The Journal of Maternal-Fetal & Neonatal Medicine

ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20

The association of placenta previa and assisted

reproductive techniques: a meta-analysis

Manoochehr Karami, Ensiyeh Jenabi & Bita Fereidooni

To cite this article: Manoochehr Karami, Ensiyeh Jenabi & Bita Fereidooni (2017): The association
of placenta previa and assisted reproductive techniques: a meta-analysis, The Journal of Maternal-
Fetal & Neonatal Medicine, DOI: 10.1080/14767058.2017.1332035

To link to this article: http://dx.doi.org/10.1080/14767058.2017.1332035

Accepted author version posted online: 17

May 2017.

Submit your article to this journal

Article views: 6

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20

Download by: [Cornell University Library] Date: 30 May 2017, At: 21:42
The association of placenta previa and assisted reproductive techniques: a meta-analysis

Manoochehr Karami (PhD)

Social Determinates of Health Research Center, Hamadan University of Medical Sciences,
Hamadan, Iran
Email: ma.karami@umsha.ac.ir

Ensiyeh Jenabi (PhD student)

Department of Midwifery, Toyserkan Branch, Islamic Azad University, Toyserkan, Iran

E-mail: en.jenabi@yahoo.com

D
Bita Fereidooni (PhD student)

TE
Midwife in Social Security Organization, Hamadan Branch, Iran
E-mail: barshimah@yahoo.com
EP
Corresponding author: Ensiyeh Jenabi (PhD student)
C

Department of Midwifery, Toyserkan Branch, Islamic Azad University, Toyserkan, Iran.

AC

E-mail: en.jenabi@yahoo.com

Zip code: 6517838695

Tel: +98 81 34920253

ST

Fax: +98 81 34923553

Running title
JU

The association of placenta previa and ART

Abstract

Background: Several epidemiological studies have determined that assisted reproductive

techniques (ART) can increase the risk of placenta previa. To date, only a meta-analysis has
been performed for assessing the relationship between placenta previa and ART. This meta-
analysis was conducted to estimate the association between placenta previa and ART in
singleton and twin pregnancies.
Methods: A literature search was performed in major databases PubMed, Web of Science,
and Scopus from the earliest possible year to April 2017. The heterogeneity across studies
was explored by Q-test and I2 statistic. The publication bias was assessed using Begg's and
Egger's tests. The results were reported using odds ratio (OR) and relative risk (RR) estimates
with its 95% confidence intervals (CI) using a random-effects model.

Results: The literature search yielded 1529 publications until September 2016 with 1,388,592

D
participants. The overall estimate of OR was 2.67 (95% CI: 2.01, 3.34) and RR was 3.62

(95% CI: 1.26, 1.74) based on twin pregnancies. TE

(95% CI: 0.21, 7.03) based on singleton pregnancies. The overall estimate of OR was 1.50

Conclusions: We showed based on based on odds ratio reports in observational studies that
EP
ART procedures are a risk factor for placenta previa.

Keywords: placenta previa; assisted reproductive techniques; pregnancy; meta-analysis

C
AC
ST
JU
Introduction

Over recent decades, the use of assisted reproductive techniques (ART) has increased
enormously [1, 2]. It is suggesting that between 1 and 4% of the newborn population in
industrialized countries conceived by ART [3]. Assisted reproductive techniques include all
fertility treatments in which the gametes are handled outside the human body [4]. The impact
of ART conception on the course of pregnancy is not yet fully understood, however there are
concerns regarding poor obstetric outcomes in these pregnancies [5]. Recent studies indicated
that infertility and ART increase the incidence of some obstetric complications such as
preeclampsia, gestational diabetes, placenta abruption, and placenta previa [6, 7, 8, 9, 10].

