The relationship of endometriosis to spontaneous abortion

Transcription

1 FERTILITY AND STERILITY Copyright ~ 1983 The American Fertility Society Prinred in U.sA. The relationship of endometriosis to spontaneous abortion James M. Wheeler, M.D.* Bruce M. Johnstont L. Russell Malinak, M.D. *:j: Baylor College of Medicine, Houston, Texas, and University of Melbourne School of Medicine, Melbourne, Victoria, Australia Seventy-seven of 226 pregnancies (34%) conceived prior to conservative surgical treatment of endometriosis ended in first-trimester spontaneous abortion. Mild endometriosis was associated with a significantly greater proportion of abortions (49% in 87 pregnancies) than moderate (25% in 32 pregnancies) or severe disease (24% in 107 pregnancies). Following operation, only 7 of 76 pregnancies (9%) conceived by the same group of patients ended in spontaneous abortion. In primary infertility patients, 17 of 128 pregnancies (13%) ended in abortion following operation. The postoperative abortion rates were not significantly different between degree of severity of endometriosis. Speculation is presented on the mechanism of the increased preoperative abortion rate in patients with mild endometriosis. Fertil Steril 39:656, 1983 In 1942, Haydon! reported a 51% spontaneous abortion rate in 262 previously gravid women with endometriosis diagnosed at surgery. His study documented significantly fewer abortions following conservative operation. A recent report 2 has rekindled interest in the association and implied causation of spontaneous abortion and endometriosis, demonstrating less pregnancy loss following surgery. It is the purpose of this report to confirm a high spontaneous abortion rate in patients with endometriosis prior to treatment, to document a decrease in the abortion rate following conservative surgery, and to evaluate the severity of disease in relation to the likelihood of abortion. Received June 14, 1982; revised and accepted January 19, *Department of Obstetrics and Gynecology, Baylor College of Medicine. tuniversity of Melbourne School of Medicine. :j:reprint requests: L. Russell Malinak, M.D., Department of Obstetrics and Gynecology, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas Wheeler et al. Spontaneous abortion and endometriosis MATERIALS AND METHODS From June 1967 to March 1982, 479 patients underwent conservative surgical therapy at laparotomy for endometriosis by L. R. M. at the Baylor College of Medicine Affiliated Hospitals. The. office and hospital charts of these patients were reviewed for the following: (1) histologic diagnosis of endometriosis; (2) detailed preoperative and postoperative obstetric history; (3) age at operation (mean, 29.1 years; range, 20 to 42); (4) presenting complaint (primary infertility in 60% of patients, secondary infertility in 30%, pelvic pain in 10%); (5) duration of infertility (mean, 3.1 years; range, 1 to 16); (6) interval from previous pregnancies to operation; and (7) severity of endometriosis as classified by Acosta et al. 3 In addition to the conservative treatment of endometriosis,4 operative correction of pelvic adhesions, leiomyomata uteri, and Mullerian fusion defects, factors known to be associated with abortion, were tabulated. Over the same 15 years studied, a smaller group of patients (n = 23) had no medical or Fertility and Sterility

2 Table 1. Preoperative Pregnancy Outcome Related to Severity of Endometriosis Mild Moderate Severe Total No. of patients No. of pregnancies preoperatively Full-term live-born Spontaneous abortion 43 (49%)a 8 (25%)a 26 (24%)a 77 (34%) Termination, ectopic, or stillborn ap < surgical therapy of endometriosis following laparoscopic diagnosis. These patients' records were reviewed for the same data as outlined above. Statistical analysis was by R x C tables of independence using the chi-square distribution and Yates' correction for n < 200 when applicable. 