Pelvic surgery, reproductive factors and risk of ectopic pregnancy: a case controlled study

Pelvic surgery, reproductive factors and risk of ectopic pregnancy: a case controlled study

101 Int J Gynecol Obster, 1992, 38: 101-105 International Federation of Gynecology and Obstetrics Pelvic surgery, reproductive factors and risk of ...

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101

Int J Gynecol Obster, 1992, 38: 101-105

International Federation of Gynecology and Obstetrics

Pelvic surgery, reproductive factors and risk of ectopic pregnancy: a case controlled study S. Michalas, First Department

D. Minaretzis, of Obstetrics

Ch. Tsionou,

and Gynecology,

G. Maos, E. Kioses and D. Aravantinos

University of Athens, Alexandra

Maternity

Hospital, Athens (Greece)

(Received September 16th, 1991) (Revised and accepted November 22nd, 1991)

Abstract A case controlled study among 361 women with surgically treated ectopic pregnancy and 420 women delivered at term was designed, aiming at characterization of the association among previous pelvic operations, selected reproductive factors and ectopic pregnancy. All types of previous pelvic operations increase the risk of ectopic pregnancy from a 2-fold increase for appendectomy to a 9-fold increase for ectopic pregnancy, if maternal age, parity, history of spontaneous and induced abortions and history of infertility is controlled. This study suggests that a previous pelvic operation may increase the risk of ectopic pregnancy.

Keywords: Ectopic pregnancy; Pelvic surgery; Reproductive pendectomy; Abortion.

Relative risk; factors; Ap-

Introduction Despite the progress in the diagnosis and management of ectopic pregnancy, the etiology still remains elusive since in most instances no direct cause-and-effect relationship can be determined [I]. Moreover, a worldwide epidemic of ectopic pregnancy, particularly in women who have postponed bearing children 0020-7292/92/$05.00

0 1992 International Federation of Gynecology and Obstetrics Printed and Published in Ireland

until later in their reproductive life, has been taking place [4, lo]. In many studies, several reproductive risk factors have been related to ectopic pregnancy with different attributable relative risks and conflicting results [I]. Only a few studies have attempted to quantitatively correlate common reproductive events such as parity, spontaneous and induced abortion and pelvic surgery in a case controlled way. Moreover, we were not able to cite any study in the available literature, to correlate the type of previous pelvic operations and the reproductive outcome. In order to further investigate the association between the type and number of previous pelvic operations, we designed a case controlled study among women with surgically treated ectopic pregnancy and women delivered at term. Patients and methods The obstetrical history of all the cases with pathological documentation of ectopic pregnancy, treated in the Alexandra Maternity Hospital during the period 1988-1990, were reviewed. As a control group, subjects were chosen among the women having an even register number who delivered on the davs of case admission. The studv included only an indigent Greek population of Christian orthodox religion. Article

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Control definition is the major problem in the ectopic case controlled studies [2,1 I]. Our control group has been originally matched for age with the cases, since the woman’s age mainly influences the chance of the reproductive event which we analysed. Subjects with a history of clinical pelvic inflammatory disease were excluded, from both the case and control groups, since pelvic infections have already been insistently identified as a reliable risk factor of ectopic pregnancy [ 1,121. Furthermore, subjects with a history of hormonal contraception or previous use of intrauterine devices were excluded from both groups, Table 1. Distribution

of 361 ectopic

pregnancies

and 420 controls

and relative

risks according

to selected characteristics. Mantel-Haenzel

Controls

Ectopic

Patients characteristics

because these factors interfere with exposure to pregnancy and implantation [l,l 11. We have chosen primarily the above restrictions for the control determination at the expense of a high control/case ratio. The analysis finally included 361 ectopic pregnancies and 420 women delivered at term and matched for age. The study was confined to the following reproductive factors: parity (stratified as 0, 1,2,3+, and l+), spontaneous and induced abortions (stratified as 0, 1, 2+ and l+), previous pelvic operations (stratified as 0, 1, 2+ and l+) and history of infertility. Pelvic operations were further analysed accor-

RR

95% CI

38.1 31.0 17.8

1 0.6 1.0

0.4-0.8 1.0-1.0

55

13.1

0.3 0.6

0.2-0.6 0.5-0.8

56.8 31.4 5.8

346 66 8

82.4 15.7 1.9

1 3.5 4.4 3.6

2.5-4.8 2.0-9.6 2.6-4.9

74.5 15.8 9.7

293 89 38

69.8 21.2 9.0

1 0.6 1.0 0.8

No

%

No

%

<20 20-29 30-39 >40

9 162 168 21

2.5 45.0 46.7 5.8

11 182 204 24

2.6 43.3 48.4 5.1

Parity 0 1 2

179 80 81

49.6 22.2 22.4

160 130 15

21

5.8

205 135 21

269 57 35

Age (years)