Placenta previa, placentation in the lower segment of the uterine cavity, occurs in about 5 in
1,000 pregnancies [11] and associated with serious maternal and adverse fetal outcomes,
including morbid adherence of the placenta, maternal hemorrhage, thrombophlebitis, preterm

D
labor, septicemia and perinatal outcomes [12, 13]. The pathogenesis of the disease is not

TE
clearly understood, but several studies have reported the risk of placenta previa in
pregnancies of women [14] multiparity [13, 14], smoking [15], prior cesarean delivery [16,
EP
17], underlying infertility [18] and assisted reproductive technology (ART) [14, 19].
Infertility and ART increase the incidence of some obstetric complications. The risk of
placenta previa may be increased in pregnancies conceived ART compared natural
C

conception. Whether the increased risk is due to factors related to the reproductive
AC

technology, or associated with maternal factors, is not known [7].

Only a meta-analysis has been conducted by Qin et al. in 2016 were showed that placenta
previa increased in singleton and twin pregnancies after assisted reproductive technology
ST

(ART) compared with those conceived naturally. The number of studies included in singleton
and twin pregnancies was 12 and 4 cohort studies, respectively. However, they searched
PubMed, Google Scholar, Cochrane Libraries and Chinese database as well as this meta-
JU

analysis was limited to cohort studies [20, 21].

Our aim was to perform a meta-analysis to ensure a comprehensive and unbiased summary of
the available evidence of the effect of ART on placenta previa compared with natural
conceptions in singleton and twin pregnancies.
Materials and methods

Definition

Placenta previa: Placenta previa occurred when the placenta is implanted in segment of the
uterus lower. Placenta previa is included complete previa (the cervical opening is completely
covered), partial previa (a portion of the cervix is covered by the placenta) and marginal
previa (extends just to the edge of the cervix).

IVF (In vitro fertilization): IVF is the process of fertilization by extracting eggs, retrieving a
sperm sample, and then manually combining an egg and sperm in a laboratory dish. The
embryo is then transferred to the uterus.

ICSI (Intracytoplasmic sperm injection): ICSI is an IVF method that a single sperm is
injected directly in an egg.

D
Eligibility criteria

TE
The exposure of interest was ART and the outcome of interest was placenta previa. Placenta
EP
previa in all studies should be confirmed at term pregnancy. Observational studies, such as
cohort, case-control, and cross-sectional studies, finding the association between ART and
placenta previa were included irrespective of language, date of publication, nationality, race
C

and age.
AC

Information sources and search

Major electronic databases, such as PubMed, Web of Science and Scopus were searched until
April 2017. The reference lists of the included studies were searched to identify additional
ST

studies. Also, we contacted with authors of published studies for further details.
The following search key words were conducted individually and in combination: (placental
previa or placenta previa) and (Assisted reproductive technology OR ART OR Assisted
JU

conception OR Assisted reproduction OR In vitro fertilization OR IVF OR Test tube baby OR

Intracytoplasmic sperm injection OR ICSI OR Artificial insemination OR Intrauterine
insemination OR IUI OR Cervical canal insemination OR Embryo transfer).
Study selection
The search results from different databases were combined by conducting EndNote reference
manager software and deleted duplicate records of the same report. Then, titles and abstracts
by two authors screened independently to remove ineligible studies. Disagreements were
resolved by discussion. We retrieved the full text of the potentially eligible studies and
examined full-text reports for further evaluation.
Data extraction
We extracted data from relevant studies using an electronic data collection form prepared in
Stata software. We contacted study authors to request further information, such as missing
results. We extracted the following information: first author’s name, year of publication,
country, language, design of the studies (cohort, case-control, cross-sectional), type of
pregnancy (singleton, twin), type of ART, effect estimate (risk ratio, odds ratio), sample size,
effect sizes and related 95% confidence intervals (CIs).
Methodological quality
The NOS is a practical scale for assessing the quality of observational studies.The NOS
assigns up to a maximum of nine points for the least risk of bias in three domains: 1) selection

D
of study groups (four points); 2) comparability of groups (two points); and 3) ascertainment of
exposure and outcomes (three points) for case–control and cohort studies, respectively.

