General obstetrics

DOI: 10.1111/j.1471-0528.2011.02976.x
www.bjog.org

Placenta accreta is associated with IVF

pregnancies: a retrospective chart review
E Esh-Broder,a I Ariel,b N Abas-Bashir,a Y Bdolah,a D Hochner Celnikiera
Departments of a Obstetrics and Gynecology and b Pathology, Hadassah-Hebrew University Medical Center, Mt Scopus, Jerusalem, Israel
Correspondence: Dr E Esh-Broder, Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Mt Scopus,
PO Box 24035, Mt Scopus, Jerusalem, Israel. Email efratesh@hadassah.org.il
Accepted 2 March 2011. Published Online 18 May 2011.

Objective To study the association between placenta accreta (PA)

and in vitro fertilisation (IVF) pregnancies.

Design Retrospective chart review.
Setting Tertiary care centre in Jerusalem, Israel.
Sample During January 2004February 2009, 25 193 deliveries

occurred in our hospital, including 752 (3%) deliveries of IVF

pregnancies.
Methods Placenta accreta was only diagnosed when there were

histological findings from the placenta associated with the

suitable clinical course. Demographic, obstetrical and fertility
characteristics of these patients were retrieved from hospital files.
Main outcome measure Rates of PA in pregnancies achieved with

Results The rate of PA in the IVF group was 12/752 (16/1000)

pregnancies, compared with 30/24 441 (1.2/1000) among
spontaneous pregnancies (P < 0.0001; OR 13.2; 95% CI
6.725.8). Among the variables examined, parity, rate of
caesarean delivery in the index pregnancy, and birthweight
differed significantly between IVF and spontaneous
pregnancies.
Conclusions The odds of developing PA are significantly

higher in IVF pregnancies than in spontaneous pregnancies.

These differences may stem from differences in the
endometrial environment, or from changes to the
endometrium wrought by IVF treatment protocols.
Keywords In vitro fertilization, placenta accreta.

IVF versus rates of PA in spontaneous pregnancies.

Please cite this paper as: Esh-Broder E, Ariel I, Abas-Bashir N, Bdolah Y, Hochner Celnikier D. Placenta accreta is associated with IVF pregnancies: a retrospective chart review. BJOG 2011;118:10841089.

Introduction
Placenta accreta (PA) is a potentially catastrophic obstetric
complication. Whether the placenta is completely or focally
adherent to the myometrium, PA is associated with massive
postpartum haemorrhage, and has become one of the most
common indications for emergent peripartum hysterectomy.13 PA develops when the placental implantation is
abnormal: the decidua basalis that normally separates the
anchoring placental villi and the myometrium is missing.
More invasive types include placenta increta and placenta
percreta, in which the placenta extends to and through the
uterine myometrium, respectively. The exact pathogenesis
is unknown. Possible hypotheses include: (1) a mechanical
factor, i.e. primary deficiency of the decidua caused by
local trauma to the uterine wall; (2) a biological factor, i.e.
abnormal maternal response to trophoblast invasion; and
(3) a combination of both processes.

1084

The most common and defined risk factor associated

with PA is a previous caesarean delivery. The most common
setting is placenta previa after a prior caesarean delivery.
The risk of PA increases progressively in correlation with
the number of repeated caesarean deliveries.4,5 Other significant independent risk factors include coexistent placenta
previa and maternal age.5,6 Multiparity, previous uterine
curettage and previous uterine surgery other than caesarean
sections were found to be risk factors in some studies,
whereas no significant association between these factors and
PA was found in others.3,79 In addition, in trisomy
21 screening programmes, an association was found
between PA and abnormally elevated second-trimester alpha
fetal protein (AFP) and free b subunit of human chorionic
gonadotrophin (b-hCG) levels in maternal serum.10
The reported incidence of PA varies widely, mainly as it
is affected by differences in diagnostic criteria, i.e. whether
the diagnosis was based on clinical findings only or

