Fertility after ectopic pregnancy

Transcription

1 Gynecology-endocrinol.ogy FERTILITY AND STERILITY Copyright 1993 The American Fertility Society Vol. 60. No.2, August 199:1 Printed on acid-free paper in U. S. A. Fertility after ectopic pregnancy Steven J. Ory, M.D.*t Evarista Nnadi, B.S.:j: Rebekah Herrmann* Peter S. O'Brien, Ph.D. L. Joseph Melton III, M.D.II Mayo Clinic and Mayo Foundation, Rochester, Minnesota Objectives: To compare pregnancy rates (PRs) after radical or conservative surgical treatment for tubal pregnancy over a 12.S-year interval (minimum of 3 years) and to assess the relative contribution of various risk factors to future fertility performance. Design: A retrospective cohort study examining the influence of various risk factors on PRs with stepwise discriminant analysis using a jackknife-type validation program. Patients: Eighty-eight Olmsted County, Minnesota, women who presented over a lo-year interval with their first ectopic pregnancy (EP), undergoing either radical or conservative surgery at laparotomy, who actively attempted conception after surgery and who were available for follow-up at Mayo Clinic. Main Outcome Measures: The primary end point for analysis was the occurrence of a livebirth or EP at 3 years of follow-up after the index EP. Results: No difference in PR was identified in patients treated with radical or conservative surgery. Patients who underwent conservative surgery had a higher risk of subsequent EP. Patients with a prior history of infertility had significantly reduced fertility potential. Conclusions: Prior history of infertility was the most significant determinant for fertility potential after surgical treatment for EP. Patients with prior infertility had markedly impaired fertility after surgical treatment of EP, and outcome was not influenced by choice of surgical procedures. Patients without prior infertility had comparable encouraging fertility potential with both conservative and radical therapy. These findings have relevance for future management of infertility in affected patients. Fertil Steril1993;60:231-S Key Words: Ectopic pregnancy, fertility, surgical treatment The management of ectopic pregnancy (EP) has evolved dramatically over the past 20 years. Between 1970 and 1987, the United States Centers for Disease Control described a fourfold increase in the incidence of EP (1). Although the contributing factors have not all been identified, the epidemic of Received November 17, 1992; revised and accepted April 7, * Department of Obstetrics and Gynecology. t Reprint requests: Steven J. Ory, M.D. Section of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW, Charlton 4A, Rochester, Minnesota :j: Medical student. Department of Health Science Research. II Section of Clinical Epidemiology, Department of Health Sciences Research. pelvic inflammatory disease (PID) that began in the 1960s, the greater use of tubal reparative procedures, more prevalent use of intrauterine devices (IUDs), and a trend toward more conservative tubal surgery have been cited as components. Diagnostic accuracy has also improved over the interval, with the advent of more sensitive assays for hcg, enhanced ultrasound resolution, and more frequent use of laparoscopy. These advances have permitted more consistent and earlier intervention, often before significant tubal distortion and rupture. During the same 20-year interval, improved fertility potential has been attributed to the more frequent use of conservative procedures when compared with fertility outcomes after salpingectomy 10 to 20 years earlier. However, few data that compare fertility outcomes between patients treated Ory et al. Fertility after EP 231

2 conservatively and those treated with extirpative surgery during this time of dramatic change in clinical practice are available. This study was undertaken to compare fertility outcomes in patients treated for EP at Mayo Clinic during the decade January 1, 1976, through December 31, In particular, we sought to determine whether the choice of surgical procedure, history of infertility, year of presentation, history of anovulation, and prior history of tubal disease were significant determinants of subsequent fertility outcome. MATERIALS AND METHODS The records of 188 Olmsted County, Minnesota, women with surgically confirmed EP presenting between 1976 and 1985 were reviewed. The present study was confined to patients who presented during that interval with their first tubal pregnancy and underwent conservative or radical treatment at laparotomy, who actively attempted conception after surgery, and who were available and willing to participate in follow-up for at least 3 years. No laparoscopic procedures were performed during this interval. One hundred patients who satisfied all criteria were identified, and their