CEOG Clinical and Experimental

Obstetrics & Gynecology

The impact of chorionicity and type of conception

on maternal-neonatal outcome in twin pregnancies

S. D’Arpe, S. Franceschetti, M.G. De Stefano, R. D’Amelio, A.M. Maragno,

M. Candelieri, L. Muzii, P. Benedetti Panici
Department of Gynecology, Obstetrics and Urology, Policlinico Umberto I, University “Sapienza”, Rome (Italy)

Summary
Purpose of Investigation: To evaluate the maternal and neonatal outcomes in twin pregnancies according to chorionicity (mono-
chorionic (MC) versus dichorionic (DC) and type of conception [spontaneously conceived (SC) versus assisted reproduction technol-
ogy (ART)]. Materials and Methods: A retrospective study of 196 twin pregnancies admitted to the Department of Gynecology,
Obstetrics and Urology of the University of Rome Sapienza, from January 2008 to April 2013. Results: There were 55 MC and 141 DC
twin pregnancies (82 SC and 59 ART). MC twin pregnancies had a higher incidence of preterm birth (p < 0.008), twin-twin transfusion
syndrome (TTTS) (p < 0.021), and intrauterine growth restriction (IUGR) (p < 0.05). MC pregnancies had lower neonatal birth weight
(p < 0.05), and lower Apgar score. ART DC pregnancies had a higher incidence of preterm delivery (p < 0.05). Conclusions: MC twin
pregnancy is associated with higher risk of adverse maternal and perinatal outcomes. In the DC subgroup, ART is associated to a higher
incidence of preterm delivery.

Key words: Twin pregnancy; Assisted reproduction technology; Mode of conception; Chorionicity; Monochorionic; Dichorionic.

Introduction to two different parameters, namely chorionicity (MC ver-

The rate of multiple pregnancies in developed countries sus DC) and mode of conception (SC versus ART).
continues to rise as a consequence of assisted conception
and increasing maternal age [1]. In the United States, be-
tween 1980 and 2007, the twin rate climbed 101% [2]. In Materials and Methods
Italy, between 1990 and 2005, the number of twin births has The authors performed a retrospective analysis of the multiple
increased by 25% and twin gestation today represents 1.5% pregnancies that delivered at the Department of Gynecology, Ob-
stetrics and Urology of the University of Rome Sapienza, from
to 3% of all pregnancies. About 80% of twin pregnancies January 2008 to April 2013. Exclusion criteria were gestational
are dichorionic (DC) and 20% are monochorionic (MC) [3]. age (GA) less than 24 weeks at delivery and early or late miscar-
Chorionicity is the most important determinant of mor- riages.
tality and morbidity in twins. Most studies confirmed The authors acquired the details of the pregnancies and deliv-
higher risks for MC compared with DC pregnancies in re- eries from the medical records. In particular, they collected de-
mographic data, relevant past history, parity, mode of conception
lation to perinatal outcomes [4, 5]. Indeed, the main risks
(SC versus ART), chorionicity (MC versus DC), GA at admission
for MC twins are the twin-twin transfusion syndrome and at delivery, time of maternal hospital stay ante- and post-par-
(TTTS) (15%) [6] and prematurity (50%) [7]. However, the tum, pregnancy outcomes, and maternal-fetal complications, ther-
recent rise in twin pregnancies results mainly from a greater apy during gestation, short-term neonatal outcomes.
proportion of DC pregnancies, that is largely explained by The chorionicity was determined at 10-14 weeks on the basis of
the increasing use of assisted reproduction technology the presence or absence of the lambda sign or a projection of
choriodecidual tissue into the inter twin membrane. Gestational
(ART). In the USA and Europe between 20% and 30% of age was calculated from the last menstrual period and confirmed,
deliveries following ART are twins, compared with ap- or corrected, by means of ultrasounds examination through the
proximately 1% following spontaneous conception (SC) measurement of the crown-rump length.
[8]. In Caucasian populations, about 22% of SC twins are The authors recorded the following maternal-fetal complica-
MC, whereas this rate falls to about 2% in ART [9]. Liter- tions: preterm delivery, threatened preterm labour, preterm pre-
ature data concerning the influence of ART on the outcome mature rupture of membranes (pPROM), intrauterine growth
restriction (IUGR), TTTS according to Quintero’s criteria [10],
of twin pregnancies are controversial. and selective IUGR, pregnancy induced hypertension (PIH),
The purpose of this study was to evaluate the maternal preeclampsia (PE), hemolysis, elevated liver enzyme levels, and
and neonatal outcomes in multiple pregnancies, according low platelet count (HELLP) syndrome, gestational diabetes mel-

