Borderline ovarian tumours, or tumours of low malignant potential (LMP), consitute approximately 10-15% of all epithelial malignancies. It was not until 1971 that borderline tumours were recognised as a specific clinical entity.

1. Review
Pregnancy rates after conservative treatment for borderline
ovarian tumours: A systematic review
Alexander Swanton a
, Clare R. Bankhead b
, Sean Kehoe a,*
a
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom
b
Cancer Research UK, Primary Care Education Research Group, University of Oxford, United Kingdom
Received 5 February 2007; received in revised form 14 May 2007; accepted 24 May 2007
Abstract
Borderline ovarian tumours account for 10–15% of all ovarian cancers, and there have been numerous studies indicating their excellent
long-term prognosis. As this disease commonly affects younger women, the issue of fertility-preserving surgery is increasingly important.
A systematic review of the literature, searching the relevant electronic databases was performed analysing conservative surgery, borderline
ovarian tumours and pregnancy rates/fertility outcome.
Overall, 19 studies met the inclusion criteria. From these studies, 2479 patients had borderline ovarian tumours of which 923 (37%)
patients were treated by conservative surgery. Nine studies recorded data regarding pregnancy outcome. A pregnancy rate of 48% was
calculated on these data, where recorded, analysing the number of women wanting to conceive and the actual number of pregnancies achieved.
The recurrence rate after conservative treatment was 16% with only five recorded disease-related deaths.
Knowledge of the pregnancy rates is important to permit appropriate counselling of women diagnosed with this malignancy.
# 2007 Published by Elsevier Ireland Ltd.
Keywords: Borderline ovarian tumour; Conservative surgery; Pregnancy; Fertility; Low malignant potential
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2. Material and methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.1. Search strategy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
5. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1. Introduction
Borderline ovarian tumours, or tumours of low malignant
potential (LMP), constitute approximately 10–15% of all
epithelial malignancies [1]. Originally described by Taylor
[2], it was not until 1971 that borderline tumours were
recognised as a specific clinical entity [3]. The histological
subtypes are mainly serous (69%) or mucinous (30%), with
rarer subtypes such as endometrioid, clear-cell and Brenner
borderline tumours. Histological features are defined and
characterised by epithelial cellular proliferation greater
than that seen in benign tumours. Borderline tumours
have a stratified epithelium with varying degrees of nuclear
atypia and increased mitotic activity but their distinction
www.elsevier.com/locate/ejogrb
European Journal of Obstetrics & Gynecology and
Reproductive Biology 135 (2007) 3–7
* Corresponding author. Tel.: +44 1865 857942; fax: +44 1865 221001.
E-mail addresses: alexander.swanton@obs-gyn.ox.ac.uk (A. Swanton),
sean.kehoe@obs-gyn.ox.ac.uk (S. Kehoe).
0301-2115/$ – see front matter # 2007 Published by Elsevier Ireland Ltd.
doi:10.1016/j.ejogrb.2007.05.011

2. from invasive carcinomas is the lack of stromal invasion
[4,5].
The prognosis for borderline tumours, even with wide-
spread disease, is generally good. Indeed, a review of
approximately 2000 cases with stage 1 serous borderline
tumours showed a 5-year survival rate greater than 99.5%
[6], as supported by other studies [7,8]. For all stages, the
overall 10-year survival rate is 83–91% [9–11]. The
excellent prognosis for this disease is related to the fact
that these tumours rarely metastasize and are therefore stage
I at diagnosis (50–80%). Even patients with stage III disease
have a good prognosis with 5-, 10-, 15-, and 20-year survival
rates of 97, 95, 92, and 89%, respectively [12].
