Human Reproduction, Vol.26, No.5 pp. 1220– 1226, 2011
Advanced Access publication on February 26, 2011 doi:10.1093/humrep/der039
ORIGINAL ARTICLE Reproductive epidemiology
Predictive factors of healthy term birth
after single blastocyst transfer
Lionel Dessolle 1,*, Thomas Fréour 1, Célia Ravel 2, Miguel Jean 1,
Agnès Colombel 1, Emile Daraı̈ 3, and Paul Barrière 1
1
CHU Nantes, service de médecine et biologie de la reproduction, Centre Hospitalier Universitaire de Nantes, 38, Bd Jean Monnet, 44093
Nantes Cedex 1, France 2Service d’histologie et biologie de la reproduction, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France
3
Service de gynécologie obstétrique et médecine de la reproduction, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France
*Correspondence address. Tel: +33-2-40-08-32-33; Fax: +33-2-40-08-32-28; E-mail: [email protected]
Submitted on October 8, 2010; resubmitted on January 16, 2011; accepted on January 26, 2011
background: Blastocyst culture and elective single embryo transfer programmes are increasingly used to reduce multiple pregnancies
after IVF. To optimize the results, there is a need to better select embryos, to implement efficient cryopreservation programmes and to
refine selection criteria. In the present study, we set out to identify relevant clinical predictors of healthy term birth (HTB) after single
blastocyst transfer (SBT).
methods: Design: analysis of prospectively collected database. Setting: University IVF centre in Nantes, France. In 872 infertile women
undergoing their first IVF cycle with SBT between January 2007 and December 2008, multivariable analysis and logistic regression were used
to identify predictive factors of HTB, i.e. delivery of a live born term singleton of ≥2500 g, surviving at least 28 days with no reported
congenital anomaly.
results: Of 304 deliveries, there were 16 twin pairs (5.5%) and no high order deliveries. The rate of HTB was 266/872 (30.5%). Univariate analysis showed that the probability of HTB was significantly higher in women under 35 years [odds ratio (OR):1.75, 0.95 confidence
interval (CI): 1.2 –2.5, P ¼ 0.001], in women with a BMI , 30 kg/m2 (OR: 3.0, 0.95 CI: 1.5 –5.9, P ¼ 0.001), in non-smoking women (OR:
2.2, 0.95 CI: 1.5 –3.2, P , 0.0001), and after Day 5 compared with after Day 6 transfer (OR: 2.65, 0.95 CI: 1.8 –3.8, P , 0.0001). Multivariable analysis showed that BMI, smoking and day of embryo transfer were independent predictors of HTB, regardless of female age.
conclusions: After SBT, female obesity and smoking reduce the chance of HTB, independent of female age. Day 6 transfer should be
avoided.
Key words: IVF / blastocyst / elective single embryo transfer / live birth / prediction models
Introduction
Elective single embryo transfer (eSET) as well as the use of extended
culture for blastocyst transfer are increasingly used as an effective
means of reducing multiple pregnancies and especially high order pregnancies after IVF (Pandian et al., 2009). Studies comparing eSET with
multiple-embryo transfer highlight the benefit of this approach and
suggest that with careful patient selection, the transfer of good-quality
embryos and the availability of an effective cryopreservation programme (Veleva et al., 2009), the risk of a high-order pregnancy can
be reduced without significantly decreasing live birth rates (Gardner
et al., 2004; Thurin et al., 2004; Styer et al., 2008). Extended culture
to the blastocyst stage is thought to result in embryos with a high
implantation potential (Gardner and Lane, 1997) and fresh blastocyst
transfer yields better delivery rates than the transfer of equal numbers
of cleavage stage embryos (Gardner et al., 1998; Papanikolaou et al.,
2006, 2008; Blake et al., 2007; Guerif et al., 2009). Moreover, introducing perinatal health into the outcome, a recent population-based
study in Australia showed that single blastocyst transfer (SBT) optimizes the chance of delivering a healthy term singleton (Wang et al.,
2010). In the near future, the characterization of genetic markers
after blastocyst biopsy (Jones et al., 2008) or metabolic and proteomic
profiles (Nagy et al., 2008; Vergouw et al., 2008; Katz-Jaffe et al., 2009)
will probably improve the selection of the most viable embryos and
allow better correlation with outcomes. To improve pregnancy rates
after IVF, there is also a need for a better understanding of the prognostic factors to optimize patient selection for the various techniques
available. For that purpose, prediction models could be useful
(Ottosen et al., 2007; Leushuis et al., 2009; Dessolle et al., 2010a).