Revised manuscript accepted for publication October 22, 2014

Clin. Exp. Obstet. Gynecol. - ISSN: 0390-6663 7847050 Canada Inc.
XLIII, n. 1, 2016 www.irog.net
doi: 10.12891/ceog2069.2016
 S. D’Arpe, S. Franceschetti, M.G. De Stefano, R. D’Amelio, A.M. Maragno, M. Candelieri, L. Muzii, P. Benedetti Panici 89

litus (GDM), cholestasis, oligohydramnios, polyhydramnios, ab- Table 1. — Comparison between MC and DC pregnancies.
normal placentation, placental abruption, and intrauterine death Variables MC group DC group p
(IUD). (n=55) (n=141)
With regards to short-term neonatal outcome, the authors col-
lected the following parameters: birth weight and related per- Characteristics of patients
centile according to classification proposed by Parazzini et al. Maternal age
[11], Apgar score at one and five minutes, and the discordance of 32 ± 6 32.6 ± 5.3 NS
(years) (mean ± SD)
twin weight. Discordance was calculated by using the following
formula: larger twin – smaller birth weight x 100/larger twin birth
weight. Parity
Patients were grouped according to chorionicity (MC vs DC) 0 41 (74.5%) 104 (73.7%) NS
and the mode of conception (SC vs ART), to evaluate the impact ≥1 14 (25.5%) 37 (26.3%) NS
of these variables. The data were analyzed with SPSS 16.5 Win- ART pregnancies 6 (10.9%) 59 (41.8%) <0.05
dows program. Comparisons between the two groups were per- SC pregnancies 49(89.1%) 82(58.2%) <0.05
formed with the Student’s t-test and chi-square test. Significance
was assumed at p < 0.05. Length of hospital stay
Ante-partum stay
6 ± 11 4±8 NS
(days) (mean ± SD)
Results Post-partum stay
4±2 4±2 NS
(days) (mean ± SD)
The authors collected 196 twin pregnancies, further sub-
grouped into 55 MC and 141 DC. The MC subgroup in- Mode of delivery
cluded 49 SC pregnancies (89.1%) and six conceived by Vaginal delivery 3 (5.5%) 5 (3.5%) NS
ART (10.9%). In particular, three pregnancies were ob- Cesarean section 52 (94.5%) 136 (96.5%) NS
tained by intracytoplasmic sperm injection (ICSI), one
pregnancy by fertilization in vitro and embryo transfer Short-term neonatal outcome
(IVF-ET), and two pregnancies after intrauterine insemi- Birthweight (grams)
1,990 ± 526 2,246 ± 473 <0.05
(mean ± SD)
nation (IUI). The DC subgroup included 82 SC pregnan-
Birthweight percentile 38.7 ± 26 46.4 ± 23.7 <0.05
cies (58.2%) and 59 conceived by ART (41.8%). In Apgar 1 minute ≤7 40% 29.8% <0.05
