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An approach to endometriosis with infertility.

Owing to the lack of an ideal treatment for endometriosis when fertility must be preserved, there are differences of opinion between those in favour of a mainly surgical approach to therapy, those favouring expectant management of the disease's less severe forms and those who prefer an active medical approach. Such controversy has made endometriosis a constantly reviewed subject. According to the figures published in the medical literature regarding different treatment strategies for improving fertility in endometriosis cases, none of them shows any clear advantage over the next. Apparently, in minimal endometriosis, the expectation and correction of associated factors should produce identical results to any other therapy. Severe endometriosis should be treated surgically, since no response can be expected from medical therapy. Discussion on the best way to proceed arises in moderate endometriosis. The selection of the clinical treatment should be individualised with regard to the patient's condition: age, length of infertility, degree of severity of the condition, the patient's wishes and the surgical risks involved.

Endometriosis↗

Evaluation of the correlation between endometriosis extent, age of the patients and associated symptomatology.

Two-hundred-and-six patients newly diagnosed to have endometriosis at laparoscopy were evaluated in order to see if endometriosis-associated symptoms are proportional to the extent of the disease, as assessed using the Revised American Fertility Society Classification, and if the extent worsens with age. At hospital admission 81% of the patients complained of dysmenorrhea, 54% of chronic pelvic pain and 27% of dyspareunia. At laparoscopy, 39% of the patients had stage I endometriosis, 13% stage II, 35% stage III and 13% stage IV. At statistical analysis, no significant differences were found in total endometriosis scores, in active scores or in adhesion scores in different age groups. Although a difference in prevalence rate for dysmenorrhea and dyspareunia stage I versus III was found, a trend of increasing severity of symptoms with more widespread disease was not evident. There was not a significant difference in prevalence rate of symptoms for different aspects of endometriosis (implants, cysts or adhesions). Our data show that the American Fertility Society classification does not reflect the intensity of endometriosis-associated symptoms, probably underestimating the most active forms of this disease, and does not allow to follow a possible natural progression of the disease.

Abdominal Pain↗

Radiation-induced endometriosis in Macaca mulatta.

Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.

Animals↗

Endometriosis of the terminal ileum simulating the clinical, roentgenographic, and surgical findings in Crohn's disease.

A 38-yr-old nulliparous female presented with endometriosis of the terminal ileum which mimicked the clinical, roentgenographic, and surgical findings of Crohn's disease. The patient presented with diarrhea, right lower quadrant pain, fever, and significant weight loss. At surgery, the terminal ileum was inflamed, indurated, thickened, and angulated. Ileal endometriosis may be expected to simulate Crohn's disease, because intestinal endometriosis frequently produces local bowel inflammation, adhesions, stricture, and angulation. Ileal endometriosis should be carefully considered in the differential diagnosis of Crohn's disease in menstruating females who are nulliparous and have dysmenorrhea, dyspareunia, dyschezia, menometrorrhagia, or other perimenstrual symptoms. It is important not to mistake endometriosis for Crohn's disease because endometriosis has a different therapy.

Adult↗

[Autoimmune reaction factors of infertility in patients with endometriosis].

The presence of immunoprotein depositions in endometrium and antiendometrial autoantibodies in serum was detected in 59 infertile patients with endometriosis, 45 infertile patients without endometriosis and 11 fertile women by the methods of immunohistochemistry determination and immunodiffusion assay. The immunoprotein depositions in endometrium of endometriosis were significantly increased. The antiendometrial auto-antibodies in serum were positive in 32.2% for infertile patients with endometriosis, 6.7% for infertile patients without endometriosis and 0% for fertile women. This suggested that an autoimmune response might be an etiologic factor of infertility in patients with endometriosis.

Adult↗

[Achromatic endometriosis].