fertility histories were retrospectively followed from 3 to 12.5 years after the target EP. The other 88 patients were ineligible for the study; 47 did not attempt conception and 41 were lost to follow-up. Pertinent information regarding each patient's age, gravidity, menstrual pattern, fertility history and treatment, surgical history, pelvic infections, IUD use, and subsequent fertility after the index data were abstracted from their complete inpatient and outpatient medical records. The Mayo Clinic and Olmsted Medical Group provided virtually all medical care for the residents of Olmsted County, and all histories were obtained and reviewed. Thus, all information about prior pregnancies and infertility evaluations was consistently available. A detailed questionnaire was mailed to all 100 eligible subjects, and nonrespondents were contacted by telephone. Ultimately, 88 patients (88%) responded. Of the 88 patients in the study, 50 had a radical procedure, complete or partial salpingectomy, at which time the proximal segment was ligated. In addition, 2 patients in this group had an ipsilateral oophorectomy. Thirty-eight patients had a conservative procedure, including 33 patients who underwent salpingostomy or salpingotomy and 5 who underwent fimbrial expression. Eight patients in the conservatively treated group also underwent a tubal reparative procedure at initial laparotomy, which consisted of salpingolysis or ovariolysis. No tubal anastomoses were performed in either group. All patients in both groups had a remaining contralateral fallopian tube. The surgical procedures were performed by numerous surgeons, including residents. Comparison between groups with respect to dichotomous variables were made using two-sided X 2 tests. Fisher's exact test was used when the sample size was too small for the usual X2 test. Comparisons with respect to quantitative variables used two-sided two-sample t-tests. Statistical analyses focused on two end points: the occurrence of a livebirth within 3 years of the index EP and the occurrence of a subsequent EP within 3 years of the index event. A stepwise discriminant analysis was used to identify the factors most strongly related to the end point of interest and was validated using a jackknife technique in which 10% of the data was omitted in developing the discriminant equation, and the resulting equation was used to make predictions on the persons left out. This analysis was repeated 10 times. RESULTS There were no significant differences in age, prior history ofpid, IUD use, tubal adhesions, previous abdominal or pelvic surgery, or history of anovulation between the groups treated with conservative surgery and radical surgery (Table 1). There Table 1 Frequency of Risk Factors Among The Conservative and Radical Treatment Groups Conservative Radical Risk factor(s) (n = 38) (n = 50) P value Age (yr) (mean ± SEM) 26.3 ± ± 0.7 * Gravidity (mean± SEM) 1.3 ± ± t Prior infertility (n = 25) 42:1: 18:1: PID (n = 10) 16 8 * IUD (n = 12) * Tubal adhesions (n = 5) 11 2 * Previous abdominal pelvic surgery (n = 7) 8 8 * Prior tubal surgery (n = 4) History anovulation (n = 11) No risk factor identified (n = 46) * * NS, not significant. t Rank sum test; all others, X 2 analysis. :I: Values are percents. 232 Ory et al. Fertility after EP Fertility and Sterility

3 8 D Conservative 7 CI Radical Figure 1 Conservative and radical procedures were performed throughout the lo-year period. More radical procedures were performed early and more conservative procedures performed later in the time period. was a tendency for more radical procedures to have been performed early and more conservative procedures to have been performed later in the 10-year interval (Fig. 1), but both types of procedures were performed throughout the 10-year interval. The groups differed in the prevalence of prior infertility (42% in the conservative group and 18% in the radically treated group, P = 0.013), prior tubal surgery (11 % in the conservative group and none in the radically treated group, P = 0.019), and gravidity (P = 0.008). Gravidity and prior tubal surgery are directly correlated with history of infertility. Surgical findings were comparable between the two groups. Tubal rupture was more prevalent in the radically treated group and dictated the choice of procedure when present. The condition of the contralateral tube was not consistently noted in the operative report and was not included in the analysis. Among the conservatively treated patients, 19 of 38 (50%) achieved a term pregnancy within 3 years versus 29 of 50 (58%) patients treated with radical surgery (P = 0.455, Table 2). Using a stepwise discriminant analysis, age and prior history of infertility were found to have an association with subsequent fertility outcome. These factors also entered 