ECTOPIC PREGNANCY

Risk factors for ectopic pregnancy in women with

symptomatic first-trimester pregnancies
Kurt T. Barnhart, M.D., M.S.C.E.,a,b Mary D. Sammel, Sc.D.,b
Clarisa R. Gracia, M.D., M.S.C.E.,a,b Jesse Chittams, M.S.,b
Amy C. Hummel, M.S.,b and Alka Shaunik, M.D.b
a b
Penn Fertility Care, Department of Obstetrics and Gynecology, University of Pennsylvania; and Center for Clinical
Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania

Objective: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among
women presenting with pain and/or bleeding in early pregnancy.
Design: Nested case– control study.
Setting: University medical center.
Patient(s): Women with symptomatic early pregnancies of unknown location presenting for care between January
1, 1990 and July 31, 1999.
Intervention(s): None.
Main Outcome Measure(s): Clinical and historical risk factors were compared between women with EP and
women with ongoing intrauterine pregnancies or spontaneous abortions.
Result(s): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95%
confidence interval, 1.88 – 4.73] for one prior EP and 16.04 [5.39 – 47.72] for 2 or more), pelvic inflammatory
disease history (1.5 [1.11–2.05]), pain at presentation (1.42 [1.06 –1.92]), vaginal bleeding at presentation (1.42
[1.04 –1.93]), and hCG of 501–2,000 mIU/mL (1.73 [1.24 –2.42]). Age younger than 25 years (0.59 [0.41– 0.85])
and a history of abortion were protective from EP (0.58 [0.38 – 0.90]). Prior nontubal pelvic surgery, past
intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association
with EP.
Conclusion(s): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the
classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an
unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal
surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of
historical and clinical factors associated with EP may aid in early diagnosis. (Fertil Steril威 2006;86:36 – 43. ©
2006 by American Society for Reproductive Medicine.)
Key Words: Ectopic pregnancy, risk factors, diagnosis

Ectopic pregnancy (EP) is defined as a pregnancy that
occurs outside of the uterus. Ruptured EP is a leading
cause of morbidity and mortality for women during the
first trimester of pregnancy (1). Approximately 2% of all
pregnancies in the United States are diagnosed as ectopic
(1). Recent studies indicate that the incidence of EP has
increased sixfold during the last 25 years, and hospital
admissions for this condition have increased dramatically,
Received September 19, 2005; revised and accepted December 5, 2005.
Supported by National Institutes of Health (Bethesda, MD) grant R01:
HD-36455-05.
Reprint requests: Kurt T. Barnhart, M.D., M.S.C.E., Penn Fertility Care,
Department of Obstetrics and Gynecology, University of Pennsylva-
nia Medical Center, 3701 Market Street, Suite 810, Philadelphia,
Pennsylvania 19104 (FAX: 215-615-4200; E-mail: kbarnhart@mail.
obgyn.upenn.edu).
from 17,800 in 1970 to 88,400 in 1992 (1, 2). Conserva-
tive medical and surgical treatments now are widely avail-
able for ectopic pregnancies that are diagnosed early. It
has been shown clearly that early diagnosis and outpatient
treatment of an early unruptured EP can lead to reduced
morbidity and mortality, preservation of future fertility,
and substantial cost savings compared with inpatient care
(1, 3– 6). Counseling of high-risk patients before concep-
tion and early screening of patients with heightened risk
of EP can significantly affect patient prognosis and med-
ical costs.
The apparent increase in the incidence of EP may be a
result of improved diagnostic aids, heightened awareness
by clinicians, or increased prevalence of risk factors of the
disease (7–9). There is a large body of literature reporting

