- Email: [email protected]
Relation between anatomical courses of the intramural portions of the uterine tubes and pelvic endometriosis
Relation between anatomical courses of the intramural portions of the uterine tubes and pelvic endometriosis Stanislaw Rozewicki, M.D., Ph.D., Anna Radomska, M.D., and Rafal Kurzawa, M.D., Ph.D.ⴱ Department of Reproductive Medicine and Gynecology, Pomeranian Medical University, Szczecin, Poland
Objective: Endometriosis may originate from implants of endometrium due to retrograde flow of menstrual blood. The flow may be stimulated by anatomical anomalies of uterine tubes or uterus. The aim of the study was to find links between anatomical courses of the intramural portions of the uterine tubes and endometriosis. Design: Retrospective comparative study. Setting: Academic hospital. Patient(s): Women (n ⫽ 227) operated on because of various gynecological indications. Intervention(s): Total or subtotal abdominal hysterectomies. Main Outcome Measure(s): Pathological reports correlated with courses of the intramural parts of uterine tubes. To evaluate the intramural courses of uterine tubes, specimens were injected with barium sulfate and x-rayed. Result(s): The intramural portions were categorized into three patterns: straight, curved, or tortuous. Logistic regression identified the course of the intramural portion of the uterine tubes and the parity to be associated with endometriosis. Endometriosis was more frequent in women with straight courses and was infrequent in women with tortuous ones. Conclusion(s): We suggest that a tortuous course of the intramural portion of the uterine tubes constitutes a normal anatomical finding. It controls the retrograde flow of blood during menstruation and limits the possibility of developing endometriosis. Straight or curved intramural portions represent an anatomical abnormality that may predispose women to endometriosis. (Fertil Steril威 2005;84:60 – 6. ©2005 by American Society for Reproductive Medicine.) Key Words: Endometriosis, uterine tubes, etiology of endometriosis
Many theories have been formulated to explain the etiology of endometriosis (1, 2). They may be divided into three groups: endometriosis may be attributed to epithelial metaplasia, it may originate from transplantation of endometrial cells, or it can be a combination of both. According to the theory of metaplasia (theory of Meyer), endometriosis originates in situ from embryonic cells of the urogenital system. The theory indicates nondifferentiated coelomic cells as a source of ectopic endometrium (2, 3). The cells are present in peritoneum and ovarian germinal epithelium. The cells, as a result of hormonal and inflammatory stimuli, may undergo metaplasia into endometrial cells. Menstrual blood may constitute another stimulus that directly or indirectly acts on nondifferentiated mesenchymal cells and induces metaplasia. However, no factors involved in the process have been identified so far. Sampson’s hypothesis, which is the most widely accepted assumption, supports the theory of transplantation (4, 5). According to the theory, ovarian endometrial cysts and peritoneal endometriotic foci originate from implants of endoReceived June 2, 2004; revised and accepted January 3, 2005. Reprint requests: Rafal Kurzawa, M.D., Ph.D., Department of Reproductive Medicine and Gynecology, Pomeranian Medical University, 1 Unii Lubelskiej St., Szczecin 71-252, Poland (FAX: 48-91-4253312; E-mail: [email protected]).
60
metrium secondary to the retrograde flow of menstrual blood (6 – 8). Retrograde flow may be promoted by a partial blockage in a physiological route of menstrual blood passage through the uterine cervix, or else it may be stimulated by enhanced retrograde flow through uterine tubes as a result of inborn or acquired anatomical anomalies. Not only the fact of retrograde menstruation, but also the amount of blood reaching the peritoneum may contribute to the origin and natural history of endometriosis (9, 10). The current study suggests that the tortuous course of the intramural portion of the uterine tubes constitutes a normal anatomical finding. This particular anatomy controls the retrograde flow of blood during menstruation and limits the possibility of a woman developing endometriosis. Straight or curved intramural portions represent an anatomical abnormality that may predispose women to endometriosis. Besides genetic background, relative estrogen overload, or altered immunity, the anatomy of the intramural part of uterine tubes is a key factor responsible for endometriosis. MATERIALS AND METHODS Patients and Materials The intramural part of the uterine tubes was evaluated in uteri or corpora of uteri taken out during abdominal operations performed because of various gynecological indica-
Fertility and Sterility姞 Vol. 84, No. 1, July 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2005.01.120
tions. The final diagnosis was made exclusively on the basis of pathological reports. A thorough gynecological history obtained from the patients who had been operated on included the dates of the first and last menstrual cycles, parity, previous gynecological interventions, and complaints. The reproductive life span (time from menarche to menopause) was excluded from the study because a substantial number of the operated patients were premenopausal. Patients with suspected ovarian malignancies (based on ultrasound scans and Ca-125 levels), or with distal or proximal tubal occlusion were also excluded from the study. The project was approved by the local Ethics Commission. Preparation and Evaluation of Specimens The specimens were removed with intact cornua and fundi of the uteri. During the operations, particular attention was paid that no damage was done to proximal parts of the uterine tubes. The specimens were flushed with saline and thereafter injected carefully with a radio opaque contrast medium (barium sulfate), with a curved, blunt (1 mm in diameter) needle placed close to the uterine ends of the uterine tubes. After injection, the ligatures were placed on both ends of the uterine tubes and the specimens were fixed with 10% formalin and x-rayed (40 kV, 0.4 mA, 6 minutes) at parallel and perpendicular planes in relation to the long axis of the removed uterus. The assessment of uterine tubes was carried out by one investigator who, while assessing, did not know the histopathological diagnosis on the basis of which endometriosis was confirmed. However, she did know the initial diagnosis established during the operation and the macroscopic evaluation of the specimens. Statistics The studied groups were compared by means of the 2 test or the Mann-Whitney test. Logistic regression was used to analyze associations between diverse factors and endometriosis. The analysis included such independent factors as parity, previous cesarean sections, course of the intramural portion of the uterine tubes, and pathological reports. The calculations were done with Statistica for Windows (StatSoft, Tulsa, OK). P⬍.001 was considered statistically significant. RESULTS A total of 227 specimens testing the course of the intramural portion of the uterine tubes were qualified for the study. The cases with either bilateral or unilateral tubal occlusions were excluded from the project. Primary indications for the operations were uterine fibroids (n ⫽ 164; 72.3%); endometriosis, endometrial cysts, and adenomyosis (n ⫽ 23; 10.1%); urinary incontinence (n ⫽ 22; 9.7%); adnexal masses (n ⫽ 17; 7.5%); and pathology of the cervix (n ⫽ 1; 0.4%). Fertility and Sterility姞
