The effect of treatment on experimentally produced endometrial peritoneal implants.

Endometriosis was induced surgically by implanting pieces of endometrium in the uterine mesenteries of 50 rats. Their fertility was then assessed after various treatments. Ten rats with endometriosis were treated with microsurgical excision of implants, 10 with high-frequency diathermy, 10 with danazol, and 10 with intraperitoneal indomethacin. Ten more rats had implants that were left untreated. The results were compared with those of ten rats that had sham surgery with implantation of fat in the uterine mesenteries. Reproductive performance was better in control animals with sham surgery than in animals with endometrial implants. Maximum restoration of fertility was achieved with indomethacin. Microsurgery and danazol therapy both were effective in preventing residual endometriosis, but the animals tended to be less fertile after treatment. Adhesions were most pronounced after diathermy and least pronounced after microsurgery or indomethacin therapy. In rats treated with indomethacin, persistent endometriotic cysts were invariably smaller near the site of intraperitoneal injection: this suggests a local antiprostaglandin effect.

A prostaglandin analogue (ONO-802) in treatment of missed abortion, intrauterine fetal death and hydatiform mole: a dose-finding trial.

Forty-eight patients affected with missed abortion, intrauterine fetal death and hydatiform mole were treated with vaginal suppositories containing 1 mg of 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802). The patients were divided into two treatment groups. The first, Group A, was given one vaginal suppository every 3 h to a maximum of five suppositories. The product of conception was expelled in 95.8% of patients. In Group B the maximum number of suppositories was reduced to three. The product of conception was expelled in 100% of cases and the average duration of treatment was similar to that for the first group. Although side-effects were mild in both groups, they were reduced in the patients of Group B.

Scanning electron microscopy of rabbit tubes at different intervals after anastomosis using fibrin glue.

Eighteen New Zealand White rabbits were submitted to tubal anastomosis using fibrin glue. The animals were then killed at different intervals (2-56 days) and the tubes were removed for analysis with the scanning electron microscope in order to study re-epithelialization and ciliogenesis. For the first 4 days after the operation the epithelium seemed to suffer considerable traumatic effects and was de-epithelialized. On the 6th day cells with microvilli appeared and towards the 10th day the first cilia were seen. Ciliogenesis was complete between 2 and 4 weeks after the operation, at which time the cilia re-acquired the ability to beat in coordination, as well as attaining normal quantity and length. The time required for recovery by the epithelium after anastomosis with fibrin glue would thus seem similar to that required when other suture materials are used. Fibrin glue thus combines the advantage of a considerable reduction in operating times with the ability to be rapidly reabsorbed, with complete restitutio ad integrum of the tissues.

Fibrin glue vs. nylon in the anastomosis of rabbit fallopian tubes.

Fibrin glue was used in end-to-end tubal anastomosis on eight sexually mature female New Zealand white rabbits. The right fallopian tubes were anastomosed with 10/0 nylon and the left with fibrin glue (Tissucol). The animals were mated with males of proven fertility six weeks after surgery and killed two weeks later. The gestational sacs and corpora lutea on the right and left sides were counted separately and the nidation index calculated for each. The presence of adhesions was also evaluated. All the tubes were finally examined under a scanning electron microscope. The fibrin glue was satisfactory in terms of patency, pregnancy and morphology of the epithelium.

Evolution and reversibility of damage to rabbit fallopian tubes after five sterilization methods.

The authors used a scanning electron microscope to study epithelial damage to the rabbit fallopian tube after sterilization with different methods and its subsequent capacity to regenerate after recanalization. Thirty female NZW rabbits were divided into five groups and sterilized using the following methods: 1) Madlener 2) Pommeroy, 3) clips, 4) unipolar coagulation, 5) bipolar coagulation. Each group was divided into subgroups of two and submitted at differing intervals to a second laparotomy, during which one tube was removed and the other anastomosed according to Winston's method. Four weeks after the second laparotomy all the rabbits were sacrificed, the remaining tube removed, and all tubes examined with the scanning electron microscope. The results indicate that mechanical methods of occlusion such as clips offer greater recovery possibilities than those in which the lesion is extended to the mesosalpinx. There further exists a correlation between the time that elapses after sterilization and regeneration of the epithelium.

Fulguration versus resection of experimental endometrial peritoneal implants in the rat.

Endometriosis was induced in 20 rats. Treatment by diathermy was compared to treatment by microsurgical resection of endometrial implants. No significant differences were found between the 2 groups regarding ovulation, nidation index or pregnancy rates but significant difference in the extent of adhesion formation after surgery was evident. There were fewer adhesions in the microsurgical group. As the adhesions here were periuterine (and not peritubal as in the human) this could explain the lack of impact on the actual fertility of these rats.

Experimental endometriosis and fertility: compared effects of an antigonadotropin (danazol) and an antiprostaglandin (indomethacin).

The possible role of prostaglandins in infertility associated with endometriosis is not fully understood. We therefore compared the efficacy of danazol, the drug chosen for treating this disease with that of indomethacin, an anti-prostaglandin, in rats affected with experimentally produced endometriosis. Endometriosis was induced in two groups of ten rats. The rats in group A were given danazol orally and those in group B were given peritoneal injections of indomethacin. The resulting fertility rates were very good in group B and less so in group A. Group A showed better anatomical findings, but group B gave improved results regarding adhesions.

GNRH therapy in hypothalamic primary amenorrhea.

Pulsatile administration of GnRH appears to be the most rational and physiological treatment of infertility in patients affected by hypothalamic amenorrhea. The authors conclude that the results obtained with this method of treatment (all patients became pregnant) suggest that the choice of pulsatile GnRH therapy is an effective and practical method for induction of ovulation.

Current therapeutic possibilities of GIFT.