9 of 10 validation models. In one model, only infertility was selected, and in another single model abdominal-pelvic surgery was selected. Of patients without a prior history of infertility, 68 % conceived (Table 3). In contrast, of the 25 patients who were determined to be infertile before experiencing EP, only 4 (25%) experienced a subsequent livebirth after conservative surgical treatment, and only 1 (11 %) after radicat'treatment. History of prior infertility adversely affected the risk of a subsequent EP as well. In the group with prior infertility, 31 % of those treated conservatively experienced a recurrent EP along with 22% of the radically treated group. Only 14% of the conservatively treated patients without a history of infertility had a repeat EP, and only 5% of the radically treated patients did not have pre-existing infertility. In this series, salpingectomy did not adversely affect subsequent fertility, and the frequency of subsequent EP was significantly reduced. DISCUSSION These data are unique in that they represent the first extended series of patients treated with conservative and radical surgery for tubal EP during an interval of significant change in the incidence and management of that condition in the United States. A detailed description of the epidemiologic features of a subset of the EP patients has been published previously (2). The two groups of patients were generally comparable, with the notable exception of a significant difference in their prevalence of prior infertility (44% of the conservative group and 18% of the radical group) and associated features (gravidity and prior tubal surgery). This difference is critical and was the single factor that appeared to affect subsequent fertility. When the analysis was stratified on this factor, there was no difference in fertility outcome between the two surgically treated groups for women with or without prior infertility. These data are consistent with other recent reports from the United States, Israel, Finland, France, and Sweden that noted a substantial Table 2 Three-Year Fertility Follow-Up in Women With Conservative Versus Radical Treatment Treatment No. of term pregnancies Partial salpingectomy (n = 8) 2 (25)* Complete salpingectomy (n = 42) 27 (64) Total radical surgery (n = 50) 29 (58)t Salpingostomy (n = 33) 17 (52) Removal of conceptus through ampulla (n = 5) 2 (40) Total conservative surgery (n = 38) 19 (50)t * Values in parentheses are percents. t P = 0.455, not significant. :j:p = No. of subsequent EPs 1 (13) 2 (5) 3 (6):j: 8 (24) 0(0) 8 (21):j: Ory et al. Fertility after EP 233

4 Table 3 Fertility After EP Outcome Term pregnancy EP History of infertility With history (n = 25) Without history (n = 63) With history (n = 25) Without history (n = 63) Conservative Radical Total 4/16 (25)* 1/9 (11)* 5 (20) 15/22 (68)t 28/41 (68)t 43 (68) 5/16 (31):1: 2/9 (22):1: 7 (28) 3/22 (14) 2/41 (5) 5 (8) * P = Values in parentheses are percents. t P = :I: P = P = improvement in fertility outcome when compared with historical controls, but improvement could not be attributed to choice of surgical procedure (3-9). These data are also consistent with the earlier findings of DeCherney and Kase (10) that radical and conservative surgery offered comparable fertility potential and with those of Sultana et al. (11) who described similar results in patients treated by laparoscopic salpingostomy or salpingotomy or salpingectomy performed at laparotomy. Although our overall fertility rate is slightly lower than that reported in other recent articles, we believe that this is accounted for by a higher prevalence of infertility in our study population (28%). When patients with a prior history of infertility are omitted, subsequent fertility is comparable with other reports, and there is no significant difference between the radically and conservatively treated groups (68% for both). The observation that prior infertility is the major determinant of future fertility potential is also supported by recent European data (3, 4, 6, 8, 9). The general improvement in subsequent fertility noted after comparison with historical controls is probably more attributable to earlier diagnosis and intervention than to the type of procedure. These findings also confirm other recent reports of a higher risk of recurrent EP after conservative surgery and reaffirm infertility as an independent risk factor for future EP (7,8). Patients with a prior diagnosis of infertility had a twofold to fourfold greaterriskoffuture EP. Pouly et al. (12) also recognized that, in addition to tubal status, prior infertility is a major risk of postectopic fertility. Patients with a high "therapeutic score" (calculated by adding arbitrarily assigned values based on varying significance of different risk factors) had a higher