Borderline tumours tend to affect younger women when
compared with invasive ovarian tumours [13,14]. In a
population-based study in Norway, a total of 2343 borderline
tumours were diagnosed between the years of 1970–1993
[15]. Median age at diagnosis was 53 years for borderline
tumours compared with 60 years for invasive carcinoma. Of
these women who were diagnosed with a borderline tumour,
27% were less than 40 years of age. The management is the
same as that of frankly malignant tumours in terms of staging
and surgical treatment [16]. However, conservative manage-
ment is acknowledged as acceptable in order to preserve
fertility potential [7,17,18]. Counselling and informing
patients of the outcomes in terms of relapse and successful
pregnancy are important. Whilst randomized trials would
achieve the optimum evidence base for outcomes, this would
be ethically impossible.
This systematic review of fertility outcomes attempts to
enhance the information base regarding such management
and thereby improve patient counselling.
2. Material and methods
The following electronic databases were searched:
CENTRAL (in The Cochrane Library, current issue);
MEDLINE (Silver Platter, from 1966 to 2006);
EMBASE (from 1980 to 2006);
Specialised Register of the Cochrane Gynaecological
Cancer Group.
2.1. Search strategy
For MEDLINE we developed a search strategy based on
terms relating to the review topic: OVARIAN; OVARY;
CANCER; CARCINOMA; MALIGNANT TUMOUR;
MALIGNANT NEOPLASM; BORDERLINE; LOW
MALIGNANT POTENTIAL; SURGERY; CONSERVA-
TIVE; FERTILITY SPARING; PROGNOSIS; PREG-
NANCY; FERTILITY; RECURRENCE; SUVIVAL
(OVERALL AND DISEASE-FREE); MORTALITY.
Free text (including alternative spellings) MeSH terms
and MeSH headings were exploded. For databases other than
MEDLINE, such as EMBASE, the search strategy was
adapted accordingly. From the results of the searches,
relevant articles were identified and scanned. Any new terms
found were fed into the search strategy, and new searches
run. The reference lists of the relevant papers found were
scrutinized for further studies. Papers in all languages were
sought, and translated. Relevant articles were re-entered into
PubMed (up to May 2006), and using the ‘related articles’
feature, a further search was carried out. The inclusion
criteria were publications including pregnancy and fertility
outcomes after conservative treatment for borderline ovarian
tumours. Exclusion criteria included all case reports, studies
with a sample size <10, and duplicate publication. In cases
of duplicate publication, the most recent study was included.
There were no language restrictions. Two investigators
independently extracted the data from the remaining studies.
Finally, relevant studies were scrutinized by the reviewers
and a decision made on their inclusion in this systematic
review.
3. Results
The electronic database literature search identified 1875
studies of which 457 articles related to ovarian cancer, 90
related to borderline tumours and 12 were case reports. The
remaining articles related to other diseases. Overall, 19
studies met the inclusion criteria (Table 1).
From these articles, 2479 patients had borderline ovarian
tumours of which 923 (37%) patients were treated by
conservative surgery. All studies were retrospective in their
study design.
The disease stage was recorded in 664 (76%) of patients
who were treated conservatively. Of these, 552 (83%) had
stage I disease, 630 (95%) stage I or stage II disease and 34
(5%) patients with stage III disease. Regarding histological
subtypes for patients treated conservatively and where
recorded, 283 (56%) were serous, 188 (37%) were mucinous,
31 (6%) were mixed and 5 (1%) were other (including
endometrioid).
The recurrence rate after conservative treatment was 16%
with only five recorded disease-related deaths.
The majority of women undergoing conservative surgery
were 40 years of age or less, though in two publications there
were women over this age group having similar surgery
[19,20].