5 RESULTS One hundred sixty-five patients conceived 226 pregnancies prior to the histologic diagnosis of endometriosis at laparotomy. Seventy-seven of the 226 pregnancies (34%) ended in first-trimester spontaneous abortion (Table 1). When abortion was correlated with severity of disease, 43 of 87 pregnancies (49%) in patients with mild endometriosis, 8 of 32 (25%) with moderate disease, and 26 of 107 (24%) with severe disease ended in abortion. The difference in preoperative abortion rates is highly significant (P < 0.001) between degrees of severity of endometriosis. In the 145 patients presenting with secondary infertility, 7 of76 pregnancies (9%) following laparotomy ended in abortion (Table 2). The decline from preoperative to postoperative abortion rates was significant for all patients analyzed collectively (P < 0.001) and patients with mild endometriosis (P < 0.001). However, preoperative versus postoperative abortion rates did not vary significantly in patients with moderate (0.6 > P > 0.5) or severe endometriosis (0.2 > P > 0.1). The postoperative abortion rate of 9% was not significantly different between grades of severity of endometriosis (0.99 > P > 0.98) (Table 2). The preoperative obstetric history, including previous abortion, did not predict the postoperative pregnancy outcome. Ninety-three nulligravid women with treated endometriosis subsequently conceived 128 pregnancies (Table 3). Seventeen of the 128 pregnancies (13%) ended in abortion, a rate not significantly different from the 9% postoperative abortion rate observed in the previously gravid group (0.5 > P > 0.4). Once again, there were no significant differences (0.3 > P > 0.2) in the postoperative abortion rates among grades of severity of endometriosis (Table 3). There was no significant difference in preoperative (0.4 > P > 0.3) or postoperative (0.5 > P > 0.4) spontaneous abortion rates when endometriosis coexisted with leiomyomata uteri or Mullerian fusion defects. As moderate and severe endometriosis are commonly associated with pelvic adhesions, it was impossible to determine an independent effect of adhesions alone on abortions. " Ten patients presenting with secondary infertility underwent diagnostic laparoscopy only, with no previous or subsequent treatment of endometriosis. Mild endometriosis was present in seven patients and moderate in three. In 13 pregnancies conceived prior to the diagnosis of endometriosis, 4 (31%) ended in spontaneous first-tri- Table 2. Postoperative Pregnancy Outcome in Previously Gravid Patients Related to Severity of Endometriosis No. of patients No. of pregnancies postoperatively Full-term live-born Spontaneous abortion Premature, ectopic, or stillborn ao.99 > P > Mild 37 4 (9%)a 2 Moderate Severe Total (lo%)a 2 (9%)a 7 (9%) Wheeler et al. Spontaneous abortion and endometriosis 657

3 Table 3. Postoperative Pregnancy Outcome in N ulligravid Patients Related to Severity of Endometriosis Mild Moderate Severe Total No. of patients No. of pregnancies postoperatively Full-term live-born Spontaneous abortion 9 (19%)a 2 (6%)a 6 (13%)a 17 (13%) Premature or ectopic ao.3 > P > 0.2. mester abortion. The average interval from pregnancy to laparoscopic diagnosis was 43 months (range, 13 to 72). The observed abortions all occurred in the 2 years prior to laparoscopy (13 to 24 months). Following laparoscopy, this group often patients conceived 12 pregnancies an average of 16 months (range, 3 to 41) postoperatively. There were no abortions observed in the 12 postlaparoscopy conceptions. Because of the small number of patients and pregnancies, the prelaparoscopy and postlaparoscopy abortion rates did not differ significantly (0.2 > P > 0.1). Thirteen patients presented with primary infertility and underwent diagnostic laparoscopy only. Eleven had mild endometriosis, and 2 had moderate endometriosis. This group of 13 patients conceived 14 pregnancies an average of 15 months (range, 2 to 52) postoperatively. One (7%) ended in spontaneous abortion. DISCUSSION Abortion rates prior to operative diagnosis of endometriosis1, 2, 6-10 range from 10%9 to 51%,1 with an average of 33%. Unfortunately, the patient populations, the operations performed, and the severity of endometriosis varied such that interpretation of the data is difficult. Abortion rates following conservative surgical treatment of endometriosis1, 2, 6-16 range from 0%16 to 21%,12 with an average of 13%. In one study,11 there were no significant differences in postoperative