36 Fertility and Sterility姞 Vol. 86, No. 1, July 2006 0015-0282/06/$32.00

Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc. doi:10.1016/j.fertnstert.2005.12.023
investigations into associations and risk factors for EP. In
aggregate, these findings suggest that the major putative
risk factors for EP are conditions that are thought to
prevent or retard migration of the fertilized ovum to the
uterus. Thus, damage to the fallopian tube from an in-
flammatory insult such as pelvic inflammatory disease
(PID), sequelae of a past pelvic surgery, and prior EP have
been determined to increase the subsequent risk of EP. It
is hypothesized that the greater the damage to the fallo-
pian tube, the greater the risk for subsequent EP (with the
exception of complete obstruction of both fallopian tubes,
which results in the prevention of any pregnancy, includ-
ing EP).
The strength of association between EP and prior cesarean
section (CS), prior nontubal pelvic surgery, exposure to a
sexually transmitted disease (in the absence of PID), and the
association of a woman’s past reproductive history (i.e.,
gravidity, lack of a prior pregnancy, prior voluntary inter-
ruption of pregnancy, prior miscarriage) have not been de-
finitively determined.
Extrapolation of results from prior studies is problem-
atic because the incidence and relative association of risk
factors for EP vary among populations. If clinical factors
are to be used to aid in the diagnosis of EP, the specific
factors and their strength of association must be investi-
gated in the specific population of interest. To date, there
are no studies that investigate the association of clinical
factors of EP in a group of women who present for care
but are unable to be diagnosed during their initial evalu-
ation. This study is the first to evaluate the associations of
both clinical symptoms and historical variables in a cohort
of women presenting with pain and/or bleeding in the first
trimester and whose diagnosis was not readily apparent
upon presentation.
MATERIALS AND METHODS
Approval to conduct this study was obtained from the insti-
tutional review board of the University of Pennsylvania. A
database is maintained at the University of Pennsylvania of
all women in their first trimester of pregnancy (positive
pregnancy test or history of a missed period) who present
with pain and/or bleeding. Data are entered directly into the
computerized database by clinical staff who are caring for
the patient.
Potential risk factors for EP were identified from the
history, clinical presentation, and diagnostic tests. Poten-
tial predictors derived from the historical factors were
age, gravity, parity, number of live births, number of CSs,
number of spontaneous abortions (SAB), number of elec-
tive abortions, number of previous ectopic pregnancies,
PID (defined as inpatient treatment), outpatient treatment
of gonorrhea and/or chlamydia, history of intrauterine
device use, and history of pelvic surgery (excluding CS).
Fertility and Sterility姞
Variables such as prior spontaneous or elective abortion,
EP, CS, and pelvic surgery were studied as both contin-
uous and dichotomous variables. Findings at presentation
analyzed as predictors included the following: amount of
bleeding, pain, hCG level, and current gonorrhea or chla-
mydia infection.
Bleeding was categorized as none, mild, moderate, or
severe (no bleeding and less than, equal to, or more than
regular menstrual bleeding, respectively), as characterized
by the patient. Pain was defined as positive if self-reported as
a presenting symptom for care. Severity of the pain was not
categorized.
Women were followed in this clinical database until they
were definitively diagnosed with an EP or with an intrauter-
ine pregnancy (IUP; viable ongoing IUP or SAB). Sponta-
neous abortion was confirmed by either the histopathology
of products of conception on suction dilatation and curettage
or by the spontaneous decline of hCG level to ⱕ5 mIU/mL.
The presence of a normal IUP was confirmed by ongoing
progression of the pregnancy by ultrasound with visualiza-
tion of an intrauterine yolk sac, fetal pole, or the presence of
fetal heartbeat. The diagnosis of EP was confirmed either
by the presence of chorionic villi in the fallopian tube or
by visualization of an extrauterine gestational sac (with
yolk sac or embryonic cardiac activity) for those treated
medically, or by a rise in hCG level after dilatation and
evacuation (and no evidence of chorionic villi in endo-
metrial curettage samples).
Statistical Analysis
Data were analyzed as a nested case– control study. Cases
were defined as women who were definitively diagnosed
with an EP. Controls were defined as women presenting with
the same symptoms but who were diagnosed with an IUP
(either an ongoing IUP or an SAB).
First, descriptive statistics were used to summarize the
entire population and to compare cases and controls. Uni-
variate associations were evaluated by using Student’s t test
for continuous variables. Categorical variables were evalu-
ated by using Pearson’s ␹2 test of association. Wald statistics
were constructed to test for an overall association between
the categorical risk factor and diagnosis. To check for dif-
ferences in univariate comparisons resulting from classifica-
tion of information, some variables (age, parity, history of
surgery) were analyzed as both continuous and categorical
variables.
Stratified analyses were performed to test for confound-
ing and effect modification. Historical and clinical-pre-
sentation variables first were tested individually to check
for interaction. For the purpose of analysis of categorical
values, one category was chosen as the reference cate-
gory. Reference categories included age 25–29 years and
hCG of ⬍500 mIU/mL. When no interaction was noted,
both historical and clinical variables were combined. A
37
 TABLE 1
Unadjusted odds ratios of historical predictors for women at risk of ectopic pregnancy.

