Nasir Rana

Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis

OBJECTIVE To evaluate basal (constitutive) and stimulated synthesis of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-8, IL-10 by peritoneal macrophages (PM) in women with endometriosis. DESIGN Peritoneal macrophages were cultured in the presence or absence of lipopolysaccharide (LPS) for 24 hours. Peritoneal fluids (PF) and PM supernatants were assayed for cytokines using ELISA. SETTING Institute for the Study and Treatment of Endometriosis and university-based research laboratories. SUBJECTS Fertile controls undergoing tubal ligation (n = 8) and women with endometriosis (n = 17). INTERVENTION Peritoneal fluid samples were obtained at the time of diagnostic laparoscopy (endometriosis group) or laparoscopy for tubal ligation; both were performed in the midluteal phase of the cycle. RESULTS Both basal and LPS stimulated production of TNF alpha, IL-8, and IL-10 by the PM were elevated significantly in women with endometriosis as compared with the fertile controls. CONCLUSIONS This study demonstrated that cytokines TNF alpha, IL-8, and IL-10 are synthesized at greater than normal levels by basal and stimulated PM from women with endometriosis. The levels of TNF alpha and IL-8 correlated with the levels in the PF, suggesting that PM are the principal source of these cytokines in the PF.

Spontaneous Apoptosis of Endometrial Tissue is Impaired in Women with Endometriosis

OBJECTIVE To evaluate spontaneous apoptosis in single-cell suspensions of eutopic and ectopic endometrium from women with endometriosis and in eutopic endometrium from fertile controls without endometriosis. DESIGN Paired specimens of eutopic and ectopic endometrial tissue from patients with endometriosis and eutopic endometrium from controls were assessed for spontaneous apoptosis. SETTING Institute for the Study and Treatment of Endometriosis and university-based research laboratories. PATIENT(S) Fertile controls (n = 10) and women with untreated endometriosis (n = 16). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Spontaneous apoptosis assessed with an ELISA-based cell death detection kit. RESULT(S) Spontaneous apoptosis (monitored by absorbance) of eutopic endometrium from patients with endometriosis and fertile controls was 0.63 +/- 0.1 and 1.43 +/- 0.11, respectively. Among patients with endometriosis, spontaneous apoptosis of ectopic endometrium was 0.26 +/- 0.06. Decreased apoptosis of ectopic versus eutopic endometrium was observed independent of cycle phase. CONCLUSION(S) The susceptibility of endometrial tissue to spontaneous apoptosis is significantly lower in women with endometriosis than in fertile controls. We suggest that decreased susceptibility of endometrial tissue to apoptosis contributes to the etiology or pathogenesis of endometriosis.

Open laparoscopy: 29-year experience.

Objective To describe the safety and efficacy of open laparoscopy as a method of access to the abdominal cavity for laparoscopic surgery. Methods We reviewed retrospectively all cases of open laparoscopy we did between August 1970 and June 1999. Results Twenty-seven (0.5%) of 5284 patients who had open laparoscopies during the study years developed complications related to primary access. Twenty-one had minor wound infections, four had minor hematomas, one developed an umbilical hernia that required reoperation, and one had an inadvertent injury to the small bowel that was repaired intraoperatively without adverse outcome. Access to the abdominal cavity was generally secured in 3–10 minutes. Conclusion Open laparoscopy was associated with no method failure or life-threatening complications. Minor and medium risk complications occurred at a rate of 0.5%. Open laparoscopy is a safe, effective method of accessing the abdominal cavity.

The development of cytotoxicity in peritoneal macrophages from women with endometriosis

OBJECTIVE To assess the activation status of peritoneal macrophages from women with endometriosis. DESIGN Peritoneal macrophages from patients undergoing laparoscopy were tested for cytotoxic activity against a cultured hepatoma cell line. SETTING Patients were tested at initial laparoscopy or at the completion of therapy. PATIENTS AND PARTICIPANTS Fertile controls (n = 27), infertile controls (n = 20), untreated endometriosis (n = 43), danazol-treated endometriosis (n = 22), and gonadotropin-releasing hormone agonist (GnRH-a)-treated endometriosis (n = 13) were tested. INTERVENTIONS Danazol (800 mg/d) or GnRH-a therapy for 6 months. RESULTS Cytotoxicity was elevated in stage I and II endometriosis (P less than 0.02) and in infertile controls (P less than 0.05) compared with fertile controls. Cytotoxicity in stage III and IV endometriosis was lower (P less than 0.02) than in stage I and II endometriosis. Indomethacin in vitro increased cytotoxicity (P less than 0.05) in stage III and IV endometriosis but not in the other groups tested. Cytotoxicity in danazol or GnRH-a-treated patients was increased (P less than 0.05 or greater) compared with untreated patients with comparable stage of disease. CONCLUSIONS Peritoneal macrophage cytotoxicity in women with endometriosis is affected by (1) the extent of endometriosis, (2) prostaglandin metabolism, and (3) treatment with danazol or GnRH-a.

Monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis * †

OBJECTIVE To investigate the capacity of monocytes from women with endometriosis to influence endometrial cell proliferation. DESIGN Uterine endometrial cells were cultured in the presence and absence of autologous blood monocytes for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING Patients were tested at initial presentation for evaluation of infertility and/or endometriosis. PATIENTS, PARTICIPANTS Fertile controls, n = 17; infertile controls, n = 9; untreated endometriosis, n = 29. INTERVENTIONS None. RESULTS Endometrial cell proliferation was enhanced significantly by blood monocytes in patients with endometriosis but was suppressed significantly by blood monocytes in fertile controls. Endometrial cell proliferation was not affected significantly by blood monocytes in infertile controls analyzed as a group, but a subset of infertile patients also showed enhancement of endometrial cell proliferation by blood monocytes. CONCLUSIONS Blood monocytes from patients with endometriosis and a subset of patients with unexplained infertility enhance autologous endometrial cell proliferation, whereas blood monocytes from fertile patients suppress endometrial cell proliferation. The capacity of monocytes to enhance endometrial cell proliferation appears to require both monocyte-derived factors that stimulate endometrial cell proliferation and endometrial cells capable of responding to those stimulatory factors. If either of these factors is absent, monocytes either suppress or have no effect on endometrial cell proliferation.

Cycle-specific and cumulative fecundity in patients with endometriosis who are undergoing controlled ovarian hyperstimulation-intrauterine insemination or in vitro fertilization-embryo transfer

OBJECTIVE To compare controlled ovarian hyperstimulation-intrauterine insemination (COH-IUI) or IVF-ET pregnancy rates per cycle (PR) and cycle and cumulative fecundity (f and cf) with COH-IUI or IVF-ET in endometriosis. DESIGN Retrospective analysis. SETTING Endometriosis research institute. PATIENT(S) Women with endometriosis and infertility (n = 313) who underwent consecutive COH-IUI (202 patients, 648 cycles), IVF-ET (111 patients, 139 cycles), or IVF-ET after failed COH-IUI (56 patients, 68 cycles). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Crude PR and life table-estimated f and cf. RESULT(S) With COH-IUI, 69 patients conceived; 65 conceived with IVF-ET; and 30 conceived with IVF-ET after COH-IUI (PR 11%, 47%, and 44%). With COH-IUI, six-cycle cf was 41%, and f for cycles 1-6 was 15%, 12%, 8%, 7%, 7%, and 0. With IVF-ET, three-cycle cf was 73%, whereas f for cycles 1-3 was 47%, 27%, and 33%. First-cycle f with IVF-ET was significantly higher than cf of six COH-IUI cycles. When the data were stratified according to the stage of endometriosis and womens age, the benefit of IVF over COH was even more pronounced. Prior COH-IUI failure did not adversely affect IVF-ET outcome. CONCLUSION(S) In endometriosis, PR, f, and cf are significantly higher with IVF-ET than COH-IUI, especially in stage IV and in women >38 years of age. Considering adverse effects of prolonged ovarian stimulation on endometriosis, IVF-ET should be the first-line approach in the management of infertility in this disease. If COH-IUI is attempted, it should not exceed three to four cycles.

Relationship between apoptosis and the number of macrophages in eutopic endometrium from women with and without endometriosis

OBJECTIVE To investigate the relationship between apoptotic cells and macrophages in the eutopic endometrium of women with and without endometriosis. DESIGN Retrospective analysis of archival uterine endometrial biopsy specimens. SETTING Institute for the Study and Treatment of Endometriosis, and university-based pathology and research laboratories. PATIENT(S) Fifty-one women with endometriosis and 24 healthy control subjects without endometriosis. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The number of TUNEL+ (terminal deoxynucleotide transferase [TdT]-mediated deoxyuridine triphospate [dUTP] nick end-labeling-positive) (apoptotic) cells and CD68+ (CD68 positive) (macrophages). RESULT(S) Apoptotic cells and macrophage numbers were positively correlated in the eutopic endometrium of women with and without endometriosis. However, the number of apoptotic cells and the macrophage content in the endometrium of women with endometriosis was significantly reduced compared with that of healthy control subjects without endometriosis. Differences between apoptosis and macrophage numbers between the two populations were observed predominantly during the early proliferative phase of the menstrual cycle. CONCLUSION(S) The reduction in apoptosis described for endometrial cells in women with endometriosis may be related to reduced macrophage trafficking into the eutopic endomtrium during the early-proliferative phase of the menstrual cycle.