As the wish of our patients is to take home a healthy baby, we set
out to identify relevant predictors of healthy term birth (HTB) after
SBT.
& The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
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Predictors of birth after single blastocyst transfer
Materials and Methods
Patients
We analysed the data of consecutive patients who had undergone IVF with
extended culture and SBT. These data had been collected prospectively
and recorded in a registered database between 2007 and 2008 in our fertility centre in Nantes, France.
Couples were selected for the use of extended culture in IVF if they
were undergoing their first IVF cycle and had at least five zygotes on
Day 1 after fertilization.
All the patients gave written informed consent for the procedures and
for digital recording and use of the data related to their history.
IVF and laboratory procedures
All patients underwent IVF and embryo transfer according to standard
protocols, as previously described (Jean et al., 2001; Dessolle et al.,
2010a). Women underwent either a long GnRH agonist protocol with
step-up gonadotrophin dosing, a short agonist protocol or an antagonist
protocol (Table I). Recombinant hCG was administered when three or
more follicles were .15 mm in diameter, with the lead follicle being
≥18 mm. Oocyte retrieval was performed 34 – 36 h later. Insemination
was achieved by either conventional IVF or ICSI.
For conventional IVF and ICSI, fertilization (Day 0) was performed in
G-IVFTM medium (Vitrolife, Gothenburg, Sweden). The following
morning (Day 1), fertilized oocytes were individually placed in 30 ml microdrops of G1-plusTM medium (Vitrolife) under mineral oil until Day 3. On
Day 3, the embryos were placed in 30 ml microdrops of G2-plusTM (Vitrolife) under mineral oil until Day 5/6. All the cultures were incubated at
378C with 6% CO2, 5% O2 and 89% N2. Extended culture always involved
the entire embryo cohort.
Oocytes were optically assessed for fertilization 18 –20 h after insemination (Day 1) using an inverted microscope with Hoffman modulation
Table I Epidemiological characteristics of 872 couples
undergoing a first SBT.
Study period
2007–2008
Number of couples
872
Female age
31.9 years (31.6– 32.2)
Female BMI
23 kg/m2 (22.7 –23.3)
Smokers
211 (24.2%)
Male age
34.7 years (34.3– 35.1)
Duration of infertility
4 years (3.9– 4.1)
Primary infertility
576 (66%)
Ovulation disorders
532 (61%)
PCOS
314 (36%)
Tubal factor
175 (20%)
Endometriosis
434 (49.8%)
Male factor
535 (61.3%)
Sperm concentration
41 M/ml (37.7– 44.3)
Sperm motility (a + b)a
20% (19.2–20.8)
Donor sperm IVF
25 (2.8%)
PCOS, polycystic ovary syndrome.
Data are n (%) or mean (95% CI).
a
According to the World Health Organization WHO Laboratory Manual for
Examination of Human Semen.
contrast (×200 and ×400 magnifications). On Day 3, individually cultured
embryos were evaluated on the basis of the number of blastomeres, blastomere size, fragmentation rate and presence of multinucleated blastomeres (Scott et al., 2000). On Day 5, blastocyst development and
morphology were checked for blastocoelic cavity expansion and the
number, cohesion and regularity of trophectoderm and inner cell mass
cells. The blastocysts were assigned quality grades as described by
Gardner and Schoolcraft (Gardner et al., 2000). Blastocyst quality was
categorized as excellent (AA), good (AB, BA, BB), fair (BC, CB) or
poor (CC) based on trophectoderm and inner cell mass quality scores.