2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2011 RCOG

Placenta accreta is associated with IVF pregnancies

together with histological criteria.7 The average reported

incidence has increased ten-fold in the last 50 years, from
0.03 to 0.3% in studies from the last two decades. The
highest incidence, 0.9%, was reported in a recent study
based on clinical diagnostic criteria.11 The increase in
PA in recent years is attributed to the increase in the
prevalence of known risk factors, particularly caesarean
deliveries.
Pathologically, PA is defined as the direct apposition of
placental villi to the myometrium. A finding of basal plate
myometrial fibres adherent to the placenta confirms the
diagnosis of PA that was suspected clinically, but it is not
indicative of PA in the absence of a clinical history. Another
feature of PA is larger radial and arcuate arteries showing
pregnancy-induced changes (a loss of muscular and elastic
tissue from their walls), which are morphological changes
usually confined to the smaller spiral arteries.12,13
The early prenatal diagnosis of PA is based on the presence of characteristic findings on targeted ultrasound
examination, whenever PA is suspected or in the presence
of risk factors.14 Magnetic resonance imaging (MRI) is also
effective in prenatal diagnosis, and is useful in the case of
inconclusive findings.15 Sonographic signs suspicious of PA
have been described as early as the first trimester in a highrisk population.16 Prenatal diagnosis of PA is critical to
obstetric outcome, by enabling early arrangements for elective caesarean section and possible hysterectomy, and
decreases PA-associated complications such as the need for
the transfusion of blood products.17
In recent years we have had a clinical impression of a
higher incidence of PA among women undergoing in vitro
fertilization (IVF) treatment. No association between pregnancies achieved by assisted reproductive techniques (ART)
and PA has been described in the literature. This study
aimed to assess the hypothesis of increased incidence of PA
among IVF pregnancies.

sampling of all placentas was performed by a perinatal

pathologist (IA), according to the guidelines developed by
the Placental Pathology Practice Guideline Development
Task Force of the College of American Pathologists,18
which provides general recommendations related to indications and methods for placental examination. Emphasis was
put on sampling the mixed (intact and torn) areas of maternal surface, according to the method described by Khong
and Werger.13 A similar number of slices (average five) was
examined in clinically suspected PA in both groups.
The original diagnosis was made on the basis of muscle
fibres, and in cases of doubt immunochemistry staining for
desmin was also performed. In cases of inconclusive results,
immunochemistry and haematoxylin/eosin-stained slides
were reviewed. All cases of complete as well as partial PA
were included in the study.
The study was approved by our institutional review
board (Helsinki committee). We surveyed all placenta
pathology reports performed during the study period and
found 51 cases of histologically confirmed PA. We excluded
one case in which the gestational age was <23 weeks
(owing to the dearth of published data in the literature
regarding PA at these early, pre-viable gestational ages),
and another case of PA in which the histologic material
was obtained at curettage, and not at vaginal or caesarean
delivery, and therefore did not meet the inclusion criteria.
After matching the pathology results with clinical data
we further excluded seven cases of histologically proven PA
not suspected clinically. Demographic, obstetrical, current
pregnancy and delivery data, as well as fertility characteristics, were retrieved from hospital files. PA cases were
divided into spontaneous (SP) and IVF pregnancy groups.
Pregnancies achieved after treatment with clomiphene
citrate, gonadotropins or intrauterine insemination were
assigned to the SP group.

Statistical analysis

Methods
During the 5 years between January 2004 and February
2009, there were 25 193 deliveries in Hadassah Mt Scopus,
Jerusalem, Israel, a university-affiliated tertiary care centre
in the north of Jerusalem. Seven hundred and fiftytwo deliveries (3%) were of IVF-achieved pregnancies.
According to our departmental protocols, whenever there
is a clinical suspicion of PA in vaginal or caesarean delivery, the placenta is sent for pathological examination. This
included cases that were clinically suspected as PA. Cases
were defined as clinically suspected PA if significant difficulty was encountered in placental separation, requiring
manual lysis of the placenta or uterine revision, and in caesarean sections, cases with heavy bleeding from the placental bed requiring haemostatic sutures. The histopathology

sas v9.2 (SAS Institute Inc., Cary, NC, USA) was used for
statistical analysis. The exact Wilcoxon test was applied to
continuous variables, and Fishers exact test was applied
to categorical variables. All tests were two-tailed. Results
were considered statistically significant when P 0.05.