Experience with laparoscopic hysterectomy

We conducted laparoscopic hysterectomy on 62 consecutive patients; 12 had laparoscopically assisted vaginal hysterectomy (LAVH), 16 had total laparoscopic hysterectomy (TLH), and 34 had supracervical laparoscopic hysterectomy (SLH). The groups were comparable with regard to age, weight, history of abdominal surgery, number of additional procedures performed, and weight of specimens; 74% had previous abdominal surgery, and 69% had additional procedures at hysterectomy. The mean estimated blood loss associated with LAVH was 2.5 times greater than that with TLH and 3 times greater than with SLH. The length of surgery was influenced by patient selection, surgeons experience, and equipment malfunction, with a mean of 213 minutes for LAVH, 244 for TLH, and 212 for SLH. The mean hospital stay for LAVH was 1.9 days and less than 1 day for TLH and SLH. There were nine total complications in the series (15%). Twelve (19%) of the specimens showed no abnormalities on pathologic examination. Total and supracervical laparoscopic hysterectomy and LAVH are appropriate operations for selected patients and compare favorably with standard abdominal or vaginal hysterectomy. The procedures demand sophisticated instrumentation and a dedicated endoscopy team to ensure safe and efficient performance.

Cytolysis of Eutopic and Ectopic Endometrial Cells by Peripheral Blood Monocytes and Peritoneal Macrophages in Women with Endometriosis

OBJECTIVE To compare the ability of peripheral blood monocytes (PBM) and peritoneal macrophages (PM) to mediate the in vitro cytolysis of endometrial cells from eutopic and ectopic endometrium in women with endometriosis. DESIGN Prospective study of immune function. SETTING Institute for the Study and Treatment of Endometriosis and university-based research laboratories. PATIENT(S) Twenty-four women with endometriosis (15 in stage I/II, 9 in stage III/IV) and 4 patients treated with GnRH agonists. INTERVENTION(S) Peritoneal fluid and peripheral blood were sampled and eutopic and ectopic endometrium were biopsied during diagnostic laparoscopy. MAIN OUTCOME MEASURE(S) Lysis of autologous endometrial cells. RESULT(S) Peripheral blood monocytes were significantly more cytolytic than peritoneal macrophages against autologous uterine endometrial cells. However, PBM and PM displayed a similar degree of cytolysis against a hepatoma cell line. Ectopic endometrial cells were significantly more resistant to cytolysis by autologous PBMC than were matched eutopic endometrial cells, and were completely resistant to cytolysis by autologous PM. CONCLUSION(S) The reduced capacity of PM from women with endometriosis to mediate the destruction of endometrial cells coupled with the increased resistance of ectopic endometrial cells to macrophage-mediated cytolysis may facilitate the survival of these cells within the peritoneal cavity of women with endometriosis.

Ovarian remnant syndrome after laparoscopic hysterectomy and bilateral salpingo-oophorectomy for severe pelvic endometriosis

Ovarian remnant syndrome is a rare complication of total abdominal hysterectomy and bilateral salpingo-oophorectomy (BSO). Ovarian enlargement and dense periovarian adhesions are the predisposing factors. Recurrent ovarian remnant syndrome was associated with recurrence of symptomatic endometriosis in a woman who underwent laparoscopic supracervical hysterectomy and BSO for severe endometriosis and extensive pelvic adhesions. After primary surgery she required five additional procedures for complete resection of all ovarian remnants. Definitive surgery for advanced endometriosis with extensive periovarian adhesions may be complicated by ovarian remnant syndrome and reactivation of the disease. Careful retroperitoneal resection of all ovarian tissue is of paramount importance in preventing the syndrome. This, however, may be a limitation of laparoscopic surgery. The choice between laparoscopy and laparotomy in such cases should be individualized and based on the degree of surgical difficulty and the surgeons level of experience.