DOI: 10.1111/1471-0528.

14011 General Gynaecology

www.bjog.org

Risk factors for recurrent ectopic pregnancy: a

case–control study
D Zhang,a,b,* W Shi,a,b,* C Li,a,b J-J Yuan,a,b W Xia,a,b R-H Xue,a,b J Sun,c,† J Zhanga,b,†
a
Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong
University, Shanghai, China b Institute of Embryo-Fetal Original Adult Disease Affiliated to School of Medicine, Shanghai Jiaotong University,
Shanghai, China c Department of Obstetrics and Gynaecology, Shanghai First Maternity and Infant Hospital, Tong Ji University School of
Medicine, Shanghai, China
†
Correspondence: J Zhang, Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China. Email zhangjian_ipmch@sjtu.edu.cn and J Sun, Department of Obstetrics and
Gynaecology, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai, China. Email
sunjing61867@126.com

Accepted 25 February 2015.

Objective To study the risk factors for recurrent ectopic
pregnancy (REP).
Design A retrospective case–control study.
Setting A university medical centre.
Population 554 women with a history of ectopic pregnancy (EP)
were included. Among them were 181 women with current EP,
184 women with current intrauterine pregnancy (IUP) and 189
nonpregnant women (NonP).
Methods The three groups were matched at a ratio of 1:1 with
respect to current age, age of initial EP and gestational week of
initial EP. Socio-demographic characteristics, reproductive history,
gynaecological and surgical history, and experience of
contraception were compared among the three groups. A
multivariable logistic regression analysis was used to adjust for
confounders and calculate adjusted odds ratios (AORs).
Results The risk of REP increased with history of infertility (AOR
= 3.84, 95%CI 2.16–6.86) in REP women compared with IUP
controls. Compared with NonP controls, salpingotomy (AOR =
3.04, 95%CI 1.21–36.51) for previous EP was a risk factor for
REP. Multiparous women were less likely to suffer REP when
compared with NonP women (AOR = 0.36, 95%CI 0.18–0.62) or
IUP controls (AOR = 0.35, 95%CI 0.20–0.62). Current use of an
intrauterine device (IUD) (REP versus NonP, AOR = 0.02, 95%CI
0.00–0.08) or condoms (REP versus NonP, AOR = 0.16, 95%CI
0.07–0.38) significantly reduced the risk of REP compared with
those not using any contraception. Similarly, previous use of
condoms also prevented REP compared with those with no
previous condom use (REP versus NonP, AOR = 0.20, 95%CI
0.08–0.49; REP versus IUP, AOR = 0.40, 95%CI 0.22–0.71).
Conclusions Women with history of infertility or salpingotomy
should be alert for the recurrence of EP. Multiparous women are
*These authors contributed equally to this work.
less likely to suffer REP. We propose the use of condoms for
effective prevention of REP.
Keywords Case–control study, contraception, recurrent ectopic
pregnancy, risk factors.
Tweetable abstract History of infertility and salpingotomy for last
EP are risk factors for recurrent EP.
摘要
目的 探讨重复异位妊娠(recurrent ectopic pregnancy,REP) 的危
险因素。
研究类型 回顾性病例对照研究。
研究单位 大学附属医院。
研究人群 本研究共纳入554例有异位妊娠(ectopic pregnancy,EP)
史的病例。其中此次重复EP 181例,宫内妊娠(intrauterine
pregnancy, IUP)184例、非妊娠(non-pregnant, NonP)189例。
方法 三组病人按照年龄、首次EP年龄和首次EP孕周以1:1比例匹
配(EP组、IUP组、NonP组)。记录并比较三组社会人口学资料、
生育史、妇科史、手术史以及避孕方法使用情况。应用单因素
条件logistic回归分析和多因素logistic回归分析分别计算组间变量
的粗比值比(crude odds ratios, CORs)、95%置信区间(confidence
intervals,CI)以及调整比值比(adjusted odds ratios, AORs)。
结果 与IUP组相比,不孕史增加REP风险(AOR = 3.84, 95%CI:
2.16-6.86)。相较于NonP组,前次EP时的输卵管切开术是REP的
危险因素(AOR = 3.04, 95%CI: 1.21–36.51)。与NonP组(AOR =
0.36, 95%CI: 0.18–0.62)或IUP组(AOR = 0.35, 95%CI: 0.20–0.62)
相比,多产者REP风险降低。与不使用任何避孕方式者相比,本周
期使用宫内节育器(intrauterine devices, IUDs) (REP versus
NonP, AOR = 0.02, 95%CI: 0.00–0.08)和避孕套(REP versus
NonP, AOR = 0.16, 95%CI: 0.07–0.38)均显著降低REP风险。此
外,既往曾使用避孕套是REP保护因素(REP versus NonP, AOR
= 0.20, 95%CI: 0.08-0.49; REP versus IUP, AOR = 0.40, 95%
CI: 0.22–0.71)。

