J Med Sci, Volume 50, No.Muhammad2,2018April:Buchori163-172etal.

, Neonatal outcomes in in vitro fertilization (IVF) pregnancies

Neonatal outcomes in in vitro

fertilization (IVF) pregnancies
Muhammad Buchori1,2*, Suryono Yudha Patria1, Tunjung Wibowo1, Ita Fauzia Hanoum3
1Department of Child Health, Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito

General Hospital, Yogyakarta, 2Faculty of Medicine, Universitas Mulawarman, Samarinda,

3Permata Hati Infertility Clinic, Dr. Sardjito General Hospital, Yogyakarta, Indonesia.

DOI: http://dx.doi.org/10.19106/JMedSci005002201805

ABSTRACT
In vitro fertilization (IVF) has been associated with poor neonatal outcomes. Preterm birth,
small-for-gestational age (SGA), and low birth weight (LBW) rates are approximately twice
as high in IVF pregnancies than in natural pregnancies. The IVF procedures have become
more routine in recent years in Indonesia, but there have been few assessments of neonatal
outcomes. The study aimed to evaluate the risk of preterm birth, SGA, and LBW in IVF
infants. This was a retrospective cohort study performed in Dr. Sardjito General Hospital,
Yogyakarta from January 2012 to December 2016. Pre-coded questionnaires were used to
collect data from medical records. The relative risk of preterm birth, SGA, and LBW among
IVF infants were calculated and compared to naturally conceived infants. A total sampling
method was used for the IVF infants and a simple random sampling method was used for
naturally conceived infants, who were born on the same day as an infant in the IVF group.

A total of 108 infants were recruited, consisting of 54 IVF infants and 54 naturally conceived
infants. The IVF infants had increased risk of preterm birth (RR = 2.0; 95%CI 0.52 - 7.58)
and LBW (RR = 1.25; 95%CI 0.53 - 2.92). However, the IVF infants did not have an
increased risk of SGA (RR = 1.0; 95%CI 0.21 - 4.73). In conclusion, the risk of preterm birth
and LBW in IVF infants are higher than in naturally conceived infants, but not statistically
significant. However, there is no increased risk of SGA in IVF infants.

ABSTRAK
Fertilisasi in vitro (FIV) dihubungkan dengan luaran neonatus yang rendah. Tingkat kelahiran
preterm, bayi kecil untuk usia kehamilan, berat badan lahir rendah sekitar dua kali lebih
tinggi pada kehamilan FIV dibandingkan kehamilan normal. Teknik FIV telah rutin dilakukn di
Indonesia beberapa tahun belakangan ini, tetapi sedikit dilakukan penilaian terhadap luaran
neonatusnya. Penelitian ini dilakukan bertujuan untuk mengkaji risiko kelahiran preterm, bayi
kecil untuk usia kehamilan, berat badan lahir rendah pada anak dengan FIV. Penelitian ini
merupakan penelitian kohort retrospektif yang dilakukan di RSUP Dr. Sardjito, Yogyakarta
dari Januari 2012 sampai Desember 2016. Kuesioner berkode digunakan untuk
mengumpulkan data dari rekam medik. Risiko relatif kelahiran preterm, bayi kecil untuk usia
kehamilan, berat badan lahir rendah dihitung dan dibandingkan dengan bayi lahir normal.
Metode sampling total digunakan untuk bayi dengan FIV dan metode sampling acak
sederhana digunakan untuk bayi normal yang lahir pada hari yang sama. Total sebanyak
108 bayi direkrut yang terdiri dari 54 bayi dengan FIV dan 54 bayi normal. Fertilisasi in vitro
meningkatkan risiko kelahiran preterm (RR = 2,0; 95%CI 0,52
– 7,58) dan berat badan lahir rendah (RR = 1,25; 95%CI 0.53 – 2,92). Namun demikian,

* corresponding author : mbuchori11@yahoo.com

163
J Med Sci, Volume 50, No. 2, 2018 April: 163-172

FIV tidak mempunyai risiko bayi kecil untuk usia kehamilan (RR = 1,0; 95%CI 0,21-4,73).
Dapat disimpulkan, risiko kelahiran preterm dan berat badan lahir rendah pada FIV lebih
tinggi daripada bayi normal, tetapi tidak berbeda nyata. Namun demikian, tidak ada kenaikan
risiko terjadinya bayi kecil untuk usia kehamilan.