abortion rates among degrees of severity of endometriosis. The present study, reporting postoperative abortion rates of 9% in previously gravid women and 13% in nulligravidas, confirms previous reports that document less fetal wastage following surgical treatment. Despite the attractiveness of attributing the significant decline in the abortion rate to surgical technique alone, other factors must be considered. For example, the differences in preoperative and postoperative abortions could be explained by flaws in demography. Naples et a1.2 noted that patients who had conceived within 2 years of operative diagnosis of endometriosis had an abortion rate of 63%, versus 43% for the interval 2 to 4 years prior to diagnosis, versus 26% for all pregnancies over a 10-year period. Our data are similar (Table 4), in that 71% of conceptions within the 2 years prior to operative diagnosis resulted in abortion. Thus, a woman who has spontaneously aborted may be more likely to seek a fertility specialist; and the result might be a diagnosis of endometriosis. Nevertheless, our patients, as did those of Naples et al.,2 demonstrated a higher than expected abortion rate even 10 years prior to operation. This fact supports the thesis that surgical removal of endometriosis is causative, and not merely corollary, of the decline in abortions observed. Another way that the postoperative decline in abortion rates could be explained is that careful follow-up by an infertility specialist could somehow lessen pregnancy loss. This may reflect higher patient motivation and better prenatal care. The small number of patients presented in this report who underwent laparoscopic diagnosis Table 4. Preoperative Pregnancy Outcome Related to Time Interval Before Surgery Years from preceding conception to operation ",9 No. of pregnancies Full-term live-born Spontaneous abortions 39 (71%) 14 (27%) 10 (22%) 6 (20%) 8 (19%) 77 (34%) Premature, ectopic, still born, or termination Total 658 Wheeler et at. Spontaneous abortion and endometriosis Fertility and Sterility

4 only, did not have a statistically different prelaparoscopy versus postiaparoscopy abortion rate. Perhaps this relationship may be clarified in other surgeons' greater experience with expectant therapy following laparoscopic diagnosis. Factors known to be associated with abortion17 other than endometriosis have not been evaluated in the literature documenting a decline in abortion rates following conservative surgical treatment of endometriosis. Although most factors known to influence abortion17 were not evaluated in this study, those that could be reliably evaluated and treated at operation were recorded. Because leiomyomata and anatomic abnormalities were similarly distributed among grades of severity of endometriosis, with no significant effect on either preoperative or postoperative abortion rates, their causative role in abortion is uncertain in these patients. Pelvic adhesions have been observed to increase the risk of spontaneous abortion by a theoretic pathophysiologic tubal factor.18 Thus, insofar as adhesions are pertinent to the classification of severity of endometriosis, severe disease could be expected to have an associated higher abortion rate. ll The present study demonstrated a statistically significant inverse relationship between the severity of endometriosis and the preoperative abortion rate. The mechanism behind this paradox is unclear but merits speculation. Evidence exists that foci of endometriosis produce prostaglandins (PGS) PGs have demonstrable effects on tubal and uterine physiology in vitro21 and in vivo.20 Thus, endometriosis could produce increased abortions by tubouterine effects mediated by PGs rather than by mechanical distortion relevant to moderate and particularly severe disease. It is likely that early metabolically active lesions are associated with a greater PG production than the fibrotic lesions of advanced endometriosis. PGs have been found to be elevated in women with unexplained infertility, with microscopic endometriosis postulated as the cause of infertility.19 In another study, biopsy specimens of petechia-like peritoneal lesions not typical of endometriosis had microscopic endometrial glands and stroma.22 Women with unexplained infertility have been treated successfully with danazo ; two of these authorsl9. 