82 ª 2016 Royal College of Obstetricians and Gynaecologists


结论 具有不孕史或经输卵管切开取胚治疗者须警惕REP的发
生。多产者REP风险较小。我们提倡合理使用避孕套以有效预
防REP发生。
Please cite this paper as: Zhang D, Shi W, Li C, Yuan J-J, Xia W, Xue R-H, Sun J, Zhang J. Risk factors for recurrent ectopic pregnancy: a case–control
study. BJOG 2016; 123 (S3): 82–89.
Introduction
Ectopic pregnancy (EP) is one of the most common gynae-
cological emergencies, and worldwide causes more than
three-quarters of maternal deaths occurring during the first
trimester of pregnancy.1,2 It accounts for 4–10% of total
pregnancy-related deaths, and leads to a high incidence of
recurrent ectopic pregnancy (REP).3
Although mortality due to EP has declined sharply in
recent years, the incidence of EP is still steadily rising at a
global level.1,4,5 Accordingly, the number of women diag-
nosed with REP is increasing.5 Among women with history
of previous EP the risk of REP ranges from 10–27%,
approximately five to ten times the general population risk
for EP.5,6 REP, as a long-term complication of EP, can
impair subsequent fertility and negatively affect quality of
life.7 Unfortunately, there are currently no effective means
of predicting REP.
Over a decade ago, two epidemiological studies explored
the risk factors for REP.5,8 However, these studies did not
thoroughly investigate the relationship between current/
previous use of contraceptives and the recurrence of EP. In
addition, the study by Butts et al.5 used women who had
had a single EP as the control group. This is somewhat
inappropriate because they did not consider the possibility
that women in the control group may develop another EP
in the future.5 Furthermore, the recent changes in preferred
contraceptive methods and the increased use of assisted
reproductive technology (ART) have been suggested as
additional risk factors for EP.8,9 As it remains unclear
whether there is any association between REP and contra-
ceptive use or ART, we performed a case–control study in
Shanghai, China. The objective of this study was to explore
the risk factors for REP.
Methods
Ethical considerations
This case–control study was approved by the institutional
review board of the International Peace Maternity and
Child Health Hospital in Shanghai, China. Before recruit-
ment, written informed consent was obtained from each
subject. For women under 18 years of age, written
informed consent was obtained from their guardians.
Patients were also informed that they had the right to
ª 2016 Royal College of Obstetricians and Gynaecologists
Recurrent ectopic pregnancy risk factors
refuse the interview and quit the study at any time. All
subjects were assured that their information would be trea-
ted confidentially.
Study design and participants
This case–control study was conducted at the International
Peace Maternity and Child Health Hospital from March
2011 to April 2013. Recruited participants were women of
reproductive age ranging from 17 to 45 years who did not
have a history of cardiovascular disease, venous throm-
boembolic disease, epilepsy, diabetes mellitus, cancer or
other disease that could have influenced the choice of con-
traceptive. All participants had a history of EP. Patients
who were diagnosed with present EP (based on the Ameri-
can College of Obstetricians and Gynecologists Practice
Bulletin) from the inpatient department of gynaecology
were defined as the case group (REP group).10,11 Women
with an intrauterine pregnancy (IUP) and nonpregnant
(NonP) women came from the prenatal clinic and the fam-
ily planning clinic, and the physical examination centre of
the same hospital, respectively. They were recruited into
the two control groups (i.e. the IUP group and the NonP
group). The IUP controls and REP group were matched at
a ratio of 1:1 with respect to current age ( 5 years), age
of the initial EP ( 5 years) and gestational week of the
initial EP ( 7 days). The NonP controls were matched
with the REP group in a 1:1 ratio for these same variables.
Data collection and patient examination
Information was collected from each patient in a face-to-
face interview and included: socio-demographic characteris-
tics (age, marital status, educational attainment, occupa-
tion, individual annual income, smoking status); history of
reproduction and gynaecology [number of previous termi-
nations of pregnancy (TOP), parity, history of infertility
and tubal infertility, the mode of pregnancy including
natural conception, in vitro fertilisation-embryo transfer
(IVF-ET) or other ART (ovarian stimulation, intrauterine
insemination, Chinese herbs, luteal phase support, combi-
nation of ovarian stimulation and luteal phase support)];
surgical history [history of caesarean section, adnexal sur-
gery, appendectomy and treatment of last EP including
expectant treatment, methotrexate, salpingectomy, salpingo-
tomy and other surgical procedures (fimbrial ‘milking-out’
of the ectopic gestation, removal of trophoblastic tissue in
83
 Zhang et al.
pelvic cavity and ovarian wedge resection)]; previous contra-
ceptive experience [IUD, oral contraceptive pill (OCP), levo-
norgestrel emergency contraceptive (LNG-EC), condom and