Keywords: in vitro fertilization – preterm - small for gestational age - low birth weight –
relative risk

INTRODUCTION intracytoplasmic sperm injection (ICSI

In vitro fertilization (IVF) is one of several Studies in Taiwan and India reported that the
assisted reproductive technologies (ART). The prevalence of preterm birth was increased in
number of babies conceived through this IVF pregnancies compared to natural
procedure is increasing, with an estimated 3-5 pregnancies.8,9
million IVF babies worldwide.1–3 As the A study in eight infertility centers in
number of newborns increase, several studies Indonesia showed a pregnancy success rate
have been conducted to evaluate neonatal of 29.46%.10 In 2014, the IVF program at Dr.
outcomes of low birth weight (LBW), preterm Sardjito General Hospital, Yogyakarta, had a
birth, and small-for-gestational age (SGA). 25.4% pregnancy success rate, while the
These outcomes occur almost twice as often percentage of live births was 19.8%. These
compared to natural pregnancies, even in percentages increased in 2015 to 30.9% and
singleton IVF pregnancies.4–7 Guidelines 25.1%, respectively.11,12 The IVF program in
provided, to optimize obstetrical management Indonesia has existed for approximately 29
and counselling (counseling) of Canadian years with an increasing percentage of live
women using ART, and to identify areas births, but the data on neonatal outcomes
specific to birth outcomes and ART requiring remains unclear. Hence, this study aimed to
further research. Perinatal outcomes of ART evaluate the risk of poor neonatal outcomes
pregnancies in subfertile women are compared in IVF infants.
with those of spontaneously conceived
pregnancies. Perinatal outcomes are compared MATERIALS AND
between different types of ART. This guideline METHODS Subjects
discusses the adverse outcomes that have been
This retrospective cohort study was done
recorded in association with ART, including
from January 2012 to December 2016. Infants
obstetrical complications, adverse perinatal
outcomes, multiple gestations, structural who were born at Dr. Sardjito General
congenital abnormalities, chromosomal Hospital, Yogyakarta, through IVF pregnancies
abnormalities, imprinting disorders, and (IVF group) and natural pregnancies (natural
childhood cancer. The Cochrane Library and group) were recruited as subjects. The infants
MEDLINE were searched for English-language whose mothers underwent IVF procedures
articles from 1990 to February 2005, relating to outside this hospital and those whose medical
assisted reproduction and perinatal outcomes. records were not found or incomplete were
Search terms included assisted reproduction, excluded. The data were collected from
assisted reproductive technology, ovulation medical records using questionnaires.
induction,