Eleven patients with infertility of unknown cause and symptomatology suggestive of endometriosis were studied at the INPer. México from June 1, 1986 to December 15th, 1986. All these patients were subjected to a diagnostic laparoscopy, in 7/11 cases there were peritoneal lesions which were not classical of endometriosis in 2/11 there were typical endometriosical lesions and in the other 2/11 there was no evidence of lesion. Biopsies of nonpigmented endometriosis were obtained and in 7/11 endometriosis without hemosiderin were reported; in 2/11 endometriosis with hemosiderin and finally in 2/11 just an inflammatory process. We believe that the diagnosis of nonpigmented endometriosis must be suspected in all those patients with infertility of unknown cause who display endometriosic symptoms. When reorganizing nonpigmented lesions with histological evidence one must institute endometriosic therapy which will promote integral management of the problem: from the reproductive symptomatic aspects.

Adult↗

[Occult and minimal forms of endometriosis: therapeutic strategies].

The hidden forms of endometriosis, especially the microscopic or non visible endometriosis, are entities presenting difficult problems for the diagnosis and sometimes the selection of a treatment; non visible endometriosis seems to be more of an interesting theoretical concept as long as its existence and clinical significance will not have been better documented and confirmed. Minimal endometriosis (Stage I of the AFS-1985 classification) is frequent in infertility cases and its incidence is probably underestimated because of atypical aspects better known today. Its relationship with infertility still seems hypothetical, even if new data seem to implicate it to a greater degree. Numerous disorders have been found to explain the harmful effect of endometriosis on sterility. All the usual means of treatment of endometriosis may be selected; however, coelioscopic destruction at the time of the diagnosis seems most appropriate in case of pain or infertility; in the latter group, secondarily, a short medical treatment may be used before resorting to Fertilization in vitro of GIFT, which will be preferred if the patient is older and there is a long history of infertility.

Adult↗

Comparison of ultrastructure adenomyotic glandular epithelium with that of attached epithelium of inner wall of chocolate cyst, with particular reference to histogenesis of endometriosis.

Clinically we rather frequently treat infertile women with endometriosis, either external or internal. Nowadays the study of the histogenesis of endometriosis is urgently required by patients who suffer from sterility because of endometriotic foci. To evaluate the histogenesis of endometriosis, we first electron microscopically examined the adenomyotic glandular epithelium as a distinct candidate for endometriosis interna. Furthermore we studied the chocolate cyst of the ovary as representative of endometriosis externa which is very important from the standpoint of the infertility clinic. In this report we carefully compared the ultrastructure of the adenomyosis with the ovarian chocolate cyst, and endeavoured to explore the histogenesis of endometriosis through this ultrastructural comparison. As a result it was found that the nuclear membrane showed tremendous irregularity in the ovarian chocolate cyst compared with the smooth nuclear membrane in the adenomyotic glandular epithelium.

Endometriosis↗

Endometrial autoantigens eliciting immunoglobulin (Ig)G, IgA, and IgM responses in endometriosis.

Endometrial antigens from patients with endometriosis and fertile controls were tested against immunoglobulin (Ig)G, IgA, or IgM in endometrium, serum, and peritoneal fluid (PF) of the patients and controls by Western blot analysis. Endogenous IgG was detected in 78% of the endometria or endometriosis implants from the patients and 22% of the endometria from the controls. Endometrial IgA and IgM were detected in few controls and patients. Immunoglobulin G in the serum and/or PF of patients with endometriosis was specifically directed against antigens with molecular weights of 34, 42, 82, 94, 110, 120, and 140 kd found in the patients' endometrium or endometriosis implants. Immunoglobulin A and IgM in the serum or PF of the patients and controls were nonspecific in their reactivity. Endometrial antigens found in endometrium or implants of patients with endometriosis, and eliciting IgG responses, may be relevant to autoimmunity in endometriosis.

Adult↗

Etiology and histogenesis of endometriosis.

