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The objective of this study was to analyse the histological and immunohistochemical characteristics of cultured explants of human endometrium transplanted into nude mice. Biopsies of eutopic endometrium were taken from six patients during laparoscopic surgery and classified according to the phase of the cycle. All the explants were cultured with oestrogen and progesterone for 24 h before transplantation into 15 mice. Four mice were grafted with explants of menstrual endometrium, four with explants of late proliferative endometrium, and seven with explants of late secretory-premenstrual endometrium. Typical endometrial glands and stroma were observed in 87% of cases 3 weeks after the transplantation. All the grafts revealed histological characteristics of the proliferative phase, even when the endometrial biopsy was taken during the late secretory phase. Immunohistochemical studies revealed that the proliferation index was high, whatever the menstrual phase of the endometrial biopsy. An extensive vascular network developed at the interface between the graft and the surrounding tissue. Vascular endothelial growth factor (VEGF) positive stained cells were observed in all grafts, the VEGF score being significantly higher in epithelial cells than in stromal cells. In conclusion, human endometrial explants, cultured for 24 h, could be successfully transplanted into nude mice. Immunohistochemical studies proved that human cultured endometrial tissue could not only survive in nude mice but could also become very active and develop characteristics different from the tissue of origin. An active vascular network is a necessary condition for the survival of the graft and may be explained by the high VEGF content.

The cell proliferation-associated antigen Ki 67 and the immunohistochemical content of oestrogen receptors (ER), progesterone receptors AB (PRAB) and progesterone receptors B (PRB) were evaluated in leiomyomata and adjacent myometrium during the menstrual cycle and in leiomyomata under gonadotrophin-releasing hormone agonist (GnRHa) therapy. The proliferative status of muscular cells was measured by evaluating the percentage of nuclei staining positive for Ki 67 (proliferation index). Quantitative analysis (QH-score) was carried out using advanced stereographic computer technology to investigate ER, PRAB and PRB. Leiomyoma and myometrial biopsies were taken from 30 patients undergoing hysterectomy or myomectomy because of symptomatic leiomyomata (subgroup I). Leiomyoma biopsies were taken from 10 patients suffering from symptomatic submucosal leiomyomata, after 2 month GnRH therapy (subgroup II). During the secretory phase, the proliferation index (Ki 67) was found to be higher in leiomyomata than in myometrium, but the difference was not significant. Oestrogen receptor content was significantly higher in leiomyomata than in myometrium only during the proliferative phase of the cycle. PRAB and PRB content were found to be higher in leiomyomata than in adjacent myometrium with a statistically significant dominance of PRAB over PRB. Under GnRHa therapy, a dramatic decrease was observed in PRAB and B content as well as Ki 67 but ER content remained comparable with the results obtained during the menstrual cycle. The results suggest that leiomyomata may be under the influence of progesterone which may play a major role in their growth.

Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. The VEGF protein was evaluated immunohistochemically in the eutopic endometrium of 10 women without endometriosis (group I) at laparoscopy and the eutopic endometrium and peritoneal endometriotic lesions of 43 women with endometriosis (group II). VEGF histological scores were 9.7 +/- 4.3 and 4.0 +/- 2.6 respectively in the epithelium and stroma of the eutopic endometrium of group I women, and 10.3 +/- 2.3 and 3.6 +/- 2.3 respectively in women of group II. In red lesions, the VEGF scores were 11.1 +/- 3.0 in the epithelium and 5.1 +/- 3.0 in the stroma, and in black lesions were 8.6 +/- 2.7 and 1.6 +/- 1.6, respectively. Significantly lower values were observed in black lesions as compared with eutopic endometrium and red lesions, the values of which were similar. Scores were also evaluated according to the phase of the cycle. In eutopic as well as ectopic endometrium, no significant cyclic variations were observed throughout the cycle. However, VEGF content was found to be higher in the eutopic glandular epithelium of women with endometriosis during the late secretory phase, possibly suggesting a more likely tendency to implant. In contrast, significantly higher VEGF content was noted in red lesions as compared with black lesions. During all phases of the cycle, the VEGF content in stromal cells of red lesions was higher than in black lesions. Similarities in VEGF content were observed in the glandular epithelium of the eutopic endometrium of women with endometriosis and red

