Feza Burak

Role of Endometrial Suppression on the Frequency of Intrauterine Adhesions after Resectoscopic Surgery

STUDY OBJECTIVES To evaluate long-term effects of operative hysteroscopy on the development of intrauterine adhesions (IUA), and to determine whether hypoestrogenism has a modulatory role in preventing IUA. DESIGN Prospective, randomized study (Canadian Task Force classification I). SETTING Tertiary-care teaching hospital. PATIENTS Ninety-five women requiring resectoscopic surgery. Intervention. Hysteroscopic surgery using the resectoscope and 1.5% glycine for uterine distention. MEASUREMENTS AND MAIN RESULTS Indications for hysteroscopy were polyps (28 patients), solitary myoma (32), multiple myomata (20), and uterine septa (15). Patients in each group were randomized to endometrial suppression with danazol or placebo. Second-look office hysteroscopy with CO2 for uterine distention was performed after the first menses after surgery to assess the frequency, extent, and severity of IUA. The likelihood and severity of IUA depended on the pathology treated at initial surgery. Of women treated for polyps and uterine septa, in only one with septa (placebo group) developed IUA. Mild IUA formation was present in 10 patients (31.3%) with solitary fibroids and 9 (45.5%) with multiple myomata. The frequency was similar in placebo- and danazol-treated groups with both solitary and multiple myomas (50% and 44.4% vs 50% and 55.6%). All IUA were lysed during second-look surgery, except in one woman with multiple myomata who required repeat resectoscopy. CONCLUSION Intrauterine adhesions are the major long-term complication of operative hysteroscopy, with frequency dependent on the pathology initially treated. Second-look office hysteroscopy is a cost-effective method of diagnosing and lysing IUA after resectoscopy.

The effects of duration of CO2 insufflation and irrigation on peritoneal microcirculation assessed by free radical scavengers and total glutathion levels during operative laparoscopy.

STUDY OBJECTIVE To investigate the effects of peritoneal exposure to carbon dioxide (CO2) on peritoneal microcirculation and free radical scavenger (FRS) metabolism, and its role in potential adhesion formation after operative laparoscopy. DESIGN Randomized, controlled study (Canadian Task Force classification I). SETTING University-affiliated hospital. PATIENTS Twenty-eight women undergoing operative laparoscopy for adnexal masses. INTERVENTION For each patient, a 1 x 1-cm sidewall peritoneal flap was excised at the end of laparoscopy and numbered randomly. Similar flaps obtained from 24 women immediately after entering the abdomen during laparotomy served as controls. MEASUREMENTS AND MAIN RESULTS Changes in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were studied in homogenized peritoneal tissues. The duration of CO2 exposure and amount of CO2 used were correlated with levels of free radical scavengers and compared with controls. Mean CO2 exposure, amount of CO2 used, and CO2 pressure (15 mm Hg) was similar between low irrigation and irrigated laparoscopy (118.3 +/- 25 and 39.2 +/- 8.81 min and 125 +/- 20 and 44.5 +/- 6.81 min, respectively). The change in FRS levels was significantly correlated with duration and amount of CO2 exposure (r = -0.92). Levels of GSH-Px, SOD, CAT, and GSH were significantly lower in the CO2 exposure group than in controls (0.57 micro mol, 1.8 ng, 48.5 micro mol, 1.5 nmol vs 0.8 micro mol, 2.6 +/- 0.4 ng, 79 micro mol, 3.6 nmol, respectively). CONCLUSION Exposure to CO2 has adverse effects on peritoneal microcirculation and cell-protective systems, which are proposed mechanisms in adhesion formation. Avoiding long CO2 exposure and copiously irrigating the abdominal cavity throughout surgery may lessen these effects. The potential role of the peritoneal FRS system on postoperative adhesion formation and its relation to estrogen status mandates further studies.

Effectiveness of tibolone on hypoestrogenic symptoms induced by goserelin treatment in patients with endometriosis.