Pathology Endometriosis was found in 45 women (19.8%): American Fertility Society stage I (AFS I) (n ⫽ 9; 4.0%), AFS II (n ⫽ 2; 0.9%), AFS III (n ⫽ 21; 9.3%), and AFS IV (n ⫽ 13; 5.7%). There were 182 women (81.2%) without endometriosis. The average age of the women with and without endometriosis ranged from 30 to 69 years (mean, 48 years) and from 37 to 75 years (mean, 51 years), respectively, and did not differ significantly. The other major pathologies included uterine fibroids (n ⫽ 184; 81.1%), adenomyosis (n ⫽ 15; 6.6%), and ovarian pathologies (benign ovarian cysts and tumors, excluding endometriotic cysts; n ⫽ 69; 30.4%). Course of the Intramural Portion of the Uterine Tubes The uterine tubes were categorized into three major patterns on the basis of the x-rays that were carried out on the intramural parts: straight, curved, or tortuous (Fig. 1). The courses of the uterine tubes differed significantly in women with and without endometriosis (Table 1). In women with endometriosis, there were 11 cases with bilaterally straight (24.4%), 3 cases with straight and curved (6.7%), 12 cases with straight and tortuous (26.7%), 8 cases with bilaterally curved (17.8%), 8 cases with curved and tortuous (17.8%), and, finally, 3 cases with bilaterally tortuous (6.7%) courses of uterine tubes. In women without endometriosis, there were 7 cases with bilaterally straight (3.9%), 3 cases with straight and curved (1.7%), 15 cases with straight and tortuous (8.2%), 3 cases with bilaterally curved (1.7%), 16 cases with curved and tortuous (8.8%), and 138 cases with bilaterally tortuous (75.8%) courses of intramural portions of uterine tubes. With significance accepted at P⬍.001, logistic regression identified the course of the intramural portion of the uterine tubes and parity as the factors associated with endometriosis (P⬍.001; 2 ⫽ 87.2; quasi-Newton estimation). The course of the intramural portion of the uterine tubes in relation to other pathologies and parity is shown in Tables 2 and 3, respectively. Reproductive History of Women with and without Endometriosis Women with endometriosis were pregnant less often than those without the disease (2 ⫽ 26.4; P⬍.001). Out of 45 women with endometriosis, 10 (22.2%) delivered once, 19 (42.2%) delivered twice, and 3 (6.7%) delivered three times. Out of 182 women without endometriosis, 24 (13.2%) delivered once, 109 (59.9%) delivered twice, 26 (14.3%) delivered three times, and 12 (6.6%) delivered 4 or more times. The history of infertility was more common (2 ⫽ 19.9; P⬍.001) in women with endometriosis (13/45, 28.9%) than in women without the disease (11/182, 6.0%). There were no differences between the ways of delivery in both groups of patients. Women with endometriosis had a history of at least 61
FIGURE 1 The contrast x-rays presenting three patterns of intramural portions (between the arrows) of uterine tubes. (A) straight; (B) curved; (C) tortuous.
Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
one cesarean section in 6 cases (6/32; 18,8%), while there were 17 cases (17/171; 9.9%) of cesarean sections among women without the disease.
portion of uterine tubes was straight in a vast majority of cases. Now it is recognized that the course of the intramural portion may be straight, curved (arched), or tortuous (convoluted) (18, 19).
DISCUSSION The results of the studies indicate that endometriosis develops in women with uterine tube anatomy that prompts retrograde blood flow from the uterus to the peritoneal cavity. The conclusion was drawn on the basis of the observation that women with bilaterally tortuous courses of the intramural parts of the uterine tubes had a significantly lower incidence of endometriosis. However, it is thought that not only anatomical factors predispose women to endometriosis, but other factors may act on the cellular level and may include genetic, hormonal, or immune disturbances (11–15).
Our data are similar to those published by Sweeney (18), who reported 69% tortuous, 23% straight, and 8% curved courses of the intramural portions of the uterine tubes. We noticed differences between patients with and without endometriosis. Straight and curved courses were more common in women with endometriosis. Out of 45 women with endometriosis, only three (6.7%) had a bilaterally tortuous course of the intramural portion of the uterine tubes. On the other hand, the tortuous course was seen most frequently in women without endometriosis. However, the remaining 24.2% of women without endometriosis had at least one intramural portion that was either straight or curved.
The above conclusions were reached in an experimental setting, which related the anatomy of the intramural parts of the uterine tubes with the pathological diagnosis of endometriosis. The anatomical findings were elicited thanks to contrast-medium x-rays performed at two perpendicular planes. The applied methods were superior to hysterosalpingography (HSG) or laparoscopy. Neither procedure allows the simultaneous comparison of anatomical findings with pathological reports. HSG does not provide insight into pathology, and laparoscopy does not allow for visualization of the intramural parts of uterine tubes. Historically, the course of the intramural portion of uterine tubes was first outlined in 1924 by Hermstein and Neustein (16). They based their studies on contrast-medium x-rays of excised uteri and classified the courses of uterine tubes as straight or slightly curved (half of cases) or tortuous (the other half of cases). According to Rubin (17), the intramural 62
Rozewicki et al.
The lower prevalence of endometriosis in these women can probably be linked to a protective mechanism. Besides normal hormonal status and immune function, one cannot exclude the role of a putative sphincter, which, located around the uterotubal junction, protects women from retrograde menstruation (19, 20). According to Rocca et al., the intramural segment of uterine tubes is considered normal when it has a tortuous course with double curves (21). Its length ranges from 1 to almost 2 cm. At the uterotubal junction the mucosal folds of the endosalpinx are directed toward the tubal lumen (20, 21). It was also proved that round and longitudinal layers of uterine smooth muscles and vascular patterns can effectively close the uterine tubes (20, 22–25). The existence of the spasm of uterotubal junction can be seen in radiograms and recorded during measurements with manometers (17). This can also be the reason for false positive diagnoses of proximal occlusion of uterine
