Hisao Osada

Surgical procedure to conserve the uterus for future pregnancy in patients suffering from massive adenomyosis

The treatment for severe adenomyosis has usually been hysterectomy, because there is no line of demarcation between diseased and normal tissue. Yet many such women wish to retain their uterus and some even wish to bear children. This report evaluates the efficacy of a new method of adenomyomectomy, where adenomyotic tissues are radically excised and the uterine wall is reconstructed by a triple-flap method, without overlapping suture lines, to prevent uterine rupture in subsequent pregnancies. This is a prospective case series followed for 10 years from June 1998 to August 2008 of 104 women with severe adenomyosis verified histologically and with magnetic resonance imaging. There was a dramatic reduction in both dysmenorrhoea and hypermenorrhoea and all patients returned to having normal menstrual cycles. Of 26 women who wished to conceive, 16 became pregnant, 14 (53.8%)went to term and delivered a healthy baby and there were no cases of uterine rupture. Adenomyosis symptoms recurred in only four out of 104 cases. The procedure thus resulted in a dramatic reduction in symptoms and allowed over half of women who wished to conceive to go to term without uterine rupture.

Clinical Evaluation of a Haemostatic and Anti-Adhesion Preparation Used to Prevent Post-Surgical Adhesion

TachoComb® consists of equine collagen in a sponge-like form coated on one side with human fibrinogen and bovine thrombin. This product functions as a haemostatic and physical barrier to inhibit post-surgical adhesion. In this study, we investigated TachoComb® to control oozing in 16 patients who required haemostasis. Evaluation of post-surgical adhesion by second-look laparoscopy was performed at 3 months and 7 months after initial surgery. Observation via laparotomy during Caesarean section was also performed at 13 months, 3 years and 4 years after initial surgery. In all but one patient, no macroscopic evidence of TachoComb® persistence was found. Furthermore, no de novo adhesions were detected at the TachoComb® application site. We have thus demonstrated that TachoComb® can be used to control oozing haemorrhage effectively from surgical sites and can prevent adhesion formation at the application site, and may thus be an effective method of preventing adhesion-induced infertility.

The effect of hyaluronic acid-carboxymethylcellulose in reducing adhesion reformation in rabbits.

The effect of hyaluronic acid-carboxymethylcellulose film (Seprafilm®)* in reducing postoperative adhesion formation was examined in a rabbit induced-adhesion model. During laparotomy, the ileocaecal region was mechanically and chemically abraded to induce lesions. After a 28-day recovery period, adhesions were lysed by microsurgery and Seprafilm® was applied to the lysed lesion in 10 rabbits and six rabbits received physiological saline. A third laparotomy was performed 10 – 14 days later and the area of adhesion reformation was compared to that found prior to application of test materials. The area of adhesion reformation with Seprafilm® decreased to (mean ± standard deviation) 11.71 ± 10.97% of the originally lysed lesion and, the area was significantly reduced compared with controls treated with physiological saline. These results suggest that the use of Seprafilm® may be a valuable new anti-adhesion material for abdominal or pelvic surgery and may be superior to existing anti-adhesion materials and techniques.

The Effect of Cross-Linked Hyaluronate Hydrogel on the Reduction of Post-Surgical Adhesion Reformation in Rabbits

The effects of cross-linked hyaluronate hydrogel and liquid sodium hyaluronate on post-surgical adhesion reformation were examined using a rabbit model. Primary adhesions in the ileocaecal region of Japanese white rabbits were induced by mechanical and chemical irritants during laparotomy. After 1 month the primary adhesions were lysed by microsurgery and cross-linked hyaluronate hydrogel or liquid sodium hyaluronate was applied to the lysed lesions. After 10 − 14 days the area of adhesion reformation was measured to assess any inhibitory effect of the test materials. Rabbits treated with cross-linked hyaluronate hydrogel showed a significant reduction in adhesion reformation area compared with liquid sodium hyaluronate or physiological saline treatment, and the area reduced to (mean ± standard deviation) 0.6 ± 1.95% of the original lesion. In a separate study, histological evaluation of rabbits treated with cross-linked hyaluronate hydrogel revealed a better healing pattern and a lower inflammatory response compared with controls. All these findings suggest cross-linked hyaluronate hydrogel may be a valuable anti-adhesion material to prevent post-surgical adhesion in abdominal or pelvic surgery.

Outpatient evaluation and treatment of tubal obstruction with selective salpingography and balloon tuboplasty

OBJECTIVE To compare selective salpingography and balloon tuboplasty for the treatment of tubal obstruction. DESIGN A retrospective evaluation of results of women treated for tubal obstruction by outpatient methods at a single center. SETTING Tertiary-care, university-affiliated hospital. PATIENT(S) A total of 3,424 infertile women, of whom 418 had bilateral tubal obstruction by hysterosalpingography, treated at Nihon Medical Center from 1982 to 1997. INTERVENTION(S) Women with tubal obstructions who had visual evidence of an intact uterine tubal ostium at hysteroscopy were treated by selective salpingography. If selective salpingography could not establish patency, then transcervical balloon tuboplasty was performed with one of three catheter systems. Patients were followed expectantly for 1 year after treatment. MAIN OUTCOME MEASURE(S) Postoperative tubal patency and overall pregnancy rates (PRs) at 1-year of follow-up. RESULT(S) The overall patency rate was 67.5%, with 30% of these patients conceiving (20.2% of all subjects). Selective salpingography was associated with a 35. 7% patency rate, and 27.3% of these patients conceived. Of the subjects who failed selective salpingography and underwent balloon tuboplasty, 66.2% achieved patency, of whom 33% spontaneously conceived. Balloon tuboplasty was effective in restoring patency in many cases after selective salpingography had failed. Statistically significant differences were found between selective salpingography and balloon tuboplasty and for the different balloon tuboplasty catheters in terms of patency rates, while a trend was seen for PRs. CONCLUSION(S) Many women diagnosed as having tubal obstruction can be treated by outpatient methods that do not require general anesthesia. Achieving patency by these methods is associated with high PRs and avoids the need for assisted reproductive technologies in some cases. Balloon tuboplasty is a more effective treatment than selective salpingography. The choice of balloon tuboplasty catheter system may affect success rates.