TE
Survey questions were developed based on the NOS’ questions covering all three domains so
that authors could provide detailed information about their studies [22]. In this meta-analysis,
EP
the studies with six star-items or less were considered low-quality and those with seven star-
items or more were considered high-quality.
C

Heterogeneity and reporting biases

AC

Heterogeneity was examined by chi-squared test and its quantity was measured by the I2
statistic [23]. The possibility of publication bias was investigated by the Egger's and Begg's
tests[24]. The relative risk (RR) and the odds ratio (OR) were used with their 95% confidence
intervals (CI) to express the association between ART and placenta previa We analyzed data
ST

and reported the results based on a random-effects model. The statistical analyses were used
at a significance level of 0.05 using Stata software, version 11 (StataCorp, College Station,
JU

TX, USA).
Subgroup analysis

Subgroup analysis
Subgroup analysis was conducted based on the quality of included studies (high-quality and
low-quality) and control for confounding (adjusted and crude).
Results
Description of studies
A total of 1529 references identified including 512 articles through searching the electronic
databases until April 2017 and 1017 articles through screening the reference list of included
studies. We excluded 721 duplicates using EndNote reference manager and 747 ineligible
studies through reading titles and abstracts. Accordingly, 61 references retrieved for further
assessment. We excluded 37 references (eight studies were letter or review and 29 study did
not meet the inclusion criteria) of this meta-analysis. Finally, 24 references remained for
meta-analysis (Fig 1) including 21 cohort studies [25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,
36, 37, 38, 39, 40, 41, 42, 43, 44, 45] , 2 case-control studies [46, 47] and 1 cross-sectional
study [48] involving 1,377,893 participants. All studies were published in English (Table 1).
The number of studies reported in Fig 2 may be more than the total number of included

D
studies. The reason is that some studies reported the association between ART and different
types of pregnancies (singleton and twin). Wherever reported, full adjusted forms of OR was used

TE
controlled for at least two or more potential confounding factors such as race, educational level,
maternal age, ethnicity, parity, year and month of birth, smoking habits, alcohol consumption,
hypertensive disorders and premature rupture of membranes (Table 1).
EP
Effects of exposure

The risk of placenta previa among ART versus spontaneous pregnancy in singleton and twin
C

pregnancies is shown in Fig 2 and Fig3.

AC

According to this forest plot, there was a significant association between ART and Placenta
previa. The overall estimate of OR was 2.67 (95% CI: 2.01, 3.34) and RR was 3.62 (95% CI:
0.21, 7.03) based on singleton pregnancies. The overall estimate of OR was 1.50 (95% CI:
1.26, 1.74) based on twin pregnancies.
ST

Heterogeneity and Publication bias

The results of studies showed moderate heterogeneity among studies estimating OR in

JU

singleton (I2 = 72.7%, P = 0.000) and severe heterogeneity among studies estimating RR in
singleton (I2 = 82.1%, P = 0.004). There was not heterogeneity in studies estimating OR in
twins (I2 = 0.0%, P = 0.990). (Figure 2 and 3) [23] .
Publication bias was assessed using Begg's and Egger's tests. On the basis of these statistical
tests, there was no evidence of publication bias among studies addressing the association
between placenta previa and ART in singleton pregnancies (P = 0.729 and P = 0.880) and
twin pregnancies (P = 0.586 and P = 0.054), respectively (fig 4 and Fig5).
Quality of the studies

There were 19 high- quality and 3 low-quality studies based on NOS scale (Table 1).

Subgroup analysis

We performed subgroup analysis based on crude/adjusted type and the quality of the included
studies. Based on studies estimating OR in singleton in crude studies, 2.78 (95% CI: 1.89,
3.67) and in adjusted studies was 2.59 (95% CI: 1.70, 3.48). Based on studies estimating OR
in twins in crude studies, 1.47 (95% CI: 1.23, 1.71) and in adjusted studies was 2.91 (95% CI:
1.08, 4.73). Based on this analysis, there was no significant difference between adjusted and crude
studies.