other contraceptive methods (withdrawal method and calen-
dar rhythm method)]; and current contraceptive experience
[IUD, OCP, LNG-EC, female sterilisation (bilateral salp-
ingectomy and bilateral tubal ligation), condom and other
contraceptive methods (rhythm method and withdrawal)].
The previous and current uses of a given contraceptive
method were defined in the same way as in our previous
study.12 If participants were unwilling to reply to a certain
question they were allowed to skip it, and we treated this as
missing information.
Blood samples were collected from each patient to measure
the level of serum Chlamydia trachomatis (CT) immunoglob-
ulin G (IgG) using an enzyme-linked immunosorbent assay
according to the manufacturer’s instructions (Beijing
Biosynthesis Biotechnology, Beijing, China).
Statistical analysis
Statistical analyses were performed using SAS software,
version 9.2 (SAS Institute Inc., Cary, NC, USA). All P-
values were calculated using two-sided tests and were con-
sidered statistically significant if P < 0.05. The Pearson
chi-squared test was applied to detect the differences
among the three groups with regard to socio-demographic
characteristics, history of reproduction, gynaecology and
surgery, and experience of contraception. Using univariable
conditional logistic regression analysis, we calculated crude
odds ratios (ORs) and their 95% confidence intervals (CIs)
for each variable. A multivariable logistic regression analy-
sis was used to adjust for potential confounders and calcu-
late adjusted odds ratio (AOR).
Results
Among the 571 patients recruited, 188 patients with cur-
rent REP were assigned to the case group (REP group) and
190 patients with IUP and 193 nonpregnant patients were
recruited to the control group (IUP group and NonP
group). After excluding patients with incomplete medical
records, 181, 184 and 189 patients in the EP, IUP and
NonP groups, respectively, remained, with a response rate
of 97% (see Figure S1). Most women in the study had had
only one previous EP. In the REP group, 15 patients had
had two previous EPs and three patients three EPs. In the
IUP and NonP groups, three and 16 patients, respectively,
had had two previous EPs.
Socio-demographic characteristics and patient
history
Table 1 outlines the socio-demographic characteristics of
all participants. Compared with women in the IUP and
84
NonP groups, there was a greater proportion of women in
the REP group whose individual annual income was equal
to or greater than ¥50,000 (P = 0.04). In terms of history
of reproduction and gynaecology (Table 2), women with
higher parity were less likely to suffer from REP (REP ver-
sus NonP, OR1 = 0.15, 95%CI 0.10–0.24; REP versus IUP,
OR2 = 0.32, 95%CI 0.21–0.49) compared with nulliparous
women. Moreover, history of infertility (OR1 = 3.69, 95%
CI 2.29–5.95; OR2 = 4.03, 95%CI 2.47–6.58) or tubal infer-
tility (OR1 = 3.67, 95%CI 2.23–6.03; OR2 = 3.43, 95%CI
2.10–5.61) could be risk factors for REP.
With regard to surgical history (Table 2), 86% (155/181)
of patients in the REP group had received adnexal surgery,
and 75% (132/176) and 77% (139/180) of women were
treated by adnexal surgery in the IUP and NonP groups,
respectively. Among the 155 women in the REP group with
previous adnexal surgery, 151 (97%) of them were treated
for previous EP. Women who had a history of adnexal sur-
gery (P = 0.03), or who had experienced salpingotomy
(P < 0.01) for previous EP, were more likely to develop
another EP compared with women without these surgical
histories.
Contraceptive use
The contraceptive experiences of all subjects are shown in
Table 3. Compared with women with IUP and NonP
women, women with REP were less likely to have previ-
ously used LNG-EC (P = 0.01) or condoms (P < 0.001).
Further, using the NonP group as controls, the risk of EP
decreased with current use of an IUD (OR1 = 0.02, 95%CI
0.00–0.08), LNG-EC (OR1 = 0.32, 95%CI 0.12–0.88), con-
doms (OR1 = 0.09, 95%CI 0.05–0.18), female sterilisation
(OR1 = 0.18, 95%CI 0.04–0.75) or other methods of con-
traception (OR1 = 0.23, 95%CI 0.11–0.45) compared with
those not currently using any contraceptives.
Multivariable analysis of risk factors for REP
Results of the multivariable analysis are listed in Table 4.
Multiparity was a protective factor for REP (REP versus
NonP, AOR1 = 0.36, 95%CI 0.18–0.62; REP versus IUP,
AOR2 = 0.35, 95%CI 0.20–0.62). In women with previous
EP, those with a history of infertility (AOR2 = 3.84, 95%CI
2.16–6.86) were more likely to experience another EP than
were women who had no history of infertility. Moreover,
the AOR of REP increased as a consequence of salpingo-
tomy (AOR1 = 3.04, 95%CI 1.21–36.51) with expectant
treatment as the reference. But the risk of REP following
salpingotomy did not increase when using the IUP group
as the control group. In addition, expectant treatment,
methotrexate, salpingectomy and other surgical procedures
did not relate to risk of REP.
Previous condom use was associated with a significantly
lower risk of REP (AOR1 = 0.20, 95%CI 0.08–0.49; AOR2
ª 2016 Royal College of Obstetricians and Gynaecologists
 Recurrent ectopic pregnancy risk factors