Fimbrial Capture of the Ovum and Tubal Transport of the Ovum in the Rabbit, with Emphasis on the Effects of β2-Adrenoreceptor Stimulant and Prostaglandin F2α on the Intraluminal Pressures of the Tubal Ampullae

Purpose:Our purpose was to elucidate the roles of the ampullar and isthmic portions of the oviduct and the effects of drugs on oviductal contractility.Methods:Prostaglandin F2α (PGF2α; Ono Pharmaceuticals, Osaka) and oxytocin (Atonin-O; Teikoku Hormone Manufacturing Co. Ltd., Tokyo) were used to stimulate oviductal contractility, and ritodrine hydrochloride (Utemerin; Solvay-Duphar Corp., Denmark) to inhibit the contractility.Results:Both PGF2α and Atonin-O were involved in ovum capture by the ampullar oviduct by stimulating contractility, thus altering the intraductal pressures. Utemerin is effective in inhibiting the enhanced contractility induced by PGF2α and Atonin-O.Conclusions:Variations in pressure of the ampullar portion of the oviduct seem necessary for the capture of ova expelled from the ovary. Once in the isthmic portion of the oviduct, transport appears to be under the influence of ciliary activity rather than variations in contractility.

Use of fibrin adhesive to reduce post-surgical adhesion reformation in rabbits

Following surgery on fallopian tubes, the development of adhesions is a natural consequence of wound healing and may result in infertility. Using a rabbit model, we evaluated the anti-adhesive properties of a sponge-like equine collagen sheet (TachoComb®), which is coated on one side with human fibrinogen and bovine thrombin. TachoComb® is applied by affixing the sheet over the area of perforation or bleeding and acts as a haemostatic agent, capable of sealing perforations to prevent leakage. In our rabbit model, adhesions were induced by mechanical and chemical irritants during laparotomy. After a 1-month recovery period, adhesions were lysed using microsurgical techniques and TachoComb®, or physiological saline applied. Evaluation of adhesion reformation was determined after a minimum of 10 days. TachoComb® significantly reduced the area of adhesion reformation compared with rabbits treated using physiological saline only. Our study demonstrated that TachoComb® is effective not only as a haemostatic agent, but is also capable of reducing adhesion reformation.

The Yield of Abnormal Unfertilized Eggs Observed after Repeated Gonadotrophin-Induced Ovulation

This study investigated whether or not the yield of abnormal eggs produced after repeatedly induced ovulation could be reduced by increasing the interval between gonadotrophin (GTH) administrations. Ovulation was induced, in a mouse model, by subcutaneous injection of pregnant mare serum GTH and human chorionic GTH given once (n = 10), twice (n = 10), three times (n = 10) or four times (n = 10) at intervals of 5 days. In 30 further mice, a fifth induction was performed either 5 (n = 10), 10 (n = 10) or 20 days (n = 10) following the fourth injection. Oviducts were examined microscopically, and the eggs were counted and examined for morphological abnormalities. In the mice who had received four GTH treatments, 33.3% (12 of 36) of the eggs were abnormal. After the fifth induced ovulation performed after an interval of 5, 10 or 20 days, the yield of abnormal eggs was 50.0% (five of 10), 23.1% (nine of 39) and 15.2% (seven of 46), respectively. These results indicate that prolongation of the interval between GTH administrations reduced the yield of abnormal eggs produced following repeatedly induced ovulation.

Investigation of Ovum Transport in the Oviduct: The Dynamics of Oviductal Fluids in Domestic Rabbits

Ova are captured by the oviductal fimbria and rapidly transported to the ampullary-isthmic junction of the fallopian tube. Fertilized ova and oviductal fluids are then carried medially in the fallopian tube, while undergoing maturation in preparation for entering the uterine cavity, where nidation and further development take place. This movement of oviductal fluids was visualized in a rabbit model with human chorionic gonadotropin-induced ovulation, by injection of a contrast medium into the ampulla region of the oviduct. In the ampulla, the opaque medium was observed to oscillate at 0 − 85.4 mm/s. This medial transport of the fluid towards the uterus decreased to 0 − 9.6 mm/s in the isthmic portion of the tube. This decrease substantiates previous findings that the transport of material in the isthmic portion of the oviduct is more strongly under the control of ciliary action than under peristaltic activity.

Inhibitory effects of indomethacin on implantation and its related phenomena.

The dose-response relationship for the inhibitory effect of indomethacin on implantation and continuance of pregnancy was examined in four groups of rabbits administered with indomethacin (2.5, 5.0, 7.5 and 10.0 mg/kg) during the implantation period and compared with a control group. Implanted fetuses and corpora lutea were counted by laparotomy, and the number of offspring born was noted. The inhibitory effect of indomethacin on implantation was found to be dose–dependent, and the birth rate decreased in the indomethacin groups compared with the control group. As a result, even where implantation had been achieved, death of the implanted fetuses occurred at a high rate in rabbits administered with indomethacin during the implantation period.