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This study was designed to test the effect of recombinant tissue-type plasminogen activator (rt-PA) in reducing adhesion formation and to observe its influence on peritoneal neoangiogenesis. In 20 Wistar rats, a 4-cm midline incision was made, and a square piece of Silastic, 0.5×0.5 cm and 0.2 mm thick, was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/O. The rats were randomized into two groups of 10 animals each. In the first group we injected 0.2 mg of rt-PA intraperitoneally three times a day. The second group of 10 rats was used as a control group. Each rat was reoperated on day 12. Intraperitoneal injection of rt-PA seemed not to affect adhesion formation, as a 100% adhesion rate was reported in the treated group compared with 90% of the control group. The results showed that rt-PA acts on the neoangiogenesis involved in postsurgical adhesion formation by reducing the size and length of the vessels. This action seems to slow down peritoneal healing with a negative effect on postsurgical adhesion prevention.

This study presents an animal model for the observation of adhesion formation, from a vascular viewpoint. In 60 Wistar rats, a 4 cm midline incision was made and a 0.5 cm square piece of silastic 0.2 mm thick was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/0. The rats were randomized in six groups of 10 animals and were operated on again on days 2, 4, 6, 8, 10 and 12 respectively. Biopsies for scanning electron microscopy were obtained by resecting a 2 x 2 cm square of parietal peritoneum around and covering the silastic patch. Foreign body reaction induced by the silastic patch and ischaemia caused by stitching are the stimuli for adhesion formation. The results showed a gradual progression in the type and tenacity of adhesion formation. The maximal degree of peritoneal reactive angiogenesis was noted between days 8 and 12, together with a decrease and a redistribution in the extent of adhesions. In the early stages, vascularization is part of the organization of adhesions while their extent is limited. Two parallel mechanisms take part in trauma healing: while omento-parietal adhesions are vascularized, new peritoneal tissue with its vascular network develops and covers the silastic surface and the traumatized area. This theory is supported by the presence of fibroblasts differentiating into mesothelial cells on day 8. Theoretically, a valid treatment in preventing adhesion formation should increase the peritoneal neoangiogenesis and the repair of peritoneal lesions, but at the same time prevent the vascularization of adhesions. The present model offers the possibility of testing the effect of any treatment or device for preventing post-operative adhesions in a relatively short time.

The reproductive prognosis of 115 women desiring pregnancy who underwent surgery for ectopic pregnancy between 1985 and 1990 at the Clinica Luigi Mangiagalli, was analysed after a median follow-up period of 26 months (range 2-83). Probability of reproductive events was assessed by a product-limit model. Women who underwent surgery for ectopic pregnancy had a 54% probability of becoming pregnant (cumulative pregnancy rate, CPR), and a 36% probability of giving birth to a child (cumulative livebirth rate, CLB) during the 3 years after surgery. These percentages dropped with history of previous ectopic pregnancy (respectively 33%, P = 0.07, and 7%, P or = 35 years and CPR = 37% and CLB = 20% in women with adhesions in the contralateral tube), but these findings were not statistically significant. No association emerged between fertility and parity or type of surgery. The recurrence rate of ectopic pregnancy was 20%. No significant association emerged between recurrence of ectopic pregnancy and age, history of previous pregnancy, history of previous ectopic pregnancy, non-intact contra-lateral tube and salpingotomy.

In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility, we conducted a randomized clinical trial. Eligible patients were women aged ≤ 36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis (stage I or II of the revised American Fertility Society classification) and otherwise unexplained infertility for ≥ 2 years. Eligible women were randomly assigned to resection or ablation of visible endometriosis (54 patients) or diagnostic laparoscopy only (47 patients). After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). A total of five women withdrew from the study: three for personal reasons, and two were lost to follow-up. Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period, 12 (24%) in the resection/ablation group and 13 (29%) in the no treatment group conceived; the difference was not significant. Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one. Thus the 1 year birth rate was 10 out of 51 women (19.6%) in the resection/ablation group and 10 out of 45 women (22.2%) in the no-treatment group. In conclusion, the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates.

In 1971, Ellis [8] stated that “adhesions represent a vascular response by surrounding structures to the stimulus of ischemic tissue or foreign material within the peritoneal cavity.”