164
 Muhammad Buchori et al., Neonatal outcomes in in vitro fertilization (IVF) pregnancies

Protocol of study the relationship. Statistical significance was

A total sampling method for IVF infants defined to be p<0.05. Multivariate analysis
and a simple random sampling method for the was performed using logistic regression.
natural group were used. Naturally conceived
infants born on the same day as an IVF infant RESULTS
underwent simple random sampling for Fifty-eight IVF infants were initially
inclusion. If no naturally conceived infant was screened for this study, but three infants were
found on the same dayas an IVF infant, excluded due to their IVF not having been
retrieval was extended to up to three days later. performed in Dr. Sardjito General Hospital
A minimum of 64 subjects was required and one due to loss of the medical records.
for each group to obtain 90% power with 5% Hence, 54 subjects were included in the IVF
significance level. In this study, dependent
group. No infants born from natural
variables were neonatal outcomes, i.e., birth
pregnancies were excluded, for a total of 54
weight, gestational age, and birth weight
naturally conceived subjects (FIGURE 1).
according to gestational age, while independent
variables were the process of fertilization (IVF/
natural). Confounding variables were maternal
age, parity, and placental abnormalities.
The definition of LBW was weight at birth
of less than 2,500 g, regardless of the
gestational age; the definition of SGA was
birth weight according to gestational age of
less than 10th percentile on the Lubchenco
curve. Gestational age was defined as the
length of pregnancy until the time of delivery.
By the Dubowitz score, preterm was defined as
<37 weeks gestational age.13 Maternal age was
defined as the age of the mother at the time of
delivery. Parity was defined as the number of
previous pregnancies that reached viable FIGURE 1. Flowchart of subjects recruitment
gestational age. Placental abnormalities
included placental abruptio or placenta previa. The characteristics of subjects are shown
Faculty of Medicine, Universitas , Yogyakarta in TABLE 1. The IVF group (88.9%) had a
greater proportion of parity 0 (nulliparous)
Statistical analysis than the natural group (38.9%). In addition,
Statistical analysis was done using SPSS the IVF group (22.2%) had a greater
Statistics 20. Univariate analysis was proportion of multiple pregnancies than the
performed on numerical data and was shown natural group (7.40%), though the proportion
as mean or median, while categorical data of singletons (77.8%) was still greater than
was displayed in proportion. Chi-square or the proportion of multiples (22.2%) in the
Fisher’s exact tests were used to compare IVF group. Moreover, the IVF group (92.6%)
independent and dependent variables, with had a greater proportion of caesarean section
relative risk as a measure of the strength of deliveries than the natural group (48.1%).

165
J Med Sci, Volume 50, No. 2, 2018 April: 163-172

TABLE 1. Characteristics of IVF and naturally conceived subjects

IVF Natural
Characteristics
(n = 54) (n = 54)
Maternal age [n (%)]
• 20-34 years 34 (63.0) 36 (66.7)
• ≥35 years 20 (37.0) 18 (33.3)
Maternal age (mean ± SD years) 33.2 ± 3.74 31.4 ± 5.53
Parity prior to this pregnancy [n (%)]
•0 48 (88.9) 21 (38.9)
• ≥1 6 (11.1) 33 (61.1)
Gestational age, n (%)
• Full term 48 (88.9) 51 (94.4)
• Preterm 6 (11.1) 3 (5.60)
Number of fetuses [n (%)]
• Single 42 (77.8) 50 (92.6)
• Multiple 12 (22.2) 4 (7.40)
Sex [n (%)]
• Male 27 (50.0) 34 (63.0)
• Female 27 (50.0) 20 (37.0)
Birth weight, n (%)
• Normal 44 (81.5) 46 (85.2)
• Low 10 (18.5) 8 (14.8)
Birth weight 2,875.0 2,928.4
[median (min-max)/mean (SD)] (600-3850) (400)
Birth weight for gestational age, n (%)
• AGA 51 (94.4) 51 (94.4)
• SGA 3 (5.60) 3 (5.60)
Mode of delivery [n (%)]
• Vaginal 4 (7.4) 28 (51.9)
• Caesarean section 50 (92.6) 26 (48.1)
Placental abnormalities, n (%) 4 (7.4) 0 (0)
AGA=appropriate for gestational age; SGA=small for gestational age

TABLE 2 shows the bivariate analysis 7.58; p=0.48). Other independent variables
between the independent variables and preterm. such as maternal age, parity, and placental
The IVF infants had two times the risk of abnormalities had no significantly association
preterm birth than natural infants. However, it with the occurrence of preterm birth (p>0.05).
was not significantly different (95%CI 0.52-

166
 Muhammad Buchori et al., Neonatal outcomes in in vitro fertilization (IVF) pregnancies

TABLE 2. Bivariate analysis of independent variables and preterm

Preterm Full term Bivariate

Variables
(n=9) (n=99) RR 95% CI p
Fertilization process [n (%)]
• IVF 6 (11.1) 48 (88.9)
2.0 0.52-7.58 0.48
• Natural 3 (5.6) 51 (94.4)
Maternal age [n (%)]
• 20-34 years 5 (7.1) 65 (92.9)
0.67 0.19-2.37 0.71
• ≥35 years 4 (10.5) 34 (89.5)
Parity prior to pregnancy [n (%)]
• Nulliparous 6 (8.7) 63 (91.3)
1.13 0.29-4.27 1.00
• Multiparous 3 (7.7) 36 (92.3)
Placental abnormalities [n (%)]
• Yes 1 (25) 3 (75)
3.25 0.52-20.1 0.29
• No 8 (7.7) 96 (92.3)

Bivariate analysis of the independent variables such as maternal age, parity, and
variables and SGA revealed no increased risk placental abnormalities also had no
of SGA in IVF infants (RR=1.0; 95%CI significant association with the incidence of
0.21- 4.73; p=1.0). Other independent SGA (TABLE 3).