probability of experiencing recurrent EP than an intrauterine pregnancy (IUP) in future pregnancies. They recommended that conservative treatment be reserved for patients with low scores and that patients with higher scores be treated by salpingectomy or bilateral tubal ligation with early referral for IVF. Although our study population is small, it represents a substantial subgroup thought to be particularly amenable to analysis because we were able to analyze the fertility experience after a single EP (thus excluding the effect of treatment of prior EP on fertility outcome). Also, all ofthe subjects in this analysis actively attempted conception for at least 3 years or until conception occurred, providing realistic estimates of fertility potential. Our analysis also benefited from being a population-based study not subject to referral bias, including a large number of available, cooperative subjects for follow-up, and having comparable groups for comparison. Complete medical histories for all subjects were available for review. The major weakness of this study is its retrospective nature with potential selection bias. However, we believe that the comparable groups and extensive stratification make this observational study the most valid comparison of conservative and radical treatments in the United States, and we hope that it may serve as a basis for future randomized prospective studies. In summary, our data do not support the notion that choice of surgical procedure is a significant determinant of fertility outcome in women with EP. However, we have low statistical power to exclude small differences that might be of clinical significance. A prior history of previous infertility was the single most important factor influencing future fertility potential. Of the factors analyzed, including history of IUD use, PID, anovulation, and year of presentation, it is the only one that correlated with future infertility in our series. These observations confirm other investigators' observations and support the following clinical recommendations: conservative surgery, i.e., linear salpingostomy, can be performed in women desiring subsequent pregnancy because salpingectomy may be required in the future, and the advantage of conserving at least one fallopian tube. Women with a single 234 Ory et al. Fertility after EP Fertility and Sterility

5 remammg fallopian tube have an overall 58% chance of IUP after conservative treatment (4). However, conservative surgery is not without risk and confers a substantial possibility of recurrent EP and persistent trophoblastic disease, which was not addressed in this study. Conservative surgery should not be considered in patients not desirous of future fertility and in those unwilling to assume the inherent risks. Patients with a prior history of infertility have a poor subsequent fertility prognosis regardless of the procedure chosen, and they should be advised to consider IVF. These results cannot be extrapolated to a laparoscopic approach, the risks and benefits of which must be assessed independently. More data and larger series are urgently needed to properly evaluate fertility outcomes in association with various risk factors so that the ideal therapy in a variety of circumstances can be determined. REFERENCES 1. Ectopic pregnancy-united States, MMWR 1990; 39: Strathy JH, Coulam CB, Marchbanks P, Annegers JF. Incidence of ectopic pregnancy in Rochester, Minnesota, Obstet Gynecol 1984;64: Nagamani M, London S, Amand P. Factors influencing fertility after ectopic pregnancy. Am J Obstet Gynecol 1984;149: Sherman D, Langer R, Sadovsky G, Bukovsky I, Caspi E. Improved fertility following ectopic pregnancy. Fertil Steril 1982;37: Langer R, Raziel A, Ron-El R, Golan A, Bukovsky I, Caspi E. Reproductive outcome after conservative surgery for unruptured tubal pregnancy-a 15-year experience. Fertil SteriI1990;53: Tuomivaara L, Kauppila A. Radical or conservative surgery for ectopic pregnancy? A follow-up study of fertility of 323 patients. Fertil Steril 1988;50: Makinen JI, Salmi TA, Nakkanen VPJ. Encouraging rates of fertility after ectopic pregnancy. Int J Fertil 1989;34: Querleu D, Boutteville C. Fertility after ectopic pregnancy [letter]. Fertil Steril1989;51: Thorburn J, Philipson M, Lindblom B. Fertility after ectopic pregnancy in relation to background factors and surgical treatment. Fertil Steril 1988;49: DeCherney A, Kase N. The conservative surgical management of unruptured ectopic pregnancy. Obstet Gynecol 1979;54: Sultana CJ, Easley K, Collins RL. Outcome oflaparoscopic versus traditional surgery for ectopic pregnancies. Fertil Steril 1992;57: Pouly JL, Chapron C, Manhes H, Canis M, Wattiez A, Bruhat MA. Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients. Fertil Steril 1991;56: Ory et al. Fertility after EP 235