Ectopic pregnancy and antibodies to Chlamydia trachomatis*

Transcription

1 FERTILITY AND STERILITY Copyright 1985 The American Fertility Society Vol. 44, No.3, Septemher 1985 Prinred in U.SA. Ectopic pregnancy and antibodies to Chlamydia trachomatis* Lars Svensson, M.D.t Per-Anders Mardh, M.D.:J: Mats Ahlgren, M.D. Fredrik Nordenskjold, M.D. Department of Obstetrics and Gynecology, University Hospital and Institute of Medical Microbiology, University of Lund, Lund, Sweden Ectopic pregnancy is one of the most serious sequelae to acute salpingitis. Chlamydia trachomatis seems to be the most common etiologic agent of acute salpingitis. In the present study, we tested whether women with ectopic pregnancy had serologic evidence of a current or past chlamydial infection. Sixty-five percent of the women with ectopic pregnancy had IgG serum antibodies to C. trachomatis, and 21% of women pregnant in utero had such antibodies. Eleven percent of women with infertile husbands, 42% of women with cervicitis, and 69% of women with salpingitis had IgG serum antibodies to C. trachomatis. In women with ectopic pregnancy, there was a correlation between the occurrence of IgG antibodies and a history of salpingitis or gross'evidence of a previous tubal inflammation. We conclude that previous chlamydial salpingitis may be a major etiologic factor leading to ectopic pregnancy. Fertil SteriI44:313, 1985 Acute salpingitis has been incriminated as the main factor leading to ectopic pregnancy. 1 During the 1970s, the incidence of acute salpingitis increased in industrialized countries 1 ; this parallels a reported increase in the incidence of ectopic pregnancy.2 Chlamydia trachomatis seems currently to be the most common etiologic agent in acute salpingitis. 3 Women with salpingitis associated with C. trachomatis infection have gener- Received February 11, 1985; revised and accepted May 1'7, *Supported by grants from the Faculty of Medicine, University of Lund. tpresent address: Department of Obstetrics and Gynecology, County Hospital, Halmstad, Sweden. tpresent address: Institute of Clinical Bacteriology, Uni-' versity of Uppsala, Uppsala, Sweden. Reprint requests: Fredrik Nordenskjold, M.D., Department of Obstetrics and Gynecology, Hospital of Viinersborg, S Viinersborg, Sweden. ally fewer clinical findings than women with salpingitis associated with other microbiologic agents. 4,5 We assume that many cases of chlamydial salpingitis may pass without being diagnosed because the patients do not seek medical help. This hypothesis is supported by the observation of an association between the occurrence of chlamydial serum antibodies and tubal infertility.6o B The purpose of the present study was to determine the prevalence of antibodies to C. trachomatis in women with ectopic pregnancy and in some subgroups of women, i.e., in postsalpingitic and non-postsalpingitic women, and in users and nonusers of intrauterine contraceptive devices (IUDs). The antibody titers of women with ectopic pregnancy were compared with those of four different control groups, i.e., women pregnant in utero, women with infertile husbands, women with acute cervicitis, and women with acute salpingitis. Svensson et ai. Ectopic pregnancy and C. trachomatis 313

2 SUBJECTS MATERIALS AND METHODS The study consisted of 112 women with ectopic pregnancy treated at the Department of Obstetrics and Gynecology, University Hospital in Lund during 1981 and Sera were drawn at the time of surgery for the removal of the patients' ectopic pregnancies. The diagnosis of ectopic pregnancy was in all cases confirmed by histologic features. An additional 39 women with ectopic pregnancy from whom sera were not obtained occurred during the period of study. The patients with ectopic pregnancy (group I, ectopic pregnancy group) did not differ from the 39 women not included in the study with regard to age, reproductive history, history of salpingitis, or use of IUD at the time of conception. Of the 112 women with ectopic pregnancy, 56 women were postsalpingitic, 46 women were not postsalpingitic, and 10 women were not evaluated with respect to salpingitis. The postsalpingitis group consisted of 30 women with a history of salpingitis and 26 women without such a history but with