Risk factors for uterine fibroids among women undergoing tubal sterilization.

Uterine leiomyomas are reported to be the most common benign gynecologic tumors affecting premenopausal women, and they are often associated with considerable morbidity. The purpose of this study was to identify risk factors for uterine fibroids among women undergoing tubal sterilization. Cases comprised women aged 17-44 years whose uterine fibroids were first visualized at the time of tubal sterilization (1978-1979 or 1985-1987) or who reported a history of uterine fibroids (n = 317). Controls were randomly selected from women with no laparoscopic evidence of or history of fibroids (n = 1,268). Adjusted odds ratios were estimated using unconditional logistic regression separately for White (n = 1,235) and African-American (n = 350) women. Risk factors for White women included: age 40-44 years (odds ratio (OR) = 6.3; 95% confidence interval (CI): 3.5, 11.6), > or =5 years since last delivery (OR = 1.9; 95% CI: 1.1, 3.1), lifetime cigarette smoking of > or =1 pack/day (OR = 1.6; 95% CI: 1.1, 2.3), menstrual cycle length of >30 days (OR = 1.6; 95% CI: 1.1, 3.3), and menstrual bleeding for > or =6 days (OR = 1.4; 95% CI: 1.0, 2.0). Parous women were at reduced risk compared with nulliparous women (OR = 0.2; 95% CI: 0.1, 0.3). Advancing age was the only significant risk factor for African-American women (ages 40-44 years, OR = 27.5; 95% CI: 5.6, 83.6). Current oral contraceptive use and elective abortion were not associated with fibroids.

Laparoscopic findings in patients with pelvic pain.

We have reviewed 1,194 charts of consecutive patients who had a diagnostic laparoscopy for pelvic pain from January 1, 1972, to December 31, 1980, at the Deaconess Division of the Buffalo General Hospital. A total of 749 of these patients had normal pelvic examinations prior to the diagnostic laparoscopy; 479 (63%) had abnormal findings on diagnostic laparoscopy. Of the 445 patients with abnormal pelvic examinations, 78 (17.5%) had normal findings on diagnostic laparoscopy. The laparoscopic findings and ovarian pathology are reviewed. These results are substantiated by other reports in the literature and certainly justify the increasing use of the laparoscope as a diagnostic tool in the gynecologist's armamentarium.

Complications of laparoscopic tubal sterilization.

The experience of laparoscopic sterilization in 5018 cases at the Deaconess Division of Buffalo General Hospital over a period of 8.5 years is presented. The procedure was completed in 4992 cases, with a complication rate of less than 1% and with no operative mortality. One half of the patients with complications required a laparotomy. Bleeding was the most common complication; it accounted for exactly one half the complications. The laparotomy rate for all complications was 4.6 per 1000 cases. Seven ectopic and 4 intrauterine pregnancies occurred after this procedure, for a method failure rate of 2.2 per 1000 cases. Recommendations for prevention and management of complications are presented.

PIP: 5018 cases of laparoscopic tubal sterilization were attempted by the gynecologic staff of the Deaconess Hospital, Buffalo, from February 1970-August 1978. The procedure was completed in 4992 cases. A 2-puncture technique was employed with tubal coagulation with or without resection of the tube. A single or double-burn technique was use to coagulate a 1.5-2 cm segment of the tube. The CSV Bovie Generator was the electrocoagulation unit, and the unipolar Palmer-Jacobs biopsy forceps were the coagulating forceps. Abortion was performed on 861 (17%) patients at time of sterilization. The complication rate was less than 1%, with no mortalities. Bleeding was the most common complication. Half the patients with complications required a laparotomy. The laparotomy rate for all complications was 4.6/1000. After this procedure, 7 ectopic and 4 intrauterine pregnancies occurred, for a method failure rate of 2.2/1000. Preoperative preparation consisted of a sleeping medication at the patient's request, nothing taken after midnight; and parenteral administration of atropine, .4 mg, or Robinul, .2 mg, .5 to 1 hour prior to surgery. A general anesthetic was given through a cuffed endotracheal tube and a muscle relaxant administered during the procedure to reduce unnecessary movement by the patient.

[Pregnancy following laparoscopic tubal electro-coagulation and division (author's transl)].

PIP: Between 1970-1975 the authors performed 3160 laparoscopic tubal electrocoagulations and divisions on women desiring permanent sterilization. While the literature reports a failure rate of 0.2% on sterilizations performed with such a procedure, in the series considered there were 16 pregnancies, i.e., a failure rate of 0.51%. However, 7 patients were already pregnant at the time of tubal sterilization, bringing the failure rate down to 0.28%. Of these 9 unwanted pregnancies 6 were ectopic. The result of this investigation induced the authors to modify their sterilization procedure, and to use only wide electrocoagulation with the bipolar forceps.^ieng

Pregnancy following laparoscopic tubal electrocoagulation and division.