particular, 35 pregnancies were obtained by ICSI, 21 preg- Apgar 5 minutes ≤7 2.7% 4.2% NS
nancies by IVF-ET, and three pregnancies by IUI. The au- Discordance of birthweight 14.7% 11.7% NS
thors considered only the 36 DC pregnancies obtained by IUD 5.4% 1.4% NS
IVF, namely IVF-ET and ICSI, after ovulation induction in
order to compare SC versus ART twin pregnancies. Pregnancy outcome
pPROM 31% 13.5% <0.05
Threatened preterm delivery 58.2% 32.6% <0.05
MC versus DC pregnancies
Delivery < 37 weeks 85.5% 66.7% <0.05
The authors compared 55 MC versus 141 DC pregnan- Abnormal placentation 1.8% 1.4% NS
cies. Maternal age, parity, duration of ante and post-partum Placental abruption 3.6% 1.4% NS
hospital stay, and type of delivery, were not significantly Polyhydramnios 0% 0.7% NS
different between subgroups. Oligohydramnios 11% 6.4% NS
With regards to the mode of conception, the rate of con- IUGR 28% 12% <0.05
ception by ART was significantly higher in the DC sub- Selective IUGR 11% 5.7% NS
group (41.8% vs 10.9%; p < 0.05). GA at admission was PE/HELLP 5.59% 7.8% NS
approximately two weeks earlier in MC pregnancies (33 ± PIH 3.6% 12.8% NS
Cholestasis 3.6% 11.3% NS
3 vs 35 ± 2.7 weeks, p < 0.05).
GDM 3.6% 1.4% NS
The incidence of abnormal placentation, placental abrup- TTTS 7.2% 0% <0.05
tion, IUD, PIH, PE, HELLP syndrome, cholestasis, and
GDM was not significantly different between the two sub-
groups. The MC subgroup had a higher incidence of threat-
ened preterm delivery (58.2% vs 32.6%, p = 0.001) [OR=
2.87, 95% 1.51 - 5.46], and pPROM (31% vs 13.5%, p = ticular, 85.5% of MC delivered before 37 weeks, as com-
0.007) [OR= 2.87, 95% 1.36 - 6.07]. Moreover, 7.2% of pared to 66.7% in the DC subgroup (p < 0.05) [OR= 2.94,
MC pregnancies were complicated by TTTS, while this 95% CI 1.28 - 6.72].
complication never occurred in the DC subgroup (p < 0.05). In the MC subgroup, IUGR occurred in 28% of cases, as
No case of TTTS was treated with laser therapy prior to de- compared to 12% in the DC subgroup (p < 0.05), though the
livery. difference of incidence of selective IUGR did not reach sta-
GA at delivery was on average one week earlier in MC tistically significance. In MC pregnancies, lower neonatal
group than DC group (34±3 vs 35.5 ± 2.3 weeks). In par- birth weight were found (1,990 ± 526 vs 2,246 ± 473 grams,
90 The impact of chorionicity and mode of conception on maternal-neonatal outcome in twin pregnancies