Cases, n Controls, n Crude

Variable (n ⴝ 367) % (n ⴝ 1,659) % OR 95% CI P value

Age (y)
⬍20 43 11.8 443 27.8 0.3 0.18–0.39 ⬍.0001
20–25 87 23.8 502 31.5 0.5 0.34–0.64 .0003
25–30 112 30.7 304 19.1 1.0 Ref
30–34 84 23.0 210 13.9 1.1 0.80–1.70 .4
ⱖ35 39 10.7 133 8.4 0.8 0.78–1.52 .8
Race
African-American 229 62.6 853 51.4 1.41 0.60–2.18 .69
Others 12 3.3 51 3.1 Ref
Prior live births 192 52.3 718 43.5 1.43 1.14–1.79 .002
Parity
0 174 47.4 946 57.0 Ref
1 94 25.6 319 19.2 1.6 1.21–2.12 .001
2 45 12.3 192 11.6 1.27 0.89–1.83 .19
3 29 7.9 128 7.7 1.23 0.8–1.9 .35
4 or more 25 6.8 74 4.5 1.84 1.14–2.97 .01
Prior voluntary interruption of
pregnancy
0 294 82.4 1,268 79.6 Ref
1 33 9.2 216 13.5 0.66 0.45–0.97 .04
2 or more 30 8.4 110 6.9 1.18 0.77–1.8 .45
History of spontaneous abortion
0 269 83.8 1,232 85.2 Ref
1 36 11.2 162 11.2 1.02 0.69–1.5 .93
2 or more 16 5 52 3.6 1.41 0.79–2.51 .24
History of ectopic pregnancy
0 306 83.4 1,570 94.7 Ref
1 48 13.1 82 4.9 3 2.1–4.4 ⬍.0001
2 or more 13 3.5 6 0.4 11.17 402–29.5 ⬍.0001
History of pelvic surgery 88 24 286 17.2 1.51 1.15–1.99 .003
History of prior cesarean section
0 342 93.2 1,545 93.2 Ref
1 16 4.4 89 5.4 0.81 0.47–104 .45
2 or more 9 2.4 24 1.4 1.69 0.78–3.68 .18
Past use of intrauterine device 20 5.5 67 4 1.37 0.82–2.29 .23
History of pelvic inflammatory disease 90 24.5 327 19.7 1.32 1.01–1.73 .04
History of outpatient treatment for
gonorrhea and/or chlamydia
0 289 79 1,343 81 Ref
1 60 16.4 262 15.8 1.06 0.78–1.45 .69
2 18 4.9 46 2.8 1.82 1.04–3.19 .04
3 or more 0 0 7 0.4 0 0 .99
Note: Ref ⫽ reference group.
Barnhart. Risk factors predictive of ectopic pregnancy. Fertil Steril 2006.

logistic regression model then was generated using man- process was repeated until all the variables had a P value
ual selection of confounding variables and backward step- of ⱕ.05. A variable was retained in the model as a
wise selection of variables. At each step, the largest confounder if it significantly affected the coefficient esti-
P-value variable was removed from the table, and this mates of other variables by ⱖ15% (10).

38 Barnhart et al. Risk factors predictive of ectopic pregnancy Vol. 86, No. 1, July 2006
 TABLE 2
Unadjusted clinical presentation predictors in women at risk of ectopic pregnancy.