Subgroup analysis based on quality studies was conducted in singleton. The association
between placenta previa and ART in studies estimating OR in high-quality studies was 2.77

D
(95% CI: 2.08, 3.46) and in low-quality studies was 0.55 (95% CI: -2.19, 3.29). Based on this

TE
analysis, there was significant difference between the results of high- and low-quality studies.
Discussion
EP
In this systematic review, we have performed the available evidence based on odds ratio
reports from observational studies conducting the association between ART and placenta
previa. Our results suggest that ART procedures are a risk factor for ART.
C

In 2016, a meta-analysis have been performed by Qin et al. for assessing placenta previa and
AC

ART in singleton and twin pregnancies [20, 21]. They searched PubMed, Google Scholar,
Cochrane Libraries and Chinese database until 2015. The number of studies included in
singleton and twin pregnancies was 12 and 4 cohort studies, respectively. They showed that
the risk of placenta previa increased with ART and the overall effect of ART on placenta
ST

previa in singleton and twin pregnancies was (RR 3.71; 95% CI: 2.67, 5. 16) and (RR 2.99;
95% CI: 1.51, 5. 92), respectively. These meta-analyses not searched Scopus and Web of
JU

Science database as well as the number of studies included was limited.

There was considerable heterogeneity in among the reports of the included studies in
singleton pregnancy (Q test and I2 statistic). However, care must be taken in the explanation
of the statistical tests for heterogeneity. The Q-test has low power when the sample size is
small. On the other hand, the test has high power in indicating a small amount of
heterogeneity that may be clinically unimportant when there are many studies in a meta-
analysis [49]. Therefore, we can attribute major part of the observed heterogeneity in the
results to the number of participants.
According to Subgroup analysis, results in high-quality studies was significant.

The mechanisms defined in the association between ART and poor outcomes such as placenta
previa in the singleton pregnancies are uncertain. One interpretation is that ART procedures
or maternal factors associated with infertility or a combination of these bring about increased
risks of poor outcomes in the ART pregnancies. Some studies have reported that factors
associated with ART procedures themselves, including the culture media composition, the
length of time in culture, the freezing and thawing of embryos, the potential for polyspermic
fertilization, the delayed fertilization of the oocyte, altered hormonal environment at the time
of implantation, and the manipulation of gametes and embryos or a combination of these, may
increase the risk of adverse outcomes [50, 51].

There are several limitations to this study. (a) In order to control for known risk factors of

D
placenta previa, we used the adjusted form. However, some studies reported only the
unadjusted form of OR/RR. This might introduce information bias in our results. (b) Some

TE
studies for diagnosis of placenta previa not used Ultrasound of transvaginal. Ultrasound
especially if not used transvaginally is associated with a high false positive rate. (c) Also,
EP
types of placenta previa in all studies not determined. Despite of these limitations, the meta-
analysis with 1,388,592 participants could efficiently estimate the association between ART
and placenta previa. Our results indicated based on odds ratio reports in epidemiological
C

studies that ART procedures can increase the risk of placenta previa. Therefore, ART
AC

procedures are a risk factor for placenta previa.

Conclusions: We showed based on odds ratio reports in observational studies that ART
procedures are a risk factor for placenta previa.
ST

Conflict of interest statement

The authors declare that have no conflict of interest.
JU
 References:

