2004). Now the question rises whether there is a relationship between embryo implantation competence and the subsequent evolution and outcome of the pregnancy. Does the number of embryos transferred play a role? Data by Dickey et al. (2004) illustrate that singleton births following IVF that began as a twin or a higher-order pregnancy are born prematurely. Schieve et al. (2002) demonstrate that singletons were more likely to have low birthweight if there had been more than one fetal heart on early ultrasonography.
As a first step, we wanted to investigate what happens to the outcome variables of singleton pregnancies if the twin-prone patient receives SET. We therefore analyzed the outcome of IVF/ICSI singletons that occurred after SET in a 6-year period (1998–2003) during which we progressively introduced SET and compared these to singletons conceived spontaneously in the same period.
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Materials and methods |
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Obstetrical and early neonatal outcome of all SET pregnancies originating from fresh IVF/ICSI procedures between 1 January 1998 and 31 December 2003 performed in our hospital was analyzed.
IVF/ICSI treatment
Patients were treated with the long GnRH agonist desensitization protocol, starting in the midluteal phase with 6 x 100 µg of buserelin (Suprefact, Aventis, Brussels, Belgium) intranasal for a period of 3 weeks. Thereafter, gonadotropin stimulation (Menopur, Ferring, Copenhagen, Denmark; Puregon, Organon, Oss, the Netherlands and Gonal-F, Serono, Geneva, Switzerland) was initiated. When at least three mature follicles with a diameter of 18 mm were present, 10 000 IU of HCG (human chorionic gonadotrophin) (Pregnyl, Organon) was given. The oocyte retrieval was performed exactly 37 h later under vaginal ultrasound guidance.
Two pronuclear oocytes were cultured in Ménézo B2 medium and were separated and transferred to Medi-Cult M3 medium the next day. Every embryo was scored for the total number of cells, the presence of anuclear fragments as well as multinucleated blastomeres on day 2 and day 3 (Van Royen et al., 1999). A final selection of embryos for transfer was based on implantated fractions (Van Royen et al., 2001). Supernumerary embryos were frozen. No frozen–thawed cycles are included in the analysis.
All transfers were performed on an outpatient basis using a Wallace embryo transfer catheter (Sims Portex, Hythe, Kent, UK) consisting of an inner and outer catheter.
In all cycles, luteal phase was supported with 3 x 200 mg of micronized natural progesterone (Utrogestan, Besins, Brussels, Belgium) administered vaginally.
Conception was detected by measuring HCG in serum on day 12 after day 3 embryo transfer (De Neubourg et al., 2004). When positive, HCG follow-up was advised depending on the evolution of the HCG level and/or complaints of the patient. The first ultrasound was performed at 6–8 weeks of pregnancy where after the patient was referred to her gynaecologist.
Data collection
Obstetrical and neonatal data were prospectively collected as requested by and according to methodology of the national registry of IVF/ICSI pregnancies [Belgian registry for Artificial Procreation (BELRAP)]. This questionnaire was sent after birth or termination of pregnancy to both clinicians and to patients; the clinician was either a gynaecologist from our hospital or from a referring hospital where the delivery had taken place. When there was no reply, clinicians and patients were contacted directly by the first author. Similarly, if questionnaires were not complete, clinicians or patients were contacted by the first author.
These questionnaires contained questions about the evolution of the pregnancy, the delivery and their child(ren) comprising data on the incidence of preterm contractions and/or preterm labour, the incidence of blood loss (and if so during which trimester), the occurrence of hypertension, intrauterine growth restriction, diabetes, stillbirth or other medical disorders. The data of the delivery included duration of pregnancy and mode of delivery. Data on the child(ren) were birthweight, sex, neonatal complications, admission to a neonatal intensive care unit (NICU), complications during the first 3 months and neonatal death. These questionnaires were sent to all patients with conception cycles (375) and their treating doctors. Five questionnaires belonging to patients with a pregnancy reaching beyond 12 weeks (1.3%) were missing leading to a highly representative and homogeneous cohort.
These data were compared to data from the Studiecentrum voor Perinatale Epidemiologie [Study Centre for Perinatal Epidemiology (SPE)] which is the Flemish Registry of obstetrical and neonatal data from all deliveries in Flanders. This registry includes deliveries in our own centre as well as in the hospitals referring for IVF/ICSI. The following data were taken into account: method of conception (spontaneous, hormonal, IVF/ICSI, insemination), age of the mother, the occurrence of hypertension, diabetes, stillbirth, duration of pregnancy and mode of delivery. Data collected on the child(ren) were birthweight, sex, neonatal complications and admission to a NICU. In the SPE registry, obstetrical and early neonatal data are recorded by the gynaecologist and/or midwife at the time of delivery when the patient is admitted; the paediatrician and/or paediatric nurse collects all neonatal data if the infant is admitted in NICU. In Belgium, 99% of all deliveries occur in the hospital.