Cases, n Controls, n Crude

Variable (n ⴝ 367) % (n ⴝ 1,659) % OR 95% CI P value

Pain as the presenting symptom 244 66.5 1,046 63.1 1.16 0.92–1.48 .22
Bleeding at presentation 256 75.7 1,119 69.7 1.34 1.04–1.78 .03
(moderate to severe)
Current chlamydia cervical 13 4.1 109 7.7 0.51 0.28–0.91 .02
infection
Current gonorrhea and/or 22 6.9 151 10.8 0.61 0.38–0.97 .04
chlamydia cervical infection
HCG at presentation (mIU/mL)
0–500 155 42.2 828 49.9 Ref
501–2,000 103 28.1 314 18.9 1.75 1.32–2.32 ⬍.0001
2,001–4,000 40 10.9 167 10.1 1.3 0.87–1.88 .21
ⱖ4,000 69 18.8 350 21.1 1.05 0.77–1.44 .74
Note: Ref ⫽ reference group.
Barnhart. Risk factors predictive of ectopic pregnancy. Fertil Steril 2006.

An odds ratio of ⱖ1 denotes that a particular risk factor is
more prevalent in cases (EP) than in controls (SAB or
ongoing IUP). Statistical analysis was performed by using
SAS software (Cary, NC), and a two-tailed P value of ⬍.05
was considered statistically significant.
RESULTS
A total of 2,026 patients who presented with pain and/or
bleeding in the first trimester of pregnancy from January 1,
1990 to July 31, 1999 were evaluated. Of these, 367 patients
were diagnosed with EP, and 1,659 women were diagnosed
with an IUP (467 with an ongoing IUP and 1,192 with an
SAB).
history of EP, an initial quantitative hCG value of ⬎500
mIU/mL, parity of one, prior hospitalization for PID, or the
presence of pain as the presenting symptom or moderate to
severe bleeding. Factors negatively associated with EP were
age younger than 25 years and prior history of a voluntary
interruption of pregnancy.
Notable putative risk factors for EP that did not demon-
strate a statistically significant association are listed in
Table 4. These are gravidity, prior SAB, prior live births,
past use of intrauterine device, prior history of pelvic sur-
gery, prior CS, history of outpatient treatment for cervical
infection with chlamydia and/or gonorrhea, or current infec-
tion with chlamydia and/or gonorrhea.

The mean age of the population was 25.12 years, with

an average gravity and parity of 2.4 and 0.91, respec-
tively, and a mean hCG of 3,404.66 mIU/mL. Nearly 95%
of the population was African-American. Overall, the age
of cases was slightly higher (27.5 ⫾ 1.46 y) than the
controls (24.2 ⫾ 2.2 y).
Unadjusted comparisons between cases and controls of
individual historical and presentation variables are presented
in Tables 1 and 2. Note that in these tables the results of the
univariate comparison using the variable as dichotomous,
continuous, or categorical values are presented. For the pur-
poses of modeling, only one such representation of data was
evaluated at any given time.
Adjusted odds ratios are presented in Table 3. The final
model included age, history of voluntary interruption of
pregnancy, number of ectopic pregnancies, history of PID,
parity, moderate to severe bleeding at presentation, pain as
the presenting symptom, and initial hCG level. Factors noted
to be positively associated with EP included the following:
DISCUSSION
The main objective of this study was to assess associations
for the diagnosis of EP in the population directly at risk. We
restricted our analysis to women who were presenting for
evaluation of pain and/or bleeding during the first trimester
of pregnancy (and without an initial definitive diagnosis) for
a number of reasons. First, comparison of women with EP
with women without an EP who presented with similar
symptoms and at a similar gestational age minimizes the
controversy regarding the correct control group. Earlier stud-
ies have used either women who previously have delivered a
child or nonpregnant women as controls. Both such control
populations have limitations (11). Second, this study design
limits information and selection bias because information
regarding exposures was collected before definitive ascer-
tainment of case or control status. Finally, this is the popu-
lation of clinical interest, in whom such associations may be
used to aid in the identification of women who are at high or
low risk for EP.

Fertility and Sterility姞 39

 TABLE 3
Adjusted odds ratios of risk factors associated with ectopic pregnancy.