In total, where recorded, 254 pregnancies were achieved
in 206 patients. In one study however, two patients were
pregnant at the time of diagnosis [21], and these have been
excluded in the figures. In order to calculate a pregnancy
rate we collected data from nine studies which stated the
number of patients wishing to conceive (n = 213) and the
number of pregnant women in this group (n = 103). This
gives a pregnancy rate of 48%. Data regarding the number
of patients desiring pregnancy may not be representative of
all the studies as each study population may have been
A. Swanton et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 135 (2007) 3–74

3. A.Swantonetal./EuropeanJournalofObstetrics&GynecologyandReproductiveBiology135(2007)3–75
Table 1
Studies included in review
Study group
Romagnolo
et al. [26]
Boran
et al. [27]
Fauvet et al. [25] Rao et al. [21] Olszewska
et al. [28]
Chan et
al. [19]
Donnez et al. [29] Camatte
et al. [30]
Demeter et
al. [23]
Sample size (n) 113 142 360 249 42 25 75 68 27
No. patients conservative surgery 53 (47%) 62 (44%) 162 (45%) 38 (15%) 42 (100%) 25 (100%) 16 (21%) 68 (100%) 12 (44%)
Recurrence 11 (21%) 4 (6.5%) 27 (17%) 6 (16%) 2 0 3 (19%) 16 (24%) 0 (0%)
Disease-related death 1 0 0 0 0 0 0 0 0
Desire for pregnancy 12 25 65 N/A N/A 6 11 29 12
No. patients pregnant 7 10 21 5a
10 6 7 19 6
No. pregnancies achieved 8 13 30 6 13 6 12 26 6b
Recurrence after pregnancy 2 1 5 N/A N/A 0 1 N/A N/A
Average age years conservative
group (range)
N/Ac
27.5 Æ 5.4
(16–40)
35.5 Æ 13.1
(N/A)
26 (15–39) N/A 29 (21–43) 27.2 (20–38) N/A N/A (15–40)
Stage I N/A 30 N/A 34 41 13d
14 50 12e
Stage II N/A 31 N/A 1 0 2 6
Stage III N/A 1 N/A 3 1 1 0 12 0
Serous/mucinous/mixed/other N/A 33/37/1/1 37/24/4f
21/16/1 10/21/11 11/11/3 37/36/1/1 46/16/5/1 N/A
Average follow-up of conservatively
treated patients in months (range)
44 (mean)
(6–122)g
44.3 (mean)
(3–128)
N/A (13.4–136.9) 26 (median)
(N/A)
N/A (27–50) 80 (median)
(4–157)
42.1 (mean) Æ 46.7 71.5 (median)
(N/A)
72 (median)
(24–120)
Study group
Seracchioli
et al. [6]
Zanetta et
al. [31]
Morris
et al. [32]
Papadimitriou
et al. [33]
Gotlieb et al. [34] Makarewicz
et al. [24]
Armas et
al. [35]
Ji et al. [36] Lim Tan
et al. [18]
Tazelaar
et al. [20]
Sample size (n) 19 339 518 79 82 114 53 95 35 61
No. patients conservative surgery 19 (100%) 189 (56%) 43 (83%) 15 (19%) 39 (43%) 37 (32%) 23 (43%) 25 (26%) 35 (100%) 20 (33%)
Recurrence 1 (5%) 35 (18%) 14 (33%) 5 (33%) 3 (8%) 0 N/A 4 (16%) 6 (17%)h
3 (15%)
Disease-related death 0 1 1 0 0 0 1 1 0 0
Desire for pregnancy 10 N/A 24 N/A N/A N/A N/A 19i
N/A N/A
No. patients pregnant 6 44 12 6 15 7 N/A 9 8 2
No. pregnancies achieved 6 44 25 10 22 9 8 N/A 8b
2
Recurrence after pregnancy 0 N/A 1 5 0 0 N/A N/A N/A N/A
Average age years conservative
group (range)
27.4 Æ 4.7 N/A 25 (15–39) N/A N/A N/A N/A N/A (14–33) 28 (10–68) 95%
<45 years
Stage I 19 164 15j
N/A N/A 37 N/A 95 33 20
Stage II 0 13 0 N/A N/A 0 N/A 0 1 0
Stage III 0 12 3 N/A N/A 0 N/A 0 1 0
Serous/mucinous/mixed/other 16/3/0 N/A 26/17/0 N/A N/A N/A N/A N/A 35/0/0 11/7/2
Average follow-up conservatively
treated patients months (range)
42 Æ 19 (mean) 70 (median)
(13–180)
N/A 93.4 (mean) Æ32.4 57 (mean) (N/A) 136 (63–213) 84 (mean)
(20–218)
87 (mean)
(9–256)
78 (median)
(36–216)
89 (mean)
(36–244)
Key: N/A, not available.