Calculation of BESST score
The BESST (birth emphasizing a successful singleton at term) score was calculated as the number of singletons 
37 weeks per started IVF/ICSI cycle (Min et al., 2004).
Statistical analysis
SET results were compared to the general population results. For proportions, the one-sample Chi-square test was used with the population distribution as reference distribution, and 95% confidence intervals (CI) are included. For means, a one-sample t-test was used with the population mean as the test value, and 95% confidence intervals are added. Statistical analysis was performed using SPSS statistical software (10.0). A P-value <0.05 was considered statistically significant.
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Results |
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A total of 2435 oocyte retrievals were recorded during this 6-year period. In 808 cycles, SET was performed (33.2%); the percentage of SET increased from 12.4 in 1998 to 53.8% in 2003. The proportion of singleton pregnancies increased from 66% of all ongoing pregnancies, in 1998, to 87%, in 2003. In 637 (78.3%) of the cycles, transfer of a single top-quality embryo was performed.
Of 808 SET cycles, 375 (46.4%) were conception cycles. There were 57 biochemical pregnancies, 41 clinical miscarriages between 7 and 12 weeks, 5 ectopic pregnancies and 12 miscarriages between 12 and 25 weeks. Of these, two pregnancies ended after preterm premature rupture of membranes at 21 weeks gestation (twice in the same patient who was later diagnosed with Factor V Leiden deficiency) and one pregnancy ended after preterm premature rupture of membranes at 24 weeks in a patient who was later diagnosed with lupus erythematosus. Three pregnancies were terminated because of congenital anomalies and three because of aneuploidy. The others were late miscarriages. There was one intrauterine death.
There were 259 live deliveries (32%) after SET.
The indications for IVF/ICSI leading to these births were as follows: male factor infertility in 59%, female infertility in 22.5%, mixed female and male pathology in 8.5% and idiopathic infertility in 10% of cases. In 44% of cases, IVF was performed and ICSI in 56% of cases.
There were three monozygotic twin pregnancies in this group (1.15%). The mean gestational age of these three pregnancies was 35.7 weeks (±0.9 SD). The mean birthweight of the twin babies was 2145 g (±330 SD). One pregnancy was complicated by twin-to-twin transfusion syndrome.
Of 256 singleton pregnancies after SET, data on 5 (1.9%) births are missing; therefore, 251 singleton pregnancies and births will be further analyzed and compared with 61 466 pregnancies from the SPE of which 59 535 occurred spontaneously. In 242/251 (96.4%) cases, elective SET or SET of a top-quality embryo was performed.
The maternal age of the mothers of SET singletons was 30.8 years (±3.6 SD) of age and was 29.3 years (±4.8 SD) of age for mothers of spontaneous conceived singletons (P < 0.01).
The mean birthweight of the singletons after SET was 3322 g (±538 SD) and 3330 g (±531 SD) for spontaneous conceived singletons (P = 0.82) (Figure 1). The mean birthweight difference was 8 g (95% CI, –58.1 to 73.5). The mean gestational age was 38.7 weeks (±1.9 SD) for SET singletons and 38.9 weeks (±1.8 SD) for spontaneous conceived singletons (P = 0.06) (Figure 2). The mean difference in gestational age was 0.2 weeks (95% CI, –0.019 to 0.419).
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The incidence of very low birthweight, low birthweight, very preterm birth and preterm birth is represented in Table I. Although there appears to be a higher incidence of preterm births at the expense of term births in the SET singletons (P = 0.03), when mean birthweight is calculated for the very preterm, preterm and term babies, the mean birthweight for SET singletons is similar to that in the spontaneous conceived singletons in every category of gestational age (Table II).
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Hypertensive disorders of pregnancy (including pre-eclampsia or HELLP) were diagnosed more frequently in SET singletons (7.6%) than in spontaneous singletons (4.6%) (P = 0.02).
Diabetes occurred in 1.2% of singleton pregnancies which is similar to the incidence of diabetes in spontaneous singletons (1.3%) (P = 0.88). The incidence of diabetes stratified by age is shown in Table III.
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In 51 (20%) SET pregnancies, a Caesarean section was performed which was not different from the Caesarean section rate in the control population (17%) (P = 0.13).
There were 134 boys (53.4%) and 117 girls (46.6%) born in the SET singetons which is again similar to 51.1% boys and 48.9% girls in the control group (P = 0.47).