1. Ernstad EG, Bergh C, Khatibi A, Källén KB, Westlander G, Nilsson S, Wennerholm U-B. Neonatal and
maternal outcome after blastocyst transfer: a population-based registry study. American journal of
obstetrics and gynecology. 2016;214:378. e1-. e10.
2. Ferraretti A, Goossens V, De Mouzon J, Bhattacharya S, Castilla J, Korsak V, Kupka M, Nygren K,
Nyboe Andersen A. European IVF-monitoring (EIM); Consortium for European Society of Human
Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2008: results
generated from European registers by ESHRE. Human reproduction (Oxford, England). 2012;27:2571-
84.
3. de Mouzon J, Goossens V, Bhattacharya S, Castilla J, Ferraretti A, Korsak V, Kupka M, Nygren K-G,
Andersen AN. Assisted reproductive technology in Europe, 2006: results generated from European
registers by ESHRE. Human Reproduction. 2010:deq124.
4. Inhorn MC. Middle Eastern masculinities in the age of new reproductive technologies: male infertility
and stigma in Egypt and Lebanon. Medical Anthropology Quarterly. 2004:162-82.
5. Joy J, Gannon C, McClure N, Cooke I. Is assisted reproduction associated with abnormal placentation?
Pediatric and Developmental Pathology. 2012;15:306-14.
6. Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, Hankins GD, Eddleman K, Dolan S,
Dugoff L, Craigo S, Timor IE, Carr SR, Wolfe HM, Bianchi DW, D'Alton ME. Assisted reproductive

D
technology and pregnancy outcome. Obstetrics and gynecology. 2005;106:1039-45. Epub
2005/11/02.
7.

8.
TE
Romundstad LB, Romundstad PR, Sunde A, von During V, Skjaerven R, Vatten LJ. Increased risk of
placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in
the same mother. Human Reproduction. 2006;21:2353-8.
Schieve LA, Cohen B, Nannini A, Ferre C, Reynolds MA, Zhang Z, Jeng G, Macaluso M, Wright VC,
EP
McArter. A population-based study of maternal and perinatal outcomes associated with assisted
reproductive technology in Massachusetts. Maternal and Child Health Journal. 2007;11:517-25.
9. Källén B, Finnström O, Nygren KG, Otterblad Olausson P, Wennerholm UB. In vitro fertilisation in
Sweden: Obstetric characteristics, maternal morbidity and mortality. BJOG: An International Journal
C

of Obstetrics and Gynaecology. 2005;112:1529-35.

10. Qin J, Wang H, Sheng X, Liang D, Tan H, Xia J. Pregnancy-related complications and adverse
AC

pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: A

meta-analysis of cohort studies. Fertility and sterility. 2015;103:1492-508.e7.
11. Cresswell JA, Ronsmans C, Calvert C, Filippi V. Prevalence of placenta praevia by world region: a
systematic review and meta‐analysis. Tropical Medicine & International Health. 2013;18:712-24.
12. Oyelese Y. Placenta previa and related placental disorders. Queenan’s Management of High-Risk
ST

Pregnancy. 2012:382.
13. Ananth CV, Smulian JC, Vintzileos AM. The effect of placenta previa on neonatal mortality: a
population-based study in the United States, 1989 through 1997. American journal of obstetrics and
gynecology. 2003;188:1299-304.
JU

14. Nørgaard LN, Pinborg A, Lidegaard Ø, Bergholt T. A Danish national cohort study on neonatal
outcome in singleton pregnancies with placenta previa. Acta obstetricia et gynecologica
Scandinavica. 2012;91:546-51.
15. Rosenberg T, Pariente G, Sergienko R, Wiznitzer A, Sheiner E. Critical analysis of risk factors and
outcome of placenta previa. Archives of gynecology and obstetrics. 2011;284:47-51.
16. Yang X, Li Y, Li C, Zhang W. Current overview of pregnancy complications and live-birth outcome of
assisted reproductive technology in mainland China. Fertility and sterility. 2014;101:385-91.e2.
17. Ananth CV, Savitz DA, Luther ER. Maternal cigarette smoking as a risk factor for placental abruption,
placenta previa, and uterine bleeding in pregnancy. American Journal of Epidemiology.
1996;144:881-9.
18. Thomson F, Shanbhag S, Templeton A, Bhattacharya S. Obstetric outcome in women with subfertility.
BJOG: An International Journal of Obstetrics & Gynaecology. 2005;112:632-7.
19. Takemura Y, Osuga Y, Fujimoto A, Oi N, Tsutsumi R, Koizumi M, Yano T, Taketani Y. Increased risk of
placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive
technology pregnancy. Gynecological Endocrinology. 2013;29:113-5.
20. Qin JB, Liu XY, Sheng XQ, Wang H, Gao SY. Assisted reproductive technology and the risk of
pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-
analysis of cohort studies. Fertility and sterility. 2016;105:73-+.
21. Qin JB, Wang H, Sheng X, Xie Q, Gao S. Assisted reproductive technology and risk of adverse obstetric
outcomes in dichorionic twin pregnancies: a systematic review and meta-analysis. Fertility and
sterility. 2016;105:1180-92. Epub 2016/01/24.
22. Lo CK-L, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments.
BMC medical research methodology. 2014;14:45.
23. Higgins JPT, Thompson SG, Deeks JJ, Altman D. Measuring inconsistency in meta-analyses. BMJ.
2003;327:557–60.
24. Begg CB, Mazumdar M. Operating characteristics of a rank cor relation test for publication bias.
Biometrics. 1994;50:1088-101.
25. Hayashi M, Nakai A, Satoh S, Matsuda Y. Adverse obstetric and perinatal outcomes of singleton
pregnancies may be related to maternal factors associated with infertility rather than the type of