Transfers were planned on Day 5, with the most advanced blastocyst
being chosen for transfer. Non-expanded blastocysts were further cultured until Day 6 and transferred if they had reached the quality criteria.
When more than one excellent or good blastocyst was obtained,
couples were asked if they wanted the surplus blastocysts to be
cryopreserved. This was performed using a slow freezing protocol
(Youssry et al., 2008).
There was no change in our laboratory protocols during the study
period.
Statistics
The main outcome measure was a HTB, defined by the delivery of a live
born term singleton of ≥2500 g, surviving at least 28 days with no notified
or reported congenital anomaly. The malformations that excluded HTB
status were major malformations requiring surgery, life-threatening conditions or those causing disability. Minor malformations, such as preauricular tag or instable hip, were considered HTBs.
A univariate analysis was performed using Student’s t-test or Wilcoxon
test for continuous variables, and x2 or Fischer’s test for qualitative variables. P-values of ≤0.05 were considered to denote a significant difference
and factors displaying P-values of ,0.2 were considered for multivariable
analysis.
Multivariable logistic regression analysis was used to test the association
between the selected variables and the probability of HTB. Age and BMI
were included as quantitative variables and also as qualitative variables in a
second analysis, with 35 years and 30 kg/m2 cut-offs, respectively. Backward variable selection was performed to determine independent covariates. Multivariable logistic regression analysis was used to predict individual
patient probability of HTB. Variables were eliminated from the model if
their removal actually improved the overall quality of the model (as
measured by the Akaike information criterion). The P-values in the multivariable analysis were based on Wald tests. A P-value of ,0.05 was considered significant.
The models were evaluated with regard to their discrimination (i.e.
whether the relative ranking of individual predictions is in the correct
order) that was quantified with the area under the receiver operating
characteristic (ROC) curve (Hanley and McNeil, 1982). The area under
the curve (AUC) is a summary measure of the ROC that reflects the
ability of a test to discriminate the outcomes across all possible levels of
positivity.
All analyses were performed using the R package with the Verification,
Design, Hmisc, DiagnosisMed, ROCR and Presence Absence libraries
(available at: http://lib.stat.cmu.edu/R/CRAN/).
Results
A total of 872 patients underwent a first SBT during the 2-year period
(2007– 2008). Patient and cycle characteristics are summarized in
Tables I and II.
In total, 422 women had a positive hCG test (48.4%). The clinical
pregnancy rate (presence of an ultrasound-visible gestational sac in
1222
Dessolle et al.
Table II Cycle characteristics of 872 couples
undergoing a SBT.
Study period
2007– 2008
Number of couples
872
COH protocols
Long agonist
Table III Pregnancy outcome in 872 couples
undergoing a first SBT.
Number of transfers (women)
hCG positive
558 (64%)
Antagonist
270 (31%)
Short agonist
44 (5%)
Total FSH dose
1887 IU (1842– 1932)
Number of ICSI
499 (57.2%)
Oocytes retrieved
13 (12.6–13.4)
Oocytes normally fertilized
10 (9.7–10.3)
Number of embryos cultured
6 (5.8– 6.2)
Top Day-3 embryos
1.8 (1.7– 1.9)
Usable Blastocysts on Day 5
1.1 (1– 1.2)
Additional Blastocysts on Day 6
0.9 (0.8– 0.9)
Blastulation rate
30% (28– 32)
Cycles with cryopreservation
174 (20%)
Blastocysts cryopreserved
0.3 (0.3– 0.4)
422 (48%)
Biochemical pregnancies
66
Miscarriages
46
Ectopic pregnancies
4
Medical abortionsa
2
Deliveries
Live born babies
304
319 (1 twin died in utero)
Single
288
Twin pairs
14 + 2b
Premature births (cumulative)
,28 weeks
1
,33 weeks
3 twins (18.8%) + 4 single
(1.4%)
,37 weeks
7 twins (43.7%) + 17 single
(5.9%)
Reported morbidity in term neonates
Heart anomaly
COH, controlled ovarian hyperstimulation.