There was one stillbirth in the SET singletons (0.4%) and this compared to the incidence of 0.4% in the control group (P = 0.99).
There was no neonatal mortality in the SET group, and the incidence is 0.2% in the control group.
For a number of items, no comparison could be made with data from the SPE because they are not recorded. These are listed in Table IV.
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Other perinatal complications which required admission to the NICU were hyperbilirubinemia, hypovolemic shock due to solutio placentae, observation for preterm birth (n = 5) and after intrauterine growth restriction (n = 2); all these babies remained for <7 days in the NICU. However, one very preterm born baby (28 weeks) was kept in for 4 months and developed bronchopulmonary dysplasia, retinopathy and cerebral haemorrhage.
We calculated the evolution of the BESST score (per started cycle) since the introduction of SET and found an increase of the BESST score of 19.1 in 1998 to 23.0% in 2003 (Table V).
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Discussion |
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A lot of questions regarding the safety of ART are still pending. There is concern about the in vitro technique in general, but it has been suggested that infertility per se may contain risks for the pregnancy resulting from these techniques. It is, however, difficult to separate these two aspects due to lack of adequate control groups. The adverse outcome of children after ART used to be attributed to the large incidence of multiple pregnancies (Bergh et al., 1999
). It was anticipated that with the increase of SET and singleton pregnancies, the outcome could only be more favourable. However, a number of reports showed an adverse outcome for IVF/ICSI singletons when compared to spontaneous singleton conceptions or to the general population (Helmerhorst et al., 2004; Jackson et al., 2004). This was confirmed in a study reporting on data collected by the Society for Assisted Reproductive Technology by Schieve et al. (2004). However, in the last study, it was mentioned that in >97% of cases, two or more embryos were transferred. We studied the outcome of singletons in a good prognosis patient population who now routinely receives SET and analyzed how this affects the outcome of these pregnancies. Mean gestational age as well as mean birthweight of SET singletons is the same as in spontaneously conceived children. While the incidence of preterm birth is statistically significantly higher in SET singletons versus spontaneous singletons, the birthweight of these ‘preterm born’ SET singletons is not lower than for the spontaneous singletons. When we analyzed the preterm births in SET singletons, 13 of 23 occurred at 36 weeks and this probably explains why the birthweight for this category is not different between the two groups. Although the difference of 4% in incidence of preterm birth was statistically significant, it has therefore probably no clinical significance because mean birthweights were similar.
In both the study group and the control group, confounding variables may be present in different proportions. The value of investigating their individual influence would be valid if an explanation had to be given for a negative outcome of the study population versus reference population. However, the confounders that could affect outcome in the SET singletons in a negative direction are present in this study population, for example, higher maternal age, higher incidence of hypertension and infertility. Despite the possible overrepresentation of negative confounders in the study group, no difference was encountered. The value of this observational study is to show what implementation of SET may offer to IVF/ICSI patients in terms of outcome of their child.
These data suggest that the investigation of the outcome of IVF/ICSI pregnancies should be interpreted carefully. It can be said that in the past the good prognosis patients had a high chance of twin and higher-order multiple pregnancies, whereas these patients since the introduction of SET will have singleton pregnancies. Therefore, our data strongly suggest that the population of patients who obtain a singleton pregnancy after IVF/ICSI and their babies has changed since the introduction of SET. These suggestions need to be confirmed in larger series, but we do recommend that the study of the outcome of IVF/ICSI babies be linked to the type of embryo transfer—hence the patient population—they originate from.
This was clearly shown in the debate that originated after the statement that ‘not pregnancy rate per cycle, but singleton live birth rate per cycle’ should be the golden standard to compare ART outcome (Evers, 2002). The BESST score was proposed by an Australian group (Healy, 2004; Min et al., 2004) to use similar end points when comparing data and to recognize the importance of the delivery of a single healthy baby as the most appropriate end point. However, this score is sensitive to changes in implantation rate which are not reflected in the BESST score: increasing overall success rates due to increased implantation rates yields higher multiple pregnancy rate, but the BESST score will remain unaffected. Therefore, this score does not appropriately reflect the implantation rate and the proportion of multiple pregnancies in a particular IVF/ICSI program. We found that an increase of the BESST score of 19.1 in 1998 to 23.0% in 2003 did not accurately reflect the decrease in twin pregnancies from 33.6 in 1998 to 7.3% in 2003. Analysis of the outcome of ART pregnancies by Davies et al. (2004) confirms that BESST pregnancies are lower in ART in general when compared to BESST pregnancies for the general population, but the group of BESST pregnancies after elective SET compares favourably to the general population. These data confirm that outcome of pregnancy should be related to the type of embryo transfer they originate from.