postinflammatory adhesions around the tubes. The non-postsalpingitic group consisted of 46 women who did not have a history of salpingitis or post inflammatory adhesions. The ten women whose cases could not be evaluated had no history of salpingitis. In four women the changes of the contralateral tube did not show postinflammatory adhesions, and in six women the contralateral tube had been removed because of earlier ectopic pregnancy. An IUD was used at the time of conception by 4 of the women in the postsalpingitic group, 19 of the non-postsalpingitic women, and 1 ofthe women whose cases were not evaluated. mitted diseases. None of the women in group III had a history of salpingitis. Group IV, the cervicitis group, consisted of 83 women with cervicitis treated at the Department of Gynecology during the period of study. The women in this group had no sign of tubal inflammation, as evidenced by laparoscopy performed on the suspicion of acute salpingitis. Only ten other women with cervicitis were treated at the Department of Gynecology in Lund during the period of study; no sera were drawn from them at the time of laparoscopy. These 10 women did not differ from the remaining 83 women in group IV with regard to age, reproductive history, contraceptive method used, erythrocyte sedimentation rate (millimeter per hour) on admission, or febrile illness (temperature ~ 38 C). None of the women with cervicitis had a history of salpingitis. Seventy-one women with a first episode oflaparoscopically verified acute salpingitis made up group V (the salpingitis group). During the period of study a further ten women from whom sera were not obtained were treated at the clinic for a first episode of salpingitis. These 10 women did not differ from the 71 in group V with regard to age, reproductive history, use of contraceptives, erythrocyte sedimentation rate (millimeter per hour) on admission, febrile illness, or severity of the tubal inflammatory changes. SEROLOGY A modified microimmunofluorescence test 9 employing three pools of antigen of C. trachomatis, immunotypes A-C, D-K (except J), and LGV 1-3, was used to demonstrate both IgM and IgG antibodies. The geometric mean titer (GMT) of IgG antibodies was calculated for women with a titer ~ 16. CONTROL GROUPS Four groups of women made up the control subjects. Group II (intrauterine group) consisted of86 of 90 consecutive women delivered by cesarean section. Sera were drawn at the time of surgery. Whether these women had had salpingitis or not was not known. The infertile group (group III) consisted of 66 women with infertile husbands. The male partner of these women had azoospermia or severe oligoteratozoospermia. The couples were presumptive candidates for donor insemination and were considered to be a low-risk group for sexually trans- STATISTICAL METHODS Student's t-test and the chi-square test with Yates' modification for contingency were used. RESULTS The mean and the median age of the patients in the five groups studied are shown in Table 1. The women in group I were the same mean age as those in groups II and III but were significantly older than the women in groups IV and V (Table 1). 314 Svensson et al. Ectopic pregnancy and C. trachomatis Fertility and Sterility

3 Table 1. Age of the Patients in the Different Study Groups Group Ectopic (I) Intrauterine (II) Infertile (III) Cervicitis (IV) Salpingitis (V) Age (yrs) Groups Differ Mean ± SDa Median compared ence (P) 30.0 ± ± ± ± ± 6.0 asd, standard deviation. bns, not significant I vs. II I vs. III I vs. IV I VS. V NS b NS < < Table 3. The Range of the GMT of IgG Serum Antibodies to Chlamydia trachomatis in Women with Such Antibodies Groups Difference Group Range GMT compared (P) Ectopic (I) Intrauterine (II) I VS. II < Infertile (III) I VS. III < Cervicitis (IV) I VS. IV Nsa Salpingitis (V) , I VS. V < 0.01 anot significant. IgM antibodies to C. trachomatis were not detected in any women in groups I, II, or III, whereas one woman in group IV and seven women in group V had such antibodies. IgG antibodies to C. trachomatis were found significantly more often among women in group I (ectopic) than in women in group II (intrauterine), group III (infertile), and group IV (cervicitis) (Table 2). The women in group V (salpingitis) had