Table 1. Socio-demographic characteristics

Variables REP IUP NonP OR1 [95%CI] OR2 [95%CI] P-value

n* % n* % n* % REP versus NonP REP versus IUP

Age (years)
≤24 12 6.6 13 7.1 18 9.5 Ref. Ref. 0.75
25–29 46 25 49 27 39 21 1.77 [0.76, 4.12] 1.02 [0.42, 2.46]
30–34 75 41 66 36 72 38 1.56 [0.70, 3.47] 1.23 [0.53, 2.89]
35–39 30 17 38 21 42 22 1.07 [0.45, 2.55] 0.86 [0.34, 2.14]
≥40 18 9.9 18 9.8 18 9.5 1.50 [0.56, 4.00] 1.08 [0.39, 3.01]
Marital status
Married 170 94 179 97 181 96 Ref. Ref. 0.30
Unmarried 11 6.1 5 2.7 8 4.2 1.46 [0.58, 3.73] 2.32 [0.79, 6.81]
Education attainment
Primary school or lower 55 30 42 23 57 30 Ref. Ref. 0.09
Middle school 11 6.1 25 14 26 14 0.90 [0.56, 1.45] 1.43 [0.87, 2.33]
High school 24 13 18 9.8 21 11 0.40 [0.18, 0.85] 0.48 [0.22, 1.03]
College or above 91 50 99 54 85 45 1.07 [0.55, 2.06] 1.45 [0.74, 2.85]
Occupation
Employed 122 68 141 77 138 73 Ref. Ref. 0.28
Self-employed 22 12 15 8.2 24 13 1.04 [0.55, 1.94] 1.70 [0.84, 3.41]
Unemployed 36 20 28 15 27 14 1.51 [0.87, 2.63] 1.49 [0.86, 2.58]
Individual annual income (¥)
<50 000 59 33 87 47 86 46 Ref. Ref. 0.04
50 000–100 000 75 41 57 31 60 32 1.82 [1.13, 2.93] 1.94 [1.20, 3.13]
>100 000 47 26 40 22 43 23 1.59 [0.94, 2.71] 1.73 [1.01, 2.96]
Smoking status**
Nonsmoker 165 91 166 94 168 92 Ref. Ref. 0.35
Occasional smoker 11 6.1 8 4.5 6 3.3 1.87 [0.68, 5.16] 1.38 [0.54, 3.53]
Regular smoker 5 2.8 3 1.7 9 4.9 0.57 [0.19, 1.72] 1.68 [0.39, 7.13]