Anatomy of uterine tubes and endometriosis
Vol. 84, No. 1, July 2005
TABLE 1 Intramural portion of uterine tubes of women with and without endometriosis. Endometriosis Yes SS n % Raw % Column % Total SC n % Raw % Column % Total ST n % Raw % Column % Total CC n % Raw % Column % Total CT n % Raw % Column % Total TT n % Raw % Column % Total Total % Total
No
11 61.1 (11/18) 24.4 (11/45)
7 38.9 (7/18) 3.9 (7/182)
Total 18
7.9 (18/227) 3 50 (3/6) 6.7 (3/45)
3 50 (3/6) 1.7 (3/182)
6
2.6 (6/227) 12 44.4 (12/27) 26.7 (12/45)
15 55.6 (15/27) 8.2 (15/182)
27
11.9 (27/227) 8 72.7 (8/11) 17.8 (8/45)
3 27.3 (3/11) 1.7 (3/182)
11
4.9 (11/227) 8 33.3 (8/24) 17.8 (8/45)
16 66.7 (16/24) 8.8 (16/182)
24
10.6 (24/227) 3 2.1 (3/141) 6.7 (3/45)
138 97.9 (138/141) 75.0 (138/182)
45 19.8 (45/227)
182 80.2 (182/227)
141
62.1 (141/227) 227 100.0 (227/227)
Note: 2 ⫽ 82.9; P⬍.001; C ⫽ curved; S ⫽ straight; T ⫽ tortuous. Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
tubes (26). This mechanism could be more effective in women with tortuous intramural parts of the uterine ends. The contractile activity of the uterus, normal during menses, would close more effectively the uterine ends of the uterine tubes if the intramural parts were tortuous rather than straight or curved. A vast majority of women with bilaterally tortuous intramural portions of uterine tubes had no endometriosis, which strongly supports the Sampson implantation theory. This also challenges the theory of metaplasia as women with a bilaterally tortuous intramural portion should have the same prevalence of endometriosis as women with straight or curved courses. However, the same data suggest other imFertility and Sterility姞
portant factors in the etiology of endometriosis. This conclusion is based on the observation that there were cases with either straight or curved courses, where endometriosis was not found. This can be the result of proper immune surveillance in women with normal ovulatory cycles. On the other hand, there are other decisive factors predisposing women to endometriosis. Regulation of endometrial cycles depends on E2 and P (27). The lack of normal biphasic cycles can be associated with a relatively high prevalence of endometriosis in nulliparous women or in patients with anovulatory cycles. In women with endometriosis, monophasic cycles may occur in about 25% of cases (28). A decreased viability of 63
TABLE 2 The course of intramural portion of the uterine tubes in relation to other pathologies. Other pathologies
SS n % Raw % Column % Total SC n % Raw % Column % Total ST n % Raw % Column % Total CC n % Raw % Column % Total CT n % Raw % Column % Total TT n % Raw % Column % Total Total % Total
Fibroids
Ovarian pathologya
Adenomyosis
Cervical cancer
Total
12 66.7 (12/18) 6.5 (12/184)
11 61.1 (11/18) 15.9 (11/69)
1 5.6 (1/18) 6.7 (1/15)
0 0.0 (0/18) 0.0 (0/1)
18
7.9 (18/227) 6 100.0 (6/6) 3.6 (6/184)
3 50 (3/6) 4.3 (3/69)
1 16.7 (1/6) 6.7 (1/15)
0 0.0 (0/6) 0.0 (0/1)
6
2.6 (6/227) 25 93.6 (25/27) 13.6 (25/184)
11 40.7 (11/27) 15.9 (11/69)
2 7.4 (2/27) 13.3 (2/15)
0 0.0 (0/27) 0.0 (0/1)
27
11.9 (27/227) 5 45.4 (5/11) 2.7 (5/184)
6 54.5 (6/11) 8.7 (6/69)
1 9.1 (1/11) 6.7 (1/15)
1 9.1 (1/11) 100.0 (1/1)
11
4.0 (11/227) 19 79.1 (19/24) 10.3 (19/184)
9 37.6 (9/24) 13 (9/69)
2 8 (2/24) 13.3 (2/15)
0 0.0 (0/24) 0.0 (0/1)
24
10.6 (24/227) 117 83.0 (117/141) 64.0 (117/184)
29 20.6 (29/141) 42.0 (29/69)
184 81.06 (184/227)
69 30.4 (69/227)
8 5.7 (8/141) 53.3 (8/15) 15 6.6 (15/227)
0 0.0 (0/141) 0.0 (0/1) 1 0.4 (1/227)
141
62.1 (141/227) 227 100.0 (227/227)
Note: C ⫽ curved; S ⫽ straight; T ⫽ tortuous. a Benign ovarian tumors and cysts excluding endometriotic cysts. Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
endometrial cells in the peritoneal cavity is connected with high peritoneal P levels, which in the ovulatory phase are 5–25 times higher than those in the serum. Therefore, endometriosis is more frequent in cases of anovulation or luteinized unruptured follicle syndrome. This widely accepted theory (29) found its reflection in our results. There were more cases of infertility in women with endometriosis. Also, women with endometriosis were pregnant less often and delivered fewer children than women without the disease. 64
Rozewicki et al.
An altered immunity may also contribute to endometriosis (30 –33). Under normal circumstances, the endometrial cells that reach the peritoneal cavity are cleared by the immune cells. In women with genetic background and/or in cases of relative estrogen overload, the response toward ectopic endometrium may be altered. The immunity may be changed by a secretion of cytokines, growth factors, prostaglandins, and glycodelin (30, 31, 34). A decreased activity of natural killer cells and an altered activity of B lymphocytes and macrophages may be fac-
Anatomy of uterine tubes and endometriosis
Vol. 84, No. 1, July 2005
TABLE 3 The course of intramural portion of the uterine tubes in relation to parity. Parity No deliveries SS n % Raw % Column % Total SC n % Raw % Column % Total ST n % Raw % Column % Total CC n % Raw % Column % Total CT n % Raw % Column % Total TT n % Raw % Column % Total Total % Total
3 16.7 (3/18) 12.5 (3/24)
One delivery 3 16.7 (3/18) 8.8 (3/34)
Two deliveries 10 55.6 (10/18) 7.8 (10/128)
Three deliveries 2 11.1 (2/18) 6.9 (2/29)
Four deliveries 0 0.0 (0/18) 0.0 (0/12)
Total 18
7.0 (18/227) 1 16.7 (1/6) 4.2 (1/24)
1 16.7 (1/6) 2.9 (1/34)
3 50 (3/6) 2.3 (3/128)
1 16.7 (1/6) 3.4 (1/29)
0 0.0 (0/6) 0.0 (0/12)
6
2.6 (6/227) 5 18.5 (5/27) 20.8 (5/24)
5 18.5 (5/27) 14.7 (5/34)
13 48.2 (13/27) 10.2 (13/128)
3 11.1 (3/27) 10.3 (3/29)
1 3.7 (1/27) 8.3 (1/12)
27
11.9 (27/227) 1 9.1 (1/11) 4.2 (124)
3 27.3 (3/11) 8.8 (3/34)
4 36.4 (4/11) 3.1 (4/128)
2 18.2 (2/11) 6.9 (2/29)
1 9.1 (1/11) 8.3 (1/12)
11
4.9 (11/227) 6 25 (6/24) 25 (6/24)
5 20.1 (5/24) 14.7 (5/15)
8 33.3 (8/24) 6.3 (8/128)
2 8.3 (2/24) 6.9 (2/29)
3 12.5 (3/24) 25.0 (3/12)
24
10.6 (24/227) 8 5.7 (8/141) 33.3 (8/24) 24 10.6 (24/227)
17 90 12.1 (17/141) 63.8 (90/141) 50 (17/34) 70.3 (90/128)
19 13.5 (19/141) 65.5 (19/29)
34 128 29 15 (34/227) 56.4 (128/227) 12.8 (29/227)
7 5 (7/141) 58.3 (7/12)
141
62.1 (141/227) 12 227 5.3 (12/227) 100.0 (227/227)
Note: C ⫽ curved; S ⫽ straight; T ⫽ tortuous; P ⫽ NS. Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
