Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy

OBJECTIVE: To estimate the risk of recurrence after administration of hormone replacement therapy (HRT) among women who have had endometriosis and who underwent bilateral salpingo-oophorectomy (BSO). DESIGN: Prospective randomized trial (115 women receiving HRT and 57 not receiving HRT). SETTING; Public university hospital. PATIENT(S): Women with a histologic diagnosis of endometriosis in whom BSO was performed; 91.8% had a total hysterectomy. INTERVENTION(S): Periodical clinical examination, vaginal ultrasound, and CA-125 levels; surgical evaluation and histologic study. MAIN OUTCOME MEASURE(S): Recurrence rate, prognostic factors, and a mean follow-up time of 45 months. RESULT(S): There was no recurrence among women who did not receive HRT, versus a 3.5% rate (4 out of 115), or 0.9% per year, in women who received HRT. Two recurrences required abdominal surgery. There was one additional patient who required surgery, but the relationship to the endometriosis recurrence was controversial. Among women receiving HRT, the following risk factors were detected: peritoneal involvement > 3 cm (2.4% recurrence per year vs. 0.3%) and incomplete surgery (22.2% per patient vs. 1.9%). CONCLUSION(S): Patients with a history of endometriosis in whom total hysterectomy and bilateral salpingo-oophorectomy have been performed have a low risk of recurrence when HRT is administered. In those patients, HRT is a reasonable option. However, in cases with peritoneal involvement > 3 cm, the recurrence rate makes HRT a controversial option; if HRT is indicated, it should be monitored closely.     

Combining the uterine depletion procedure and myomectomy may be useful for treating symptomatic fibroids

OBJECTIVE: To evaluate the therapeutic results of premyomectomy uterine depletion for the treatment of symptomatic fibroids, compared with myomectomy only. DESIGN: Controlled, clinical study without randomization. SETTING: University-affiliated tertiary referral center. PATIENT(S): Four hundred eighty-six women with symptomatic fibroids warranting surgical treatment and who wished to retain their uteri. INTERVENTION(S): Ligation of the uterine arteries was performed by either an abdominal or a laparoscopic approach before myomectomy. MAIN OUTCOME MEASURE(S): Operation time, intraoperative blood loss, postoperative improvement of symptoms, and recurrence rates of fibroids. RESULT(S): Of 342 women with pathology-confirmed fibroids who were included in the study, 108 received myomectomy only (group I), and 234 underwent the uterine depletion procedure followed by myomectomy (group II). Average blood loss was 250 +/- 132.5 mL for group I and 50 +/- 26.9 mL for group II. For patients with menorrhagia, 79 (84%) of 94 women in group I experienced complete resolution; all of the 194 women (100%) in group II had resolution within 2 months of surgery. The recurrence rate of ultrasound-confirmed fibroids was 19.4% (21 of 108) in group I and 0% in group II. Of the sexually active patients who were not using contraception, 50% (49 of 98) in group I and 37.5% (15 of 40) in group II had a live birth. CONCLUSION(S): This study demonstrates the value of uterine depletion before myomectomy for the management of patients with symptomatic fibroids. The procedure reduced blood loss during the operation, resulted in complete resolution of fibroid-related menorrhagia, and has the potential to prevent fibroid recurrence. Fertility capacity was apparently not compromised by this new treatment approach.     

A rare case of extrauterine adenosarcoma arising in endometriosis of the rectovaginal septum

OBJECTIVE: To present a rare case of endometrial stromal sarcoma arising in endometriosis of the rectovaginal septum. DESIGN: Case report. SETTING: Academic tertiary referral center for endometriosis treatment. PATIENT(S): A 50-year-old woman with a history of endometriosis presented with catamenial rectal pain and deep dyspareunia. Imaging findings suggested new endometriotic lesions in the rectovaginal space. INTERVENTION(S): Total hysterectomy, salpingo-oophorectomy, and excision of the lesion in the rectovaginal septum were performed. Although extemporary pathology confirmed endometriosis, the final histologic diagnosis was extrauterine adenosarcoma in the rectovaginal septum. Two years later, recurrence of the malignancy occurred and was treated by resecting the new perirectal mass. Subsequent radiotherapy and chemotherapy were administered. MAIN OUTCOME MEASURE(S): Imaging findings at follow-up evaluation. RESULT(S): The patient was in good health for 2 years after the initial surgery, when she developed a new lesion at the site of the previous resection. The histologic appearance of the lesion was consistent with recurrence of the tumor. After postoperative therapy, the patient is now without evidence of disease. CONCLUSION(S): Malignant transformation of endometriosis should be considered in the differential diagnosis of a new pelvic lesion in a patient with a history of endometriosis.     