TABLE 3. Bivariate analysis of independent variables and SGA

SGA AGA Bivariate

Variable
(n=6) (n=102) RR 95%CI p
Fertilization process [n (%)]
• IVF 3 (5.6) 51 (94.4)
1.0 0.21- 4.73 1.0
• Natural 3 (5.6) 51 (94.4)
Maternal age [n (%)]
• 20-34 years 3 (4.3) 67 (95.7)
0.54 0.11- 2.56 0.66
• ≥35 years 3 (7.9) 35 (92.1)
Parity prior to this pregnancy [n (%)]
• Nulliparous 3 (4.3) 66 (95.7)
0.56 0.12- 2.67 0.66
• Multiparous 3 (7.7) 36 (92.3)
Placenta abnormalities [n (%)]
• Yes 0 (0) 4 (100)
1.00
• No 6 (5.80) 98 (94.2)
SGA=small for gestational age; AGA=appropriate for gestational age
naturally conceived infants. However, it was
Bivariate analysis of the independent was not significantly different (95%CI 0.53
variables and LBW revealed that IVF infants
had 1.2 times higher risk of LBW compared to
 abnormalities were not also significantly
- 2.92; p= 0.6). Other independent variables associated with LBW incidence (TABLE 4).
such as maternal age, parity, and placental

167
J Med Sci, Volume 50, No. 2, 2018 April: 163-172

TABLE 4. Bivariate analysis of independent variables and LBW

LBW NBW Bivariate

Variable
(n=18) (n=90) RR 95%CI p
Fertilization process [n (%)]
• IVF 10 (18.5) 44 (81.5)
1.25 0.53- 2.92 0.60
• Natural 8 (14.8) 46 (85.2)
Maternal age [n (%)]
• 20-34 years 10 (14.3) 60 (85.7)
0.67 0.29 -1.57 0.37
• ≥35 years 8 (21.1) 30 (78.9)
Parity prior to pregnancy [n (%)]
• Nulliparous 11 (15.9) 58 (84.1)
0.88 0.37 -2.10 0.78
• Multiparous 7 (17.9) 32 (82.1)
Placenta abnormalities [n (%)]
• Yes 1 (25) 3 (75)
1.53 0.26- 8.82 0.52
• No 17 (16.3) 87 (83.7)
LBW: low birth weight; NBW: normal birth weight

Multivariate analysis could not be All infants from ART procedures may be
performed in this study due to no variables predisposed to preterm birth. Previous studies
had p values <0.25 after bivariate analysis divided ART into subgroups, i.e., fresh with
performed. frozen embryos, oocyte donors with own
oocytes, standard IVF with intracytoplasmic
sperm injection (ICSI), and third day with
DISCUSSION
fifth day embryo showed greater risk of
The proportions of preterm infants were preterm, LBW and VLBW in each
11.1% and 5.6% in the IVF and natural groups, subgroup.17,18 Maternal morbidity and
respectively. Similarly, a previous study mortality among Swedish women giving
reported that the prevalence of preterm ranged birth after in vitro fertilisation (IVF)
from 7.8 to 16.1% in IVF population and 4.5% However, Romundstad et al.19 also compared
to 8.0% in natural population.14 Nevertheless, natural conception with ART in the same
no significant association between IVF and mothers and found no significant difference.
preterm (p=0.48) was observed, whereas They concluded that ART did not harm the
several previous studies showed significant perinatal outcome, but genetics was more
results.14,15 Koivurova et al.16 found no likely to be an underlying factor of preterm
significant association between singleton IVF incidence. Another study mentioned that
and preterm (OR 1.5; 95%CI 0.7 ART pregnancies were generally more
- 3.2), in which the control was only singleton closely monitored, such that birth was more
pregnancies taken from the general population. frequently subject to induction and caesarean
However, this result became significant when section. These ART interventions also have
both singleton and multiple pregnancies were been associated with SGA incidence,
taken as control subjects (OR 5.6; 95%CI 3.7 - increased perinatal mortality, and VLBW.14
8.6). As such, sample diversity is an important The proportion of SGA in our study was
factor in the incidence of preterm.16 similar in both the IVF and natural groups
168
 Muhammad Buchori et al., Neonatal outcomes in in vitro fertilization (IVF) pregnancies