Results
During the study period there were 42 cases of clinically
suspected PA that were confirmed histologically: 30 SP and
12 IVF. The SP group included two women that each had
two pregnancies with PA during the study period. Nine
of the patients in the IVF group were treated in our IVF
unit, and we were able to retrieve detailed data including
treatment indication, protocols and early pregnancy
hormonal support from the hospital files. Three women

2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2011 RCOG

1085

Esh-Broder et al.

the rate in the IVF study group was 12/752 or 16/1000

deliveries, whereas among spontaneous pregnancies PA
occurred in 30 cases, giving a rate of 30/24 441 or 1.2/1000
deliveries (P < 0.0001; OR 13.2; 95% CI 6.725.8).
Demographic parameters, obstetric and gynaecological
history, and index pregnancy and delivery details in the
study groups are presented in Table 2. The mean age in the
IVF group was higher than in the SP group, as expected,
but did not differ significantly (37.8 versus 33.6 years).
There were also no statistically significant differences
between the two groups in ethnic origin.
When comparing known obstetric and gynecologic historical risk factors for PA, only parity differed significantly
between the groups, and was significantly lower in the IVF

Table 1. Incidence of placenta accreta

Deliveries
Spontaneous pregnancy
IVF

Total
deliveries

Placenta
accreta (%)

25 193
24 441
752

42 (0.17)
30 (0.12)
12 (1.60)

were treated in other hospitals, and therefore the complete

details of their fertility treatment were not available.
The overall rate of confirmed PA in our population was
42/25 193 or 1.67/1000 deliveries. As detailed in Table 1,

Table 2. Demographic parameters, obstetric and gynaecological history, and index pregnancy and delivery details in the study groups

Demographic parameters
Age (years, mean 2SE)
Ethnic origin (%)
Non-Jewish
Jewish
Obstetric and gynaecological history
Parity (%)
0
14
>5
Previous uterine surgery (%)
Caesarean section
0
1
>1
Other
Miscarriages
Curettage
Previous placenta accreta
Index pregnancy and delivery details
Pregnancy (%)
Single
Multiple
Maternal complications
Fetal complications
Placenta pathology visualized by ultrasound (%)
Placenta praevia (complete, partial or marginal)
Suspected placenta accreta
Gestational age (weeks), mean 2 SE
Mode of delivery (%)
Vaginal
Caesarean section
Caesarean section + hysterectomy
Fetal weight (g), mean 2 SE)

Spontaneous pregnancy
n = 30

IVF
n = 12

33.57 1.31

37.83 5.47

0.4096

4 (13)
26 (87)

1 (8)
11 (92)

1.0000

5 (17)
23 (77)
2 (6)

9 (75)
3 (25)
0

0.0007

25
3
2
0
13
10
2

(83)
(10)
(7)
(43)
(33)
(7)

29 (97)
1 (3)
Hypertension n = 1

11
1
0
1
7
5
0

(92)
(8)
(8)
(58)
(42)

9 (75)
3 (25)
Hypertension n = 1;
gestational diabetes n = 2
IUGR* n = 1

1.0000

0.4994
0.7260
1.0000

0.0634

4 (13)
1 (3)
38.03 1.36

2 (17)
0
37.58 1.64

1.0000
1.0000
0.2729

25 (84)
1 (3)
4 (13)
3151.97 282.16

5 (42)
7 (58)
0
2712.83 335.22

0.0003

0.0301

*IUGR, intrauterine growth restriction.

1086

2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2011 RCOG

Placenta accreta is associated with IVF pregnancies

Table 3. Details of the treatment protocols received in the IVF group

Case

1
2
3
4
5
6
7
8
9
10
11
12

Age

IVF indication

Induction
protocol

Endometrial
thickness (cm/days
before b-hCG)

30
43
44
31
49
35
35
40
28
31
59
29

Tubal factor
Unexplained
Male factor
Unexplained
Age
Unexplained
Male factor
Unexplained
Unexplained
Anovulatory after failed COH
Age

Short-antagonist
Long
OD
Long
OD
Short-antagonist
Frozen
Long
Frozen
Frozen
OD

0.65/2
1.1/1
0.7/8*
1.0/2
0.79/8*
0.73/0
0.87/4*
1.3/1
0.78/8*

Fertilisation

Embryo
transfer

Early
pregnancy
support

IVF
ICSI
ICSI
IVF + ICSI
ICSI
ICSI
ICSI
IVF + ICSI
IVF

Day
Day
Day
Day
Day
Day
Day
Day
Day

E
E
E
E
E
E
E
E
E

5
3
3
3
3
3
3
3
5

+
+
+
+
+
+
+
+
+

P
P
P
P
P
P
P
P
P

b-hCG, b subunit of human chorionic gonadotrophin; E + P, estrogen plus progesterone; ICSI, intracytoplasmic sperm injection; OD, ovum donor.
*Number of days before embryo transfer.