Laparoscopic treatment of pelvic pain associated with minimal and mild endometriosis with use of the Helica Thermal Coagulator

OBJECTIVE: To investigate the clinical efficacy and safety of Helica Thermal Coagulator (TC) in the treatment of pelvic pain associated with minimal (stage I) and mild (stage II) endometriosis. DESIGN: A clinical observational study. SETTING: A referral center for laparoscopic treatment of endometriosis. PATIENT(S): Eighty-one women with pelvic pain symptoms associated with minimal and mild endometriosis diagnosed at laparoscopy. INTERVENTION(S): Helica TC to treat endometriotic lesions. The revised American Fertility Society (rAFS) classification was used to stage endometriosis. Pain symptoms and patient satisfaction were assessed subjectively at 3 and 6 months follow-up. MAIN OUTCOME MEASURE(S): Improvement or relief of pelvic pain symptoms, and intra- or postoperative complications. RESULT(S): A total of 79 women completed the study to 6 months follow-up. At 3 months, 59 (74.7%) women reported resolution and satisfactory improvement of symptoms, whereas 20 (25.3%) women continued to experience painful symptoms. At 6 months, 69 (87.4%) women reported resolution and satisfactory improvement of symptoms, whereas 9 (11.4%) women reported no changes and 1 (1.2%) woman experienced worsening symptoms. No significant differences were found between minimal and mild disease. No side effects or surgical complications occurred. CONCLUSION(S): Meaningful improvements and relief in clinical symptoms can be obtained with conservative laparoscopic surgery. Helica TC is a simple, effective, and safe device for the treatment of pelvic pain in women with stages I and II endometriosis. This approach requires further evaluation as part of randomized controlled trials.     

Peritoneal fluid inhibin during the menstrual cycle.

Serum and peritoneal fluid inhibin levels were measured by radioimmunoassay throughout the menstrual cycle in 14 women with endometriosis and in 16 controls. In controls, serum values (+/- standard error of the mean) increased from the early follicular phase (49.8 +/- 6.5 microLEq/mL) to the late follicular phase (178 +/- 37.8 microLEq/mL) and the luteal phase (346 +/- 98.3 microLEq/mL). Peritoneal fluid inhibin levels were several-fold higher than those in serum and reached a maximum value during the late follicular phase (early follicular: 2404 +/- 85 microLEq/mL, late follicular: 22,922 +/- 7145 microLEq/mL, luteal: 5195 +/- 1959 microLEq/mL). There was no difference in peritoneal fluid or serum inhibin concentrations between patients with and without endometriosis. These findings suggest that human gametes in the fallopian tube may be exposed to a very high concentration of inhibin. The lack of difference in inhibin concentrations between patients with and without endometriosis suggests that this hormone does not play a role in endometriosis-related infertility.     

Effect of clomiphene citrate on follicular and luteal phase luteinizing hormone concentrations in in vitro fertilization cycles stimulated with gonadotropins and gonadotropin-releasing hormone antagonist