(5.6%). Previous studies reported SGA in growth and decidualization.26

12.7% of IVF pregnancies and 13% of natural Several previous studies have noted that
pregnancies,20 and 2.89% in both IVF and natural the underlying factors of preterm, SGA, and
newborns.21 In this study, there was no increased LBW remain unclear.7,27,28 To date, the
risk of SGA in IVF infants. However, this underlying factors are maternal age,
finding may not be conclusive, as a previous infertility/ subfertility, genetics, as well as the
meta-analysis stated that the risk of SGA in IVF IVF technique itself, but we were unable to
pregnancies was 1.3 times higher compared to assess for these variables in our study.
natural pregnancies (95%CI 1.27 to 1.53).22 In Furthermore, women who undergo ART may
contrast, other studies stated that there was no differ from the general population, as these
increased risk of SGA in IVF infants. 20,21,23 Wen women usually have high socioeconomic
et al.23 noted that general and more diverse status, good nutritional status, better
populations tended to have significant influences antenatal care, and sufficient rest during
on SGA incidence. pregnancy. These factors are believed to
The proportions of LBW in our study positively affect pregnancy and its outcome.24
were 18.5% and 14.8% in the IVF and Another study reported that most pregnancies
natural groups, respectively. Similarly, a from the IVF program had no complications
previous study reported LBW of 11.2% in and resulted in the birth of healthy babies.29
IVF and 11.6% in natural newborns.20 Our Several limitations of our study should be
bivariate analysis revealed no significant noted. The small and potentially inadequate
association between IVF and LBW incidence sample size as well as the retrospective study
(p=0.60), similar to previous studies that design may have led to information bias. The
compared LBW and preterm in ART and selection of no intervention populations
non-ART groups.20,24 In contrast, a recent (natural populations) appropriate to the IVF
meta-analysis suggested that LBW tended to population WAS also a weakness. Women who
occur in the IVF population compared to the underwent IVF treatment in this study
natural population, even if the baby is full generally had middle to upper economic status
term.25 Differences in the size of the research (because the IVF program in Indonesia is not
scale may explain our lack of association guaranteed by insurance), more routine control,
between IVF and LBW, as small-scale consultation, and treatment during pregnancy,
research tended to get no significant results.20 especially by the obstetrician. Hence, the IVF
Placental abnormalities (all placenta group may have received better attention and
previa) were only found in our IVF group care than the natural group. Another weakness
(7.4%), but there were not significantly in our study was that some important variables
different from the natural population. IVF such as socioeconomic status and maternal
procedures such as cervical catheterization, or education were not recorded completely in the
mechanically- inducing uterine contractions medical records, so they were not included in
may play a major role in implantation in the the analysis.
lower uterine segment, thus leading to placenta
previa.19 Another study explained that high
CONCLUSION
concentrations of estradiol hormone in the IVF
cycle increased complications associated with In conclusion, the risk of preterm birth and
placental aberration by affecting endometrial LBW in IVF infants tend to be higher than