Ref., reference.
*The sum does not necessarily equal the sample size for all variables because of missing data.
**Occasional smoker: smoking more than four times a week, but on average less than one cigarette per day. Regular smoker: smoking more
than one cigarette per day continuously or over 6 months.

= 0.40, 95%CI 0.22–0.71), and current IUD and condom
use had protective effects on REP (IUD, AOR1 = 0.02, 95%
CI 0.00–0.08; condoms, AOR1 = 0.16, 95%CI 0.07–0.38).
However, for all the contraceptive methods, there is the
possibility of contraceptive failure, in which case REP is
obviously not prevented.
Discussion
Main findings
This case–control study found that a history of infertility
and salpingotomy for the last EP were significant risk fac-
tors for REP, whereas multiparity, previous use of condoms
and current use of an IUD and condoms were associated
with a lower risk of REP.
Strengths and limitations
Our study has several limitations. First, REP cases might
have recalled or reported some risk factors differently from
the controls, leading to an unknown degree of bias. Sec-
ondly, few women in our study used OCPs, LNG-EC or
female sterilisation, precluding us from examining any
associations between these factors and REP. Finally, we did
not consider the duration of IUD use, either previously or
currently, which was demonstrated to be a significant risk
factor for EP in our previous study.12 Further studies with
a larger sample size are needed to confirm the association
of REP and contraceptive methods. Despite these limita-
tions, compared with previous studies,5,8 we included more
subjects, used strict inclusion criteria and improved the
study design. In addition, our study is the first to discuss
in detail both previous and current contraceptive use as a
risk factor for REP.
Interpretation
The correlation between previous infertility and the occur-
rence of EP has been well documented.2,9,13,14 Infertility
may be attributable to tubal damage resulting from previ-

ª 2016 Royal College of Obstetricians and Gynaecologists 85

 Zhang et al.

Table 2. History of reproduction, gynaecology and surgery

Variables REP IUP NonP OR1 [95%CI] OR2 [95%CI] P-value

n* % n* % n* % REP versus NonP REP versus IUP

Reproductive history
No. of previous abortions
0 15 8.3 16 9.1 12 6.7 Ref. Ref. 0.03
1 66 36 67 38 39 22 1.35 [0.58, 3.19] 1.05 [0.48, 2.30]
2 68 38 42 244 77 43 0.71 [0.31, 1.61] 1.73 [0.77, 3.85]
≥3 32 18 51 28.98 52 29 0.49 [0.21, 1.18] 0.67 [0.29, 1.54]
Parity
0 124 699 72 41 45 25 Ref. Ref. <10 3

≥1 57 31 104 59 135 75 0.15 [0.10, 0.24] 0.32 [0.21, 0.49]

Gynaecological history
Serum Chlamydia trachomatis IgG test
Negative 113 63 124 70 138 77 Ref. Ref. 0.02
Positive 66 37 52 3030 42 23 1.92 [1.21, 3.04] 1.39 [0.89, 2.17]
History of infertility
No 99 555 146 8333 147 82 Ref. Ref. <10 3