group as most of these women were nulliparous. Only five

women in 30 (17%) in the SP group and one woman in
12 (8%) in the IVF group had a previous caesarean delivery. One woman in the IVF group underwent uterine
myomectomy. The miscarriage rate was higher in the IVF
group, but this was not statistically significant (58 versus
43%; P = 0.49). Five of seven women in the IVF group
(42%) that miscarried also underwent one or more curettage procedures, compared with ten of 13 who miscarried
in the SP group (33%). Data concerning the miscarriages
of the three remaining women in the SP group were
unavailable; however, counting them either as having
undergone curettage or not did not affect the statistical significance.
Two women in the SP group had two events of PA in
two different pregnancies. Another two women in this
group had a previous event of clinically suspected PA that
was not confirmed histologically.
Regarding the index pregnancy and delivery parameters,
in the IVF group there was a higher incidence of multiple
pregnancies (three cases versus one in the SP group). The
lower mean fetal weight in the IVF group (2713 g versus
3152 in the SP group) is statistically different. No significant difference was seen in mean gestational age at delivery
between the groups. Maternal complications during the
index pregnancy included hypertension in one woman in
the IVF group and in one woman in the SP group, and
gestational diabetes in two women in the IVF group. Fetal
complications included one case of intrauterine growth
restriction in the IVF group. Four women in the SP group
and two in the IVF group had a sonographic diagnosis of
placenta praevia (PP), and one woman in the SP group

was suspected to have PA before delivery (the detection

rate of PA in our institution is similar to the known detection rate; however, most of the women in our study underwent ultrasonographic evaluation in other pregnancy care
institutions).
There was a statistically significant difference between
the two study groups in the mode of delivery. Seven of
12 women in the IVF group (58%) underwent either
elective or emergent caesarean delivery, as compared with
5/30 women in the SP group (16%). These data are in
accordance with caesarean delivery rates in our hospital
during the study period: 17% in the general population
versus 50% in IVF pregnancies.
Four women underwent hysterectomy: all of them were
in the SP group and had had previous caesarean deliveries.
Fifteen women among 42 (36%) required transfusion of
packed cells and blood products. Among them, 13 women
(11 in the SP group and two in the IVF group) consumed
more than two units of packed cells.
Fertility data and treatment protocols of the IVF group
were retrieved from hospital files and are shown in Table 3.
We have partial data of three women that were not treated
in our hospital. Women in the IVF group were classified
by indication for IVF (tubal factor, unexplained infertility,
male factor, anovulatory after failed controlled ovarian
hyperstimulation, and age-related infertility).
The 12 patients in the study group underwent ART
treatment as follows: three were treated with a long protocol; two had a short antagonist; three had a frozenthawed
transfer; and three had a transfer of ovum-donation
embryos. The IVF protocols were standard ART protocols.19 Endometrial lining thickness was recorded. All

2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2011 RCOG

1087

Esh-Broder et al.

patients were treated with luteal phase progesterone, as well

as estrogen support. The support was ceased upon completion of the first trimester.

Discussion and conclusion

According to our data, the odds ratio for developing PA is
markedly higher in IVF pregnancies compared with SPs.
To the best of our knowledge, this is the first report of
such a phenomenon. The overall incidence of PA in our
hospital shown in this study was 42/25 193 (0.167%), and
is similar to that described in studies published over the
last two decades.7
We included only PA cases diagnosed clinically and
proved histologically. These strict inclusion criteria enable
us to avoid sources of bias, and are therefore preferable to
relying on only one criterion, clinical or histological. The
inclusion of only these cases is consistent with the recently
standardised histologic definition of PA, which only defines
an accreta when a suitable clinical presentation matches the
histological findings 13. The relative rarity of PA dictated
the small study size. Our strict inclusion criteria further
decreased it, but prevented potential biases, ensuring its
reliability.
Recognised risk factors and other parameters were examined. Among all the variables examined, three were found
to be statistically significant: parity, incidence of caesarean
delivery in the index pregnancy and fetal weight. Parity was
significantly lower in the IVF group, as expected: this
should have reduced the incidence of PA in this group,
and therefore strengthens our findings. The high CS rate in
the index pregnancy in the IVF group is similar to the CS
rate in the IVF population at our hospital, and would not
influence PA incidence or diagnosis. Fetal weight was significantly lower in the IVF group, secondary to the higher
incidence of multiple pregnancies in this group; however,
this factor is not recognised as a risk factor for PA. There
were no other significant differences in the demographic,
obstetric and risk factors examined. The slightly higher
maternal mean age in the IVF group was not statistically
significant.
The higher incidence of PP after ART, described in previous studies,20,21 could not explain our findings, despite
its known association with PA, because the incidence of PP
in our study did not differ significantly between the two
groups (4/30 in the SP group and 2/12 in the IVF group).
The possible pathogenesis of PA includes a mechanical
factor (primary deficiency of decidua caused by local
trauma to the uterine wall) and a biological factor (abnormal maternal response to trophoblast invasion). In our
study groups, all four women who underwent hysterectomy
had had previous caesarean sections, supporting the notion
that mechanical PAs are predisposed to more severe out-