OBJECTIVE To investigate the efficacy and safety of tibolone on hypoestrogenic vasomotor symptoms and bone parameters in patients treated with goserelin acetate. DESIGN Prospective, randomized placebo controlled double-blind study. SETTING Human volunteers in a university-based fertility clinic. PATIENT(S) Twenty-nine women of mean age 29.2 +/- 4.8 years with mild to severe endometriosis undergoing 6 months of treatment with 3.6 mg goserelin acetate in an SC depot formulation were studied. INTERVENTION(S) The patients were allocated randomly to either 2.5 mg/d tibolone (n = 15) or an iron pill (n = 14) in a double-blinded fashion beginning in the third cycle. MAIN OUTCOME MEASURE(S) Frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were assessed by the patients using 0 to 6 point scoring system and compared. Samples of urine were obtained for calcium and creatinine (Ca:Cr) ratios at the start of treatment and monthly there after. The vasomotor scoring for each symptom and Ca:Cr ratios before the treatment and at the end of 6th month were analyzed by parametric and nonparametric tests. RESULT(S) The mean age, weight, vasomotor scores, pelvic scores, and urine Ca:Cr ratios were similar in both placebo and tibolone group (28.7 +/- 4.8 versus 27.6 +/- 6.3 years, 50.9 +/- 5.3 versus 53.1 +/- 7.1 kg, 4.7 +/- 1.1 versus 4.2 +/- 0.8, and 0.056 +/- 0.008 versus 0.059 +/- 0.006, respectively). The decreases in vasomotor scoring as regards to hot flushing, sweating, and other associated symptoms were statistically significant in tibolone group compared with placebo (10.4 +/- 1.6 versus 24.6 +/- 4.9). During the study significant reductions in urine Ca:Cr ratio was obtained in the tibolone patients compared with placebo (0.031 +/- 0.006 versus 0.0055 +/- 0.007). The incidence of side effects (weight change, vaginal bleeding) was low and did not differ from the placebo group. CONCLUSION(S) Considering the beneficial effects of tibolone on vasomotor symptoms and bone loss, our data suggest that this synthetic steroid is an effective and safe option in relieving symptoms induced by GnRH-analogue.

Adhesion formation after microlaparoscopic and laparoscopic ovarian coagulation for polycystic ovary disease

STUDY OBJECTIVE To compare the effects of microlaparoscopy and decreased CO2 exposure on peritoneal microcirculation and potential adhesion formation after ovarian surgery with those of conventional operative laparoscopy. DESIGN Prospective, randomized study (Canadian Task Force classification I). SETTING Teaching hospital. PATIENTS Eighteen women with polycystic ovary disease. INTERVENTIONS Microlaparoscopic or laparoscopic ovarian coagulation of the ovaries. MEASUREMENTS AND MAIN RESULTS Approximately 10 to 12 coagulation points were applied to each ovary. Two to 3 weeks after the initial surgery second-look microlaparoscopy was performed to determine the extent of adhesions in both groups. The frequency of adhesion formation and changes in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were studied in homogenized peritoneal tissues obtained during surgery in each group. RESULTS Clinical profiles were similar between groups. Mean exposure, amount, and pressure of CO2 were significantly less in the microlaparoscopy group (p <0.05). The laparoscopy group had significantly more adhesions than the microlaproscopy group (24% vs 48%, p <0.05). The GSH-Px, SOD, CAT, and GSH levels were significantly lower in the laparoscopy group (0. 425 micromol, 1.2 ng, 37.55 micromol, and 0.9 nmol vs 0.755 micromol, 2.l ng, 625 micromol, and 2.6 nmol, respectively). CONCLUSION Reduced exposure to and amount of CO2 during microlaparoscopy may result in decreased adhesion formation compared with conventional laparoscopy. This effect may possibly be due to lack of or minimal adverse effects on peritoneal microcirculation and cell-protective systems, which are proposed mechanisms for adhesion formation and closely related to peritoneal injury. In addition, microlaparoscopy may be a cost-effective alternative to conventional laparoscopy. (J Am Assoc Gynecol Laparosc 6(2):159-163, 1999)

The degree of fluid absorption during hysteroscopic surgery in patients pretreated with goserelin

STUDY OBJECTIVE To assess the effects of pretreatment with the gonadotropin-releasing hormone analog goserelin on fluid absorption in patients undergoing hysteroscopic endometrial ablation. DESIGN Prospective, randomized, placebo-controlled study. SETTING A university-based clinic. PATIENTS Thirteen women with dysfunctional uterine bleeding who were scheduled for electrosurgical hysteroscopic ablation. INTERVENTIONS Seven women were randomized to receive luteal phase goserelin 3.75 mg and six saline in the menstrual cycle approximately 10 weeks before surgery. Operative hysteroscopy was carried out with glycine 1.5% mixed with 2% alcohol medium under constant pressure as an irrigant. The amount of irrigant used, irrigant deficit, blood levels of albumin and ethanol, hematocrit, hemoglobin, changes in sodium levels, and central venous pressure were compared between the groups. MEASUREMENTS AND MAIN RESULTS All of the patients had an unsuccessful course of medical therapy for at least 3 months and a normal endometrial biopsy. The age, weight, and uterine size were similar between the groups. The mean volume of irrigant used and operating time were similar in both groups (4.18 +/- 0.2 vs 4.5 +/- 0.5 L, and 33.7 +/- 1.5 vs 37 +/- 2.1 min). Although operating time, volume deficit, decrease in protein level, and hematocrit were less in the goserelin than in the saline group, the differences were not statistically significant (p >0.05). The ethanol levels in blood, decrease in Na+, and irrigant deficit were significantly lower in the goserelin than in the saline group (17.4 +/- 3.8 vs 25.3 +/- 4.2 mg/ml, 6.7 +/- 1.2 vs 9.1 +/- 0.9 mEq/L, and 0.49 +/- 0.08 vs 0.66 +/- 0.05 L, respectively; p <0.05). CONCLUSION Based on these results we conclude that in women undergoing hysteroscopic endometrial ablation, pretreatment with goserelin may decrease the absorption of hysteroscopic medium, prevent fluid overload, and improve the outcome possibly by causing hypovascularity and decreased endometrial growth.