A computerized morphometrical investigation was performed on endometriotic tissue from the peritoneum (n = 225) and rectovaginal nodules (n = 65) to compare histologically and stereologically the rectovaginal septum endometriotic nodule to peritoneal endometriosis. Mitotic activity, stromal vascularization and the epithelium/stroma ratio were found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation revealed a major role of glandular epithelium in rectovaginal nodules where the stroma sometimes appeared absent around glandular epithelium. The study demonstrated opposite effects of gonadotrophin-releasing hormone agonists (GnRHa) and lynestrenol on the two lesions. Indeed, in peritoneal endometriosis, after GnRHa therapy, our study demonstrated a lower rate of mitosis and poor stromal vascularization. The same drug was unable to induce the same effects in the nodule although, in contrast, lynestrenol has a strong effect on nodule vascularization. In conclusion, it is suggested that the rectovaginal adenomyotic nodule is a specific disease, different from peritoneal endometriosis. It is not the consequence of 'deep infiltrating' endometriosis but can probably develop from Mullerian rests present in the rectovaginal septum.

Recently advanced computerized technology was applied to the investigation of morphometric, immunohistological and three-dimensional changes of the endometrial mucosa in order to evaluate quantitatively the effects of three doses of a new slow-release vaginal progesterone on the endometrium in post-menopausal women. A total of 20 menopausal women, deprived of ovarian function, were given oestrogen for 12 days and a combined therapy of oestrogen (administered orally) and progesterone for another 12 day period. Progesterone was administered vaginally through a new gel (Crinone) utilizing a bioadhesive, biocompatible polymer as a base to achieve a sustained release effect. An endometrial biopsy was taken before treatment, after oestrogen-only treatment and after the oestro-progestogen therapy. Before treatment, all the patients exhibited an atrophic endometrium. After oestrogen-only treatment, typical proliferative changes occurred: an increase in the endometrium thickness, an increase in the mitotic index, numerous cylinder-like glands and no coiled glands, and high concentrations of oestrogen receptors (ER) and progesterone receptors (PR). After the oestro-progestogen therapy, whatever the dose of progesterone given, a secretory transformation of the endometrial mucosa occurred, mitotic activity decreased significantly, more ramified and coiled glands were observed, and a decrease in PR content was noted in epithelial and stromal nuclei, and a decrease in PR content was also observed in epithelial nuclei but not in stromal nuclei. Accurate new techniques of image analysis have shown that crinone therapy could eliminate the proliferative effects of oestrogen treatment in post-menopausal women, despite doses as low as 45 mg of progesterone administered vaginally every other day. The results suggest that the sustained release effects of Crinone are clinically relevant.

This study was undertaken to evaluate the efficacy and safety of an intrauterine device designed for endometrial ablation by Nd-YAG laser interstitial hyperthermy. Eight hysterectomy specimens were treated in vitro with an output power of 30 W for 5 minutes; tissue temperatures, recorded by thermocouples, were plotted to draw time-temperature and time-distance curves. As a preliminary series, ten patients were treated, with the first five subjected to local temperature monitoring; all ten were followed-up for 6-17 months. Immediate and delayed (6 weeks) histologic data were obtained. The intramural temperature at 6 mm from the fibers ranged from 55-60C). In vivo, the cooling effect of the arterial blood flow lowered the serosal temperatures under 41C. The histologic data and the hysterographic pictures suggest that endometrial ablation was effective. This new device does not require distending medium, hysteroscopic control, or high-powered Nd-YAG laser machines. Preliminary long-term results suggest that the device could be used for endometrial ablation.

Both the electrical current of the resectoscope and the energy of the Nd:YAG laser have been effective tools in the destruction of endometrial tissue to a sufficient depth to avoid regeneration. GnRH-agonist therapy effects a decrease in the total uterine cavity area which facilitates surgical treatment and reduces the risk of fluid overload syndrome. The recurrence rate of meno/metrorrhagia is higher when the uterine cavity is more than 10 cm2. The use of GnRH-agonists represents an adjunct for preoperative reduction of submucosal myomas so that subsequent hysteroscopic myomectomy is possible. A two-step hysteroscopic therapy combined with GnRH-agonist therapy is performed when the largest portion of the submucosal myoma is located in the uterine wall. In cases of numerous submucosal and intramural myomas, a laparoscopic supracervical hysterectomy is performed because of the high risk of recurrence after the hysteroscopic procedure.