Based on the available scientific evidence, the mechanism of developing endometriosis appears to be transplantation of viable endometrial cell fragments shed during menses and regurgitated through the fallopian tubes under the influence of prostaglandin-mediated uterine contractions. As all women apparently retrograde menstruate to some extent, it is not surprising that circumstances which increase the total number of menstrual days experienced have been clinically associated with endometriosis. Similarly, factors which lead to relative uterine outflow obstruction have been associated with a higher incidence of endometriosis. There is virtually no other scientific evidence supporting alternate mechanisms of development of endometriosis. There are many unanswered questions regarding endometriosis including: 1) Are all women equally susceptible to development of the disease? 2) As the clinical presentation and course is extremely variable, what factors influence these events? 3) Does medical suppression of ovulation with oral contraceptives or continuous progestins provide a protective effect? 4) Are there systemic immunologic changes associated with endometriosis? Hopefully, this manuscript will help stimulate the next generation of clinical investigators to address these questions, as they are of paramount importance with this apparently increasingly devastating and frequent clinical disease.

Endometriosis↗

[Studies on endocrine therapy of endometriosis].

GnRH agonist and synthetic steroid such as Danazol, Medroxyprogesterone acetate (MPA) and Gestrinone are useful for the treatment of patients with endometriosis. These compounds induce atrophy and regression of endometriotic tissue, but the action mechanisms are still unclear. The present study, therefore, was undertaken to elucidate the mechanisms of these compounds in the treatment of endometriosis. In addition, a combination therapy with these compounds for endometriosis was also evaluated with an experimental animal model. Effects of GnRH agonist, Danazol and GnRH/Danazol combination on experimental endometriosis were evaluated in female rats. Endometrium autotransplanted under the renal capsule markedly decreased in size following castration. Histologic examination indicated atrophy and regression of the endometrial explant. The changes of endometrial explant were also induced by GnRH agonist, Danazol and combination treatment. However, a combination therapy with GnRH agonist and Danazol (93%) was shown to be superior to GnRH agonist (65%) and Danazol alone (45%) to induce atrophy and regression of experimental endometriosis. As expected, GnRH agonist significantly decreased serum E2, but Danazol did not at all. It is suggested that a combination therapy with GnRH agonist and Danazol may be a potential modality in the treatment of endometriosis. In order to evaluate whether Danazol, MPA, and Gestrinone has a direct inhibitory effect to synthesize estrogen, immature female rats were hypophysectomized and the ovaries were stimulated by a daily PMS injection. Administration of Danazol to the rats for two weeks stimulated the synthesis of 17, 20-lyase, 17 beta-HSD and aromatase activity, but did not inhibit any enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coitus during menses. Its effect on endometriosis and pelvic inflammatory disease.

Four hundred ninety-eight consecutive new female patients in a private obstetrics-gynecology practice were asked about their coital habits during menses (SxMs/F = frequent, SxMs/O = occasional, SxMs/N = never) and history of pelvic inflammatory disease (PID). Endometriosis and tubal infertility factor were diagnosed on laparoscopy or laparotomy. The frequency of endometriosis was higher (P less than .05) in patients with coitus during menses (SxMs/F + O) (17.5%) than in the SxMs/N group (10.9%). The frequency of PID was not different between the SxMs/F + O (10.8%) and SxMs/N (9.7%) groups. Thirty-five percent of the infertility patients had a tubal infertility factor. The frequency of tubal infertility factors was higher in the PID group (78.4%) than in the non-PID group (30.4%) (P less than .001). Endometriosis was associated with an increase in tubal infertility factors (47.9% vs. 33.3% in the nonendometriosis group) but to a lesser degree than PID. The frequency of PID in the group with a tubal infertility factor was higher (22.7% vs. no tubal factor, 3.4%) (P less than .001), and the frequency of endometriosis was higher in the group with a tubal infertility factor (19.3% vs. no tubal factor, 11.5%) (P less than .05). Coitus during menses appeared to increase the chances of endometriosis but not of PID. The rate of tubal infertility factors increased in both PID and endometriosis.