a
2 patients diagnosed during pregnancy.
b
Viable deliveries.
c
87% patients < 35 years.
d
11 patients were unstaged.
e
12 patients were stage I and II.
f
Histology only available for women wanting to conceive.
g
Follow-up for entire group of patients.
h
Persistence or recurrence.
i
1 patient lost to follow-up.
j
25 patients unstaged due to lack of information.

4. followed up in different clinic settings that may or may not
have a fertility component attached to it. However, a crude
estimate of the pregnancy rate is useful for patients and
clinicians alike based on the best available evidence.
Overall, of the 923 patients treated with conservative
surgery, 206 (22%) patients were documented to have
conceived.
The majority of pregnancies were spontaneous but some
data was available regarding fertility treatment and assisted
conception. Where recorded, 20 patients underwent assisted
conception, which gives a rate of 16% when taking into
account patients wanting to conceive for these particular
studies (n = 124). This is a similar figure to the background
rate for the general population seeking specialised fertility
help [22]. Many studies commented on patients undergoing
fertility treatment, including ovulation induction, intrauter-
ine insemination and in vitro fertilization treatment, without
any obvious increased risk of recurrence. However, not all
studies recorded whether the pregnancies were spontaneous
or not. Furthermore, studies also commented that some
patients had a history of subfertility prior to their diagnosis
of the disease, and some after surgery. Consistency of these
data is not clear and definitions of subfertility from study to
study also varied.
4. Discussion
This systematic review focuses on pregnancy rates and
fertility outcome in women with borderline ovarian tumours
who have undergone conservative surgery. The inevitable
difficulties associated with inconsistency of data available
such as the number of pregnancies, ‘healthy children deli-
vered’, number of patients desiring pregnancy, has undoubt-
edly affected the overall figures. The pregnancy rate is almost
certainly an underestimate, as the information is not clear
from all the studies. Some studies commented on viable
deliveries only [18,23], or number of ‘healthy children’ born
[24], rather than the total number of pregnancies achieved.
Furthermore, as all the studies are retrospective, data
regarding fertility outcome is only available up to when the
study finished. The lowest pregnancy rate was 32% [25], and
the highest was 100% [19]. However, in the study by Chan
et al. only 6 patients out of 15 in whom they had fertility
outcome data on wished to conceive. Although only 22% of
the patients overall were documented to have delivered
following surgery, we feel that the rate of 48% which is
yielded by the nine studies which specifically reported
pregnancy data, is a more accurate reflection of the pregnancy
success rate for this group.
There was no consistent information regarding adverse
pregnancy outcome such as miscarriage or premature
delivery, but many studies recorded ‘viable deliveries’ or
‘healthy babies’ being born. This would suggest that women
who have conservative surgery for borderline tumours have
normal pregnancy outcomes.
5. Conclusions
This study confirms that conservative surgery is a viable
option for patients wishing to retain their fertility potential
and that the recurrence rate is low. Completion of a family
should be a decision point as to whether further surgery is
necessary in order to remove the preserved ovary or ovaries
and/or uterus.
This review does not answer the question of how long the
follow-up should be and what advice should be given to
women who have had conservative surgery and completed
their families. In some studies women went on to have the
remaining ovary removed, but presumably there are a large
group of women where this is not an issue at present.
Although there are long-term studies which confirm an
extremely low risk of malignant recurrence, there are no
studies which have shown a survival benefit of additional
‘‘prophylactic’’ surgery for these women. It would seem
prudent that the decision for further surgery is managed on
an individual basis until further long-term research clarifies
optimum care.
Acknowledgments
I acknowledge my colleagues who translated the non-
English papers.
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