This study presents an animal model for the observation of adhesion formation, from a vascular viewpoint. In 60 Wistar rats, a 4 cm midline incision was made and a 0.5 cm square piece of silastic 0.2 mm thick was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/0. The rats were randomized in six groups of 10 animals and were operated on again on days 2, 4, 6, 8, 10 and 12 respectively. Biopsies for scanning electron microscopy were obtained by resecting a 2 x 2 cm square of parietal peritoneum around and covering the silastic patch. Foreign body reaction induced by the silastic patch and ischaemia caused by stitching are the stimuli for adhesion formation. The results showed a gradual progression in the type and tenacity of adhesion formation. The maximal degree of peritoneal reactive angiogenesis was noted between days 8 and 12, together with a decrease and a redistribution in the extent of adhesions. In the early stages, vascularization is part of the organization of adhesions while their extent is limited. Two parallel mechanisms take part in trauma healing: while omento-parietal adhesions are vascularized, new peritoneal tissue with its vascular network develops and covers the silastic surface and the traumatized area. This theory is supported by the presence of fibroblasts differentiating into mesothelial cells on day 8. Theoretically, a valid treatment in preventing adhesion formation should increase the peritoneal neoangiogenesis and the repair of peritoneal lesions, but at the same time prevent the vascularization of adhesions. The present model offers the possibility of testing the effect of any treatment or device for preventing post-operative adhesions in a relatively short time.

The reproductive prognosis of 115 women desiring pregnancy who underwent surgery for ectopic pregnancy between 1985 and 1990 at the Clinica Luigi Mangiagalli, was analysed after a median follow-up period of 26 months (range 2-83). Probability of reproductive events was assessed by a product-limit model. Women who underwent surgery for ectopic pregnancy had a 54% probability of becoming pregnant (cumulative pregnancy rate, CPR), and a 36% probability of giving birth to a child (cumulative livebirth rate, CLB) during the 3 years after surgery. These percentages dropped with history of previous ectopic pregnancy (respectively 33%, P = 0.07, and 7%, P0.05). Increasing age at surgery and presence of adhesions in the contra-lateral tube seemed to be associated with poor reproductive prognosis (CPR = 40% and CLB = 12% for women agedor = 35 years and CPR = 37% and CLB = 20% in women with adhesions in the contralateral tube), but these findings were not statistically significant. No association emerged between fertility and parity or type of surgery. The recurrence rate of ectopic pregnancy was 20%. No significant association emerged between recurrence of ectopic pregnancy and age, history of previous pregnancy, history of previous ectopic pregnancy, non-intact contra-lateral tube and salpingotomy.

Beginning in 1963 we have administered fast-acting insulin in three daily injections up to the maximal tolerated dose (M.T.D.), which can be defined as the highest quantity that can be given without bringing about hypoglycemic disturbances. This therapeutic criteria was applied both to gestational (280 pregnant women) and clinical (199 pregnant women) diabetes. M.T.D. was established on first admission to hospital and afterward controlled weekly in the outpatient clinic and during short periods of hospitalization (average of 53 days per patient). The average increase of the M.T.D. was 38 IU from 15 wk until delivery. As regards maternal blood sugar, at the M.T.D. average values at fasting and over the 24-h period were very close to the corresponding values of the control group (normal pregnancy). Total perinatal mortality (P.M.) was 2.9%; in the gestational diabetes group it was 2%. The incidence of congenital malformations (C.M.) (2.4%) increased with the severity of diabetes. No congenital defects were observed in 96 infants of patients treated before the 15th wk. Labor started spontaneously in 90.4% of the cases. The incidence of cesarean section was 21% in patients in White's Classes Al and A2 (as recently redefined by Freinkel and Metzger8) and 28% in other classes and that of forceps and vacuum extraction was 1% and 6%, respectively. The incidence of small-for-dates and overweight newborns from mothers with gestational and clinical diabetes without vascular complications is consistent with normal figures (macrosomia 3.4%). Small-for-dates newborns from pregnant diabetic women with vascular complications had a significant incidence. Respiratory distress syndrome (RDS) was 0.6% and hypoglycemia was 13.4%. No case of death was due to these two causes. Clinical results are discussed.

Summary. The restoration of normal tubo-ovarian function was investigated in a training programme using oviduct anastomosis in the rabbit as an experimental model. Ovulation rate, pregnancy rate, nidation index, implantation failure index and degree of adhesions were used as parameters. More than 100 anastomoses had to be performed to reach a perfect degree of atraumatic, function-restoring surgery. It is concluded that the most difficult aspect in female infertility surgery is not the use of the operating microscope but the experience in applying the principles of atraumatic surgery.