OBJECTIVE: To elucidate some biological characteristics of peritoneal endometriosis. DESIGN: A recently advanced stereographic computer technology was applied for the investigation of the three-dimensional (3-D) architectures of peritoneal endometriosis. SETTING: University Hospital of Gynecology. PATIENTS: Biopsies were taken from 42 women with peritoneal endometriosis. Twenty-six of them were in the luteal phase. Seventeen of them received Zoladex (ICI, Cambridge, United Kingdom) for 12 weeks before biopsy. RESULTS: Two different main types could be identified according to the presence or absence of ramifications. The apparently multifocal occurrence (in 2-D) of glandular epithelium was not confirmed by the 3-D study that showed that all epithelial glands are interconnected by luminal structures in each peritoneal lesion. Stereometric study suggests a stronger effect of gonadotropin-releasing hormone agonist therapy on the stroma than on the epithelium. CONCLUSIONS: The study evaluated the 3-D architectures of peritoneal endometriosis and identified two principal types of peritoneal endometriosis.

In order to assess adequately the effectiveness of danazol, Gestrinone, and Buserelin, a prospective nonrandomized study was initiated in 126 patients with laparoscopically confirmed ovarian endometriosis. After hormonal therapy, laparotomy with microsurgical resection of endometriotic cysts was carried out. Regression (greater than 25%) of ovarian endometriosis was noted in 30%, 34%, and 73% of cases after danazol, Gestrinone, and Buserelin, respectively. The pregnancy rate in moderate endometriosis (53%) differed significantly from the rate obtained in severe endometriosis (45%). The highest percentages were found after Buserelin therapy. In conclusion, Buserelin emerged superior to danazol or Gestrinone treatment. Nevertheless, hormonal treatment leads to an incomplete suppression of ovarian endometriotic implants and this suggests the necessity of surgically removing invasive ovarian endometriosis.

The present study included 118 patients undergoing a laparoscopy for infertility. In 86 patients with laparoscopically diagnosed endometriosis (group I), biopsies were taken from areas of apparent endometriosis (n = 86) and from a visually normal peritoneum (n = 52). Histology reveals the presence of endometriosis in 93% of positive sites and in 13% of negative sites. In 32 patients without endometriosis at laparoscopy (group II), biopsies were taken from normal uterosacral ligaments (n = 32). Endometriosis was observed in 6% of cases. Despite the increased ability to detect pigmented and nonpigmented endometriotic lesion, histological study revealed the presence of endometriosis in normal peritoneum in 13% (group I) and 6% (group II) of cases.

In order to adequately assess the effectiveness of danazol, gestrinone, buserelin-nasal spray (IN) and buserelin-implant (SC), a prospective non randomized study was initiated in 178 patients with laparoscopically confirmed ovarian endometriosis. After hormonal therapy, laparotomy with microsurgical resection of endometriotic cysts or laparoscopy laser was carried out. Regression (greater than 25%) of ovarian endometriosis was noted in 30, 34, 73 and 91% of cases after danazol, gestrinone and buserelin IN and buserelin SC respectively. Histological study proves that hormonal treatment leads to an incomplete suppression of ovarian endometriotic implants and this suggests the necessity to remove surgically invasive ovarian endometriosis. The pregnancy rate in moderate endometriosis (55%) differed significantly from the rate obtained in severe endometriosis (44%). The highest percentages were found after buserelin therapy. In conclusion, preoperative use of a potent GnRH agonist, administered subcutaneously, seems to be the best therapeutic approach when associated to surgery (CO2 laser or microsurgery).

To study the effect of endometriosis on follicular rupture, endometrial tissue was autografted to New Zealand White rabbits. Endometrium was surgically implanted into the peritoneal cavity. Human chorionic gonadotropin was administered to induce ovulation. The viability of the implants was demonstrated histologically during three subsequent laparotomies, the number of corpora lutea and stigmata were counted. Ovaries were then removed and ovarian serial sections were examined. In rabbits with peritoneal induced endometriosis, the percentage of stigmata per corpora lutea was significantly decreased. Macroscopic study was confirmed by histological examination. Indeed, a high incidence of entrapped oocytes was found in rabbits with peritoneal endometriosis. Our data demonstrated that endometriosis induced a failure of follicular rupture.