Data are n (%) or mean (95% CI).
the uterus) was 40%. The delivery rate per transfer was 36.7%. In all,
319 babies were born, including 14 pairs of twins. There were also
two monozygotic triplet pregnancies that were reduced to a twin
pregnancy by selective cord coagulation at 15–16 weeks (Dessolle
et al., 2010b). In both cases, healthy twins were delivered by Caesarean section at 34.5 and 34 weeks. Thus, the incidence of twin deliveries was 5.5%. The rate of HTB was 30%. Detailed results
concerning pregnancy outcome are given in Table III.
Univariate analysis (Table IV) showed that the probability of HTB
was significantly higher in women under 35 years, in women with a
BMI , 30 kg/m2, in non-smoking women compared with smokers
and after Day 5 compared with after Day 6 transfer.
The following criteria had no impact on HTB: male age, male
smoking status and semen parameters, infertility characteristics including polycystic ovary syndrome (PCOS), the protocol and duration of
controlled ovarian stimulation, the number of oocytes retrieved, the
number and quality of embryos cultured on Day 3, the number of blastocysts cultured on Day 5, the quality score of the embryo transferred,
the type of catheter used for transfer and the operator performing the
transfer. The main results of univariate analysis are summarized in
Table IV.
Multivariable analysis revealed that female BMI, female smoking and
day of blastocyst transfer were independent covariates for the prediction of HTB, regardless of female age. Two models are shown in
Table V. In the first analysis, age and BMI were included as quantitative
variables, smoking was included as qualitative variable and day of
transfer was not included. In the second model, all the covariates
were included as qualitative variables and the additional effect of
Day 6 transfer was evaluated. The second model showed better properties [higher odds ratios (OR) and better AUC] and was also simpler,
showing that Day 6 embryo transfer, female obesity and female
872 (872)
........................................................................................
2
Cleft palate
1
Sepsis
1
Healthy term singletons
266
Positive hCG tests
422 (48%)
Clinical pregnancy rate
352 (40%)
Delivery rate per embryo transferred
319 (37%)
Delivery of a healthy term
singleton ≥ 2500 g
266 (30%)
a
Concerned Down’s syndrome.
There were two monozygotic triplet pregnancies, who were reduced to twins by
cord photocoagulation at 15 weeks. In both cases, healthy twins were delivered by
Cesarean section.
b
smoking independently reduced the chance of delivering a healthy
term neonate.
The equation describing the probability of HTB was Y ¼ 1/(1 +
exp (0.3 + 0.3*V1 + 1.65*V2 +0.8*V3 + 0.9*V4)), where V1 ¼ 1 if
female age ≥ 35 years (V1 ¼ 0 if age , 35), V2 ¼ 1 if female BMI ≥
30 kg/m2 (V2 ¼ 0 if BMI , 30), V3 ¼ 1 in women who smoke
(V3 ¼ 0 if the woman is a non-smoker) and V4 ¼ 1 in case of
‘Day-6 embryo transfer’(V4 ¼ 0 in case of Day 5 transfer). This
formula shows that the probability of HTB decreases from 0.42
(in the absence of risk factor) to 0.007 (in the presence of all the
risk factors). The AUC of the ROC curve for this model was 0.66.
Discussion
This is one of the largest series of SBT reported to date and confirms
the good results obtained by this method. On the basis of 872 consecutive first IVF cycles with extended culture and SBT, we found
that female BMI and female smoking as well as the day when SBT
was performed (Day 5 or Day 6) were strong independent predictors
of delivering a healthy term singleton. Our results support that female
1223
Predictors of birth after single blastocyst transfer
Table IV Univariate analysis of 872 SBTs showing determinants of delivering a healthy term singleton.
Women
HTB (percent: 0.95 CI)
P-value
OR (0.95 CI)
.............................................................................................................................................................................................