antibodies to C. trachomatis as often as the women in group I (ectopic) (Table 2). The range and the GMT of IgG serum antibodies to C. trachomatis in the five groups tested is given in Table 3. The patients in group I (ectopic) had significantly higher GMT than the patients in group II (intrauterine) and the patients in group III (infertile) (Table 3). The difference in the GMT of IgG serum antibodies between the women in group I (ectopic) and the women in group IV (cervicitis) was not signific.ant (P < 0.1), whereas the women in group V (salpingitis) had significantly higher GMT than the women in group I (ectopic) (Table 3). The distribution of IgG serum antibodies to C. trachomatis in the postsalpingiticand the nonpostsalpingitic women with ectopic pregnancy is shown in Table 4. Postsalpingitic women had an anamnestic response to a chlamydial infection significantly more often than women who were not postsalpingitic (Table 4). Twenty-five (83.3%) of the 30 women with a history of salpingitis had IgG antibodies to C. trachomatis. This was also the case in 22 (84.6%) of the 26 women with no history of salpingitis but with postinflammatory adhesions. The difference is not significant. At the time of conception, 24 women used an IUD, 3 used low-dose progesterone pills, and 1 used combination contraceptive pills. The distribution of IgG antibodies to C. trachomatis in users and nonusers of IUDs is shown in Table 5. Women not using an IUD had antibodies to C. trachomatis significantly more often than women using an IUD (Table 5). DISCUSSION In chlamydial infections there is generally a conventional IgM to IgG switch. lo However, IgM antibodies are not regularly found, even in the first episode of chlamydial infection, at least when the patients attend once. ll This is in agreement with the paucity of IgM antibodies detected in the present study. Women with ectopic pregnancy had IgG antibodies to C. trachomatis significantly more often than women pregnant in utero. The prevalence of antibodies in this latter group was the same as that reported by Punnonen et al. 6 in pregnant women, approximately 20%. Women who were Table 2. Number (%) of Women withigg Serum Antibodies to Chlamydia trachomatis Group Ectopic (I) Intrauterine (II) Infertile (III) Cervicitis (IV) Salpingitis (V) anot significant. IgG antibodies ~ 16 Groups Difference No. of % compared (P) women I VS. II I VS. III I VS. IV I VS. V < < < Nsa Table 4. Titer oflgg Serum Antibodies to Chlamydia trachomatis in Postsalpingitic and Non-Postsalpingitic Women with Ectopic Pregnancya Postsalpingitic Non'postsalpingitic Titer (n = 56) (n = 46) n % n % achi-square = 18.65; 2 degrees of freedom; P < Svensson et al. Ectopic pregnancy and C. trachomatis 315

4 Table 5. Titer of JgG Serum Antibodies to Chlamydia trachomatis in Women with Ectopic Pregnancy Using and Not Using an JUDa IUD Titer Users (n = 24) Nonusers (n = 88) n % n % achi-square = 15.27; 2 degrees of freedom; P < candidates for donor insemination had an even lower prevalence of antibodies to C. trachomatis, as was expected because these couples were believed to have very stable sexual relations. Women with cervicitis had antibodies to C. trachomatis significantly less often than the patients with ectopic pregnancy. The women with cervicitis, however, were significantly younger than the women with ectopic pregnancy. Chlamydial infections in women are age-correlated,. i.e., the younger the woman, the higher the incidence of chlamydial infections.12 Within the cervicitis group, the distribution ofigg serum antibodies to C. trachomatis was age-independent (unpub" lished data).13 These data imply that age is not a significant factor with regard to the occurrence of serum antibodies to C. trachomatis in women with a first episode of cervicitis. The patients with acute salpingitis were the only ones who had the same high prevalence of IgG antibodies as those patients who had ectopic pregnancies. The distribution of IgG antibodies was independent of age in the salpingitis group, as well as in the cervicitis group (unpublished data)p The GMT of IgG antibodies was significantly higher in women who had acute salpingitis than in women who had an ectopic pregnancy. Such a finding can be expected if it is