23 proposed treatment of microscopic endometriosis as the mechanism. In light of the suspected association of endometriosis and spontaneous abortion, Greenblatt23 has treated habitual aborters with danazol and subsequently observed less fetal wastage. Fresh implants have been demonstrated to produce PGs in a rabbit peritoneal transplantation study.25 Unfortunately, PG levels in humans have not been correlated with the severity of endometriosis. The findings of increased rates of spontaneous abortion in women with endometriosis, particularly mild disease, warrant a prospective study to better define the relationship of spontaneous abortion to endometriosis. Acknowledgments. We wish to thank Carolyn Hayball, R.N., and Randall B. Meacham, B.A., for research assistance, and Wanda Pancamo for secretarial assistance. REFERENCES 1. Haydon GB: A study of 569 cases of endometriosis. Am J Obstet Gynecol 43:704, Naples JD, Batt RE, Sadigh H: Spontaneous abortion rate in patients with endometriosis. Obstet Gynecol 57:509, Acosta AA, Buttram VC Jr, Besch PK, Malinak LR, Franklin RR, Vanderheyden JD: A proposed classification of endometriosis. Obstet Gynecol 42:1, Malinak LR: Infertility and endometriosis: operative technique, clinical staging, and prognosis. Clin Obstet Gynecol 25:725, Sokol RR, Rohlf JF: Introduction to Biostatistics. San Francisco, W. H. Freeman, 1973, p Rock JA, Guzick DS, Sengos C, Schweditsch M, Sapp KC, Jones HW Jr: The conservative surgical treatment of endometriosis: evaluation of pregnancy success with respect to the extent of disease as categorized using contemporary classification systems. Fertil Steril 35:131, Jones GS, Jones HW Jr: Editorial. Obstet Gynecol Surv 26:539, Petersohn L: Fertility in patients with ovarian endometriosis before and after treatment. Acta Obstet Gynecol Beand 49:331, Devereux WP: Endometriosis: long-term observation with particular reference to pregnancy. Obstet GynecoI22:444, Fallas RE: Endometriosis--a study of 150 private cases. West J Surg Obstet Gynecol 59:448, Buttram VC Jr: Surgical treatment of endometriosis in the infertile female: a modified approach. Fertil Steril 32:635, Brosens la, Koninckx PR, Corvelyn P A: A study of plasma progesterone, oestradiol-17~, prolactin and LH levels, and of the luteal phase appearance of the ovaries in patients with endometriosis and infertility. Br J Obstet Gynaecol 85:246, Hammond CB, Haney AF: Conservative treatment of endometriosis. Fertil Steril 30:497, Grant A: Additional sterility factors in endometriosis. Fertil SteriI17:514, 1966 Wheeler et al. Spontaneous abortion and endometriosis 659

5 15. Sheets JL, Symmonds RE, Banner EA: Conservative surgical management of endometriosis. Obstet Gynecol 23: 625, Whitehouse DB, Bates A: Endometriosis: results of conservative surgery. J Obstet Gynaecol Br Emp 62:378, Glass RH, Golbus MS: Habitual abortion. Fertil Steril 29:257, Horne HW Jr, Clyman M, Debrovner C, Griggs G, Kistner R, Kosasa T, Stevenson CS, Taymor M: Prevention of postoperative adhesions following conservative operation: treatment for human infertility. Int J Fertil18:109, Drake TS, O'Brien WF, Ramwell PW, Metz SA: Peritoneal fluid thromboxane B2 and 6-keto-prostaglandin Pi" in endometriosis. Am J Obstet GynecoI140:401, Weed JC: Prostaglandins as related to endometriosis. Clin Obstet Gynecol 23:895, Omini C, Pasargiklian R, Folco GC, Fano M, Berti F: Pharmacological activity of PGI2 and its metabolite 6-0XO-PGFI" on human uterus and fallopian tubes. Prostaglandins 15:1045, Goldstein D, DeCholnoky C, Emans S: Adolescent endometriosis. J Adolesc Health Care 1:37, Greenblatt RB: Danazol in the treatment of infertility. Drugs 19:362, Van Dijk JG, Frolich M, Brand EC, van Hall EV: Treatment of unexplained infertility with danazol. Postgrad Med J (Suppl 5) 55:79, Schenken RS, Asch RH: Surgical induction of endometriosis in the rabbit: effects on fertility and concentrations of peritoneal fluid prostaglandins. Fertil Steril 34:581, Wheeler et ai. Spontaneous abortion and endpmetriosis Fertility and Sterility