All: 872
266/872 (30.5%: 27.4–33.6)
Age , 35: 635 (72.8%)
213/635 (33.5%: 29.9–37.2)
Age ≥ 35: 237 (27.2%)
53/237 (22.4%: 17–27.7)
BMI , 30: 798 (91.5%)
256/798 (32%: 28.8–35.3)
BMI ≥ 30: 74 (8.5%)
10/74 (13.5%: 5.7 –21.3)
Non-PCOS: 558 (64%)
168/558 (30%: 26–34)
PCOS: 314 (36%)
98/314 (31%: 26–36)
Non-smoker: 661 (75.8%)
226/661 (34.2%: 30.6–37.8)
Smoker: 211 (24.2%)
40/211 (19%: 14–24)
Day 5 transfer: 629 (72%)
224/629 (35.6%: 32–39)
Day 6 transfer: 243 (28%)
42/243 (17.3%: 12.5–22)
0.001
1.7 (1.2–2.5)
0.001
3.0 (1.5–5.9)
0.734
0.9 (0.7–1.3)
,0.0001
2.2 (1.5–3.2)
,0.0001
2.6 (1.8–3.8)
HTB, healthy term birth; OR, odds ratio.
x2 or Fischer tests were used.
Table V Multivariable analysis of 872 first SBTs showing determinants of delivering a healthy term singleton.
Covariates
Estimate
CI lower
CI upper
SE
P-value
OR (0.95 CI)
.............................................................................................................................................................................................
Model with quantitative age and BMI (AUC: 0.62)
Female age (years)
20.04
20.084
0.003
0.02
0.07
0.96 (0.92– 1.00)
Female BMI
20.08
20.125
20.033
0.02
0.001
0.92 (0.88– 0.97)
Female smoking
20.79
21.25
20.32
0.23
0.001
0.5 (0.3– 0.7)
Model with qualitative age and BMI (35 years and 30 kg/m2 cut-offs, respectively), also showing the impact of Day 6 transfer on the outcome (AUC: 0.66)
Female age ≥ 35 (years)
Female BMI ≥ 30
20.35
20.76
0.06
0.21
0.093
0.7 (0.5– 1.1)
1.65
22.59
0.71
0.48
0.001
0.2 (0.1– 0.5)
Female smoking
20.82
21.29
20.36
0.24
0.001
0.4 (0.3– 0.7)
Day 6 transfer
20.93
21.37
20.49
0.22
,0.0001
0.4 (0.2– 0.6)
AUC, area under the receiver operating characteristic curve.
obesity and female smoking reduce the chance of delivering a healthy
term singleton and we confirm that Day 6 transfer is associated with
poor results. The rate of monozygotic twins (3% of all pregnancies and
5.5% of all deliveries) is concordant with published data (Vitthala et al.,
2009). Indeed there is concern and a debate about an increased incidence of monozygotic twinning after blastocyst transfer (Vitthala et al.,
2009; Papanikolaou et al., 2010) of which patients should be informed.
How assisted reproduction technologies (ART) might lead to an
increase in monozygotic pregnancies is not fully understood (Dessolle
et al., 2010b) and international collaboration is required to identify
predictors of their occurrence.
The OR between non-obese and obese women was close to three
(0.95 CI: 1.5 –5.9), and the impact of BMI on HTB appeared independent of age and of the presence of PCOS using multivariable analysis.