169
J Med Sci, Volume 50, No. 2, 2018 April: 163-172
in naturally conceived infants. However, they
are not statistically significant. In addition,
there is no increased risk of SGA in IVF 7. Voorhis BJ Van. In Vitro Fertilization. N
infants. Further research using a larger sample Engl J Med 2007; 356: 379–86.
size is needed for more representative data of https://doi.org/10.1056/NEJMcp065743
the actual conditions in the population. 8. Chou H, Tsao P, Yang Y, Tang J, Tsou K.
Neonatal outcome of infants born after in vitro
fertilization at National Taiwan University
ACKNOWLEDGMENTS
Hospital. J Formos Med Assoc 2002; 101: 203–5.
We would like to thank Permata Hati 9. Gupta P, Nayan N, Sharma M. Perinatal
Infertility Clinic, Dr. Sardjito General outcomes among children born by assisted
Hospital, Yogyakarta for contributing to this reproductive techniques-a hospital-based case
study. control study. Med J Armed Forces India 2012;
68: 132–5.
https://doi.org/10.1016/S03
REFERENCES
7 7 - 1237(12)60019-7
1. Egbe TO, Sandjon G, Ourtchingh C, Simo A, 10. Soebijanto S. Prediction of pregnancy success
Priso EB, Benifla J-L. In vitro fertilization and rate through in vitro fertilization based on maternal
spontaneous pregnancies: matching outcomes age. Med J Indones 2009; 18: 244–8.
in Douala, Cameroon. Fertil Res Pract 2016; https://doi.org/10.13181/mji.v18i4.371
2: 1–8. 11. Klinik Permata Hati. Format laporan
https://doi.org/10.1186/s40738-015-0013-2 program TRB (Teknologi Reproduksi Berbantu).
2. Indonesia Association In Vitro Fertilization. Yogyakarta: Klinik Permata Hati-RSUP Dr.
Understanding access to ART in Indonesia. 2012. Sardjito: Yogyakarta, 2014.
[serial online] [cited 2015 Feb 12]. Availale from 12. Klinik Permata Hati. Format laporan
: http://www.ia-ifv.org/?p=33 program TRB (Teknologi Reproduksi Berbantu).
3. Ramalingam M, Durgadevi P, Mahmood T. Yogyakarta: Klinik Permata Hati-RSUP Dr.
In vitro fertilization. Obstet Gynaecol Reprod Sardjito: Yogyakarta, 2015.
Med 2016; 26: 200–9. 13. Smith V. The high-risk newborn:
https://doi.org/10.1016/j.ogrm.2016.05.006 anticipation, evaluation, management, and
4. Allen VM, Wilson RD, Cheung A. Pregnancy outcome. In: Cloherty J, Eichenwald E, Hansen
outcomes after assisted reproductive A, Stark A editors. Manual of neonatal care.
technology. J Obstet Gynaecol Canada 2006; Philadelphia: Lippincot Williams & Wilkin:
28: 220–50. Philadelphia, 2012.
https://doi.org/10.1016/S17 14. Šljivančanin T, Kontić-vučinić O. Perinatal
0 1 - 2163(16)32112-0 outcomes of pregnancies conceived by assisted
5. Gao L, Yang S. Perinatal outcomes of reproductive technologies. Srp Arh Celok Lek
children born after assisted reproduction 2015; 143: 632–8.
technology : a review. Austin J Reprod Med https://doi.org/10.2298/SARH1510632S
Infertil 2015; 2: 1–3. 15. Frangez HB, Korosec S, Verdenik I, Kotar
6. Klemetti R, Sevón T, Gissler M, Hemminki E. V, Kladnik U, Bokal EV. Preterm delivery risk
Health of children born as a result of in vitro factors in singletons born after in vitro
fertilization. Pediatrics 2006; 118: 1819–27. fertilization procedures. Eur J Obstet Gynecol
https://doi.org/10.1542/peds.2006-0735 2014; 176: 183–6.
https://doi.org/10.1016/j.ejogrb.2014.03.002

