Pier Luigi Venturini

Postsurgical medical treatment of advanced endometriosis: Results of a randomized clinical trial

OBJECTIVE Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis. STUDY DESIGN Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society, revised, classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions. Patients were assigned according to a randomization list to nasal nafarelin, 400 micrograms/day (36 subjects) or placebo nasal spray (39 subjects) for 3 months. Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale. RESULTS No marked differences in pain scores emerged among women allocated to different treatments. The mean reduction of the multidimensional score was 3.6 and 4.0, respectively, in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9. These differences were not statistically significant. Within 1 year from randomization, of the 36 women allocated to nafarelin and the 39 allocated to placebo, seven (19%) and seven (18%), respectively, became pregnant. CONCLUSION This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis.

Unidirectional Barbed Suture versus Continuous Suture with Intracorporeal Knots in Laparoscopic Myomectomy: A Randomized Study

STUDY OBJECTIVE To estimate the effectiveness of unidirectional knotless barbed suture and continuous suture with intracorporeal knots in the repair of uterine wall defects during laparoscopic myomectomy. DESIGN Randomized clinical study (Canadian Task Force Classification I). SETTING Single-center study in a university hospital. PATIENTS This study enrolled 44 women who underwent laparoscopic myomectomy. INTERVENTIONS In accord with to the randomization, the uterine wall defects were closed either with a continuous suture with intracorporeal knots (group V) or a unidirectional knotless barbed suture (group L). MEASUREMENTS AND MAIN RESULTS The time required to suture the uterine wall defect was significantly lower in group L (11.5 ± 4.1 minutes) than in group V (17.4 ± 3.8 minutes; p <.001). However, no significant difference was observed in the operative time between the 2 study groups. The intraoperative blood loss was significantly lower in group L than in group V (p =.004). The degree of surgical difficulty was significantly lower in group L (3.7 ± 1.1) than in group V (6.1 ± 2.1; p <.001). CONCLUSION The unidirectional knotless barbed suture may facilitate the suture of uterine wall defects during laparoscopic myomectomy. When compared with continuous suture and intracorporeal knots, the barbed suture reduces the time required to suture the uterine wall defect and the intraoperative blood loss.

Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study

BACKGROUND This pilot study evaluates the efficacy of norethisterone acetate in treating pain and gastrointestinal symptoms of women with colorectal endometriosis. METHODS This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded. RESULTS Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle. CONCLUSIONS In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Role of major histocompatibility complex class I expression and natural killer-like T cells in the genetic control of endometriosis

OBJECTIVE To evaluate whether the expression of human leukocyte antigen (HLA) class I on eutopic and ectopic endometrial cells modify the susceptibility to lysis mediated by lymphocytes. DESIGN Evaluation of T lymphocyte cytotoxic activity and HLA class I expression on endometrial cells. SETTING Subjects were recruited at laparoscopy. PATIENTS Patients with endometriosis (n = 7). Healthy women as controls (n = 10). MAIN OUTCOME MEASURES Human leukocyte antigen class I molecule analysis of endometrial cells was carried out by immunofluorescence and flow cytometry. Phenotyping of T lymphocytes was performed to analyze T-cell subsets. Cytotoxicity was performed to determine cytolytic activity against endometrial cells. RESULTS In vitro culture of endometrial cells down-regulates the expression of HLA class I molecules and enhances the susceptibility to lysis mediated by natural killer (NK)-like T lymphocytes. Cytolytic T-cell clones, expressing the CD94 antigen, are inhibited by the HLA-B7 allele on endometrial cells. Ectopic endometrial cells modulate the expression of HLA class I molecules. CONCLUSIONS The resistance to lysis of endometrial cells is related to expression of surface HLA class I molecules, which send a negative signal for lysis mediated by NK-like T lymphocytes. The HLA-B7 allele inhibits the cytotoxic activity, suggesting that the growth of ectopic endometrial cells might be under a genetic control.

Hemostasis by bipolar coagulation versus suture after surgical stripping of bilateral ovarian endometriomas: a randomized controlled trial.

STUDY OBJECTIVE To estimate whether the suture of the ovary is superior to bipolar coagulation in preserving ovarian reserve in infertile women undergoing laparoscopic stripping of bilateral endometriomas. DESIGN Randomized controlled trial (Canadian Task Force classification I). SETTING University teaching hospital. PATIENTS 100 patients with bilateral endometriomas. INTERVENTIONS Patients underwent stripping of bilateral endometriomas and were randomized to undergo hemostasis by use of either laparoscopic suturing (LS group) or bipolar coagulation (BC group). Changes in ovarian reserve were investigated by measuring the levels of anti-Mullerian hormone (AMH) and basal follicle-stimulating hormone (FSH) before surgery and at 3, 6 and 12 months from surgery. MEASUREMENTS AND MAIN RESULTS At 3-month, 6-month, and 12-month follow-up, in both study groups, postsurgical AMH levels were significantly lower and basal FSH levels were significantly higher than before surgery. There was no significant difference in the mean percentage decrease of AMH levels in the BC group and LS group at 3-, 6-, and 12-month follow-up. The mean percentage increase in basal FSH was higher in the BC group than in the LS group at both 3-month (p = .023) and 6-month follow-up (p = .029), but not at 12-month follow-up. Pregnancy rate, time to conception, and rate of endometrioma recurrence was similar in the 2 study groups. CONCLUSION Laparoscopic stripping of ovarian endometriotic cyst significantly decreases serum AMH levels and increases basal FSH levels independent from the method used to obtain hemostasis on the ovarian tissue.