To study the effect of endometriosis on follicular rupture, endometrial tissue was autografted to New Zealand White rabbits. Endometrium was surgically implanted into the peritoneal cavity or into the rectus muscle. Human chorionic gonadotropin was administered to induce ovulation. During three subsequent laparotomies, the number of corpora lutea and stigmata were counted. The viability of the implants was demonstrated histologically. Ovaries were removed during the last laparotomy and ovarian serial sections were examined. In rabbits with peritoneal induced endometriosis, the percentage of stigmata/corpora lutea was significantly decreased. Macroscopic study was confirmed by histological examination. Indeed, a high incidence of entrapped oocytes was found in rabbits with peritoneal endometriosis. Extraperitoneal endometriosis had no effect on ovulation. Our data demonstrated that endometriosis induced a failure of follicular rupture. After endometriumectomy, no failure to ovulate was observed, suggesting that the effect of endometriosis on the ovulation disappeared with excision of endometrial implants.

Ligation of the proximal and distal ends of the rabbit oviduct was used to induce hydrosalpinges, which shows a remarkable resemblance, both macroscopically and microscopically, to human hydrosalpinges. Isthmic and ampullary biopsies obtained at varying intervals were examined with light microscopy. Progressive deciliation and decrease of epithelial and mucosal fold height were observed in the ampulla, but not in the isthmus. Microstereological study shows progressive reduction of both the number and the relative volume of capillaries in the ampulla. Considering the parallelism of time and localization, it is suggested that epithelial deciliation is caused by vascular disorders.

The percentage of ciliated cells, the height, and the mitotic index of human oviductal epithelium were studied during the menstrual cycle and under progestogens. A total of 141 fallopian tubes were examined. During the menstrual cycle, a process of ciliation and deciliation was observed. Maximal ciliation was attained around the time of ovulation, particularly in the fimbria where significant differences were noted. Deciliation was observed under progestogen therapy, but this progestogen effect was easily reversible. The decrease of epithelial height observed after ovulation was also found after progestogen therapy. Cyclic mitotic activity was noted during the menstrual cycle. Estrogens influence the mitotic activity of tubal epithelium, whereas endogenous progesterone and progestogens inhibit this estrogenic effect.

Histological study was carried out on human fallopian tubes one hour and one month after various methods of laparoscopic sterilization. Ciliated cells were counted and histological lesions were observed. Deciliation is proved at a distance from the site of sterilization. Taking into account these two data, it has been possible to display the substance loss provoked by each of the usual sterilization methods (unipolar electro-coagulation, bipolar electrocoagulation, silicone ring and Hulka-Clements clip) which have to be taken into consideration in case of surgical re-anastomosis.

Ligation of the proximal and distal ends of the rabbit oviducts was used to induce hydrosalpinges. The adrenergic innervation of the induced hydrosalpinx was studied. Depletion of adrenergic innervation in rabbit hydrosalpinges was found. Our findings suggest that not only mucosal changes, but also loss of adrenergic nerves must be taken into account as factors in the pathology of hydrosalpinx.

Eighty-two women with symmetric cornual blockage were selected for evaluation of the results of microsurgical anastomosis in relation to data from preoperative hysterosalpingography and histologic study of excised tubal specimens. Serial sections from 164 occluded tubal portions were examined. The term pregnancy rate was 44%. Several prognostic factors influencing the postoperative pregnancy rate were revealed: maximized tubal length; preserved intramural portion; absence of chronic inflammation; absence of tubal inclusion in the tubal wall; and absence of tubal endometriosis.

From January 1978 to December 1983, 600 infertile women underwent microsurgery for tubal infertility. Only 257 women with the same extent of distal lesions on both sides or with unilateral occlusion (after contralateral salpingectomy) were considered. Patients were classified in four subgroups on the basis of the extent of occlusion. After fimbrioplasty for occlusion of degree I and salpingostomy for occlusion of degree II, the term pregnancy rate was more than 50%. After salpingostomy for occlusion of degrees III and IV, the term pregnancy rate was, respectively, 25% and 22%. The ectopic pregnancy rate was the highest (12%) after salpingostomy for occlusion of degree IV. After microsurgical salpingolysis, the term pregnancy rate reached 64%, whereas the ectopic pregnancy rate was as low as 2%. Ampullary dilatation, as determined by hysterosalpingography and laparoscopy, influences the postoperative pregnancy rate. Fimbrial microbiopsies were taken, and the ciliated cell percentage was obtained. Results suggest that the ciliation index is a valuable method of prognosis of tubal surgery. In conclusion, the pregnancy rate after distal surgery is related to the tubal morphologic findings: ampullary dilatation, fimbrial ciliated cell percentage, and tubal wall thickness.