170
 Muhammad Buchori et al., Neonatal outcomes in in vitro fertilization (IVF) pregnancies

16. Koivurova S, Hartikainen A, Gissler M, study. Hum Reprod 2002; 17: 1755–61.
Hemminki E, Sovio U, Jarvelin M. Neonatal https://doi.org/10.1093/humrep/17.7.1755
outcome and congenital malformations in 22. Pandey S, Shetty A, Hamilton M,
children born after in vitro fertilization. Hum Bhattacharya S, Maheshwari A. Obstetric and
Reprod 2002; 17: 1391–8. perinatal outcomes in singleton pregnancies
https://doi.org/10.1093/humrep/17.5.1391 resulting from ivf/icsi: A systematic review and
https://doi.org/10.1093/humrep/17.11.3005 meta-analysis. Hum Reprod Update 2012; 18:
17. Källén B, Finnström O, Nygren KG, 485– 503.
Otterblad Olausson P, Wennerholm UB. In vitro https://doi.org/10.1093/humupd/dms018
fertilisation in Sweden: obstetric characteristics, 23. Wen S, Leader A, White R, Leveille M, Wilkie
maternal morbidity and mortality. BJOG 2005; V, Zhou J et al. A comprehensive assessment of
112: 1529–35. outcomes in pregnancies conceived by in vitro
https://doi.org/10.1111/j.14 fertilization/intracytoplasmic sperm injection. Eur J
7 1 - 0528.2005.00745.x Obs Gynecol Reprod Biol 2010; 150: 160–5.
18. Schieve L, Cohen B, Nannini A, Ferre C, https://doi.org/10.1016/j.ejogrb.2010.02.028
Reynolds M, Zhang Z. Massachusetts 24. Fitzsimmons BP, Bebbington MW, Fluker
Consortium for Assisted Reproductive MR. Perinatal and neonatal outcomes in multiple
Technology Epidemiologic Research gestations : Assisted reproduction versus
(MCARTER). A populationbased study of spontaneous conception. Am J Obs Gynecol
maternal and perinatal outcomes associated with 1998; 179: 1162–7.
assisted reproductive technology in https://doi.org/10.1016/S00
Massachusetts. Matern Child Heal J 2007; 11: 0 2 - 9378(98)70125-5
517–25. https://doi.org/10.1007/s10995-007- 25. Bruggeman JW. The effect of in vitro
0202-7 fertilization on low birth weight and preterm
19. Romundstad L, Romundstad P, Sunde A, V delivery in Singletons : a brief review and meta-
von D, Skjaerven R, Gunnell D. Effects of analysis. Hum Body 2016; 1: 40–5.
technology or maternal factors on perinatal 26. Farhi J, Ben-Haroush A, Andrawus N,
outcome after assisted fertilisation: a population- Pinkas H, Sapir O, Fisch B. High serum
based cohort study. Lancet 2008; 372: 737–43. oestradiol concentrations in IVF cycles increase
https://doi.org/10.1016/S01 the risk of pregnancy complications related to
4 0 - 6736(08)61041-7 abnormal placentation. Reprod BioMed Online
20. Reubinoff BE, Samueloff A, Ben-Haim 2010; 21: 331–7.
M, Friedler S, Schenker JG, Lewin A. Is the https://doi.org/10.1016/j.rbmo.2010.04.022
obstetric outcome of in vitro fertilized 27. Jackson RA, Gibson KA, Wu YW, Croughan
singleton gestations different from natural MS. Perinatal outcomes in Singletons following in
ones ? a controlled study. Fertil Steril 1997; vitro fertilization : a meta analysis. Am Coll Obstet
67: 1077–83. Gynecol 2004; 103: 551–63.
https://doi.org/10.1016/S00 https://doi.org/10.1097/01.
1 5 - 0282(97)81442-2 AOG.0000114989.84822.51
21. Isaksson R, Gissler M, Tiitinen A. Obstetric 28. Royal College of Obstetricians and
outcome among women with unexplained Gynaecologist. In vitro fertilisation : perinatal
infertility after IVF: a matched case–control risks and early childhood outcomes. Sci Impact
Pap 2012; 8:1-12.

171
J Med Sci, Volume 50, No. 2, 2018 April: 163-172 29. Okun N, Sierra S, Wilson RD, Audibert
F, Brock J-A, Campagnolo C et al.
Pregnancy outcomes after assisted human
reproduction.
J Obstet Gynaecol Canada 2014; 36: 64–83.
https://doi.org/10.1016/S17
0 1 - 2163(15)30685-X

172