OBJECTIVE: To investigate the effect that clomiphene citrate exerts on luteinizing hormone (LH) concentrations in gonadotropin/gonadotropin-releasing hormone (GnRH) antagonist cycles. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Two groups of patients undergoing in vitro fertilization (IVF) were compared. In group I, 20 patients were stimulated with clomiphene citrate (CC) in combination with gonadotropins and 0.25 mg of Cetrorelix (ASTA Medica AG; Frankfurt am Main, Germany) and in group II, 20 patients were stimulated with gonadotropins and 0.25 mg of Cetrorelix. INTERVENTION(S): Blood sampling was performed in the late follicular, periovulatory, early, mid, and late luteal phases. MAIN OUTCOME MEASURE(S): Luteinizing hormone (LH), estradiol, and progesterone. RESULT(S): LH levels were significantly higher in group I than in group II on all the days studied. Progesterone serum concentrations were significantly higher in group II in the early luteal phase, but not in the follicular or the middle and late luteal phases. CONCLUSION(S): LH concentrations are significantly higher in the follicular and luteal phases in cycles stimulated with CC, despite GnRH antagonist administration. This observation might have implications for the dose of GnRH antagonist needed to suppress LH in the follicular phase and questions the need for luteal-phase supplementation in cycles in which CC was used.     

Serum CA 125 measurements in the diagnosis of endometriosis recurrence

Seventy-one women underwent follow-up laparoscopy for persistent infertility six to 24 months after conservative treatment of endometriosis. The disease was staged according to the revised American Fertility Society classification of 1985. The serum CA 125 concentration was also measured in each patient to evaluate its efficacy in the diagnosis of endometriosis recurrence. The patients with stages I and II endometriosis had serum CA 125 levels not significantly higher than in the patients with negative findings, whereas those with stages III and IV endometriosis presented significantly higher levels (P less than .005 and P less than .001, respectively) than the disease-free women. The sensitivity of serum CA 125 measurements in the diagnosis of endometriosis recurrence was 14.8%, the specificity was 100%, and the predictive values of normal (less than 35 U/mL) and elevated levels were 27 and 100%, respectively. In some cases, serum CA 125 measurements may be used instead of follow-up laparoscopy, or to indicate when laparoscopy should be performed or postponed.     

Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis

OBJECTIVE: To determine the concentrations of interleukin-18 (IL-18) in peritoneal fluid and serum in patients with endometriosis in comparison with the control group. DESIGN: A prospective analytical study. SETTING: The obstetrics and gynecology department of an academic training hospital. PATIENT(S): Forty-four patients who underwent laparoscopic surgery for benign gynecologic diseases. INTERVENTION(S): Specimens of peripheral blood and peritoneal fluid were obtained before and during laparoscopic procedures, and the levels of IL-18 were analyzed. MAIN OUTCOME MEASURE(S): The concentrations of IL-18 in peritoneal fluid and serum were correlated with the presence of endometriosis, disease stage, and the phase of the menstrual cycle. RESULT(S): Interleukin-18 was detectable in 98% of the peritoneal specimens and 84% of the serum specimens of the patients tested. Peritoneal fluid IL-18 concentrations were statistically significantly lower in patients with endometriosis than in patients without endometriosis; the difference in serum IL-18 levels showed no statistically significant difference between the patients with and without endometriosis. The concentrations of IL-18 in peritoneal fluid and serum were not correlated with the stage of endometriosis or the phase of the menstrual cycle. CONCLUSION(S): Our results suggest that the decreased levels of IL-18 in peritoneal fluid in patients with endometriosis as compared with the control group may play an important role in the pathogenesis of this disease.     

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.     

Use of intraperitoneal interferon alpha-2b therapy after conservative surgery for endometriosis and postoperative medical treatment with depot gonadotropin-releasing hormone analog: a randomized clinical trial