tors contributing to ectopic implantation of endometrium (35–38). Autoimmunity may also play a role (39, 40). These factors may promote proliferation of endometrial cells and a Fas-L-mediated apoptosis of immune cells (34). Finally, peritoneal fluid also influences implantation and proliferation of ectopic endometrium and its volume increases along with the progression of endometriosis (34, 41, 42). The obtained results confirm the hypothesis linking endometriosis with retrograde menstruation. A tortuous Fertility and Sterility姞
course of the intramural part of the uterine tubes may protect women from a reflux of menstrual blood into the peritoneal cavity. When the reflux does in fact take place, altered endocrine and immune functions may promote implantation and development of endometriotic foci. The pathogenesis of endometriosis is multifactorial, and it should not be solely connected to the course of the intramural part of the uterine tubes. However, a diverse anatomy of uterine tubes in women with and without endometriosis gives another insight into the development 65
of the disease and raises questions about its complex origin. REFERENCES 1. Prentice A. Endometriosis. Br Med J 2001;323:93–5. 2. Redwine DB. Was Sampson wrong? Fertil Steril 2002;78:686 –93. 3. Meyer R. Uber den staude der frage der adenomyosites adenomyoma in allgemeinen und adenomyometitis sarcomatosa. Zentralbl Gynakol 1919;36:745–9. 4. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Obstet Gynecol 1927;4:422– 69. 5. Sampson JA. The development of the implantation theory for the origin of peritoneal endometriosis. Am J Obstet Gynecol 1940;40:549 –55. 6. Brosens IA, Puttemans PJ, Deprest J. The endoscopic localization of endometrial implants in the ovarian chocolate cyst. Fertil Steril 1994; 61:1034 – 8. 7. Hughesdon PE. The structure of endometrial cysts of the ovary. J Obstet Gynaecol Br Emp 1957;64:481–7. 8. Vercellini P, Aimi G, De Giorgi O, Maddalena S, Carinelli S, Crosignani PG. Is cystic ovarian endometriosis an asymmetric disease? Br J Obstet Gynaecol 1998;105:1018 –21. 9. Arumugam K, Lim JM. Menstrual characteristics associated with endometriosis. Br J Obstet Gynaecol 1997;104:948 –50. 10. Bahtiyar MO, Seli E, Oral E, Senturk LM, Zreik TG, Arici A. Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells. Hum Reprod 1998;13:3492–5. 11. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001;75:1–10. 12. Taylor RN, Lundeen SG, Giudice LC. Emerging role of genomics in endometriosis research. Fertil Steril 2002;78:694 – 8. 13. Vignali M, Infantino M, Matrone R, Chiodo I, Somigliana E, Busacca M, et al. Endometriosis: novel etiopathogenetic concepts and clinical perspectives Fertil Steril 2002;78:665–78. 14. Woodworth SH, Singh M, Yussman MA, Sanfilippo JS, Cook CL, Lincoln SR. A prospective study on the association between red hair color and endometriosis in infertile patients. Fertil Steril 1995;64: 651–2. 15. Wyshak G, Frisch RE. Red hair color, melanoma, and endometriosis: suggestive associations. Int J Dermatol 2000;39:798 – 802. 16. Hermstein A, Neustadt A. Intramural portion of the uterine tube. Z Geburtshilfe Gynakol 1924;88:431–5. 17. Rubin IC. Observation on the intramural and isthmic portion of the uterine tubes with special reference to so-called isthmospasm. Surg Gynecol Obstet 1928;4:87–90. 18. Sweeney WI. The intramural portion of the uterine tube—its gross anatomy course and length. Obstet Gynecol 1962;19:3–5. 19. Merchant RN, Prabhu SR, Chougale A. Uterotubal junction—morphology and clinical aspects. Int J Fertil 1983;28:199 –205. 20. Eddy CA, Pauerstein CJ. Anatomy and physiology of the uterine tube. Clin Obstet Gynecol 1980;23:1177–93. 21. Rocca M, el Habashy M, Nayel S, Madwar A. The intramural segment and the uterotubal junction: an anatomic and histologic study. Int J Gynaecol Obstet 1989;28:343–9. 22. Brokelmann J. Functional morphology of the uterine tube. Arch Gynecol Obstet 1989,245:391–5.
66
Rozewicki et al.
23. DeCherney AH. Anything you can do I can do better or differently! Fertil Steril 1987;48:374 – 6. 24. Fortier KJ, Haney AF. The pathologic spectrum of uterotubal junction obstruction. Obstet Gynecol 1985;65:93– 8. 25. Lisa JR, Gioia JD, Rubin IC. Observations on the intramural portion of the uterine tubes. Surg Gynecol Obstet 1954;92:159 – 69. 26. Sienkiewicz R, Róz˙ewicki S. Evaluation of combined administration of diazepam, fenoterol and metamizole in prevention of uterotubal spasm during hysterosalpingography. Ginekol Pol 1992;63:512– 4. 27. Tabibzadeh S. The signals and molecular pathways involved in human menstruation, a unique process of tissue destruction and remodeling. Mol Hum Reprod 1996;2:77–92. 28. Soules MR, Makinak LR, Bury R, Poindexter A. Endometriosis and anovulation: a coexisting problem in the infertile female. Am J Obstet Gynecol 1976;125:412–7. 29. Mc Artur JW, Ulfelder WH. The effect of pregnancy upon endometriosis. Obstet Gynecol Surv 1965;20:709 –33. 30. Braun DP, Dmowski WP. Endometriosis: abnormal endometrium and dysfunctional immune response. Curr Opin Obstet Gynecol 1998;10: 365–9. 31. De Placido G, Alviggi C, Di Palma G, Carravetta C, Matarese G, Landino G, et al. Serum concentrations of soluble human leukocyte class I antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions. Hum Reprod 1998;13:3206 –10. 32. Dmowski WP, Steele RW, Baker GF. Deficient cellular immunity in endometriosis. Am J Obstet Gynecol 1981;143:377– 83. 33. Muscato JJ, Haney AF, Weinberg JB. Sperm fagocitosis by human peritoneal macrophages: a possible cause on infertility in endometriosis. Am J Obstet Gynecol 1982;144:503–10. 34. Garcia-Velasco JA, Arici A, Zreik T, Naftolin F, Mor G. Macrophage derived growth factors modulate Fas ligand expression in cultured endometrial stromal cells: a role in endometriosis. Mol Hum Reprod 1999;5:642–50. 35. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 1984;64:151– 4. 36. Semino C, Semino A, Pietra G, Mingari MC, Barocci S, Venturini PL, et al. Role of major histocompatibility complex class I expression and natural killer–like T cells in the genetic control of endometriosis. Fertil Steril 1995;64:909 –16. 37. Somigliana E, Vigano P, Gaffuri B, Guarneri D, Busacca M, Vignali M. Human endometrial stromal cells as a source of soluble intercellular adhesion molecule (ICAM)-1 molecules. Hum Reprod 1996;11:1190 – 4. 38. Somigliana E, Vigano P, Vignali M. Endometriosis and unexplained recurrent spontaneous abortion: pathological states resulting from aberrant modulation of natural killer cell function? Hum Reprod Update 1999;5:41–52. 39. Gleicher N, El-Roeiy A. The reproductive autoimmune failure syndrome. Am J Obstet Gynecol 1988;159:223–7. 40. Kennedy SH, Starkey PM, Sargent IL, Hicks BR, Barlow DH. Antiendometrial antibodies in endometriosis measured by ELISA before and after treatment with danazol and nafarelin. Obstet Gynecol 1990;75: 914 – 8. 41. Hill JA. Immunology and endometriosis. Fertil Steril 1992;58:262– 4. 42. Surrey ES, Halme J. Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro. Am J Obstet Gynecol 1990;162:792–7.