Side Effects of Tamoxifen in Oophorectomized Rats

Objective: Our objective was to evaluate the direct effect of tamoxifen citrate (TAM) on the endometrium, liver, breast tissue and the lipid profile in oophorectomized (OX) rats. Study Design: An experimental animal study. Material and Methods: Forty-one mature rats (33 OX) were randomly divided into four groups and received either TAM (0.4 or 0.8 mg/kg p.o.) therapy or placebo over 60 days as follows: (1) sham; (2) OX + TAM (0.4 mg/kg); (3) OX + TAM (0.8 mg/kg); (4) OX. All histological changes in the endometrium, liver and breast tissue were evaluated under the light microscope by comparing the TAM-treated groups with the OX and sham-operated groups. Blood total cholesterol and low-density lipoprotein cholesterol levels were also analyzed. Results: TAM-treated rats showed a significant reduction in body weight, blood cholesterol and low-density lipoprotein cholesterol levels, but the wet uterine weight was not affected. Estrogenic effects of TAM were not detected with either dosage on the endometrium. TAM-treated groups showed atrophic breast tissue. No histopathological changes were detected in the liver with TAM treatment. Conclusion: The data suggests that TAM may not act as an estrogen receptor agonist with the given dosage on the endometrium in OX rats. Two different doses of TAM do not cause histological changes in liver over 60 days of treatment.

Endometrial Na+, K+-ATPase pump function and vasopressin levels during hysteroscopic surgery in patients pretreated with GnRH agonist *

STUDY OBJECTIVE To investigate the effects of gonadotropin-releasing hormone (GnRH) analog pretreatment on endometrial Na+, K+-adenosine triphosphatase (ATPase) pump function and peripheral blood vasopressin levels, and their role in fluid absorption and mechanisms of hyponatremia in patients undergoing hysteroscopic endometrial ablation. DESIGN Prospective, randomized, placebo-controlled study (Canadian Task Force classification I). SETTING University-affiliated hospital. PATIENTS Seventeen women with dysfunctional uterine bleeding. INTERVENTION Nine women received a GnRH analog and eight received saline approximately 6 to 8 weeks before hysteroscopic ablation by electrosurgery. MEASUREMENTS AND MAIN RESULTS Both before randomization and immediately before surgery, endometrial biopsy samples were obtained and numbered consecutively without patient identification. Operative hysteroscopy was performed with glycine 1.5% mixed with 2% alcohol. The amount of irrigant and irrigant deficit; blood levels of albumin and ethanol; hematocrit and hemoglobin; changes in sodium levels; and central venous pressure were compared. The Na+, K+-ATPase pump activity was significantly increased in the GnRH analog group compared with the saline group and correlated with decreased estradiol levels (0.4 +/- 0.08 vs 0.26 +/- 0.06 micro mol/min/ml). Vasopressin levels were significantly lower in the GnRH group (3.2 +/- 0.9 vs 7.6 +/- 1.7 micro mol/L). Mean volume of irrigant used and operating time were similar in both groups. Volume deficit, decrease in protein, and hematocrit were less in GnRH than in the saline group. Blood ethanol levels, decrease in sodium, and irrigant deficit were significantly lower in GnRH group. CONCLUSION Pretreatment with GnRH analogs may prevent the adverse effects of estradiol on endometrial Na+, K+-ATPase and creates a protective mechanism against iatrogenic hyponatremia, which is more critical in women than men in case of absorption of irrigating fluid. Moreover, created hypoestrogenism may enhance Na+, K+-ATPase activity in brain as well as endometrium, thus decreasing womens susceptibility to hyponatremic complications and brain damage. Suppressed vasopressin levels may be protective against fluid absorption in GnRH analog-treated patients.