OBJECTIVE: To evaluate the possible therapeutic effects of interferon alpha-2b left in the peritoneum after surgery, followed by or not followed by treatment with GnRH analogs. DESIGN: A prospective, randomized clinical trial. SETTING: University hospital. PATIENT(S): Fifty-two infertile patients with moderate or severe endometriosis. INTERVENTION(S): Laparotomic conservative surgery and either interferon alpha-2b or saline alone left in the pouch of Douglas followed by administration of either GnRH analogs depot or oral indomethacin with transvaginal echography and analysis of CA-125, immunoglobulins, and lymphocyte populations. MAIN OUTCOME MEASURE(S): Recurrence of endometriosis was considered clinically, echographically, and laparoscopically. RESULT(S): Recurrence of endometriosis in four cases without interferon (15.4%) versus 11 patients (42.3%) with interferon alpha-2b. Life table analysis showed significant differences between the groups with and without interferon 21 months after conservative surgery. There were no differences in the recurrence between the groups with or without GnRH analogs. Likewise, there were no significant changes in immunoglobulins and lymphocyte populations among patients with and without recurrence of endometriosis. The patients that received GnRH analogs depot showed a decrease in the number of CD16 and an increase of CD11b cells after treatment. CONCLUSION(S): The use of interferon alpha-2b within the peritoneal cavity after conservative surgery may be inappropriate because it increased later recurrence of endometriosis. The postoperative treatment with GnRH analogs did not significantly reduce the recurrence rate. Immunoglobulins and lymphocyte populations did not change in relation to the recurrence of endometriosis.     

Treatment of endometriosis associated infertility

During the last 13 years, 2,080 infertile patients were subjected to diagnostic laparoscopy. The mean age was 32.3 and their mean infertility period was 6.0 years. Of these, 1,263(60.7%) patients were diagnosed to have endometriosis: 587(46.5%) were stage I (R-AFS), 348(27.6%) were stage II, 184(14.6%) were stage III and 144(11.4%) were stage IV. The age and the infertility period were almost the same among the stage of the disease. The overall pregnancy rate was 34.6%, after minimum 2 month follow up. The presence of endometriosis did not affect the prognosis of infertility: 34.2% pregnancy rate for patients with endometriosis, and 35.3% for those without endometriosis. There was an inverse relationship between the stage of the disease and the subsequent pregnancy rate: 37.8% for stage I, 34.8% for stage II, 32.1% for stage III and 20.8% for stage IV. But statistical significant difference was observed only between stage I and II, and stage IV. To elucidate the mechanism of endometriosis associated infertility, peritoneal fluid volume, intratubal sperm transport (peritoneal sperm recovery test), and phagocytosis of sperm in the tube and in the peritoneal fluid were examined in more than 1,000 cases. However, no positive relationship was found between the disease and these parameters. Fimbrial microbiopsy also revealed that endometriosis did not affect the ciliation index of the fimbria, nor changed the fine surface structure. Patients with minimal-mild disease were first managed expectantly for one year after laparoscopy: The pregnancy rate was 36.1% for stage I, and 29.7% for stage II. Ninety-eight patients who failed to conceive by expectant management were put on danazol therapy (600 mg/day, for 6 months). However, the results were very disappointing. Of 44 patients with stage I disease, only 3(6.8%) achieved a pregnancy, and none of 54 stage II patients conceived so far. Moreover, second-look laparoscopy revealed that danazol had no effect on the eradication of minimal-mild endometriosis. The patients with stage I-II disease were then treated exclusively by electrocautery at the time of initial laparoscopy: The pregnancy rate was 30.8% (57/185) for stage I, and 23.8% (25/105) for stage II. At second-look laparoscopy, 45.5% (10/22) of stage I and 73.7% (14/19) of stage II were disease free or improved, although the pregnancy rate was not so good as expected.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prostaglandin F2 alpha in the peritoneal fluid of patients with endometriosis

The amounts of PGF2 alpha in peritoneal fluid were determined by radioimmunoassay in 21 patients undergoing exploratory laparotomy or diagnostic laparoscopy for infertility during the follicular phase of the cycle. Detectable levels of PGF2 alpha were found only in that group with moderate and severe endometriosis who also had blood-tinged or chocolate material in the peritoneal cavity. A patient with blood-tinged peritoneal fluid and pelvic adhesions without endometriosis also had elevated peritoneal fluid PGF2 alpha. In contrast, peritoneal fluid without evidence of old hemorrhage from patients with endometriosis or pelvic adhesions as well as from a group of normal women did not contain PGF2 alpha. None of the endometriosis patients had evidence of a short luteal phase by standard criteria.     

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis.     

Luteal rescue in in vitro fertilization-embryo transfer

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.     