Variable Adjusted OR 95% CI P value

Age (y)
⬍20 0.34 0.22–0.52 ⬍.0001
20–24 0.59 0.41–0.85 .01
25–29 Ref
30–34 1.18 0.79–1.76 .42
ⱖ35 1.00 0.61–1.64 .99
Voluntary interruption of pregnancy
0 Ref
1 0.58 0.38–0.90 .02
2 or more 0.99 0.61–1.6 .96
History of ectopic pregnancy
0 Ref
1 2.98 1.88–4.73 ⬍.0001
2 or more 16.04 5.39–47.72 ⬍.0001
History of pelvic inflammatory disease: yes 1.50 1.11–2.05 .01
Parity
0 Ref
1 1.71 1.21–2.42 .003
2 1.13 0.72–1.78 .60
3 0.95 0.56–1.59 .83
4 or more 1.26 0.68–2.36 .46
Bleeding at presentation (moderate to severe): yes 1.42 1.04–1.93 .03
Pain as the presenting symptom: yes 1.42 1.06–1.92 .02
hCG at presentation (mIU/mL)
0–500 Ref
501–2,000 1.73 1.24–2.42 .001
2,001–4,000 1.38 0.88–2.16 .16
ⱖ4,000 0.97 0.67–1.39 .86
Note: Ref ⫽ reference group.
Barnhart. Risk factors predictive of ectopic pregnancy. Fertil Steril 2006.

There is extensive literature regarding potential risk fac-
tors for EP, including a meta-analysis summarizing the re-
sults from 27 case– control studies and nine cohort studies
(12). Our results confirm and refute some of these putative
risk factors.
Previous EP was confirmed to have one of the strongest
associations of all the possible risk factors of EP. The risk of
experiencing a repeat EP increased dramatically with the
number of prior ectopic gestations. We found that women
with an EP were almost three times as likely to have had one
prior EP compared with controls (odds ratio [OR], 2.98; 95%
confidence interval [CI], 1.88 – 4.73) and were 16 times more
likely to have had two prior EPs compared with women with
an IUP (OR, 16.04; 95% CI, 5.39 – 47.72). Our findings confirm
other research studies that have found a history of prior EP to be
strongly associated with subsequent EP (OR ranging from
2.4 –25.0) (13–21). The meta-analysis estimated the risk to be
6.6 (95% CI, 5.2– 8.4) (12). Recurrent EP likely reflects persis-
tent tubal pathology, which may lead to an increased incidence
of subsequent EP in the same patient.
Prior PID long has been thought to have a strong associ-
ation with EP. The strength of association was noted to be
2.5 (2.1–3.0) in the meta-analysis (12), with an OR ranging
in the literature from 2.0 to 10.1 (13–15, 22–25). Although
we also noted a statistically significant positive association
between PID and EP, the strength of that association was
surprisingly weak (OR 1.5; 95% CI, 1.11–2.05). It is possi-
ble that this association has been overestimated in other
studies as a result of improper selection of controls. It also is
possible that it is not a strong risk factor in an inner-city
population with a relatively high rate of pelvic infection,
such as the population studied at our institution.
Previous tubal surgery also has been reported to be a
significant risk factor for EP, with an estimated OR of 4.7
(2.4 –9.5) according to one study (12). However, the associ-
ation between other types of pelvic surgery and CS has been

40 Barnhart et al. Risk factors predictive of ectopic pregnancy Vol. 86, No. 1, July 2006
 TABLE 4
Adjusted odds ratios of factors not associated with risk of ectopic pregnancy.

Variables Adjusted OR 95% CI P value

Gravity: yes 1.62 0.93–2.82 .09

Number of prior spontaneous abortions
0 Ref
1 0.81 0.53–1.26 .36
2 or more 0.94 0.49–1.82 .85
Prior live birth: yes 0.30 0.05–1.96 .21
Past use of intrauterine device: yes 1.06 0.58–1.94 .86
Number of prior cesarean sections
0 Ref
1 0.56 0.29–1.11 .1
2 or more 1.35 0.47–3.87 .58
History of pelvic surgery: yes 0.95 0.67–1.35 .78
History of outpatient treatment for chlamydia and/or gonorrhea
infection
0 Ref
1 0.97 0.65–1.43 .86
2 or more 1.22 0.58–2.56 .60
Current cervical infection with gonorrhea and/or chlamydia: yes 0.82 0.48–1.39 .46
Note: Ref ⫽ reference group.
Barnhart. Risk factors predictive of ectopic pregnancy. Fertil Steril 2006.