3+ 1+ Pelvic operations

(without

0 1 2+ 1+ spontPnems 0 1 2+

cesarean

section)

abortion

1+

0.3-1.0 1.0-1.0 0.6-1.0

Induced abortion

0 1 2+ 1+

History of infertility No Yes

Int J Gynecol Obstet 38

182

50.4

280

66.7

1

82 97

22.7 26.9

75 65

17.8 15.5

1.7 2.3 2.0

1.2-2s 1.6-3.3 1.5-2.7

340 21

94.2 5.8

410 10

97.6 2.4

1 2.5

1.2-5.3

Risk of ectopic pregnancy

ding to their type classification in subgroups: appendectomy, ectopic pregnancy, ovarian cyst, tuboplasty, other surgery of the internal organs (myomectomy, rereproductive construction of the uterus) and cesarean section. Odds ratios were used as estimators of relative risks, to define the association between the exposure and outcome (ectopic pregnancy) together with their 95% confidence intervals, by the Mantel-Haenszel procedure [5]. The effect of confounding was assessed by simultaneous entering of all variables into a multiple logistic regression model and calculating the adjusted relative risk of ectopic pregnancy for each variable 191. Results The distribution of cases and controls according to age, parity, pelvic operations, spontaneous and induced abortions and history of infertility are presented in Table 1. Compared with nulliparous women, parous women had a significantly lower risk of ectopic pregnancy (Table 1). There is a decline in risk with increasing number of births, except for para 2 women who did not show any decrease in relative risk of ectopic pregnancy (RR 1). The risk of ectopic pregnancy increased significantly with the history and the number of pelvic operations (RR 3.4 for one and 4.4 for two or more previous operations; adjusted RR 2.5 and 3, respectively). Regarding the type of pelvic operation, appendectomy increased the risk of ectopic pregnancy 1.8-fold, previous ectopic pregnancy increased 12-fold the risk of subsequent ectopic pregnancy, ovarian cystectomy and tuboplasty 2.9-fold and 5.9-fold, respectively, while previous cesarean section was associated with reduced risk (RR 0.4) of ectopic pregnancy (Table 2). The history of spontaneous abortion has no significant relation to ectopic pregnancy, either overall compared or in stratification of women with 1 (RR 0.6) or 2+ previous abor-

103

Table 2. Relative risk of ectopic pregnancy according to different type of pelvic operations. Operation

Ectopic

Controls

Mantel-Haenszel RR

Appendectomy Ectopic pregnancy Ovarian cyst Tuboplasty Cesarean section Other

95% CI

105

71

1.8

1.3-2.5

47 12 10 18 6

5 5 2 52 2

12.4 2.9 6 0.4 3.5

5.8-26.4 1.0-7.8 1.6-22.7 0.2-0.6 1.3-16.0

tions (RR 1). Induced abortions were positively related to ectopic pregnancy (overall RR 2). There was an increase in risk with increasing numbers of induced abortions. RR for 1 and 2+, 1.7 and 2.3, respectively (Table 1). The multivariated relative risks, are shown in Table 3. All the associations examined continued to be significant, after controlling for confounding, except for the parity and the history of infertility which became insignificant. Discussion In our study, several risk factors of ectopic pregnancy were explored as implicated. We excluded primarily an important causative risk factor, the history of clinical pelvic inTable 3. Adjusted relative risks of ectopic pregnancy according to selected characteristics (using the multiple logistic regression model). Characteristics

RR

95% CI

Parity History of 1 pelvic operation History of 2+ pelvic operations History of appendectomy History of ectopic pregnancy History of ovarian cystectomy History of tuboplasty History of other pelvic surgery Previous cesarean section History of 1 induced abortion History of 2+ induced abortions History of 1 spontaneous abortion History of 2+ spontaneous abortions History of infertility

0.8 2.5 3.0 1.8 9.0 2.7 4.5 2.8 0.4 1.5 1.8 0.7 1.0 1.3

0.6- 1.O 1.9-3.4 1.5-6.2 1.4-2.4 4.9-16.0 1.2-6.0 1.6-12.2 0.8-10.5 0.3-0.5 1.1-2.0 1.3-2.5 0.4- 1.2 1.0-1.0 0.7-2.3 Article

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Michalas et al.

flammatory disease, while we tried to theoretically expose the controls to similar reproductive factors by matching them with the cases for age. Previous pelvic surgery, infertility and induced abortion were associated with a significant increase in the risk of ectopic pregnancy. Moreover, the risk increased with increasing number of pelvic operations or induced abortions. In contrast, spontaneous abortions have no significant relation to ectopic pregnancy, while the number of live births was inversely related with the risk of ectopic pregnancy. Interestingly, this inverse association between ectopic pregnancy and parity was evident in the primipara and para 3+ women. This is difficult to explain. However, it must be taken into account that two live births is the usual standard parity in the Greek indigent population. All types of previous pelvic operations increase the risk of ectopic pregnancy. However, the small number of exposed patients, except for appendectomy, yielded a large confidence interval around the relative risks. Analytic studies, examining the association between pelvic operations and ectopic pregnancy have been inconclusive, with results ranging from no association to a 2.6-S-fold excess risk [3,7,12]. However, the types of surgery have not been evaluated. It seems that any open surgery intervention within the pelvis may complicate subsequent fertility at a different intensity. It is unknown how this procedure can be accomplished. The reason for surgery or intraoperative and postoperative complications may be incriminated, but this needs further evaluation. From all types of operation, ectopic pregnancy is the major risk factor for subsequent ectopic pregnancy. Since the risk after a previous ectopic pregnancy is 4-fold over the risk of a previous pelvic operation, it is reasonable to assume that the excess risk may be attributed to unknown risk factors of the first ectopic pregnancy that still exist. Further studies are required to elucidate the precise role of these factors. Int J Gynecol Obstet 38