Yes 82 45 30 17 33 18 3.69 [2.29, 5.95] 4.03 [2.47, 6.58]

History of tubal infertility
No 105 59 146 83 151 84 Ref. Ref. <10 3

Yes 74 41 30 17 29 16 3.67 [2.23, 6.03] 3.43 [2.10, 5.61]

Mode of current pregnancy
Natural conception 88 79 73 86 34 79 Ref. Ref. 0.43
IVF-ET 13 12 4 4.7 6 14 1.42 [0.37, 5.39] 1.14 [0.44, 2.99]
Other ART** 11 9.8 8 9.4 3 7.0 0.84 [0.29, 2.38] 2.70 [0.84, 8.62]
Surgical history
Previous caesarean section***
No 35 61 55 50 55 41 Ref. Ref. 0.03
Yes 22 39 55 50 80 59 0.43 [0.23, 0.82] 0.63 [0.33, 1.21]
Previous adnexal surgery
No 26 14 44 25 41 23 Ref. Ref. 0.03
Yes 155 86 132 75 139 77 1.76 [1.02, 3.02] 1.99 [1.16, 3.40]
Previous appendectomy
No 169 95 166 94 161 89 Ref. Ref. 0.09
Yes 9 5.1 10 5.7 19 11 0.45 [0.20, 1.03] 0.88 [0.35, 2.23]
Treatment of last EP
Expectant treatment 17 9.4 29 16 26 14 Ref. Ref. <10 2

Methotrexate 13 7.2 15 8.5 15 8.3 1.33 [0.51, 3.47] 1.48 [0.57, 3.84]
Salpingectomy 99 55 92 52 118 66 1.28 [0.66, 2.50] 1.84 [0.95, 3.56]
Salpingotomy 51 28 39 22 17 9.4 4.59 [2.02, 10.43] 2.23 [1.08, 4.63]
Other surgical procedure*** 1 0.6 1 0.6 4 2.2 0.38 [0.04, 3.72] 1.71 [0.10, 29.07]

Ref, reference.
*The sum does not necessarily equal the sample size for all variables because of missing data.
**Other ART includes ovarian stimulation, intrauterine insemination, Chinese herbs, luteal phase support and combination of ovarian stimulation
and luteal phase support.
***The number of women who had delivered a child was used as the denominator to calculate the percentage.
****Other surgical procedures refer to fimbrial ‘milking-out’ of the ectopic gestation, removal of trophoblastic tissue in the pelvic cavity and
ovarian wedge resection.

ous EP and surgical treatment.15,16 Tubal damage can dis-
turb the passage of the zygote through the fallopian tube
and into the uterine cavity, and thus predisposes women to
another EP.15,16 Furthermore, women with infertility tend
to receive infertility work-up and surgical treatment, which
may also increase their risk for EP.8,17 Thus, the association
between a history of infertility and REP could be due to a
common underlying tubal factor (i.e. a mere association)
or the tubal damage caused by infertility treatment could,
in turn, have caused REP (i.e. causation).

86 ª 2016 Royal College of Obstetricians and Gynaecologists

 Recurrent ectopic pregnancy risk factors

Table 3. Previous and current experience of contraception

Variables REP IUP NonP OR1 [95%CI] OR2 [95%CI] P-value

n* % n* % n* % REP versus NonP REP versus IUP

Previous contraceptive experience

IUD**
No 159 88 138 78 148 82 Ref. Ref. 0.05
Yes 21 12 38 22 32 18 0.61 [0.34, 1.11] 0.48 [0.27, 0.86]
OCP
No 166 94 164 93 168 93 Ref. Ref. 0.89
Yes 10 5.7 12 6.8 12 6.7 0.84 [0.36, 2.01] 0.82 [0.35, 1.96]
LNG-EC
No 107 59 83 47 7 43 Ref. Ref. 0.01
Yes 74 41 93 53 102 57 0.53 [0.35, 0.80] 0.62 [0.41, 0.94]
Condom
No 54 31 27 15 24 13 Ref. Ref. <10 3

