Human Reproduction Vol.17, No.10 pp. 2626–2631, 2002
Elective single day 3 embryo transfer halves the twinning
rate without decrease in the ongoing pregnancy rate of an
IVF/ICSI programme
Jan Gerris1, Diane De Neubourg, Katelijne Mangelschots, Eric Van Royen,
Miet Vercruyssen, Jorge Barudy-Vasquez, Marion Valkenburg and Greet Ryckaert
Center for Reproductive Medicine, Middelheim Hospital, Lindendreef 1, 2020 Antwerp, Belgium
1To
whom correspondence should be addressed. E-mail: [email protected]
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
Introduction
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
2626
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 retrospec© European Society of Human Reproduction and Embryology
Judicious eSET halves the twinning rate without changing the pregnancy rate
tive 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.
Materials and methods
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 艌7 blastomeres
on day 3; 艋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 6⫻100 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 18⫻18 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
2627
J.Gerris et al.
Table I. Proportion of transfers of a single, two, three or more than three embryos over a 4 year period
Year
No. of oocyte retrievals
No. of transfers (%)
SET (%)
TOP SET (%)
DET (%)
3 embryos at transfer (%)
⬎3 embryos at transfer (%)
Total
1998
1999
2000
2001
340
317 (93)
42 (13)
31 (9.8)
195 (62)
55 (17)
25 (8)
408
388
100
75
224
47
17
395
370
122
101
197
39
12
416
389
121
92
237
24
7
(95)
(26)
(19.3)
(58)
(12)
(4)
(94)
(33)
(27.3)
(53)
(11)
(3)
(93)
(31)
(23.6)
(61)
(6)
(2)
1559
1464
385
299
853
165
61
(27)
(20.4)
(58)
(11)
(4)
SET ⫽ single embryo transfer; TOP SET ⫽ top quality SET; DET ⫽ double embryo transfer.
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 3⫻200 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.
Results
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).
2628
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 χ2-test showed no significant
difference between the different years, neither per oocyte
retrieval nor per embryo transfer.
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.
Discussion
Prevention has been focused until now mainly on highorder 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
Judicious eSET halves the twinning rate without changing the pregnancy rate
Table II. Percentage of single embryo transfers, mean number of embryos transferred, ongoing implantation
rate (OIR), ongoing pregnancy rate (OPR), twinning rate and total multiple pregnancy rate in an IVF/ICSI
programme where elective single embryo transfer was introduced over a 4 year period
All cycles (n ⫽ 1559)
% SET
No. of embryos/transfer
OIR (%)
OPR/oocytes retrieval (%)
OPR/embryo transfer (%)
Twins (%)
Total multiple pregnancy rate (%)
aValues
Year
1998
1999
2000
2001
1998–2001a
13
2.26
23.5
35.9
38.5
29.5
33.6
26
1.96
20.1
27.9
29.4
30.7
32.5
33
1.85
22.7
31.9
34.1
20.6
22.2
31
1.79
22.4
31.0
33.2
16.3
18.6
26
1.95
22.1
31.5
33.5
24.0
26.5
are means for the 4 year period.
Figure 1. Evolution of the total multiple pregnancy rate and of the
mean number of day 3 embryos transferred with gradual
introduction of elective single embryo transfer in an IVF/ICSI
programme over a 4 year (1998–2001) period. OR ⫽ oocyte
retrieval; PR ⫽ pregnancy rate.
Figure 2. 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 elective single
embryo transfer. OPU ⫽ oocyte pickup; PR ⫽ pregnancy rate.
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 goodprognosis 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%, 531⫻35.1% ⫽ 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).
2629
J.Gerris et al.
Table III. Outcome of the transfer of a single top quality embryo (TOP SET, n ⫽ 299), a single non-top quality embryo (non-TOP SET, n ⫽ 86), two
embryos (DET, n ⫽ 853) or more than two embryos (n ⫽ 226) in an IVF/ICSI programme
No. of transfers
No. of conceptions
No. of ongoing
pregnancies
No. of singletons
No. of twins ⫹
no. of triplets
TOP SET
(%)
Non-TOP
SET (%)
DET
(%)
⬎2 embryos at
transfer (%)
Total non-SET
(%)
Total
(%)
299 (20.4)
149 (49.8)
105 (35.1)
86 (5.9)
26 (30.2)
19 (22.1)
853 (58.3)
424 (49.7)
309 (36.2)
226 (15.4)
93 (41.2)
57 (25.2)
1079 (73.7)
517 (47.9)
366 (33.9)
1464
692 (47.3)
490 (33.5)
104 (99)
1 (1)
19 (100)
0
200 (64.7)
104 ⫹ 5 (35.3)
37 (64.0)
13 ⫹ 7 (37.7)
237 (64.7)
117 ⫹ 12 (35.2)
360 (73.5)
130 (26.5)
Table IV. Clinical outcome variables in patients receiving one (SET) or two (DET) embryos, as a function of the number of top quality embryos (TOP)
No. of transfers
No. of conceptions (A)
No. of ongoing pregnancies (B)
No. of biochemical pregnancies
No. of miscarriages
No. of ectopics
No. of singletons
No. of twins
No. of dizygotic triplets
Ongoing implantion rate
TOP SET
(%)
Non-TOP
SET (%)
2 TOP
DET (%)
1 TOP
DET (%)
0 TOP
DET (%)
299
147 (49.8)
105 (35.1)
25 (17) (of A)
16 (10.9)
3 (2)
104 (99) (of B)
1
0
105/299
(35.1)
86
26 (30.2)
19 (22.1)
5 (19.2)
2 (2.3)
0
19 (100)
0
0
19/86
(22.1)
322
207 (64.3)
160 (49.7)
26 (12.6) (of A)
17 (8.2)
4 (1.9)
90 (56.3) (of B)
65 (40.6)
5 (3.1)
235/644
(36.5)
209
117 (56)
84 (40.2)
22 (18.8)
10 (8.5)
1 (0.8)
56 (66.7)
28 (33.3)
0
112/418
(26.8)
322
99 (30.7)
65 (20.2)
22 (22.2)
10 (10.1)
2 (2)
54 (83.1)
11 (16.9)
0
76/644
(11.8)
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
2630
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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Submitted on February 25, 2002; resubmitted on May 14, 2002; accepted on
June 20, 2002
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