Women with a previous cesarean section are at lower risk of ectopic pregnancy. This may be incidental to the lower risk of parous women, but is strong evidence that cesarean section is not associated with ectopic pregnancy [6]. The main problem in the comparison of results between the studies of risk factors of ectopic pregnancy is that existing differences, particularly the borderline ones, are most likely to occur because of differences in population, design and control selection of the studies. Regarding spontaneous abortions, our results are in agreement with most studies that have not found any relation between the history of one, two or more spontaneous abortions and ectopic pregnancies [3,8]. One previous induced abortion increases the risk of ectopic pregnancy 1.5fold, while two or more induced abortions increase the risk of ectopic pregnancy 1.8-fold. A recent study from Boston, using multivariate techniques, found no detectable increase in the risk of ectopic pregnancy for women who had one prior induced abortion and a 2.6-fold increase of the risk after two or more induced abortions, but not statistically significant [3]. In this study, the incidence of induced abortions in either cases or control subjects, is 3-fold less compared to our study. This fact may explain the narrow 95% confidence limit around our odds ratios and the documentation of the statistic significance. Panayotou et al. [8], 20 years ago, found in a similar population to our study, a tenfold increase in the risk of ectopic pregnancy after induced abortions. The possible explanation for this decrease may be associated with the fact that at that time, induced abortion was illegal in Greece and postabortal infection appears to be more common after illegal abortion. From the beginning of the 197Os,induced abortions were performed mainly in large private maternity hospitals and since 1982 became totally legal. Our study population would have undergone their induced abortions during the above period. In this case controlled study we have tried

Risk of ectopic pregnancy

to eliminate the possible sources of bias, aiming at increase the validity of the results. Selection bias is not likely. Both cases and controls were equally likely to be admitted to the hospital. Neither is ascertainment bias likely. Both groups were given the same questionnaire and ‘previous exposure and pelvic surgery are not things that patients would be more likely to forget in one group as opposed to the other group. Possible confounding by age is controlled by matching. Inclusion of an indigent population of orthodox religion reduces, as much as possible, confounding associated with the attitude of sex life and contraception. Exclusion of women on oral contraceptives, using intrauterine devices, or women with previous known pelvic infection, from both groups, also reduces confounding. The present study has attempted to elucidate the relationship of several reproductive factors and previous pelvic operations with the risk of ectopic pregnancy in a case controlled manner. It seems that any type of pelvic operation may increase the risk of ectopic pregnancy. However, the existence of several risk factors which are further interrelated nessecitate extremely large studies, in a well defined population, in order to clarify the precise role of each risk factor. References 1 Chow W-H, Daling JR, Cates Jr W , Greenberg RS: Epidemiology of ectopic pregnancy. Epidemiol Rev 9: 70, 1987.

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Hayden GF, Kramer MS, Horwitz RI: The case control study. A practical review for a clinician. J Am Med Assoc 247: 326, 1982. Levin AA, Schoenbaum SC, Stubblefield PG, Zimiski S, Monson RR, Ryan KJ: Ectopic pregnancy and prior induced abortion. Am J Public Health 72: 253, 1982. Makinen JI, Erkkola RU, Laippala PJ: Causes of the increase in the incidence of ectopic pregnancy. A study on 1017 patients from 1966 to 1985 in Turku, Finland. Am J Obstet Gynecol 160: 642, 1989. Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Nat1 Cancer Inst 22: 719, 1959. Nielsen, TF, Hokegard K-H: The course of subsequent pregnancies after previous cesarean section. Acta Obstet Gynecol Stand 63: 13, 1984. Pagan0 R: Ectopic pregnancy: a seven-year survey. Med J Aust 2: 586, 1981. Panayotou PP, Kaskarelis DB, Miettinen OS, Trichopoulos DB, Kalandidi AK: Induced abortion and ectopic pregnancy. Am J Obstet Gynecol 114: 507, 1972. Prentice R: Use of the logistic model in retrospective studies. Biometrics 32: 599, 1976. Weinstein L: Epidemiology of ectopic pregnancy. In: Ectopic Pregnancy (ed AH DeChemeyl pp 1- 13. Aspen, Rockville, MD, 1986. Weiss NS, Daling JR, Chow W-H: Controls definition in case-control studies of ectopic pregnancy. Am J Pub1 Health 75: 67, 1985. World Health Organization: Task Force on Intrauterine Devices for Fertility Regulation. A multinational casecontrol study of ectopic pregnancy. Clin Reprod Ferti13. 131, 1985.

Address for reprints: s. Micbalas 1st Department of Obstetrics and Gynecology University of Athem Alexaodra Maternity Hospital 80 Vas. Sophias Ave. 115 28 Athens, Greece

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