Table 2. — Comparison between spontaneous and ART DC twin pregnancies conceived by ART versus SC
pregnancies. The authors compared 56 DC pregnancies conceived by
Variables SC group ART group p ART (IVF-ET/ICSI) and 82 DC pregnancies conceived
(n=82) (n=56) spontaneously. Maternal age, duration of ante and post-par-
tum stay, type of delivery, birth weight, and short-term
Characteristics of patients
neonatal outcome were not significantly different between
Maternal age
(years) (mean ± SD)
33±5 32.4±5.4 NS subgroups. Parity in the ART subgroup was 0.05 ± 0.22,
and 0.41 ± 0.49 in the SC group (p < 0.05).
Parity The incidence of abnormal placentation, placental abrup-
0 48 (58.5%) 53 (94.6%) P<0.05 tion, IUD, PIH, PE, HELLP syndrome, cholestasis, GDM,
≥1 34 (41.5%) 3 (5.4%) P<0.05 and IUGR was not significantly different between the two
subgroups.
Ante-partum stay The ART pregnancies showed a higher incidence of
4±9 4±6 NS
(days) (mean ± SD) preterm delivery before 37 weeks (76.8% vs 61.0%, p <
Post-partum stay
4±2 5 ± 2.6 NS 0.05) (Table 2).
(days) (mean ± SD)
Additionally, women in the ART subgroup received more
Mode of delivery frequently drug treatments, in particular low-molecular-
Spontaneous delivery 4 (5%) 1 (1.8%) NS weight heparin LMWH (50.0% vs 22.0%, p = 0.001), car-
Cesarean section 78 (95%) 55 (98.2%) NS dioaspirin (23.2% vs 6.1%, p = 0.005), and prednisone
(14.3% vs 0%; p = 0.001), as well as the administration of
Neonatal outcome progesterone (30.4% vs 12.2%, p = 0.01). Similarly, the an-
Birthweight (grams) tenatal corticosteroid therapy with betamethasone was ad-
2,176 ± 523 2,186 ± 456 NS
(mean ± SD) ministered more frequently in the ART subgroup (35.7%
Percentile 47 ± 24 45.5 ± 23 NS
vs 19.5%, p = 0.01).
Apgar 1 minute ≤7 30% 30.5% NS
Apgar 5 minutes ≤7 3.6% 5.3% NS
IUD 3.7% 0% NS Discussion
Pregnancy outcome Twin pregnancy is burdened by a higher risk of adverse
pPROM 12.2% 16.1% NS outcomes compared with singleton. This issue is becoming
Threatened preterm delivery 29.3% 37.5% NS more frequent in clinical practice, and subsequently topical
Delivery < 37 weeks 61% 76.8% <0.05 in clinical literature, due to the dramatic increase of the in-
Abnormal Placentation 1.2% 1.8% NS cidence of multiple births in the developed countries over
Placental abruption 3.6% 1.4% NS the past decades.
Polyhydramnios 1.2% 0% NS
Most studies showed a higher incidence of preterm births
Oligohydramnios 8.5% 3.6% NS
IUGR 11% 13% NS and adverse neonatal outcomes in MC pregnancies, possi-
Selective IUGR 4.9% 7.1% NS bly related to TTTS and selective IUGR [5, 7]. According
PE/HELLP 6.1% 10.7% NS to Acosta-Rojas et al., the adverse perinatal outcomes of
PIH 12.2% 14.3% NS MC twins appear to be associated with selective IUGR [6].
Cholestasis 11% 12.5% NS In accordance with literature data, the present study
GDM 1.2% 3.6% NS found that in the MC subgroup GA at admission was one
TTTS 0% 0% NS week earlier than DC, likely related to the higher incidence
of pPROM, preterm births, IUGR, and TTTS. However, the
present data confirmed the greater incidence of selective
IUGR, though not statistically significant in MC pregnan-
p < 0.05), as well as lower birth weight percentile (38.7 ± 26 cies. Additionally, the present authors found a higher inci-
vs 46.4 ± 23.7, p < 0.05), and larger discordance of twin dence of adverse short-term neonatal outcomes in the MC
weight (14.7 ± 10.6% vs 11.7 ± 8.4%, p > 0.05). Additionally, subgroup, as fairly expected.
Apgar score ≤ 7 at one minute was found in 40% of MC, as Literature data concerning the maternal complications
compared to 29.8% of DC (p < 0.05), though the rate of are controversial [7, 12, 13]. The present study did not dis-
Apgar score ≤ 7 at five minutes was similar in the two sub- close any difference between MC and DC twin pregnan-
groups (Table 1). cies. Hypertensive disorders were more frequently
With regards to the drug treatments, there were no sta- associated to DC pregnancy, though this evidence was not
tistically significant differences between the two groups, statistically significant. Nonetheless, a limitation of the
except for a greater use of antenatal corticosteroid therapy present study may be represented by the low number of MC
in the MC subgroup (38.2% vs 26.2%, p < 0.05). pregnancies.
 S. D’Arpe, S. Franceschetti, M.G. De Stefano, R. D’Amelio, A.M. Maragno, M. Candelieri, L. Muzii, P. Benedetti Panici 91