D
assisted reproductive technology procedure used. Fertility and sterility. 2012;98:922-8.
26. Isaksson R, Gissler M, Tiitinen A. Obstetric outcome among women with unexplained infertility after

27.
TE
IVF: A matched case-control study. Human Reproduction. 2002;17:1755-61.
Poikkeus P, Tiitinen A. Does single embryo transfer improve the obstetric and neonatal outcome of
singleton pregnancy? Acta obstetricia et gynecologica Scandinavica. 2008;87:888-92. Epub
2008/08/23.
EP
28. Romundstad LB, Romundstad PR, Sunde A, von Düring V, Skjærven R, Vatten LJ. Increased risk of
placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in
the same mother. Human Reproduction. 2006;21:2353-8.
29. Sazonova A, Kllen K, Thurin-Kjellberg A, Wennerholm UB, Bergh C. Factors affecting obstetric
C

outcome of singletons born after IVF. Human Reproduction. 2011;26:2878-86.

30. Smithers PR, Halliday J, Hale L, Talbot JM, Breheny S, Healy D. High frequency of cesarean section,
AC

antepartum hemorrhage, placenta previa, and preterm delivery in in vitro fertilization twin
pregnancies. Fertility and sterility. 2003;80:666-8.
31. Tsutsumi R, Fujimoto A, Osuga Y, Ooi N, Takemura Y, Koizumi M, Yano T, Taketani Y. Singleton
pregnancy outcomes after assisted and non-assisted reproductive technology in infertile patients.
Reproductive Medicine and Biology. 2012;11:149-53.
ST

32. Yang H, Choi YS, Nam KH, Kwon JY, Park YW, Kim YH. Obstetric and perinatal outcomes of dichorionic
twin pregnancies according to methods of conception: spontaneous versus in-vitro fertilization. Twin
research and human genetics : the official journal of the International Society for Twin Studies.
2011;14:98-103. Epub 2011/02/15.
JU