1088

comes. Nevertheless, biological PAs, although milder in

clinical presentation, are not free of complications. In our
study 13 women with PA consumed at least two units of
packed cells after delivery, and among these nine could be
categorised as biological PA, as they had no previous
uterine surgeries.
Our findings support the existence of biological factor(s)
in PA formation that are not coincidental. The early recognition or higher index of suspicion could therefore enable
proper preparation, and improve such outcomes in the
biological cases.
The main question remains, therefore, as to the reason
for this observed higher incidence of PA among the IVF
population. Differences may stem from alterations in the
endometrial environment of the IVF patient population.
This notion is partially supported by the high proportion of
unexplained infertility cases among our patients, as compared with the general IVF population in our IVF unit.
However, some of the patients in the IVF study group could
not be presumed to suffer from endometrial problems, as
their indication for IVF was male factor or anovulation.
Another hypothesis may attribute the higher incidence of
PA in IVF patients to the treatment protocols. Previous
studies have shown that the stimulation protocols in IVF
induce morphological and structural changes, and disturb
the expression of relevant genes in the endometrium; such
changes could contribute to abnormal implantation.22 This
cannot explain the phenomenon in all patients in the IVF
study group, as some patients underwent frozenthawed
embryo transfer or ovum donation cycles without ovarian
stimulation.
Another factor that could theoretically influence implantation and early embryo development is the fertilisation
and embryo culture in vitro that, as described before, can
change key metabolic pathways in the embryo.23 Scrutinizing the endometrial environment in the first week of pregnancy, when implantation occurs, the main difference
between IVF and spontaneous pregnancies is the hormonal
support routinely given to women in the IVF group.
During the study period women treated in our IVF unit
received estrogenic and progestative support in the first
1012 weeks of pregnancy [usually Estrofem (estradiol;
Novo Nordisk, Begsraerd, Denmark), 2 mg three times
daily orally, and Utrogestan (micronised progesterone; Ferring Pharmaceuticals Ltd, Saint-Prex, Switzerland) 400 mg
twice daily intravaginally].
In mice, it has been demonstrated that different doses of
exogenous estrogen influenced the duration of the window
of implantation;24 therefore, we may speculate that the hormonal support of estrogen in addition to the progesterone
given in the first 10 weeks of pregnancy to IVF patients
might have an adverse effect on implantation, and may
play an important role in the pathological implantation

2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2011 RCOG

Placenta accreta is associated with IVF pregnancies

seen in this study. Further studies are needed to explore

the influence of hormonal administration in the
peri-implantation period on parameters important for the
adherence of the placenta to the uterine wall.
In conclusion, we present here for the first time a markedly higher incidence of PA in IVF pregnancies. Larger
studies are needed to confirm this finding and elucidate its
causes. Nevertheless, IVF pregnancies should be considered
as being associated with a higher risk of PA. We therefore
recommend considering a targeted ultrasound survey of
IVF pregnancies prior to delivery, as well as a higher level
of suspicion when managing complications in the third
stage of delivery in this population.

Disclosure of interest
None.

Contribution to authorship
EE-B coordinated the study, assisted in chart review, and
prepared the article. IA examined placentas and participated in article preparation, NA-B assisted in chart review,
YB assisted in chart review, and reviewed and commented
on the manuscript draft, DHC coordinated the study and
prepared the manuscript.

Details of ethics approval

Our institutional ethical review board (Helsinki committee)
at Hadassah Medical Center, Jerusalem, Israel, reviewed the
protocol and approved this study. Date of approval:
11 December 2009; ref. no. 204-11.12.09.

Funding
None.