Yes 123 69 149 85 156 87 0.35 [0.21, 0.60] 0.41 [0.25, 0.69]
Other contraceptive method***
No 55 30 56 32 45 25 Ref. Ref. 0.33
Yes 126 70 120 68 135 75 0.76 [0.48, 1.21] 1.07 [0.68, 1.67]
Current contraceptive experience
None used 134 75 125 71 49 27 Ref. Ref. <10 3

IUD 2 1.1 0 0.0 38 21 0.019 [0.004,0.082] NA

OCPs 0 0.0 0 0.0 0 0.0 NA NA
LNG-EC 8 4.5 13 7.4 9 5.0 0.32 [0.12, 0.88] 0.56 [0.22, 1.39]
Condom 13 7.3 23 13 51 28 0.09 [0.05, 0.18] 0.51 [0.25, 1.05]
Female sterilisation**** 3 1.7 4 2.3 6 3.3 0.18 [0.04, 0.75] 0.68 [0.15, 3.09]
Other contraceptive method***** 19 11 11 6.3 27 15 0.23 [0.11, 0.45] 1.18 [0.55, 2.53]

Ref., reference; NA, not available.

*The sum does not necessarily equal the sample size for all variables because of missing data.
**Previous experience of IUD was defined as women who used an IUD in the previous cycle and have since had it removed.
***‘Other’ methods include rhythm method and withdrawal.
****Female sterilisation includes bilateral salpingectomy and bilateral tubal ligation. All female sterilisations are classified as current contraceptive
experience.
*****‘Other’ methods include rhythm method and withdrawal.

Other factors, including Chlamydia trachomatis (CT)
infection, can damage tubal anatomy, causing disruption of
ciliary action, tubal obstruction and pelvic adhesions.2,3,6
Women with REP were previously shown to have signifi-
cantly higher levels of CT antibody and/or antigen com-
pared with women with an IUP.6 However, our study
showed that serum CT levels did not differ significantly
between women with REP and controls. It is necessary to
point out that the controls in the present study were IUP
women with a history of EP, but the IUP controls in the
previous study by Kuroda et al.6 were not restricted to
those with previous EP, which might contribute to the dif-
ference. Similarly, although salpingitis (i.e. infection and
inflammation of the fallopian tube) has been shown to be
an important risk factor for the first EP, it does not neces-
sarily increase the risk for REP.18 This phenomenon can be
explained by the fact that once salpingitis has induced irre-
versible tubal damage and caused an initial EP, any further
tubal damage caused by the EP and its corresponding treat-
ment may prevent any future pregnancies from occurring
at all. Therefore, after the initial EP, the effect of salpingitis
on the fallopian tube may not be related to the occurrence
of REP.
Tubal disorders have been widely recognised as a major
risk factor for EP, accounting for a third of all cases of
EP.1,2,19 An epidemiological study showed that a previous
tubal disorder is a risk factor for REP,6 but whether the
different surgical procedures used to treat EP are risk fac-
tors for REP remains unclear. Some studies report a higher
incidence of REP after conservative surgery than after radi-
cal surgery,20,21 whereas others show no difference,6,22–24
Although we found that salpingotomy for previous EP was
a risk factor for REP in this study, the confidence interval
was relatively wide. We found that multiparous women
were less likely to experience REP than nulliparous women,
which is consistent with the results of a previous epidemio-

ª 2016 Royal College of Obstetricians and Gynaecologists 87

 Zhang et al.