Anatomy of uterine tubes and endometriosis
Vol. 84, No. 1, July 2005
Objective: Endometriosis may originate from implants of endometrium due to retrograde flow of menstrual blood. The flow may be stimulated by anatomical anomalies of uterine tubes or uterus. The aim of the study was to find links between anatomical courses of the intramural portions of the uterine tubes and endometriosis. Design: Retrospective comparative study. Setting: Academic hospital. Patient(s): Women (n ⫽ 227) operated on because of various gynecological indications. Intervention(s): Total or subtotal abdominal hysterectomies. Main Outcome Measure(s): Pathological reports correlated with courses of the intramural parts of uterine tubes. To evaluate the intramural courses of uterine tubes, specimens were injected with barium sulfate and x-rayed. Result(s): The intramural portions were categorized into three patterns: straight, curved, or tortuous. Logistic regression identified the course of the intramural portion of the uterine tubes and the parity to be associated with endometriosis. Endometriosis was more frequent in women with straight courses and was infrequent in women with tortuous ones. Conclusion(s): We suggest that a tortuous course of the intramural portion of the uterine tubes constitutes a normal anatomical finding. It controls the retrograde flow of blood during menstruation and limits the possibility of developing endometriosis. Straight or curved intramural portions represent an anatomical abnormality that may predispose women to endometriosis. (Fertil Steril威 2005;84:60 – 6. ©2005 by American Society for Reproductive Medicine.) Key Words: Endometriosis, uterine tubes, etiology of endometriosis
Many theories have been formulated to explain the etiology of endometriosis (1, 2). They may be divided into three groups: endometriosis may be attributed to epithelial metaplasia, it may originate from transplantation of endometrial cells, or it can be a combination of both. According to the theory of metaplasia (theory of Meyer), endometriosis originates in situ from embryonic cells of the urogenital system. The theory indicates nondifferentiated coelomic cells as a source of ectopic endometrium (2, 3). The cells are present in peritoneum and ovarian germinal epithelium. The cells, as a result of hormonal and inflammatory stimuli, may undergo metaplasia into endometrial cells. Menstrual blood may constitute another stimulus that directly or indirectly acts on nondifferentiated mesenchymal cells and induces metaplasia. However, no factors involved in the process have been identified so far. Sampson’s hypothesis, which is the most widely accepted assumption, supports the theory of transplantation (4, 5). According to the theory, ovarian endometrial cysts and peritoneal endometriotic foci originate from implants of endoReceived June 2, 2004; revised and accepted January 3, 2005. Reprint requests: Rafal Kurzawa, M.D., Ph.D., Department of Reproductive Medicine and Gynecology, Pomeranian Medical University, 1 Unii Lubelskiej St., Szczecin 71-252, Poland (FAX: 48-91-4253312; E-mail: [email protected]).
60
metrium secondary to the retrograde flow of menstrual blood (6 – 8). Retrograde flow may be promoted by a partial blockage in a physiological route of menstrual blood passage through the uterine cervix, or else it may be stimulated by enhanced retrograde flow through uterine tubes as a result of inborn or acquired anatomical anomalies. Not only the fact of retrograde menstruation, but also the amount of blood reaching the peritoneum may contribute to the origin and natural history of endometriosis (9, 10). The current study suggests that the tortuous course of the intramural portion of the uterine tubes constitutes a normal anatomical finding. This particular anatomy controls the retrograde flow of blood during menstruation and limits the possibility of a woman developing endometriosis. Straight or curved intramural portions represent an anatomical abnormality that may predispose women to endometriosis. Besides genetic background, relative estrogen overload, or altered immunity, the anatomy of the intramural part of uterine tubes is a key factor responsible for endometriosis. MATERIALS AND METHODS Patients and Materials The intramural part of the uterine tubes was evaluated in uteri or corpora of uteri taken out during abdominal operations performed because of various gynecological indica-
Fertility and Sterility姞 Vol. 84, No. 1, July 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2005.01.120
tions. The final diagnosis was made exclusively on the basis of pathological reports. A thorough gynecological history obtained from the patients who had been operated on included the dates of the first and last menstrual cycles, parity, previous gynecological interventions, and complaints. The reproductive life span (time from menarche to menopause) was excluded from the study because a substantial number of the operated patients were premenopausal. Patients with suspected ovarian malignancies (based on ultrasound scans and Ca-125 levels), or with distal or proximal tubal occlusion were also excluded from the study. The project was approved by the local Ethics Commission. Preparation and Evaluation of Specimens The specimens were removed with intact cornua and fundi of the uteri. During the operations, particular attention was paid that no damage was done to proximal parts of the uterine tubes. The specimens were flushed with saline and thereafter injected carefully with a radio opaque contrast medium (barium sulfate), with a curved, blunt (1 mm in diameter) needle placed close to the uterine ends of the uterine tubes. After injection, the ligatures were placed on both ends of the uterine tubes and the specimens were fixed with 10% formalin and x-rayed (40 kV, 0.4 mA, 6 minutes) at parallel and perpendicular planes in relation to the long axis of the removed uterus. The assessment of uterine tubes was carried out by one investigator who, while assessing, did not know the histopathological diagnosis on the basis of which endometriosis was confirmed. However, she did know the initial diagnosis established during the operation and the macroscopic evaluation of the specimens. Statistics The studied groups were compared by means of the 2 test or the Mann-Whitney test. Logistic regression was used to analyze associations between diverse factors and endometriosis. The analysis included such independent factors as parity, previous cesarean sections, course of the intramural portion of the uterine tubes, and pathological reports. The calculations were done with Statistica for Windows (StatSoft, Tulsa, OK). P⬍.001 was considered statistically significant. RESULTS A total of 227 specimens testing the course of the intramural portion of the uterine tubes were qualified for the study. The cases with either bilateral or unilateral tubal occlusions were excluded from the project. Primary indications for the operations were uterine fibroids (n ⫽ 164; 72.3%); endometriosis, endometrial cysts, and adenomyosis (n ⫽ 23; 10.1%); urinary incontinence (n ⫽ 22; 9.7%); adnexal masses (n ⫽ 17; 7.5%); and pathology of the cervix (n ⫽ 1; 0.4%). Fertility and Sterility姞