Adult↗

Pathogenesis, diagnosis and treatment of genital endometriosis.

The etiology of genital endometriosis remains unclear, but it is evident that persisting endometriotic foci are stimulated by ovarian steroid hormones. Many cases are treated by surgery either via laparotomy or pelviscopy. Endocrine treatments with testosterone, gestagens, danazol and gestrinone have also been used to some effect. Recently developed analogs of gonadotropin-releasing hormone (GnRH) have demonstrated the high binding capacities of receptors involved in the down-regulation of the normal cycle which result in atrophy of the endometrium. These agents could therefore be used in the treatment of endometriosis. To date, 924 patients with pelvic endometriosis have been treated in our department with conventional endocrine therapies, 40 patients were treated with buserelin (D-Ser (Bu)6 luteinizing hormone-releasing hormone monopeptide-ethylamide), 900 micrograms/day intranasally, and 50 patients with goserelin depot, a GnRH analog of D-Ser (Bu)6- Azegly10-GnRH, with depot applications (3.6 mg per 4 weeks). The stage of development of endometriosis was determined using the endoscopic endometriosis classification prior to and after endocrine treatment. A complete check of the pelvis was carried out each time and a careful revision of the endometriotic foci undertaken. Endocrine treatment of endometriosis allowed 60% of previously sterile patients to become pregnant. Ovarian function in these patients was normal. The analogs proved to be clinically effective, safe and were well tolerated. Gestrinone proved to be the endocrine treatment of preference.

Endometriosis↗

Epidemiology of endometriosis-associated infertility.

To explain the great discrepancy between the prevalence estimates for endometriosis in the literature, a series of operations was studied from a combined patient population derived from a 21-physician collaborative. The reported discrepancy appears to have to do more with operative indications and technique than with an actual increase in the prevalence of endometriosis over time. The least-biased estimate for the overall prevalence of endometriosis in reproductive-age women is about 10% on the basis of a study of women operated on for symptoms other than those associated with endometriosis. Accepted criteria for causality applied to the endometriosis literature failed to demonstrate an association between endometriosis and infertility.

Endometriosis↗

[Hysterosalpingographic aspects of ovarian and peritoneal endometriosis. Case-control study].

A clustering of radiologic signs is associated with the presence of ovarian and/or peritoneal endometriosis: some indicate fibrosis of utero-sacral ligaments (isthmic dissection of the uterus, fixed retroversion); others are linked to pathology of the tube (ampullar retention of dye after evacuation, sometimes inducing false aspects of hydrosalpinx); the last ones suggesting peritoneal adhesions (incomplete peritoneal diffusion). All these signs have been systematically studied, independently of the diagnosis, on 154 hysterosalpingograms of infertile patients known to have patent tubes at laparoscopy: in 107 out of these cases endometriosis was diagnosed at laparoscopy; the 47 last cases constituted the control group. The results confirm that all the signs described are significantly more frequent in cases of endometriosis, although non-specific for this condition. On the contrary, neither adenomyosis, tubal diverticulosis, nor intramural polyps are significantly linked to external endometriosis. In conclusion, some radiologic signs suggest the presence of peritoneo-ovarian endometriosis. Their detection is possible only on high quality pictures, including a last one taken after 10 to 20 minutes walking, to feature the anomalies of tubal evacuation and peritoneal diffusion. The clustering of these signs allows the clinician to propose an early laparoscopy in the work-up of an infertility case. Furthermore, some of these salpingograms provide evidence of a functional disorder of tubal motility in endometriosis, possibly responsible for the low fertility associated with the disease.

Endometriosis↗

Steroidal regulation of endometriosis tissue: lack of induction of 17 beta-hydroxysteroid dehydrogenase activity by progesterone, medroxyprogesterone acetate, or danazol.