Pharmacological Treatment of Endometriosis

Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents. In the last 10 years, it has been demonstrated that aromatase P450, a key enzyme for estrogen biosynthesis, may have a pathogenic role in endometriosis because it is aberrantly expressed in endometriotic implants and in eutopic endometrium of women with endometriosis. Therefore, inhibition of aromatase activity may represent a new therapeutic option for endometriosis. Case reports and observational studies have shown that pain symptoms caused by endometriosis quickly improve after administration of aromatase inhibitors. Limited data are available on the long-term course of pain symptoms after completion of treatment with aromatase inhibitors; however, some recent studies suggest that symptoms may recur at short-term follow-up. A range of results are reported on the effects of aromatase inhibitors on endometriotic lesions, with some authors describing improvements and other authors reporting persistence of pelvic lesions at second-look laparoscopy after treatment. No severe adverse effect has been reported during treatment with aromatase inhibitors both in pre- and post-menopausal women. On the basis of the available data, administration of aromatase inhibitors should now be offered only to the small number of women who have severe pain despite previous surgical and hormonal therapies. Further research in the form of randomized controlled trials will be required before recommending the routine use of these agents.

Letrozole and norethisterone acetate in colorectal endometriosis.

OBJECTIVE Up to now limited attention has been given to the medical treatment of bowel endometriosis. This study evaluates the efficacy of aromatase inhibitors and norethisterone acetate in treating pain and gastrointestinal symptoms caused by bowel endometriosis. STUDY DESIGN This prospective pilot study included six women with colorectal endometriosis; all women had intestinal nodules infiltrating at least the muscularis propria of the bowel and did not have a stenosis of the bowel lumen >60%; the patients suffered from pain and intestinal symptoms. The study subjects received letrozole (2.5 mg/day) and norethisterone acetate (2.5 mg/day) continuously for 6 months. The presence and intensity of symptoms were evaluated before starting the treatment, and after 3 and 6 months of treatment. RESULTS The double-drug regimen improved pain, non-menstrual pelvic pain, deep dyspareunia, dyschezia, symptoms mimicking diarrhoea-predominant irritable bowel syndrome, intestinal cramping, abdominal bloating and passage of mucus in the stools, and 67% of the patients declared that the treatment improved their gastrointestinal symptoms. CONCLUSIONS The administration of letrozole and norethisterone acetate reduces pain and gastrointestinal symptoms of women with colorectal endometriosis, particularly when patients suffer from symptoms mimicking diarrhoea-predominant irritable bowel syndrome.

Sperm aneuploidy and recurrent pregnancy loss

Experiments of double target in-situ hybridization were performed separately for chromosomes 1-17, 8-18 and sex chromosomes on sperm samples from 20 couples suffering from three or more recurrent first trimester abortions. For a subset of this study population, additional experiments of multicolour fluorescence in-situ hybridization for chromosomes 4, 7, 12, 13, 15, 18, 21, and 22, were performed on the bases of the available data from abortive tissue karyotyping. A markedly high rate of sperm disomy (14.5-15.5%) was scored in only two cases. For three other patients, the cumulative disomy rates for chromosomes 1, 17, 8, 18, X and Y also increased but at a lower level (7.8-9.5%). For the remaining 15 patients, the frequency of sperm aneuploidy was moderately increased or normal. Men with recurrent pregnancy loss (RPL) and poor semen quality had baseline sperm aneuploidy and diploidy rates higher than men with normal semen parameters (with or without RPL). Using probes for chromosomes 1, 17, 8, 18, X and Y, significantly elevated frequencies of sperm aneuploidy (not diploidy) were found in 10% of men with a history of RPL. Their rate of sperm aneuploidy was 30-34%. For the other men, changes in sperm aneuploidy were not thought to affect RPL. Poor semen quality per se impacted negatively on sperm aneuploidy and diploidy, thus making the interpretation of clinical data more difficult.

Determinants of adenomyosis in women who underwent hysterectomy for benign gynecological conditions: results from a prospective multicentric study in Italy

OBJECTIVE We conducted a cross-sectional study on the frequency and risk factors for adenomyosis in women who underwent hysterectomy for benign gynecological conditions. STUDY DESIGN All women who consecutively underwent hysterectomy during the study period for benign gynecological conditions at 18 gynecological departments were eligible for the study. A total of 820 women entered the study. Pathological data were collected prospectically. RESULTS Adenomyosis was identified in 231 women (28.2%, 95% confidence interval, CI, 24.6-32.5). The frequency of adenomyosis was similar in women with indication for surgery fibroids/menorrhagia (143 cases, 28.5%) or genital prolapse (69 cases, 28.2%). The rate ratio (RR) of adenomyosis was 1.9 (95% CI 1.2-2.8) in women reporting one or more induced abortions, in comparison with those reporting no induced abortion. Women with adenomyosis reported more frequently dysmenorrhoea and chronic pelvic pain, but not dyspareunia. CONCLUSIONS This study shows that adenomyosis is common in women who undergo hysterectomy and that it is more frequent among women reporting induced abortions dysmenorrhoea and chronic pelvic pain.

Desogestrel‐only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open‐label comparative study

To compare the efficacy of two hormonal therapies in treating symptoms caused by bowel endometriosis.