We have used GIFT in 74 couples affected with unexplained sterility, male hypofertility, endometriosis, phymosis of the fimbria and adhesions impeding oocyte pick-up. We systematically desensitized the pituitary using a GnRH analog from the 20th day of the cycle preceding GIFT. All the patients were hyperstimulated with purified FSH and hMG (Metrodin and Pergonal-Serono) from the 3rd day of the cycle. When several follicles were obtained woth a diameter greater than 16 mm together with serum estradiol values of 300 pg/ml per follicle, 10,000 IU hCG were administered intramuscularly in a single dose (Profasi-Serono). A maximum of 5 oocytes per patient were transferred (2-3 per tube). Our results confirm the validity of the GIFT method, with an average success rate of 19% in all pathological conditions and a far greater success rate in couples with unexplained sterility than in those with male hypofertility (31% and 10% respectively). The Authors stress that the best results of GIFT were achieved when the ratio between E2 and follicles with a diameter greater than 16 mm was in excess of 500 pg/ml.

Polydioxanone in anastomosis of rabbit tubes. A morphological study of the epithelium.

Eight NZW rabbits were submitted to end-to-end tubal anastomosis using polydioxanone (PDS), (Ethicon). The animals were sacrificed at two-week intervals between the second and sixteenth week after operating. The tubes were removed and analysed with the scanning electron microscope for the purpose of studying the morphology of the epithelium. Ciliogenesis was completed between the second and fourth weeks. After this period the epithelial conditions observed were completely normal, except for an abundant mucous secretion which, however, was totally normal after sixteen weeks.

Pharmacological prevention of postoperative adhesions experimentally induced in the rat.

In order to evaluate the preventive action of certain drugs in the formation of adhesions, three different types of trauma were induced in the uterine horns of 105 female Wistar rats. The animals were divided into six groups of 15 rats each and to each group was administered respectively: aprotinin i.p.; hydrocortisone i.p.; dextran 70 i.p.; colchicine i.p.; saline i.p.; colchicine i.m. One more group of 15 rats was left without treatment, as control. Four weeks later the adhesions were evaluated according to a qualitative/quantitative score and the results analysed using advanced statistical analysis. Aprotinin achieved the best results both in and around the trauma areas. Dextran produced an overall reduction of adhesions, but showed no specific effect on the trauma areas. The other substances failed to improve the adhesion situation.

Indomethacin and fertility in experimental endometriosis.

Clinical and experimental evidence showed an increased concentration of prostaglandins in peritoneal fluid in cases of endometriosis. The aim of this study was to verify whether an antiprostaglandin drug can restore fertility in cases of endometriosis. For this reason endometriosis was induced in 4 groups of 10 rats. Group A was treated with indomethacin both in the pre-ovulatory and in the post-ovulatory phase. Group B was treated in the pre-ovulatory phase. Group C was treated in the post-ovulatory phase. Group D was not treated. Ten other rats (group E) underwent a sham operation and were used as a control. Twelve days after mating, gestational sacs and corpora lutea were counted and the nidation index was calculated. Only indomethacin administered during the pre-ovulatory phase completely restored fertility in these rats.

LH-HCG receptors: a study of the human corpus luteum of pregnancy.

Experiments on binding 125I-LH and 125I-HCG by the human luteal tissue of early pregnancy showed no certain presence of receptors. On the other hand, studies performed with cyclic luteal tissue demonstrated the presence of high specificity, significant affinity receptors. Possible interpretations with reference to the physiological increase in HCG and/or to the characteristics of extrauterine pregnancy are discussed.

Effect of drug-induced hyper- and hypoprolactinemia on human corpus luteum.

This study was performed on 8 patients with normal levels of PRL and ovulatory cycles. Three of these patients were treated with 5 mg/day Bromocriptine and three of them with 60 mg/day Metoclopramide from the beginning of the cycle in order to induce hypo- and hyperprolactinemia respectively. The other two women were left as control. Daily blood samples were collected for the determination of PRL, LH 17 beta-Estradiol and Progesterone. Patients were operated on between the 6th and the 8th day after the LH peak and corpora lutea enucleated and frozen for subsequent 125I-LH binding tests. An analysis of our data demonstrates that hypo- and hyper- prolactinemia induced with Bromocriptine and Metoclopramide respectively may cause luteal insufficiency, which is revealed by decreased blood levels of progesterone. Furthermore we have observed that specific binding for LH in human luteal tissue is always present (in normal, hypo- and hyperprolactinemic women) but is reduced in presence of very high or very low levels of PRL.

Induction of ovulation with purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome.

Purified urinary follicle-stimulating hormone was used to induce ovulation in 18 patients with polycystic ovarian syndrome. Each ampule contained 75 IU of follicle-stimulating hormone and less than 0.11 IU of luteinizing hormone. Initial doses were 150 to 225 IU/day, later increased to a maximum of 375 IU, according to daily clinical controls and estradiol values. After 12 to 16 days, follicle-stimulating hormone treatment was suspended. Within 36 to 48 hours each patient received 5000 or 10,000 IU of human chorionic gonadotropin, rarely more. Ovulation occurred in 39 of 43 treatment cycles and hyperstimulation in nine. Seven patients had normal pregnancies with viable fetuses, including one pair of twins. Two had abortions. Analysis of the endocrine situation during therapy does not permit either pregnancy or hyperstimulation to be predicted. However, hyperstimulation is frequently accompanied by endogenous luteinizing hormone peaks and greater estradiol increases during the final phase of induction. Purified follicle-stimulating hormone has thus demonstrated its validity in inducing ovulation in patients with polycystic ovarian syndrome, apparently with equal or lower risks of hyperstimulation than with other gonadotropin preparations.