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Acknowledgements |
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We are indebted to Guy Martens from the SPE for providing us with the data of the spontaneous conceived singletons and to Dirk Deweerdt for his assistance with the statistical artwork.
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References |
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Alexander GR, Himes JH, Kaufman RB, Mors J and Kogan M (1996) A United States national reference for fetal growth. Obstet Gynecol 87,163–167.[CrossRef][Web of Science][Medline]
Bergh T, Ericson A, Hillensjö T, Nygren KG and Wennerholm UB (1999) Deliveries and children born after in-vitro fertilisation in Sweden 1982–95: a retrospective cohort study. Lancet 354,1579–1586.[CrossRef][Web of Science][Medline]
Davies MJ, Wang JX and Norman RJ (2004) What is the most relevant standard of success in assisted reproduction? Assessing the BESST index for reproduction treatment. Hum Reprod 19,1049–1051.
De Neubourg D and Gerris J (2003) Single embryo transfer – state of the art. Reprod Biomed Online 7,615–622.[Medline]
De Neubourg D, Gerris J, Mangelschots K, Van Royen E, Vercruyssen M and Elseviers M (2004) Single top quality embryo transfer as a model for prediction of early pregnancy outcome. Hum Reprod 19,1476–1479.
Dickey R, Sartor B and Pyrzak R (2004) What is the most relevant standard of success in assisted reproduction? Hum Reprod 19,783–787.
Draper ES, Kurinczuk JJ, Abrams KR and Clarke M (1999) Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis. Lancet 353,1746–1749.[CrossRef][Web of Science][Medline]
Evers J (2002) Female subfertility. Lancet 360,151–159.[CrossRef][Web of Science][Medline]
Gerris J, De 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.
Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Vercruyssen M, Barudy-Vasquez J, Valkenburg M and Ryckaert G (2002) Elective single day-3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme. Hum Reprod 17,2621–2626.
Gerris J, de Sutter P, de Neubourg D, Van Royen E, Vander Elst J, Mangelschots K, Vercruyssen M, Kok P. Elseviers M, Annemans L et al. (2004) A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod 19, 917–923.
Healy D (2004) Damaged babies from assisted reproductive technologies: focus on the BESST (birth emphasizing a successful singleton at term) outcome. Fertil Steril 81,512–513.[CrossRef][Web of Science][Medline]
Helmerhorst FM, Perquin DAM, Donker D and Keirse MJNC (2004) Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ 328,261–264.
Jackson RA, Gibson KA, Wu YW and Croughan MS (2004) Perinatal outcome in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 103,551–563.
Lambalk C and van Hooff M (2001) Natural versus induced twinning and pregnancy outcome: a Dutch nationwide survey of primiparous dizygotic twin deliveries. Fertil Steril 75,731–736.[CrossRef][Web of Science][Medline]
Min JK, Breheny SA, MacLachlan V and Healy DL (2004) 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 19,3–7.
Ochsenkuhn R, Strowitzki T, Gurtner M, Strauss A, Schulze A, Hepp H and Hillemanns P (2003) Pregnancy complications, obstetric risks, and neonatal outcome in singleton and twin pregnancies after GIFT and IVF. Arch Gynecol Obstet 268,256–261.[CrossRef][Medline]
Pandian Z, Bhattacharya S and Templeton A (2001) Review of unexplained infertility and obstetric outcome: a 10 year review. Hum Reprod 16,2593–2597.
Schieve LA, Meikle S, Ferre C, Herbert B, Peterson HB, Jeng G and Wilcox L (2002) Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med 346,731–737.
Schieve LA, Ferre C, Peterson HB, Macaluso M, Reynolds MA and Wright VC (2004) Perinatal outcome among singleton infants conceived through assisted reproductive technology in the United States. Obstet Gynecol 103,1144–1153.[CrossRef][Web of Science][Medline]
Templeton A and Morris Jk (1998) Reducing the risks of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med 339,573–577.
Thurin A, Hausken J, Hillensjö T, Jablanowska B, Pinborg A, Strandell A and Bergh C (2004) Elective single-embryo transfer versus double-embryo transfer in in-vitro fertilization. N Engl J Med 351,2392–3402.
Van Royen E, Mangelschots K, De Neubourg 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.
Van Royen E, Mangelschots K, De Neubourg D, Laureys I, Ryckaert G and Gerris J (2001) Calculating the implantation potential of day 3 embryos in women younger than 38 years of age: a new model. Hum Reprod 16,326–332.
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.
Submitted on March 29, 2005; resubmitted on October 10, 2005; accepted on October 12, 2005.
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