Protein, progesterone, and protease inhibitors in uterine and peritoneal fluids of women with endometriosis

This study was undertaken to determine whether women with endometriosis have altered protein, progesterone (P), and protease inhibitor concentrations in their uterine fluid and peritoneal fluid (PF) compared with controls at different phases of the menstrual cycle. Uterine flushings (UFs), PF, and blood were obtained during the follicular and luteal phases of the cycle from 29 normal women and 16 women who were diagnosed as having endometriosis. Protein content in UF did not change significantly throughout the cycle in either group. However, PF protein in patients with endometriosis was significantly (P less than 0.05) higher than in controls during the luteal phase. Total UF P was significantly (P less than 0.05) reduced in women with endometriosis during the late luteal phase. During the early luteal phase, trypsin inhibitory activity in UF from normal women was significantly (P less than 0.05) higher than at any other phase of the cycle, whereas inhibitory activity in UF from patients with endometriosis remained relatively constant. Patients with endometriosis had significantly (P less than 0.05) higher total activity in PF during the early luteal phase than did controls. These results indicate that women suffering from endometriosis have significantly lower levels of P and less protease inhibitor within their uterine cavity during the luteal phase of the cycle, and significantly higher concentrations of protein and protease inhibitor in PF during the luteal phase.     

Symptom distribution among infertile and fertile endometriosis cases with different stages and localisations

OBJECTIVE: To evaluate endometriosis patients' symptoms and relate them to different stages and locations of endometriosis and also to fertility/infertility of the patients. STUDY DESIGN: Sixty-eight patients diagnosed with endometriosis constituted the population investigated in this cross-sectional observational study, 55 and 13 of whom were diagnosed from the visual findings recorded during laparoscopy and laparotomy, respectively. All cases were categorised as early- (stages I and II) or late (stages III and IV)-stage endometriosis and as fertile or infertile endometriosis. The extent of endometriosis was further divided into peritoneal, ovarian, and ovarian and peritoneal. Symptoms of dysmenorrhoea, deep dyspareunia, dyschesia and dysuria and also depressive mood state were analysed and compared among those different groups. RESULTS: Cyclic chronic pelvic pain was more relevant in late-stage endometriosis (P = 0.04). Deep dyspareunia, painful defecation, dysuria, infertility, and depressive state did not differ with stages of endometriosis or fertility status. Admission for pelvic pain of any duration was more prevalent among fertile patients with endometriosis (P = 0.008). Chronic noncyclic pelvic pain was more frequently observed in patients with fertile than in those with infertile endometriosis (P = 0.01). More cases in the fertile group experienced noncyclic pelvic pain (P = 0.04). More patients admitted with cyclic pelvic pain had ovarian or ovarian and peritoneal endometriosis than peritoneal endometriosis only (P = 0.03). Infertility was more prevalent among peritoneal endometriosis cases than among those with ovarian or peritoneal and ovarian involvement (P = 0.008). CONCLUSION: Symptoms of endometriosis may predict the stage and localisation of the disease to some extent.     

The importance of human chorionic gonadotropin support of the corpus luteum during human gonadotropin therapy in women with anovulatory infertility

One hundred ten women with anovulatory infertility (World Health Organization [WHO] group I n = 50, WHO group II n = 60) were given 341 treatment courses with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Additional hCG was given as single or repeated injections during the luteal phase in 205 ovulatory cycles. In WHO group I, the incidence of luteal phase defects was lower and the pregnancy rate higher in cycles with extra hCG administration during the luteal phase than in cycles with no extra hCG. In WHO group II, there was no such difference after supplemental hCG. The abortion rate was the same after cycles with or without extra hCG administration. It is suggested that during ovulation induction with hMG/hCG in anovulatory women with no evidence of endogenous estrogen activity, the luteal phase should be supplemented with additional hCG.     