Pathology Endometriosis was found in 45 women (19.8%): American Fertility Society stage I (AFS I) (n ⫽ 9; 4.0%), AFS II (n ⫽ 2; 0.9%), AFS III (n ⫽ 21; 9.3%), and AFS IV (n ⫽ 13; 5.7%). There were 182 women (81.2%) without endometriosis. The average age of the women with and without endometriosis ranged from 30 to 69 years (mean, 48 years) and from 37 to 75 years (mean, 51 years), respectively, and did not differ significantly. The other major pathologies included uterine fibroids (n ⫽ 184; 81.1%), adenomyosis (n ⫽ 15; 6.6%), and ovarian pathologies (benign ovarian cysts and tumors, excluding endometriotic cysts; n ⫽ 69; 30.4%). Course of the Intramural Portion of the Uterine Tubes The uterine tubes were categorized into three major patterns on the basis of the x-rays that were carried out on the intramural parts: straight, curved, or tortuous (Fig. 1). The courses of the uterine tubes differed significantly in women with and without endometriosis (Table 1). In women with endometriosis, there were 11 cases with bilaterally straight (24.4%), 3 cases with straight and curved (6.7%), 12 cases with straight and tortuous (26.7%), 8 cases with bilaterally curved (17.8%), 8 cases with curved and tortuous (17.8%), and, finally, 3 cases with bilaterally tortuous (6.7%) courses of uterine tubes. In women without endometriosis, there were 7 cases with bilaterally straight (3.9%), 3 cases with straight and curved (1.7%), 15 cases with straight and tortuous (8.2%), 3 cases with bilaterally curved (1.7%), 16 cases with curved and tortuous (8.8%), and 138 cases with bilaterally tortuous (75.8%) courses of intramural portions of uterine tubes. With significance accepted at P⬍.001, logistic regression identified the course of the intramural portion of the uterine tubes and parity as the factors associated with endometriosis (P⬍.001; 2 ⫽ 87.2; quasi-Newton estimation). The course of the intramural portion of the uterine tubes in relation to other pathologies and parity is shown in Tables 2 and 3, respectively. Reproductive History of Women with and without Endometriosis Women with endometriosis were pregnant less often than those without the disease (2 ⫽ 26.4; P⬍.001). Out of 45 women with endometriosis, 10 (22.2%) delivered once, 19 (42.2%) delivered twice, and 3 (6.7%) delivered three times. Out of 182 women without endometriosis, 24 (13.2%) delivered once, 109 (59.9%) delivered twice, 26 (14.3%) delivered three times, and 12 (6.6%) delivered 4 or more times. The history of infertility was more common (2 ⫽ 19.9; P⬍.001) in women with endometriosis (13/45, 28.9%) than in women without the disease (11/182, 6.0%). There were no differences between the ways of delivery in both groups of patients. Women with endometriosis had a history of at least 61
FIGURE 1 The contrast x-rays presenting three patterns of intramural portions (between the arrows) of uterine tubes. (A) straight; (B) curved; (C) tortuous.
Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
one cesarean section in 6 cases (6/32; 18,8%), while there were 17 cases (17/171; 9.9%) of cesarean sections among women without the disease.
portion of uterine tubes was straight in a vast majority of cases. Now it is recognized that the course of the intramural portion may be straight, curved (arched), or tortuous (convoluted) (18, 19).
DISCUSSION The results of the studies indicate that endometriosis develops in women with uterine tube anatomy that prompts retrograde blood flow from the uterus to the peritoneal cavity. The conclusion was drawn on the basis of the observation that women with bilaterally tortuous courses of the intramural parts of the uterine tubes had a significantly lower incidence of endometriosis. However, it is thought that not only anatomical factors predispose women to endometriosis, but other factors may act on the cellular level and may include genetic, hormonal, or immune disturbances (11–15).
Our data are similar to those published by Sweeney (18), who reported 69% tortuous, 23% straight, and 8% curved courses of the intramural portions of the uterine tubes. We noticed differences between patients with and without endometriosis. Straight and curved courses were more common in women with endometriosis. Out of 45 women with endometriosis, only three (6.7%) had a bilaterally tortuous course of the intramural portion of the uterine tubes. On the other hand, the tortuous course was seen most frequently in women without endometriosis. However, the remaining 24.2% of women without endometriosis had at least one intramural portion that was either straight or curved.
The above conclusions were reached in an experimental setting, which related the anatomy of the intramural parts of the uterine tubes with the pathological diagnosis of endometriosis. The anatomical findings were elicited thanks to contrast-medium x-rays performed at two perpendicular planes. The applied methods were superior to hysterosalpingography (HSG) or laparoscopy. Neither procedure allows the simultaneous comparison of anatomical findings with pathological reports. HSG does not provide insight into pathology, and laparoscopy does not allow for visualization of the intramural parts of uterine tubes. Historically, the course of the intramural portion of uterine tubes was first outlined in 1924 by Hermstein and Neustein (16). They based their studies on contrast-medium x-rays of excised uteri and classified the courses of uterine tubes as straight or slightly curved (half of cases) or tortuous (the other half of cases). According to Rubin (17), the intramural 62
Rozewicki et al.
The lower prevalence of endometriosis in these women can probably be linked to a protective mechanism. Besides normal hormonal status and immune function, one cannot exclude the role of a putative sphincter, which, located around the uterotubal junction, protects women from retrograde menstruation (19, 20). According to Rocca et al., the intramural segment of uterine tubes is considered normal when it has a tortuous course with double curves (21). Its length ranges from 1 to almost 2 cm. At the uterotubal junction the mucosal folds of the endosalpinx are directed toward the tubal lumen (20, 21). It was also proved that round and longitudinal layers of uterine smooth muscles and vascular patterns can effectively close the uterine tubes (20, 22–25). The existence of the spasm of uterotubal junction can be seen in radiograms and recorded during measurements with manometers (17). This can also be the reason for false positive diagnoses of proximal occlusion of uterine