Many reports have emphasized that, both in natural and assisted
cycles, obesity is associated with longer times to conception, lower
pregnancy rates and an increased risk of obstetrical complications
(Dokras et al., 2006; Brewer and Balen, 2010). Obese women are
more frequently infertile and often experience anovulatory cycles,
insufficient follicle development, lower oocyte numbers, increased
gonadotrophin requirements and altered pregnancy and implantation
rates after assisted conception (Brewer and Balen, 2010). The
impact of obesity on the miscarriage rate is less clear (Tian et al.,
2007; McClamrock, 2008; Metwally et al., 2008). Various mechanisms
might be involved in the poor reproductive performance of obese
women, including endocrine and metabolic disorders: impaired sex
hormone secretion and bioavailability resulting in functional hyperandrogenism, insulin resistance, altered leptin and adipokines levels
leading to ovulation dysfunction and poor response to ovulation induction agents (Maheshwari et al., 2007, Brewer and Balen, 2010). Using
the donor oocyte model, which enables a person to individualize the
recipient’s related predictors of pregnancy, Bellver et al. (2007)
observed a significant decrease in the implantation and ongoing pregnancy rates as the recipient’s BMI increased, suggesting that not only
ovarian but also probably endometrial factors contribute to the
poorer results in obese women. In a recent study of 450 frozen
thawed embryo transfers after oocyte donation, we also observed
that obesity was associated with a lower implantation rate (IR), independent of the recipient’s age (Dessolle et al., 2009). In the present
series, performing the analysis with the IR as the outcome
1224
(data available on request) showed that more implantation failures
than obstetrical complications contributed to the bad prognosis in
obese women. PCOS alone did not alter HTB, and the impact of
obesity on the outcome appeared independent of PCOS (Table IV).
However, because the number of obese women without PCOS was
small, the present study is underpowered to evaluate if and how
PCOS contributes to the impact of obesity on HTB. Some countries
have restricted the access to ART for women with high BMI, and
this has been the subject of some debate (Pandey et al., 2010).
However, as rates of obesity are growing rapidly worldwide—more
than 50% of the women in the UK and in the USA are overweight
or obese (Ogden et al., 2006; Balen and Anderson, 2007)—it will
be difficult to refuse access to fertility treatments to such a large percentage of women. Thus, future studies will have to focus on how to
improve prognosis in obese women.
Our results confirm the harmful effect of female smoking on IVF
outcome, with smokers showing HTB rates after SBT that are half
that of non-smokers. The effects of tobacco on female fertility have
been known for a long time (Augood et al., 1998). Women who
smoke experience menopause earlier than non-smokers (Jick and
Porter, 1977). Smoking is a dose-dependent risk factor of ectopic
pregnancy (Shaw et al., 2010). Studies comparing IVF cycles in
smokers and non-smokers have shown decreased ovarian reserve,
higher cancellation rates, lower numbers of retrieved oocytes and
poorer IVF outcomes in smokers (Fréour et al., 2008; Waylen et al.,
2009). Experimental observations suggest that smoking might also
alter endometrial receptivity (Shiverick and Salafia, 1999). Using the
oocyte donor model to isolate key determinants of pregnancy in the
recipient, Soares et al. (2007) evaluated the effect of smoking on
uterine receptiveness in 785 embryo transfers while other possible
cofounding variables were controlled. They found that the recipients
smoking more than 10 cigarettes/day had a lower pregnancy rate
(34.1 versus 52.2%, P ¼ 0.02) and a trend towards lower implantation
rate (25.8 versus 33.2%). Curiously, smokers had also a higher
multiple pregnancy rate (60 versus 31%, P ¼ 0.02). Moreover,
female smoking is also associated with obstetrical complications,
such as premature delivery, low birthweight and abruptio placenta
as well as with perinatal and post-natal morbidity (DiFranza et al.,
2004). Women trying to conceive should be strongly encouraged to
stop smoking.
The present series also confirms that the transfer of fresh blastocysts that expand on Day 6 is associated with poorer outcome than
the transfer of blastocysts that expand and are transferred on
Day 5. Moreover, we found that this factor was the strongest independent predictor of HTB using multivariable analysis. These findings are
in accordance with previous studies, suggesting lower viability for
slower developing embryos (Shapiro et al., 2008; Barrenetxea et al.,
2005) or inadequate synchrony between endometrium and embryo
development when fresh Day 6 transfer is performed (Van Voorhis
and Dokras, 2008): the latter hypothesis is corroborated by the
observation that blastocysts cryopreserved on Day 6 and transferred
on Day 5 in a following artificial cycle have a better prognosis (Richter
et al., 2006; Shapiro et al., 2008). These data raise the issue of
whether blastocysts that expand on Day 6 should not be systematically
cryopreserved rather than transferred during the fresh cycle. An
advantage of vitrification for that purpose would be that it allows flexibility to cryopreserve individual blastocysts at their optimal stage of
Dessolle et al.