Pentoxifylline therapy after laparoscopic surgery for different stages of endometriosis: a prospective, double-blind, randomized, placebo-controlled study

STUDY OBJECTIVE: To evaluate the effects of pentoxifylline administration on patients with different stages of endometriosis on whom laparoscopy was performed. DESIGN: Prospective, double-blind, randomized, placebo-controlled clinical (Canadian Task Force classification I). SETTING: University and private hospitals. PATIENTS: Eighty-eight women, all with infertility, some with dysmenorrhea, dyspareunia, or pelvic pain, on whom a laparoscopic diagnosis of endometriosis was made. INTERVENTIONS: The treatment group received 800 mg pentoxifylline daily for 6 months immediately after surgery. The control group received placebo capsules. All patients were followed-up for 1 year thereafter. MEASUREMENTS AND MAIN RESULTS: A comparison of pregnancy rate and recurrence of signs and symptoms in the 2 groups was performed. Forty-three patients were studied in the pentoxifylline group and 45 in the placebo group. The cumulative pregnancy rate was 39.5% and 35.6% in the treatment and control groups, respectively. The overall recurrence of signs and symptoms was 14% in the former group and 15.6% in the latter. There were no statistically significant differences between the 2 groups in rates of pregnancy and recurrence (p = .700 and .832, respectively). Nor was there any significant statistical difference between the same stages in the 2 groups regarding immunomodulation. CONCLUSIONS: According to the results of this study, and while keeping in mind that appropriate surgery is the main aspect of endometriosis treatment, there is no evidence that immunomodulation with pentoxifylline aids fertility or lessens recurrence of signs and symptoms in women with different stages of endometriosis (i.e., minimal, mild, moderate, or severe).     

Relationship between peritoneal cytology and prognosis in endometrial carcinomas

From 1971 to 1985, peritoneal cytologic examination was performed at the time of operation in 235 previously untreated patients with endometrial carcinoma. The relationship between the cytologic findings and prognoses by stage was investigated. The results were as follows: 1. In the peritoneal cytologic examination, 44 (18.7%) out of 235 cases were positive for cancer cells in all stages, 25 (14.5%) out of 173 cases in stage I, 7 (21.2%) out of 33 cases in stage II, and 8 (32.0%) out of 25 cases in stage III. 2. Among the 20 cases of stage I endometrial carcinoma that had no macroscopic metastasis and had positive peritoneal cytologic findings for cancer cells, 5- and 10-year cumulative survival rates were 94.7 and 94.7%, against 92.7% and 90.9% in cases with negative peritoneal cytology respectively. The recurrence rate in the same stage was 12.0% for positive cases, against 9.5% for negative cases. No significant differences between positive and negative cases were found. 3. In stages II and III, the difference between the survival rates for 9 cases which have positive peritoneal cytology without macroscopic peritoneal metastasis and 47 cases with negative peritoneal cytology were not statistically significant. 4. In endometrial carcinoma without macroscopic peritoneal metastasis, the appearance of cancer cells in peritoneal cytologic examination is not correlated with the prognosis.     

Increased expression of endoglin in the eutopic endometrium of women with endometriosis.

OBJECTIVE: To compare the angiogenic activities of endothelial cells in the eutopic endometrium of women with and without endometriosis. DESIGN: Vessels with active angiogenesis were identified using the monoclonal antibody to endoglin. SETTING: University department of obstetrics and gynecology. PATIENT(S): Twenty women with histologically confirmed endometriosis after laparotomy or laparoscopy. Women with carcinoma in situ of uterine cervix, but no evidence of endometriosis (n = 20), served as control subjects. INTERVENTION(S): Formalin-fixed, paraffin-embedded archival tissues were sectioned and stained. MAIN OUTCOME MEASURE(S): Number of vessels stained with monoclonal antibody to endoglin. RESULT(S): For all menstrual phases, the mean number of vessels with endoglin expression was significantly greater in patients with endometriosis compared with control subjects. In each menstrual phase, a significant difference was observed only during the late secretory phase. Within the group with endometriosis, the mean numbers of vessels with endoglin expression in stages I and II were not different from the numbers in stages III and IV. CONCLUSION(S): This study shows the expression of endoglin in the eutopic endometrium of women with endometriosis is significantly increased and the increase is observed only in the late secretory phase. It is suggested from these findings that activation of angiogenesis in the eutopic endometrium might be a key factor in the pathogenesis of endometriosis.