O-130 The effects of twisted ischemic adnexa managed by detorsion on ovarian viability and histology: An ischemia-reperfusion rodent model

This prospective controlled follow-up study was designed to examine the effects of adnexal torsion on long-term ovarian histology and radical scavenger (FRS) activity, and subsequent viability following the detorsion of twisted ischaemic adnexa, in a primate centre of a university clinic. Adnexal torsion/occlusion was created by twisting the adnexa three times and fixing on to the side wall or by applying vascular clips in cycling female rats at 70 days of age. Following an ischaemic period of 4 to 36 h, the twisted adnexas were surgically removed and fixed. In the second group of rats, following the above ischaemic periods, the torsion/occlusion were relieved by detwisting or removing the vascular clips. Then the animals were reperfused for a week and adnexas were extirpated. After both ischaemia and reperfusion, the removed adnexas were examined histologically and tissue concentrations of glutathione peroxidase, superoxide dismutase, catalase and glutathione were determined. Regardless of the ischaemia time, all the twisted adnexas were black-bluish in appearance. Despite the gross ischaemic-haemorrhagic features, histological sections revealed negligible changes, with intact ovarian structure similar to controls in 4-24 h groups. Though decreased compared with controls, the change in tissue concentrations of FRS was not significant in 4-24 h groups. Only the 36 h group showed prominent congestion on all sections and a significant decrease in all radical scavenger concentrations studied. While no long-term reperfusion injury was observed histologically in 4-24 h groups, the 36 h group ended with adnexal necrosis. Our findings support the importance of early diagnosis and conservative surgical management (detorsion) in adnexal torsion. Lack of histological changes and unimpaired FRS metabolism are consistent with the recent data that vascular compromise is caused by venous or lymphatic stasis in early torsion and that adnexal integrity is not correlated with gross ischaemic appearance, thus providing evidence of adnexal resistance against ischaemia.

The effects of daflon on pelvic pain in women with Taylor syndrome

The syndrome of chronic pelvic pain without an obvious pathology has been described as pelvic congestion (Taylor) syndrome. It is frequently associated with continuous bilateral lower abdominal pain and dyspareunia. Pelvic examination reveals tenderness without induration or masses. Although their importance in the pathophysiology of pain is uncertain, prominent enlarged broad ligament veins are observed at laparoscopy. We evaluated the effects of daflon, a venomimetic agent that regulates the circulatory tonus of the venous system, on pelvic pain and investigated the role of enlarged veins in the pathophysiology of Taylor syndrome. Ten women (age 28-35 yrs) with chronic pelvic pain were diagnosed with the syndrome at laparoscopy. They all had prominent broad ligament and ovarian veins without other pathologies such as endometriosis to explain the etiology of pelvic pain. Five women were randomized in a double-blind fashion to receive daflon 500 mg twice/day for 4 months, and five a vitamin pill placebo; they were crossed over for another 4 months. They scored the frequency and severity of lower abdominal pain and dyspareunia on a scale from 0 to 6, and the results were compared with pretreatment values. At the end of the fourth month the frequency and severity of pelvic symptoms began to decrease with daflon compared with pretreatment and placebo. The mean scores were significantly less at the end of 4 months (9.3 ± 1.1 vs 4.2 ± 1.4, respectively, p <0.05). Based on our preliminary results, we conclude that venous dysfunction and stasis may be pathophysiologic components of pelvic pain in women with Taylor syndrome. Pharmacologic enhancement of venous tonus may restore pelvic circulation and relieve pelvic symptomatology.

Effectiveness and long-term safety of prolonged gosereline and tibolone in women with endometriosis

Gonadotropin-releasing hormone (GnRH) agonists are widely administered to treat endometriosis, but generally are not prescribed for more than 6 months since they are associated with vasomotor symptoms and bone loss. A GnRH agonist and steroid add-back therapy can be given for longer times without flare-up or significant hypoestrogenic symptoms. We examined the efficacy and safety of a weak estrogenic steroid, OD14, with prolonged goserelin treatment in seven regularly menstruating women (age 26-33 yrs) with laparoscopically diagnosed, symptomatic endometriosis. The women received goserelin 3.65 mg subcutaneously/month and 2.5 mg OD14 2.5 mg/day beginning in the fourth cycle for 18 to 20 months. The frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were scored by the women on a scale of 0 to 6 and compared. Samples of blood and urine were obtained to measure serum estradiol (E2) levels, lipids, and urinary calcium:creatinine (Ca:Cr) ratios at the start of treatment and monthly thereafter. The vasomotor scores, serum E2 levels, and urine Ca:Cr ratios were consistent with the hypoestrogenism induced by goserelin (24.2 ± 3.1, 18.5 ± 7.2 pg/ml, and 0.063 ± 0.008, respectively). The decreases in vasomotor scoring with regard to hot flushing, sweating, and urinary Ca:Cr ratios were significant after adding OD14 (14.8 ± 2.2, 0.031 ± 0.005, p <0.05), whereas E2 levels remained below 40 pg/ml (23.1 ± 8.2 pg/ml, p >0.05) throughout therapy. The increased low-density:high-density lipoprotein ratio with goserelin improved with OD14, remaining at the lower limit of normal. Thus, OD14 add-back to GnRH agonist therapy enabled us to extend medical therapy of endometriosis longer than 6 months, preventing hypoestrogenic side effects, and with adequate suppression endometriosis symptoms.