PIP: In a series of 3160 sterilization procedures performed by laparoscopic electrocoagulation and division, 16 pregnancies were reported. 9 of these failures were attributable to surgical error, for a surgical failure rate of .28%. It is suggested that these patients had microscopic tuboperitoneal fistulas in the cut ends of the tubes, and that fertilization occurred on the ovarian surfaces rather than in the oviduct ampullae. 5 of the pregnancies were ectopic, and all were found in the distal ends of the tube. The authors have modified the surgical technique by eliminiating division and using only wide electrocoagulation, with the triple-burn technique of Wheeless, and the Kleppinger bipolar forceps, in hopes of improving the success rate. The modifications also eliminate the risk of burns from unipolar current and of hemorrahage from biopsy.^ieng

Progestational agents and blood coagulation. VIII. Effect of low-dose, alternate-day, estrogen-progestin combinations on blood coagulation factors in man, with a special note on the effect of freezing of blood samples.

Changes in the blood coagulation system were studied in three groups of 20 patients each. The first group received 0.5 mg. of norethindrone daily, plus 0.06 mg. of ethinyl estradiol on alternate days from cycle Day 5 through 25. The second group, all of whom had been fitted with an intrauterine contraceptive device (IUD), received no hormonal treatment and served as a control group. The third group received 0.5 mg. of norethindrone daily, combined with 0.045 mg. of ethinyl estradiol given on alternate days from cycle Day 5 through 25. Blood samples were drawn prior to the initiation of the study and after three months of treatment. Tests of the following parameters of the blood coagulation system were performed: direct platelet count; platelet adhesiveness; prothrombin time; thrombin time; fibrinogen; factor II assay; activity of factors V, VII, VIII, IX, and X; antithrombin III; and fibrin/fibrinogen degradation products. For a number of these factors, both fresh and frozen blood samples were examined. It was concluded that the two treatment regimens, with the use of alternate-day estrogen administration over a three-month period, had no clinically significant effect on the blood coagulation system.

PIP: The effect of combined, low-dose oral contraceptives on blood coagulation factors was studied in 60 healthy women. 20 women received .5 mg/day norethindrone plus .06 mg ethinyl estradiol on alternate days of the cycle from Days 5 through 25, another group of 20 received an IUD, and a 3rd group of 20 received .5 mg/day norethindrone plus .045 mg ethinyl estradiol on alternate days of the cycle from Days 5 through 25. Blood samples were taken before and after 3 months of treatment. No clinically significant (P greater than .05) effect of either treatment regimen on such blood coagulation factors as platelet count, platelet adhesiveness, prothrombin time, thrombin time, fibrinogen, Factor 2 assay, Factors 5, 7, 8, 9, and 10, and fibrin/fibrinogen degradation products could be established. Both fresh and frozen blood samples were used in the study.

Prevention of hyaline membrane disease with plasminogen. A cooperative study.

In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.

Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study.

During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.

PIP: A summary of a 10-year study on thromboembolic and other complications of oral contraceptive (OC) therapy in relationship to pretreatment levels of blood coagulation is presented. 348 women were studied for a total of 5877 patient months in 4 separate studies. Increases in certain factors of the blood coagulation and fibrinolysin systems (factors 1, 2, 7, 8, 9, and 10 and plasminogen) were observed in treated groups. 4 patients developed severe complications and all 4 had an abnormal blood coagulation profile suggesting "hypercoagulability" be fore initiation of therapy. 1 patient developed retinopathy 19 months after she began therapy and another developed thrombophebitis after 27 months of therapy. The 4th patient developed thrombophlebitis 2 weeks after initiation of therapy. All 4 patients were of the A or AB blood group. These data suggest that hematologic work-ups may be useful in women about to start OC therapy.

Studies on the prevention of respiratory distress syndrome of infants due to hyaline membrane disease with plasminogen.

Hyaline membrane disease (HMD) is leading single cause of death of newborn, premature infants. The "hyaline membranes" consist chiefly of fibrin. The clinical manifestation of HMD is the respiratory distress syndrome (RDS). Infants with RDS were treated with urokinase-activated human plasmin in a previous clinical trial. Survival rate was increased in the plasmin treated group as compared to the placebo recipients. However, cost and difficulty in the preparation of the enzyme made this treatment impractical. We, as well as others, have shown the premature infants lack serum plasminogen; thus they are unable to develop effective fibrinolysis and are defenseless against pulmonary fibrin deposition. Therefore, plamsinogen was tested as a possible preventive agent in RDS due to HMD. In a double blind, randomized study, infants between 1 and 2.5 kg birth weight received plasminogen or placebo shortly after birth, and were then followed for development of RDS. After 100 infants were entered into the study, the code was broken and results were evaluated to assure safety of the procedure. Among the 100 infants, 51 received placebo, 49 received plasminogen. Among the infants who received placebo, seven developed mild, and ten developed severe respiratory distress; of these ten, five died with histopathologically documented HMD. Two infants died from causes other than HMD. Among the 49 infants treated with plasminogen, 13 developed mild and three developed severe respiratory distress. There was no death due to HMD. Two deaths were due to other causes. Factors placing the infant at risk from HMD (degree of prematurity, sex, cesarean section, bleeding episodes during pregnancy, maternal diabetes) were found to be evenly distributed between control and treated groups. Since completing the first phase of the study, data of an additional 277 infants has become available. Although the code was not broken in this series, a preliminary look at mortality data in comparison with mortality data of the first series of 100 (in which the code was broken) suggests that preventive activity of plasminogen has been maintained in the second phase of the study.