inconsistent. The strength of association of nontubal abdom-
inal or pelvic surgery has ranged from no association (13)
to an OR as high as 2.4 –5.0 (14, 15, 22, 26 –28). Simi-
larly, the association between CS and EP has a wide range
that includes negative associations (24, 29 –31) to positive
associations (22, 27, 32). Our data do not support the asso-
ciation between nontubal surgery and EP (OR, 0.95; 95% CI,
0.67–1.35). In addition, prior CS and history of multiple CS
do not appear to be associated with EP.
Various studies have shown that the incidence of EP
increases with maternal age (24, 33, 34, 35). Our study too
shows that women with EP tend to be older than women with
IUPs. In particular, compared with women aged 25–29
years, women aged younger than 20 years had an odds ratio
of EP 0.34 (95% CI, 0.22– 0.52), and women aged 20 –24
years had an odds ratio of EP of 0.59 (95% CI, 0.41– 0.85).
No significant associations were noted for women older than
age 30 years. The cause of this association remains largely
unknown.
There has been controversy regarding the association be-
tween EP and a history of voluntary interruption of preg-
nancy. In this study, a prior induced abortion was signifi-
cantly negatively associated with risk of EP. Moreover, more
than one prior induced abortion did not increase the risk of
EP in this population. Past studies have reported mixed
results (14, 15, 23, 24, 26, 28, 36 – 40), with the meta-
analysis estimating a borderline, though statistically signifi-
cantly increased risk of EP with a history of induced abortion
(OR 1.6; 95% CI, 1.0 –1.6) (12). Perhaps the use of non-
pregnant controls in previous studies resulted in bias. In
addition, we found no association of previous SAB with risk
for EP. This also is contrary to findings of some published
reports (14, 24, 41). Interestingly, we did find a positive
association with parity.
Another important part of our study was the evaluation of
both historical risk factors as well as signs and symptoms of
presentation as risk factors for EP. We initially evaluated
these factors separately but found that these variables were
independent; therefore, we combined them in our final
model. Our study population was restricted to women who
presented with pain and/or bleeding in the first trimester of
pregnancy. However, some women presented with only
bleeding or only pain. We noted that moderate and/or severe
bleeding (compared with mild or absent bleeding) was sig-
nificantly and positively associated with the presence of an
EP. In addition, the presence of pain as the chief complaint
also was positively associated with EP. The presence of pain
may be a result of ectopic gestation and was expected.
However, heavy bleeding often is thought to be a symptom
of a spontaneous miscarriage, not of an EP. Thus, it is
imperative that all patients with presenting complaints of
pain or bleeding with a period of amenorrhea should be
treated as having a potential EP.
An interesting novel finding of this study is the evaluation
of the association of past and concomitant pelvic infections
with the risk of EP. Although we found that a past history of

Fertility and Sterility姞 41

PID is positively associated with EP, concomitant infection
at the time of presentation is not associated with an increased
risk of EP. The estimate of association, although not signif-
icant, was protective for diagnosis of a concomitant EP,
perhaps because the woman was presenting as a result of
bleeding and pain from the infection, rather than as a result
of an EP.
The hCG values at initial presentation for women with an
EP are on average lower than those for women who even-
tually are diagnosed with an ongoing viable IUP or SAB (1).
In this study, an hCG range of 501– 4,000 mIU/mL was
positively associated with risk for EP. Values of ⬍500
mIU/mL were protective of EP, whereas values of ⬎4,000
demonstrated no association. These findings are consistent
with clinical findings that very low levels of hCG are asso-
ciated with SAB and that a high percentage of women
present with EP with a range of 500 – 4,000 (9). It is impor-
tant to note that given the considerable overall variation in
hCG values at presentation and nonspecific ultrasound find-
ings, neither of these variables independently has good clin-
ical discrimination (1, 9).
In conclusion, EP is a prevalent and serious complication
of early pregnancy. This study demonstrates that identifica-
tion of historical and clinical presentation risk factors in a
symptomatic early pregnancy may aid in identifying women
at high risk for EP. If these risk factors have high predictive
value, they may aid in early detection, allowing possible
medical treatment of EP and a reduction in mortality and
morbidity, preservation of fertility, and a decrease in the
overall cost of health care. A systematic approach must be
developed to incorporate these risk factors into clinical de-
cision making.
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