Acknowledgement
None. j

References
1 Zelop CM, Harlow BL, Frigoletto FD Jr, Safon LE, Saltzman DH. Emergency peripartum hysterectomy. Am J Obstet Gynecol 1993;168:
14438.
2 Glaze S, Ekwalanga P, Roberts G, Lange I, Birch C, Rosengarten A,
et al. Peripartum hysterectomy: 1999 to 2006. Obstet Gynecol
2008;111:7328.
3 Kastner ES, Figueroa R, Garry D, Maulik D. Emergency peripartum
hysterectomy: experience at a community teaching hospital. Obstet
Gynecol 2002;99:9715.
4 Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA,
et al. Maternal morbidity associated with multiple repeat cesarean
deliveries. Obstet Gynecol 2006;107:122632.

5 Miller DA, Chollet JA, Goodwin TM. Clinical risk factors for placenta
previa-placenta accreta. Am J Obstet Gynecol 1997;177:2104.
6 Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: twentyyear analysis. Am J Obstet Gynecol 2005;192:145861.
7 Bencaiova G, Burkhardt T, Beinder E. Abnormal placental invasion
experience at 1 center. J Reprod Med 2007;52:70914.
8 Jacques SM, Qureshi F, Trent VS, Ramirez NC. Placenta accreta: mild
cases diagnosed by placental examination. Int J Gynecol Pathol
1996;15:2833.
9 You WB, Zahn CM. Postpartum hemorrhage: abnormally adherent
placenta, uterine inversion, and puerperal hematomas. Clin Obstet
Gynecol 2006;49:18497.
10 Hung TH, Shau WY, Hsieh CC, Chiu TH, Hsu JJ, Hsieh TT. Risk
factors for placenta accreta. Obstet Gynecol 1999;93:54550.
11 Gielchinsky Y, Rojansky N, Fasouliotis SJ, Ezra Y. Placenta accreta
summary of 10 years: a survey of 310 cases. Placenta 2002;23:210
4.
12 Khong TY. The pathology of placenta accreta, a worldwide
epidemic. J Clin Pathol 2008;61:12436.
13 Khong TY, Werger AC. Myometrial fibers in the placental basal plate
can confirm but do not necessarily indicate clinical placenta accreta.
Am J Clin Pathol 2001;116:7038.
14 Comstock CH. Antenatal diagnosis of placenta accreta: a review.
Ultrasound Obstet Gynecol 2005;26:8996.
15 Dwyer BK, Belogolovkin V, Tran L, Rao A, Carroll I, Barth R, et al.
Prenatal diagnosis of placenta accreta: sonography or magnetic resonance imaging? J Ultrasound Med 2008;27:127581.
16 Comstock CH, Lee W, Vettraino IM, Bronsteen RA. The early sonographic appearance of placenta accreta. J Ultrasound Med
2003;22:1923; quiz 4-6.
17 Warshak CR, Ramos GA, Eskander R, Benirschke k, Saenz CC,
Kelly TF, et al. Effect of predelivery diagnosis in 99 consecutive cases
of placenta accreta. Obstet Gynecol 2010;115:659.
18 Langston C, Kaplan C, Macpherson T, Manci E, Peevy K, Clark B,
et al. Practice guideline for examination of the placenta: developed
by the Placental Pathology Practice Guideline Development Task
Force of the College of American Pathologists. Arch Pathol Lab Med
1997;121:44976.
19 Assisted Reproductive Technologies. In: Speroff L, Fritz MA, editors.
Clinical Gynecologic Endocrinology & Infertility (Chapter 32). Philadelphia: Lippincott, Williams, Wilkins; 2005. pp. 122332.
20 Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes
in singletons following in vitro fertilization: a meta-analysis. Obstet
Gynecol 2004;103:55163.
21 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. Hum Reprod 2006;21:23538.
22 Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman
S, et al. Effect of controlled ovarian hyperstimulation in IVF on
endometrial gene expression profiles. Mol Hum Reprod 2005;11:
195205.
23 Leese HJ, Donnay I, Thompson JG. Human assisted conception: a
cautionary tale. Lessons from domestic animals. Hum Reprod
1998;13 (Suppl 4):184202.
24 Simon C, Dominguez F, Valbuena D, Pellicer A. The role of estrogen
in uterine receptivity and blastocyst implantation. Trends Endocrinol
Metab 2003;14:1979.

2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2011 RCOG

1089