Between 1978 and 1983, more than 600 microsurgical tubal operations were performed. Only 270 women with the same extent of distal tubal lesions on both sides or with unilateral tubal occlusion after heterolateral salpingectomy were considered in this study. The authors propose a classification of distal tubal lesions in order to analyze the results of microsurgery. After fimbrioplasty, salpingolysis and salpingostomy for distal occlusion without ampullary dilatation, the term pregnancies rate is more than 50%. The pregnancy rate after salpingostomy for hydrosalpinx is 25%. The prognosis after microsurgery for distal tubal lesions is related to ciliated cells percentage. The prognosis of microsurgical salpingostomy for thick-walled hydrosalpinx is poor. In these cases, in vitro fertilization should be the treatment of preference. In conclusion, the ampullary diameter and the fimbrial ciliated cells percentage are prognostic factors of distal tubal microsurgery.

Fifty patients with moderate or severe endometriosis received 5 mg/day lynestrenol for 6 months prior to microsurgery. A significant regression of the ovarian and peritoneal implants was observed in 72% of the cases after progestative treatment, but the presence of residual epithelium in all cases made surgical resection necessary. After preoperative medical treatment and microsurgery, intrauterine (living births) pregnancy rates of 60 and 47% were obtained in cases of moderate and severe endometriosis, respectively. The following prognostic factors were found in this series: the degree of endometriosis, the concomitant male factors, the decrease of endometriotic lesions after treatment, and the unilaterality of ovarian endometriosis.

Histological study was carried out on human fallopian tubes one hour and one month after various methods of laparoscopic sterilization (unipolar electrocoagulation, bipolar electrocoagulation, silicone ring and Hulka-Clemens clip). Microscopic lesions were observed. Ciliated cells were counted. Deciliation is proved at a distance from the site of sterilization. It has been possible to display the substance loss of the tubal tissues which have to be taken into consideration in case of surgical reanastomosis.

Hydrosalpinges were mechanically induced in rabbits by ligation of the proximal and distal ends of the oviduct. Isthmic and ampullary biopsies were obtained at 2, 4 and 6 months after ligation. Deciliation and decrease of epithelial height were observed in the ampulla, but not in the isthmus. Microstereological study shows a decrease of both the number and the relative volume of capillaries in the ampullary muscularis. Considering the parallelism of time and localization between deciliation and reduction of vascularization, we suggest that epithelial deciliation is caused by vascular disorders. Our study shows also adrenergic denervation occurring in the muscularis.

Microbiopsies of 191 fimbriae were obtained from 146 patients undergoing laparotomy for acute salpingitis, or tubal surgery after salpingitis. The biopsies were classified in four groups according to the diagnosis at laparotomy: salpingitis, distal occlusion, peritubal adhesions or tuberculosis. The biopsies belonging to the group of distal occlusion were further classified in four sub-groups according to the extent of the lesions observed during the hysterosalpingography and laparoscopy. Since the crucial role of the ciliated epithelium in the ovum transport has been established, the percentage of ciliated cells and the epithelial height were determined in the groups and compared to those observed in fimbriae obtained from fertile women during an ovulatory cycle. Significant differences were noted in all groups when compared to fertile women. Acute salpingitis provoked a rapid and severe deciliation which recovered 3 months after triantibiotherapy. In the groups of distal occlusion, there was a significant correlation between the rate of deciliation and the extent of lesions. This suggests that deciliation of tubal epithelium is a sequela of salpingitis and that the extent of disease allows a prognosis of the percentage of ciliated cells.

A total of 162 fallopian tubes was obtained from a sample of subjects comprising fertile women with regular ovulatory cycles, post-menopausal women taking no hormonal drugs and post-menopausal women receiving oestrogen therapy in various forms. During the menstrual cycle the highest percentage of ciliated cells was found, in all of the three tubal portions studied, around ovulation time. The epithelial height decreased significantly subsequent to ovulation. After more than 1 yr had elapsed following the menopause, the percentage of ciliated cells and epithelial height decreased significantly. Very low values were observed in women 10 yr after the menopause. In women receiving oestrogen therapy for more than 10 yr following the onset of menopause - conjugated equine oestrogens (CEE), 1.25 mg/day - the percentage of ciliated cells was significantly higher than that in subjects not receiving hormonal therapy. Similar data were obtained in the case of women taking oestriol (2 mg/day). The data presented demonstrate that oestrogen therapy influences the ciliation and height of oviductal epithelium.