Thromboembolic complications of oral contraceptive therapy.

During a ten-year period, 348 women were studied for a total of 5877 patient months for changes in hematologic parameters induced by oral contraceptives. Significant increases were observed in Factors I, II, VII, VIII, IX, X and plasminogen. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. All four patients were of A or AB blood group. It appears from these data that hematologic workups may be useful in women who are about to embark on long-term oral contraceptive therapy.

Progestational agents and blood coagulation. V. Changes induced by sequential oral contraceptive therapy.

PIP: Blood coagulation changes induced by sequential oral contraceptive (OC) therapy were studied. 112 healthy women volunteers were monitored over a 2-year period while on a regimen of sequential OC therapy (50 mcg ethinyl estradiol daily from Day 5 through 14 and 50 mcg ethinyl estradiol plus 1 mg morethindrone acetate on Day 15 through 25). The treated group showed marked increases toward hypercoagulability in the Hicks and Pitney thromboplastin generation time screening test at 3 and 9 months, Factor 5 at 9 months, Factor 8 at 3 and 9 months, and fibrinogen at 3 months. Decreases from base lines were seen in antiplasmins at 24 months and in alkaline phosphatase at all intervals (3, 9, and 24 months). It was suggested that the decrease in serum antiplasmin indicates a compensatory tesponse in the fibrinolytic system to the hyperactivity of the coagulation system.^ieng

Combined laparoscopic sterilization and pregnancy termination.

PIP: This is a report of 306 dilation and suction curettage abortions combined with laparoscopic tubal ligations over a 2 1/2 year period. Patients' ages ranged from 21 to 44 years. All were multigravida and in the first trimester of their current pregnancy. 61 had undergone previous abdominal surgery. Average hospital stay was 1 day. Patients are preferably admitted the night before so a laminaria digitata tent can be placed to dilate the cervix. General anesthesia is used and occasionally the patient is intubated if conditions indicate. Insulated instruments are sterilized for 30 minutes in a solution of aqueous cidex or activated dialdehyde. After the area is prepared with Betadine, Hegar cervical dilators are used to dilate the cervix 1 size larger than the suction curette. Care needs to be exercised in making traction on the cervix at the time the dilator is introduced. Berkley suction apparatus is used with negative pressure of 60-70 mm of mercury. Manipulation of the suction curette to reach all areas is required. Blood loss is usually 50-200 ml. This may be minimized by adding Pitocin or Syntocinon to the anesthetic solution. A single-tooth tenaculum and a tubal insufflation cannula control the uterus during the subsequent sterilization procedure. The Verres cannula is inserted paraumbilically and 2.5-3 liters of carbon dioxide injected into the peritoneal cavity. Over distention is to be avoided. A second smaller cannula is inserted. The Palmer biopsy tong is inserted. Each tube is manipulated, grasped, coagulated, severed, and a biopsy taken. Care must be taken not to touch the tip of the tongs to the trocar sleeve. After checking the area the instruments are withdrawn and the carbon dioxide allowed to escape. Incisions are approximated with adhesive bandages. The patient may be discharged 3 to 6 hours after operation. Postoperative hysterosalpingograms on 14 of the 306 women showed no tubal potency in 13 at 8 months after surgery. Tubal peritoneal fistulas were shown in 1. 1 patient became pregnant 6 months after surgery but spontaneously aborted. The uterus was perforated once but immediately repaired. Procedures as used are recommended because of ease, safety, and economy.^ieng

Progestational agents and blood coagulation. IV. Changes induced by progestogen alone.

PIP: To evaluate the effects of chlormadinone acetate upon the coagulation of blood and fibrinolysin systems, 35 healthy, young women voluntarily using some form of birth control were studied. 10 women who served as controls used intrauterine devices; 25 women took either a progestin-estrogen (1 mg norethindrone acetate and 1 mg mestranol) combination or a synthetic progestational agent (0.5 mg chlormadinone acetate) on a coded, double-blind basis. Platelet counts, thrombelastograms, and plasma assays were performed prior to and after 3 and 6 months of treatment. After 3 months, those taking progestin-estrogen showed a highly significant increase toward hypercoagulability in Quick time, Factors II, VII, and X, and increased levels in the thromboplastin generation time (TGT), Factors V and IX, and plasminogen. At 6 months all levels remained elevated except for TGT. Those on chlormadinone acetate had only a slightly significant change toward hypercoagulability in Quick time and Factor VIII, an increase in Factor IX, and a decrease in Factor X. In the control group only TGT was elevated. The progestin alone induced only minimal changes in comparison to the marked rises accompanied with progestin-estrogen therapy.^ieng