assumed that a chlamydial infection is etiologically related to ectopic pregnancy and that ectopic pregnancy is a sequel to such an infection. The postsalpingitic women with ectopic pregnancy had antibodies to C. trachomatis significantly more often than the non-postsalpingitic women. Of the 56 women in the postsalpingitic group, 26 (46%) had no history of salpingitis but had postinflammatory adhesions of the contralateral tube. Twenty (43%) of the 46 women in the non-postsalpingitic group had IgG antibodies to C. trachomatis, and 9 (20%) of these 46 women had a titer of 128. These results suggest that a chlamydial salpingitis may be clinically silent, and also that the tubes may look normal macroscopically but nevertheless may be damaged by a chlamydial infection. It has been speculated that the use of an IUD could be an "ectopic promoting factor.,,14 Smith and Soderstrom15 found histologic evidence of salpingitis in 23 (47%) of 49 IUD users subjected to sterilization but in only 10 (1%) of 1500 non IUD users undergoing the same procedure. The inflammation of the tubes in IUD users is probably noninfectious,15 and it could explain the tubal implantation in IUD users without gross evidence of previous salpingitis and the paucity of antibodies to C. trachomatis in this subgroup of women with ectopic pregnancy. The results of our study are also in accordance with those reported by Meirik and Nygren,14 who found that non-iud users with ectopic pregnancy had tubal adhesions more often than women with ectopic pregnancy using IUDs. In conclusion, the results of our study show that women with ectopic pregnancy have serologic evidence of a previous chlamydial infection as often as women with acute salpingitis and more often than the control groups consisting of women pregnant in utero, women healthy and nonpregnant, and women with acute cervicitis. The study also suggests that chlamydial salpingitis can often pass unnoticed by the patient and still be an etiologic factor in ectopic pregnancy. REFERENCES 1. Westrom L: Incidence, prevalence and trends of acute pelvic inflammatory disease and its consequences in industrialized countries. Am J Obstet Gynecol 138:880, Barnes AB, Wennberg CN, Barnes BA: Ectopic pregnancy: incidence and review of determinant factors. Obstet Gynecol Surv 38:345, Mardh P-A, Svensson L: Chlamydial salpingitis. Scand J Infect Dis (Supp!) 32:64, Svensson L, Westrom L, Ripa T, Mardh P-A: Differences in some clinical and laboratory parameters in acute salpingitis related to culture and serological findings. Am J Obstet GynecoI138:1017, Gj9Jnnaess H, Dalaker K, Anestad G, Mardh P-A, K vile G, Bergan T: Pelvic inflammatory disease: etiologic studies with emphasis on chlamydial infection. Obstet Gynecol 59:550, Punnonen R, Terho P, Nikkanen V, Meurman 0: Chlamydial serology in infertile women by immunofluorescence. Fertil Steril 31:656, Moore DE, Foy HM, Daling JT, Graystone JT, Spadoni LR, Wang SP, Kuo C-C, Eschenbach DA: Increased fre- 316 Svensson et at. Ectopic pregnancy and C. trachoma tis Fertility and Sterility

5 quency of serum antibodies to Chlamydia'trachomatis in infertility due to distal tubal disease. Lancet 2:574, Gump DW, Gibson M; Ashikaga T: Infertile women and Chlamydia trachomatis infection. In Chlamydial Infections, Edited by P-A Mardh, KK Holmes, JD Oriel, P Piot, J Schachter. Amsterdam, Elsevier Biomedical Press" 1982, p Treharne JD, Darougar S, Jones BR: Modification of the microimmunofiuorescence test to provide a routine serodiagnostic test for chlamydial infection. J Clin Pathol 30:510, Schachter J, Grossman M: Chlamydial infections. Annu Rev Med 32:45, Taylor-Robinson D, Thomas BJ: The role of Chlamydia trachomatis in genital tract and associated diseases. J Clin PathoI33:205, Mardh P-A, Helin J, Bobeck S, Laurin J, Nilsson T: Colonisation of pregnant and puerperal women and neonates with Chlamydia trachomatis. Br J Vener Dis 56:96, 1980' 13. Authors: Unpublished data 14. Meirik 0, Nygren K-G: Ectopic pregnancy and IUDs: in. cidence, risk rate and predisposing factors. Acta Obstet Gynecol Scand 59:425, Smith R, Soderstrom R: Salpingitis: a frequent response to intrauterine contraception. J Reprod Med 16:159, 1976 Svensson et ali Ectopic pregnancy and C. trachomatis 317