development and expansion (Liebermann, 2009). Another option to
avoid Day 6 transfers could be to transfer the most advanced
embryo on Day 5, even if it is not expanded. However, there is no
evidence from controlled studies in the literature to recommend
this option. Therefore randomized studies are now required to evaluate what is the best strategy for extended culture when no blastocyst
has expanded on Day 5.
In this series, although the HTB was significantly higher in women
,35 years than in the older group after univariate analysis, age was
the weakest predictor after multivariable analysis, showing that the
effect of age on HTB was dependent on BMI and smoking. Age is
well known to be a strong factor in determining the success of infertility treatments. Although increasing age is associated with lower
implantation and pregnancy rates after IVF/ICSI (Templeton et al.,
1996), the incidence of multiple pregnancies after IVF remains high
in women over 35 years (Kissin et al., 2005) and the obstetrical
risks of multiple pregnancies are also increased in older women
(Simchen et al., 2009). This raises the question of including older
women in eSET programmes. Veleva et al. (2006) compared eSET
with double embryo transfer in women aged 36 –39 years and
showed that, while there was no significant difference in pregnancy
rate per embryo transfer and live birth rate between the two
groups, there was a higher cumulative pregnancy rate (54.0 versus
35.0%), a significantly higher cumulative live birth rate (41.8 versus
26.7%, P , 0.001) and a much lower cumulative multiple birth rate
(1.7 versus 16.6%, P , 0.0001) with eSET. These results are in
favour of the use of eSET in patients of a broad age range.
We used data from first IVF cycles to guarantee independence
between cycles, thus ensuring that our results are applicable to
second, and following transfers should be evaluated in a further
study. Another limitation could be that this was a retrospective
analysis of a single centre. However, the selection criteria for this
study were not very restrictive because extended culture was
offered to a majority of couples undergoing their first cycle at
that time. Therefore, in our opinion, the external validity of the
analysis is acceptable.
A strong point of the present analysis is, in our opinion, the use of a
hard end-point. Although increasing age, female obesity and smoking
are well-known negative factors of success after IVF, most of the published studies have evaluated these factors using raw success rates as
the outcome. However, what actually matters to our patients is to
take home a healthy baby. Moreover, as the advantage of SBT is to
reduce multiple births and related morbidity after IVF, delivering a
healthy term singleton is the only outcome that should be used to
compare SBT with other transfer policies. We have also developed
a simple model which, using binary data (e.g. presence/absence of
the identified risk factors), might help physicians informing their
patients by showing how the identified risk factors influenced the
outcome in our centre. This model should not be used to calculate
individual probability of HTB out of our department before international external validation is performed.
In conclusion, our data confirm that SBT provides good results in
terms of HTB. Negative predictive factors of delivering a healthy
term singleton have been identified and a simple model has been
developed to help with informing patients before IVF. Women
trying to conceive should be encouraged to stop smoking and normalize their weight. Day 6 transfer should be avoided.
Predictors of birth after single blastocyst transfer
Author’s roles
L.D. was involved in study conception and design, data analysis and
interpretation, and drafting the manuscript. T.F. played a role in data
acquisition, analysis and interpretation, and drafting of the article.
C.R. was involved in data interpretation and drafting of the manuscript.
A.C. was involved in acquisition and interpretation of data and drafting
of the manuscript. M.J. played a role in acquisition and interpretation
of data, and revision of the manuscript. E.D. was involved in interpretation of data and revision of the manuscript. P.B. was involved in study
conception and design, interpretation of data and revision of the
manuscript. All the authors approved the final version of the
manuscript.
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