Anatomy of uterine tubes and endometriosis
Vol. 84, No. 1, July 2005
TABLE 1 Intramural portion of uterine tubes of women with and without endometriosis. Endometriosis Yes SS n % Raw % Column % Total SC n % Raw % Column % Total ST n % Raw % Column % Total CC n % Raw % Column % Total CT n % Raw % Column % Total TT n % Raw % Column % Total Total % Total
No
11 61.1 (11/18) 24.4 (11/45)
7 38.9 (7/18) 3.9 (7/182)
Total 18
7.9 (18/227) 3 50 (3/6) 6.7 (3/45)
3 50 (3/6) 1.7 (3/182)
6
2.6 (6/227) 12 44.4 (12/27) 26.7 (12/45)
15 55.6 (15/27) 8.2 (15/182)
27
11.9 (27/227) 8 72.7 (8/11) 17.8 (8/45)
3 27.3 (3/11) 1.7 (3/182)
11
4.9 (11/227) 8 33.3 (8/24) 17.8 (8/45)
16 66.7 (16/24) 8.8 (16/182)
24
10.6 (24/227) 3 2.1 (3/141) 6.7 (3/45)
138 97.9 (138/141) 75.0 (138/182)
45 19.8 (45/227)
182 80.2 (182/227)
141
62.1 (141/227) 227 100.0 (227/227)
Note: 2 ⫽ 82.9; P⬍.001; C ⫽ curved; S ⫽ straight; T ⫽ tortuous. Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
tubes (26). This mechanism could be more effective in women with tortuous intramural parts of the uterine ends. The contractile activity of the uterus, normal during menses, would close more effectively the uterine ends of the uterine tubes if the intramural parts were tortuous rather than straight or curved. A vast majority of women with bilaterally tortuous intramural portions of uterine tubes had no endometriosis, which strongly supports the Sampson implantation theory. This also challenges the theory of metaplasia as women with a bilaterally tortuous intramural portion should have the same prevalence of endometriosis as women with straight or curved courses. However, the same data suggest other imFertility and Sterility姞
portant factors in the etiology of endometriosis. This conclusion is based on the observation that there were cases with either straight or curved courses, where endometriosis was not found. This can be the result of proper immune surveillance in women with normal ovulatory cycles. On the other hand, there are other decisive factors predisposing women to endometriosis. Regulation of endometrial cycles depends on E2 and P (27). The lack of normal biphasic cycles can be associated with a relatively high prevalence of endometriosis in nulliparous women or in patients with anovulatory cycles. In women with endometriosis, monophasic cycles may occur in about 25% of cases (28). A decreased viability of 63
TABLE 2 The course of intramural portion of the uterine tubes in relation to other pathologies. Other pathologies
SS n % Raw % Column % Total SC n % Raw % Column % Total ST n % Raw % Column % Total CC n % Raw % Column % Total CT n % Raw % Column % Total TT n % Raw % Column % Total Total % Total
Fibroids
Ovarian pathologya
Adenomyosis
Cervical cancer
Total
12 66.7 (12/18) 6.5 (12/184)
11 61.1 (11/18) 15.9 (11/69)
1 5.6 (1/18) 6.7 (1/15)
0 0.0 (0/18) 0.0 (0/1)
18
7.9 (18/227) 6 100.0 (6/6) 3.6 (6/184)
3 50 (3/6) 4.3 (3/69)
1 16.7 (1/6) 6.7 (1/15)
0 0.0 (0/6) 0.0 (0/1)
6
2.6 (6/227) 25 93.6 (25/27) 13.6 (25/184)
11 40.7 (11/27) 15.9 (11/69)
2 7.4 (2/27) 13.3 (2/15)
0 0.0 (0/27) 0.0 (0/1)
27
11.9 (27/227) 5 45.4 (5/11) 2.7 (5/184)
6 54.5 (6/11) 8.7 (6/69)
1 9.1 (1/11) 6.7 (1/15)
1 9.1 (1/11) 100.0 (1/1)
11
4.0 (11/227) 19 79.1 (19/24) 10.3 (19/184)
9 37.6 (9/24) 13 (9/69)
2 8 (2/24) 13.3 (2/15)
0 0.0 (0/24) 0.0 (0/1)
24
10.6 (24/227) 117 83.0 (117/141) 64.0 (117/184)
29 20.6 (29/141) 42.0 (29/69)
184 81.06 (184/227)
69 30.4 (69/227)
8 5.7 (8/141) 53.3 (8/15) 15 6.6 (15/227)
0 0.0 (0/141) 0.0 (0/1) 1 0.4 (1/227)
141
62.1 (141/227) 227 100.0 (227/227)
Note: C ⫽ curved; S ⫽ straight; T ⫽ tortuous. a Benign ovarian tumors and cysts excluding endometriotic cysts. Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
endometrial cells in the peritoneal cavity is connected with high peritoneal P levels, which in the ovulatory phase are 5–25 times higher than those in the serum. Therefore, endometriosis is more frequent in cases of anovulation or luteinized unruptured follicle syndrome. This widely accepted theory (29) found its reflection in our results. There were more cases of infertility in women with endometriosis. Also, women with endometriosis were pregnant less often and delivered fewer children than women without the disease. 64
Rozewicki et al.
An altered immunity may also contribute to endometriosis (30 –33). Under normal circumstances, the endometrial cells that reach the peritoneal cavity are cleared by the immune cells. In women with genetic background and/or in cases of relative estrogen overload, the response toward ectopic endometrium may be altered. The immunity may be changed by a secretion of cytokines, growth factors, prostaglandins, and glycodelin (30, 31, 34). A decreased activity of natural killer cells and an altered activity of B lymphocytes and macrophages may be fac-
Anatomy of uterine tubes and endometriosis
Vol. 84, No. 1, July 2005
TABLE 3 The course of intramural portion of the uterine tubes in relation to parity. Parity No deliveries SS n % Raw % Column % Total SC n % Raw % Column % Total ST n % Raw % Column % Total CC n % Raw % Column % Total CT n % Raw % Column % Total TT n % Raw % Column % Total Total % Total
3 16.7 (3/18) 12.5 (3/24)
One delivery 3 16.7 (3/18) 8.8 (3/34)
Two deliveries 10 55.6 (10/18) 7.8 (10/128)
Three deliveries 2 11.1 (2/18) 6.9 (2/29)
Four deliveries 0 0.0 (0/18) 0.0 (0/12)
Total 18
7.0 (18/227) 1 16.7 (1/6) 4.2 (1/24)
1 16.7 (1/6) 2.9 (1/34)
3 50 (3/6) 2.3 (3/128)
1 16.7 (1/6) 3.4 (1/29)
0 0.0 (0/6) 0.0 (0/12)
6
2.6 (6/227) 5 18.5 (5/27) 20.8 (5/24)
5 18.5 (5/27) 14.7 (5/34)
13 48.2 (13/27) 10.2 (13/128)
3 11.1 (3/27) 10.3 (3/29)
1 3.7 (1/27) 8.3 (1/12)
27
11.9 (27/227) 1 9.1 (1/11) 4.2 (124)
3 27.3 (3/11) 8.8 (3/34)
4 36.4 (4/11) 3.1 (4/128)
2 18.2 (2/11) 6.9 (2/29)
1 9.1 (1/11) 8.3 (1/12)
11
4.9 (11/227) 6 25 (6/24) 25 (6/24)
5 20.1 (5/24) 14.7 (5/15)
8 33.3 (8/24) 6.3 (8/128)
2 8.3 (2/24) 6.9 (2/29)
3 12.5 (3/24) 25.0 (3/12)
24
10.6 (24/227) 8 5.7 (8/141) 33.3 (8/24) 24 10.6 (24/227)
17 90 12.1 (17/141) 63.8 (90/141) 50 (17/34) 70.3 (90/128)
19 13.5 (19/141) 65.5 (19/29)
34 128 29 15 (34/227) 56.4 (128/227) 12.8 (29/227)
7 5 (7/141) 58.3 (7/12)
141
62.1 (141/227) 12 227 5.3 (12/227) 100.0 (227/227)
Note: C ⫽ curved; S ⫽ straight; T ⫽ tortuous; P ⫽ NS. Rozewicki. Anatomy of uterine tubes and endometriosis. Fertil Steril 2005.