Cytosol and nuclear estrogen receptors were detected in 73% and 89% of untreated endometriosis specimens, respectively. The corresponding figures for cytosol and nuclear progestin receptors were 94% and 100%, respectively. Compared with the endometrium, the concentrations in endometriosis tissue were low. The anatomic site, the severity of the disease, and the phase of the menstrual cycle had no significant influence on receptor concentrations in endometriosis tissue. The activities of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not increase during the luteal phase. Danazol for 1, 3, 7 to 11, and 18 to 30 days, or medroxyprogesterone acetate for 5 days, had no effect on receptor concentrations or 17 beta-HSD activity in endometriosis tissue. The frequent presence of the receptors suggests that endometriosis lesions are under the control of steroid hormones. The lack of effect by progesterone and progestins on 17 beta-HSD shows that this regulation is different in endometriosis tissue and in the endometrium.

17-Hydroxysteroid Dehydrogenases↗

[Usefulness of measurement of serum CA125 levels in diagnosing and treating endometriosis].

We investigated the usefulness of the measurement of serum CA125 levels for the diagnosis and therapeutic monitoring of endometriosis. An additional study concentrated on the production of CA125. 1. Elevated levels of serum CA125 were noted in 52 of 66 patients with endometriosis in which the positive rate was 78.8% and mean was 119.8 U/ml. The mean value and positive rate of serum CA125 levels in patients with adenomyosis were higher than those in pelvic endometriosis. 2. The correlation between preoperative serum CA125 levels and the extracted tissue weight was statistically significant. The tissue concentration of CA125 of adenomyosis was 1,479.3 +/- 1,087.1 U/g and that of pelvic endometriosis was 309.7 +/- 23.1 U/g wet weight. 3. The serum CA125 levels in patients with adenomyosis fell postoperatively, and all were below 35 U/ml within two weeks. The serum CA125 levels were below 35 U/ml in 13 out of 15 patients (86.7%) with pelvic endometriosis treated with danazol and the change in the serum CA125 levels was closely related to the clinical course. 4. Clinicopathological states with a high level of serum CA125 were observed in patients with normal and ectopic pregnancy, puerperium, ovarian hyperstimulation syndrome (OHSS) and peritonitis. It was concluded that the measurement of serum CA125 levels was useful in the diagnosis and therapeutic monitoring of endometriosis, and CA125 might be produced and/or secreted not only from the endometrium but also from the peritoneum.

Antigens, Neoplasm↗

Variable effects of danazol on endometriosis at 4 low-dose levels.

Danazol was administered in a daily dose of 100, 200, 400, or 600 mg for 6 months in a double-blind fashion to 27 women with pelvic endometriosis. Symptoms and pelvic findings were observed and recorded monthly. Laparoscopy and laparoscopic biopsies were performed before and on the last day of treatment to evaluate the extent of endometriosis and the effect of the drug. The findings were documented with drawings and photography. The degree of clinical improvement varied with the daily dose used, from just over 50% on a regimen of 100 mg/day to 83% on a regimen of 600 mg/day. Laparoscopic improvement in the extent of endometriosis was noted in all patients but residual disease was common. The degree of laparoscopic improvement appeared to be related to the dose of danazol and to the effect of the drug on the menstrual cycle. The highest, 81%, laparoscopic improvement was observed in patients who developed amenorrhea during the study. After the completion of treatment, 6 patients required operation for residual endometriosis or for its early recurrence. The recurrence of endometriosis during 24 months of follow-up was observed in 29% of patients. Six of 15 infertile patients conceived spontaneously within 6 months after treatment in spite of mild (5) or moderate (1) residual disease. There was no difference in the extent of endometriosis between infertile patients who did or did not conceive. There was, however, a statistically significant difference in the adhesion score between these 2 groups. The authors conclude that danazol may be less effective in doses lower than the standard 800 mg/day. However, downward adjustment of the individual dose may be attempted on the basis of the development of amenorrhea and clinical improvement.

Adolescent↗