The present study further investigated the impact of ART suggested [20]. Higher rates of placenta previa and placen-
on the outcome of DC pregnancies. ART has been related tal abruption occur more frequently in the ART group. This
to a higher risk of maternal-fetal complications and preterm could be a consequence of embryo transfer through the
birth in some studies, that compare the outcomes of sin- vagina and cervix, as well as defective uteroplacental in-
gleton pregnancies conceived by ART with those conceived teractions related to female fertility problems [14, 27]. Fi-
spontaneously [14-17]. On the contrary, several studies in- nally, a higher percentage PIH has been hypothesized to be
vestigating the outcome of twin pregnancies conceived by eventually explained by the different initiation of the
ART have produced conflicting results [14, 18-27]. chorion formation while the embryo is in vitro, leading to
Interestingly, a recent meta-analysis of perinatal risks in an abnormal placentation in both location and function
twins, which selected studies that matched or controlled for [18].
maternal age and others factors, showed that ART twins A recent review about ART twin pregnancies reported in-
had an increased risk of preterm birth and low birth weight creased obstetrical risks only in women with a pre-existing
compared to SC twins [28]. However, this meta-analysis medical condition such as hypertensive disorders or dia-
was not adjusted for chorionicity, albeit this is an impor- betes [32], albeit most of these risks can be avoided with
tant prognostic factor in both ART and SC twin pregnan- single-embryo transfer or with two single-embryo transfers
cies. resulting in two singleton pregnancies [33].
In the present study, the authors restricted their analysis In the present study, the incidence of maternal complica-
of the impact of ART to the DC subgroup in order to avoid tions was not significantly different between SC and ART
the bias of monochorionicity. Other studies carried out this subgroups. It is worth to note that in the ART subgroup
analysis after controlling for chorionicity or zygosity but there was a greater use of drugs, in particular LMWH, car-
their results are inconsistent [24, 29]. Furthermore, mater- dioaspirin, and prednisone. The impact of this medical ther-
nal age is supposed to be an additional variable eventually apy on preventing maternal complications, in particular the
affecting the outcome of ART twin pregnancies. In fact, hypertensive disorders, is far from being understood.
women delivering after ART are often older than the aver-
age population of pregnant women and almost always nul-
Conclusion
liparae, and this fact has often been used to explain the
adverse obstetric and perinatal outcomes observed in these The present study did not disclose any significant differ-
patients. ence in the short-term neonatal outcomes between SC and
In the present study, the authors found lower parity in the ART DC twins. MC twin pregnancy was associated with
ART women, as fairly expected. Interestingly, the mater- higher risk of adverse outcomes compared with DC preg-
nal age (ART versus SC) was similar in the two subgroups, nancy, as previously reported. In particular, a higher inci-
thus reducing the influence of this variable. Thus, the pres- dence of TTTS, IUGR, preterm birth, a related more
ent findings may be considered controlled for chorionicity, frequent use of antenatal corticosteroid therapy, and worse
due to methodological limitations, and for maternal age, by short-term neonatal outcome were noticed. Moreover, the
chance. Actually, the outcomes of ART twin pregnancies present analysis of DC twin pregnancies suggests that ART
were generally comparable with SC twin pregnancies, ex- is possibly related to a higher incidence of preterm delivery
cept for a higher incidence of preterm delivery and a re- and a related use of antenatal corticosteroid therapy if com-
lated use of antenatal corticosteroid therapy. pared to SC twin pregnancies.
In the literature, the increased risk of preterm birth has Further studies are advocated to confirm the present find-
been suggested to be secondary to higher concentrations of ings and investigate possible difference in neonatal mor-
relaxin throughout gestation following gonadotropin stim- bidity (incidence of respiratory distress syndrome,
ulation [30]. Another factor that may contribute to higher intraventricular haemorrhage, necrotizing enterocolitis, etc).
rates of preterm birth is the increased rate of obstetric in-
tervention, since ART birth is often the first birth after a
history of infertility, so that both the physician and mother Ackowledgements
may be more worried about delivery than in SC pregnan- In memory of Professor M. M. Anceschi.
cies [31]. With regards to maternal complications, most
studies do not find any statistically significant difference
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