tors contributing to ectopic implantation of endometrium (35–38). Autoimmunity may also play a role (39, 40). These factors may promote proliferation of endometrial cells and a Fas-L-mediated apoptosis of immune cells (34). Finally, peritoneal fluid also influences implantation and proliferation of ectopic endometrium and its volume increases along with the progression of endometriosis (34, 41, 42). The obtained results confirm the hypothesis linking endometriosis with retrograde menstruation. A tortuous Fertility and Sterility姞
course of the intramural part of the uterine tubes may protect women from a reflux of menstrual blood into the peritoneal cavity. When the reflux does in fact take place, altered endocrine and immune functions may promote implantation and development of endometriotic foci. The pathogenesis of endometriosis is multifactorial, and it should not be solely connected to the course of the intramural part of the uterine tubes. However, a diverse anatomy of uterine tubes in women with and without endometriosis gives another insight into the development 65
of the disease and raises questions about its complex origin. REFERENCES 1. Prentice A. Endometriosis. Br Med J 2001;323:93–5. 2. Redwine DB. Was Sampson wrong? Fertil Steril 2002;78:686 –93. 3. Meyer R. Uber den staude der frage der adenomyosites adenomyoma in allgemeinen und adenomyometitis sarcomatosa. Zentralbl Gynakol 1919;36:745–9. 4. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Obstet Gynecol 1927;4:422– 69. 5. Sampson JA. The development of the implantation theory for the origin of peritoneal endometriosis. Am J Obstet Gynecol 1940;40:549 –55. 6. Brosens IA, Puttemans PJ, Deprest J. The endoscopic localization of endometrial implants in the ovarian chocolate cyst. Fertil Steril 1994; 61:1034 – 8. 7. Hughesdon PE. The structure of endometrial cysts of the ovary. J Obstet Gynaecol Br Emp 1957;64:481–7. 8. Vercellini P, Aimi G, De Giorgi O, Maddalena S, Carinelli S, Crosignani PG. Is cystic ovarian endometriosis an asymmetric disease? Br J Obstet Gynaecol 1998;105:1018 –21. 9. Arumugam K, Lim JM. Menstrual characteristics associated with endometriosis. Br J Obstet Gynaecol 1997;104:948 –50. 10. Bahtiyar MO, Seli E, Oral E, Senturk LM, Zreik TG, Arici A. Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells. Hum Reprod 1998;13:3492–5. 11. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001;75:1–10. 12. Taylor RN, Lundeen SG, Giudice LC. Emerging role of genomics in endometriosis research. Fertil Steril 2002;78:694 – 8. 13. Vignali M, Infantino M, Matrone R, Chiodo I, Somigliana E, Busacca M, et al. Endometriosis: novel etiopathogenetic concepts and clinical perspectives Fertil Steril 2002;78:665–78. 14. Woodworth SH, Singh M, Yussman MA, Sanfilippo JS, Cook CL, Lincoln SR. A prospective study on the association between red hair color and endometriosis in infertile patients. Fertil Steril 1995;64: 651–2. 15. Wyshak G, Frisch RE. Red hair color, melanoma, and endometriosis: suggestive associations. Int J Dermatol 2000;39:798 – 802. 16. Hermstein A, Neustadt A. Intramural portion of the uterine tube. Z Geburtshilfe Gynakol 1924;88:431–5. 17. Rubin IC. Observation on the intramural and isthmic portion of the uterine tubes with special reference to so-called isthmospasm. Surg Gynecol Obstet 1928;4:87–90. 18. Sweeney WI. The intramural portion of the uterine tube—its gross anatomy course and length. Obstet Gynecol 1962;19:3–5. 19. Merchant RN, Prabhu SR, Chougale A. Uterotubal junction—morphology and clinical aspects. Int J Fertil 1983;28:199 –205. 20. Eddy CA, Pauerstein CJ. Anatomy and physiology of the uterine tube. Clin Obstet Gynecol 1980;23:1177–93. 21. Rocca M, el Habashy M, Nayel S, Madwar A. The intramural segment and the uterotubal junction: an anatomic and histologic study. Int J Gynaecol Obstet 1989;28:343–9. 22. Brokelmann J. Functional morphology of the uterine tube. Arch Gynecol Obstet 1989,245:391–5.
66
Rozewicki et al.
23. DeCherney AH. Anything you can do I can do better or differently! Fertil Steril 1987;48:374 – 6. 24. Fortier KJ, Haney AF. The pathologic spectrum of uterotubal junction obstruction. Obstet Gynecol 1985;65:93– 8. 25. Lisa JR, Gioia JD, Rubin IC. Observations on the intramural portion of the uterine tubes. Surg Gynecol Obstet 1954;92:159 – 69. 26. Sienkiewicz R, Róz˙ewicki S. Evaluation of combined administration of diazepam, fenoterol and metamizole in prevention of uterotubal spasm during hysterosalpingography. Ginekol Pol 1992;63:512– 4. 27. Tabibzadeh S. The signals and molecular pathways involved in human menstruation, a unique process of tissue destruction and remodeling. Mol Hum Reprod 1996;2:77–92. 28. Soules MR, Makinak LR, Bury R, Poindexter A. Endometriosis and anovulation: a coexisting problem in the infertile female. Am J Obstet Gynecol 1976;125:412–7. 29. Mc Artur JW, Ulfelder WH. The effect of pregnancy upon endometriosis. Obstet Gynecol Surv 1965;20:709 –33. 30. Braun DP, Dmowski WP. Endometriosis: abnormal endometrium and dysfunctional immune response. Curr Opin Obstet Gynecol 1998;10: 365–9. 31. De Placido G, Alviggi C, Di Palma G, Carravetta C, Matarese G, Landino G, et al. Serum concentrations of soluble human leukocyte class I antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions. Hum Reprod 1998;13:3206 –10. 32. Dmowski WP, Steele RW, Baker GF. Deficient cellular immunity in endometriosis. Am J Obstet Gynecol 1981;143:377– 83. 33. Muscato JJ, Haney AF, Weinberg JB. Sperm fagocitosis by human peritoneal macrophages: a possible cause on infertility in endometriosis. Am J Obstet Gynecol 1982;144:503–10. 34. Garcia-Velasco JA, Arici A, Zreik T, Naftolin F, Mor G. Macrophage derived growth factors modulate Fas ligand expression in cultured endometrial stromal cells: a role in endometriosis. Mol Hum Reprod 1999;5:642–50. 35. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 1984;64:151– 4. 36. Semino C, Semino A, Pietra G, Mingari MC, Barocci S, Venturini PL, et al. Role of major histocompatibility complex class I expression and natural killer–like T cells in the genetic control of endometriosis. Fertil Steril 1995;64:909 –16. 37. Somigliana E, Vigano P, Gaffuri B, Guarneri D, Busacca M, Vignali M. Human endometrial stromal cells as a source of soluble intercellular adhesion molecule (ICAM)-1 molecules. Hum Reprod 1996;11:1190 – 4. 38. Somigliana E, Vigano P, Vignali M. Endometriosis and unexplained recurrent spontaneous abortion: pathological states resulting from aberrant modulation of natural killer cell function? Hum Reprod Update 1999;5:41–52. 39. Gleicher N, El-Roeiy A. The reproductive autoimmune failure syndrome. Am J Obstet Gynecol 1988;159:223–7. 40. Kennedy SH, Starkey PM, Sargent IL, Hicks BR, Barlow DH. Antiendometrial antibodies in endometriosis measured by ELISA before and after treatment with danazol and nafarelin. Obstet Gynecol 1990;75: 914 – 8. 41. Hill JA. Immunology and endometriosis. Fertil Steril 1992;58:262– 4. 42. Surrey ES, Halme J. Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro. Am J Obstet Gynecol 1990;162:792–7.
Anatomy of uterine tubes and endometriosis
Vol. 84, No. 1, July 2005