control study, current use of most types of contraceptives

Table 4. Multivariable logistic regression analysis predicting risk
factors for REP reduced the risk of IUP and EP.12 In the present study,
current use of an IUD was shown to help to reduce the
Variables Adjusted OR1 Adjusted OR2 risk of REP. However, another study regarded current use
[95%CI] [95%CI]
of IUD as a risk factor for EP due to IUD-induced inflam-
REP versus NonP REP versus IUP
mation, which leads to deciliation of endosalpinx and thus
delays transportation of the ovum.13 A previous study
Parity
reported that women who are currently using an IUD tend
0 Ref. Ref.
≥1 0.36 [0.18, 0.62] 0.35 [0.20, 0.62]
to believe in their ability to conceive but have less desire to
History of infertility fall pregnant as they are at the end of their reproductive
No Ref. Ref. lives or are satisfied with the number of children they
Yes 0.84 [0.41, 1.74] 3.84 [2.16, 6.86] have.8 Therefore, these women are less likely to expose
Previous adnexal surgery themselves to the possibility of becoming pregnant, and
No Ref. Ref. their risk of REP is lower. Similarly, Saada et al.28 regarded
Yes 2.55 [0.14, 46.77] 7.25 [0.37,141.20]
previous use of an IUD as an indicator of good fertility
Treatment of last EP
Expectant treatment Ref. Ref.
rather than as a protective factor for REP, despite its asso-
Methotrexate 2.99 [0.86, 10.37] 2.26 [0.75, 6.86] ciation with a decreased risk of REP (OR = 0.27).
Salpingectomy 1.15 [0.06, 21.36] 0.41 [0.02, 7.87] The reason for the link between REP and previous con-
Salpingotomy 3.04 [1.21, 36.51] 0.47 [0.02, 8.88] dom use may be explained by the fact that the consistent
Other surgical procedure* 0.31 [0.01, 9.11] 0.99 [0.03, 36.89] and correct use of condoms can prevent most sexually
Previous condom use transmitted infections and therefore may reduce the tubal
No Ref. Ref.
damage, which is a high risk factor for EP.29 Therefore, for
Yes 0.20 [0.08, 0.49] 0.40 [0.22, 0.71]
Current contraceptive experience
women with history of EP, condoms should be used con-
None used Ref. Ref. sistently and correctly to effectively prevent REP.
IUD 0.02 [0.00, 0.08] NA
OCP NA NA
LNG-EC 0.51 [0.15, 1.63] 1.40 [0.51, 3.95]
Conclusions
Condom 0.16 [0.07, 0.38] 1.51 [0.66, 3.47] A history of infertility and salpingotomy for previous EP
Female sterilisation** 0.11 [0.02, 0.67] 0.52 [0.08, 3.62]
are major risk factors for REP. In addition, multiparous
Other contraceptive 0.38 [0.16, 1.02] 3.40 [0.97, 8.98]
method***
women are less likely to suffer from REP. Condom use can
protect women with a history of EP from developing REP.
Ref, reference; NA, not available. Therefore, for women with a history of infertility and pre-
*Other surgical precedures: fimbrial ‘milking-out’ of the ectopic vious adnexal surgery we suggest that condoms are used to
gestation, removal of trophoblastic tissue in pelvic cavity and
ovarian wedge resection.
prevent REP.
**Female sterilisation includes bilateral salpingectomy and bilateral
tubal ligation. All female sterilisations are classified as current Disclosure of interests
contraceptive experience. Full disclosure of interests available to view online as Sup-
***‘Other’ methods include rhythm method and withdrawal. porting Information.

logical study.8 This is probably due to the fact that multi-
parous women have proven fertility and less tubal damage
than nulliparous women who may have fertility problems.
Another reason for the reduced REP in multiparous
women is the Chinese one-child policy; most women who
already have a child will use contraception to prevent a fur-
ther pregnancy, irrespective of whether it would turn out
to be an IUP or EP.
With regard to contraception, long-acting contraceptive
methods are common in China, a situation very different
from that in Western countries.25 Following a change in
family planning policy, contraceptive choices have also
changed in China in recent years.26,27 In our previous case–
Contribution to authorship
JZ and JS conceived the study and participated in its design,
as well as supervising the study and critically revising the
manuscript. DZ was responsible for drafting and writing the
manuscript. CL participated in the revision of the manu-
script. JJY, WS and WX contributed to statistical analysis.
RHX contributed to the data collection. All authors substan-
tially contributed to the revision of the manuscript.
Details of ethics approval
This study was approved by the institutional review board
of the International Peace Maternity and Child Health
Hospital in Shanghai, China (approval date 28 November
2014; reference no. 2014-21).

88 ª 2016 Royal College of Obstetricians and Gynaecologists


Funding
Funding came from Shanghai Scientific and Technical
Committee (grant number 124119a4802).
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Figure S1. Recruitment profile of subjects included in
this study. &
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