33. Schieve LA, Cohen B, Nannini A, Ferre C, Reynolds MA, Zhang Z, Jeng G, Macaluso M, Wright VC. A
population-based study of maternal and perinatal outcomes associated with assisted reproductive
technology in Massachusetts. Maternal and Child Health Journal. 2007;11:517-25.
34. Tan SL, Doyle P, Campbell S, Beral V, Rizk B, Brinsden P, Mason B, Edwards RG. Obstetric outcome of
in vitro fertilization pregnancies compared with normally conceived pregnancies. American journal of
obstetrics and gynecology. 1992;167:778-84. Epub 1992/09/01.
35. Katalinic A, Rosch C, Ludwig M. Pregnancy course and outcome after intracytoplasmic sperm
injection: a controlled, prospective cohort study. Fertility and sterility. 2004;81:1604-16. Epub
2004/06/15.
36. Kozinszky Z, Zadori J, Orvos H, Katona M, Pal A, Kovacs L. Obstetric and neonatal risk of pregnancies
after assisted reproductive technology: a matched control study. Acta obstetricia et gynecologica
Scandinavica. 2003;82:850-6. Epub 2003/08/13.
37. Reubinoff BE, Samueloff A, Ben-Haim M, Friedler S, Schenker JG, Lewin A. Is the obstetric outcome of
in vitro fertilized singleton gestations different from natural ones? A controlled study. Fertility and
sterility. 1997;67:1077-83. Epub 1997/06/01.
38. Kuivasaari-Pirinen P, Raatikainen K, Hippeläinen M, Heinonen S. Adverse outcomes of IVF/ICSI
pregnancies vary depending on aetiology of infertility. ISRN obstetrics and gynecology. 2012;2012.
39. Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, Talbot JM, Baker HW. Prevalence
and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive
technology in Victoria Australia. Human reproduction (Oxford, England). 2010;25:265-74. Epub
2009/11/10.
40. Agarwal P, Loh SK, Lim SB, Sriram B, Daniel ML, Yeo SH, Heng D. Two-year neurodevelopmental
outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study. BJOG :
an international journal of obstetrics and gynaecology. 2005;112:1376-83. Epub 2005/09/20.
41. Vasario E, Borgarello V, Bossotti C, Libanori E, Biolcati M, Arduino S, Spinelli R, Delle Piane L, Revelli A,
Todros T. IVF twins have similar obstetric and neonatal outcome as spontaneously conceived twins: a
prospective follow-up study. Reproductive biomedicine online. 2010;21:422-8. Epub 2010/07/20.
42. Choi SJ, Kim HS, Roh CR. Pregnancy outcomes of twins after in vitro and spontaneous fertilization.

D
International Journal of Gynecology and Obstetrics. 2006;94:49-51.
43. Suzuki S, Miyake H. Perinatal outcomes of elderly primiparous dichorionic twin pregnancies

44. TE
conceived by in vitro fertilization compared with those conceived spontaneously. Archives of
gynecology and obstetrics. 2010;281:87-90.
Luke B, Gopal D, Cabral H, Stern JE, Diop H. Adverse pregnancy, birth, and infant outcomes in twins:
Effects of maternal fertility status and infant gender combinations The Massachusetts Outcomes
EP
Study of Assisted Reproductive Technology. American journal of obstetrics and gynecology. 2017.
Epub 2017/04/30.
45. Zhu L, Zhang Y, Liu Y, Zhang R, Wu Y, Huang Y, Liu F, Li M, Sun S, Xing L. Maternal and Live-birth
Outcomes of Pregnancies following Assisted Reproductive Technology: A Retrospective Cohort Study.
C

Scientific reports. 2016;6.

46. Hill GA, Bryan S, Herbert CM, III, Shah DM, Wentz AC. Complications of pregnancy in infertile couples:
AC

Routine treatment versus assisted reproduction. Obstetrics and gynecology. 1990;75:790-4.

47. Nassar AH, Usta IM, Rechdan JB, Harb TS, Adra AM, Abu-Musa AA. Pregnancy outcome in
spontaneous twins versus twins who were conceived through in vitro fertilization. American journal
of obstetrics and gynecology. 2003;189:513-8. Epub 2003/10/02.
48. Fujii M, Matsuoka R, Bergel E, Van Der Poel S, Okai T. Perinatal risk in singleton pregnancies after in
ST

vitro fertilization. Fertility and sterility. 2010;94:2113-7.

49. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions Version 5.0.0: The
Cochrane Collaboration; 2008 [rom: URL|.
50. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic
JU

sperm injection and in vitro fertilization. The New England journal of medicine. 2002;346:725-30.
Epub 2002/03/08.
51. Tavaniotou A, Albano C, Smitz J, Devroey P. Impact of ovarian stimulation on corpus luteum function
and embryonic implantation. Journal of reproductive immunology. 2002;55:123-30. Epub
2002/06/14.
Table 1: Summary of the study's results

1st aut, year Country Design Sample Esti Adjust Ag Qual Type of pregnancy
size mate ment e ity Type of ART

Hill 1990 USA Case- 110 OR Crude N Low Singl IVF

control o eton
da
ta
Sazonova 2011 Sweden Ret. 8941 OR Adjust N Hig Singl IVF
cohort ed o h eton
da
ta
Tsutsumi 2012 Japan Ret. 564 OR Crude N Hig Singl IVF/ICSI/
cohort o h eton FER
da
ta
Romundstad Norway Ret. 84538 OR Adjust N Hig Twin IVF/ICSI

D
2006 cohort 4 ed o h and
da Singl

Isaksson 2002 Finland Ret.

cohort
2206 OR
TE
Adjust
ed
ta
20
-
49
Hig
h
eton
Singl
eton
IVF/ICSI
EP
Fujii 2010 Japan Cross- 55347 OR Crude 33 Hig Singl IVF
sectional .5 h eton
Hayashi 2012 Japan Ret. 24271 OR Adjust 33 Hig Singl IVF /IUI
cohort 5 ed h eton
C

Kozinszky 2003 Hungar Ret. 718 OR Crude N Hig Twin IVF

y cohort o h and
da Singl
AC

ta eton
Yang 2011 South Ret. 210 OR Adjust 31 Hig Twin IVF
Korea cohort ed .6 h
Reubinoff 1997 Israel Pro. 520 OR Crude 33 Low Singl IVF
cohort .1 eton
ST

Kuivassaari- Finland Pro. 27125 OR Crude N Hig Singl IVF/ICSI

pirinen 2012 cohort o h eton
da
ta
JU

Healy 2010 AustraliRet. 9871 OR Crude 33 Hig Singl IVF/ICSI/

a cohort .5 h eton GIFT
Choi 2006 South Ret. 467 OR Crude 31 Hig Twin IVF
Korea cohort .8 h
Nasser 2003 Lebano Case- 168 OR Crude 31 Hig Twin IVF
n control h
Suzuki 2010 Japan Ret. 151 OR Crude 37 Hig Twin IVF
cohort .8 h
Agarwal 2005 Singapo Pro. 337 OR Crude 33 Hig Twin IVF/ICSI
re cohort .7 h and
Singl
eton
Polikkeus 2007 Finland Pro. 15037 OR Crude 32 Hig Singl IVF/ICSI
cohort .4 h eton
Smithers 2003 Australi Ret. 2581 OR Adjust N Hig Twin IVF
a cohort ed o h
da
ta
Vasario 2010 Italy Pro. 223 OR Adjust N Hig Twin IVF
cohort ed o h
da
ta
Schieve 2007 USA Ret. 16038 RR Adjust N Hig Singl IVF
cohort 2 ed o h eton
da
ta
Tan 1992 Englan Pro. 1638 RR Crude 34 Low Singl IVF
d cohort .2 eton
Katalinic 2004 German Pro. 3198 RR Crude N Hig Singl IVF/ICSI
y cohort o h eton
da
ta

D
Zhu 2016 China Ret. 1071 OR Adjust N Hig Twin IVF/ICSI
cohort ed o h and

TE
da Singl
ta eton
Luke 2017 USA Pro. 9628 OR Crude 32 Hig Twin IVF
cohort .3 h
EP
C
AC
ST
JU
Figures titles

Figure 1: Flow of information through the different phases of the systematic review

Figure 2: Forest plot of the association between ART and placenta previa based on OR

Figure 3: Forest plot of the association between ART and placenta previa based on RR

Figure 4: Funnel plot of the association between ART and placenta previa in singleton
pregnancies

Figure 5: Funnel plot of the association between ART and placenta previa in twin
pregnancies

D
TE
EP
C
AC
ST
JU
JU
ST
AC
C
EP
TE
D
JU
ST
AC
C
EP
TE
D
JU
ST
AC
C
EP
TE
D
JU
ST
AC
C
EP
TE
D