A gonadotrophin-releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis.

OBJECTIVE: To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post-operative hormonal therapy compared with women treated with surgery only. Pregnancy rates and time to conception in women wanting children were also evaluated. DESIGN: A multicentre, prospective, randomised controlled study. SETTING: Nineteen Italian academic departments and teaching hospitals specialising in reparative and reconstructive surgery. POPULATION: A total of 269 women undergoing conservative surgery for mild to severe symptomatic endometriosis. METHODS: After surgery the women were assigned to treatment with subcutaneous goserelin depot injections for six months or to expectant management. Dysmenorrhoea, deep dyspareunia, nonmenstrual pain and general discomfort were graded according to a verbal rating scale from 0 (absent) to 3 (severe) and the scores summed to give a total symptoms score. Only patients with at least one preoperative moderate or severe symptom were enrolled. The women were evaluated regularly for two years. MAIN OUTCOME MEASURES: Post-operative pain recurrences (total symptoms scores > or = 5), time to recurrence, pregnancy rates and time to conception in the two study groups. RESULTS: At one- and two-year follow up visits, 14/107 (13.1%) and 19/81 (23.5%) patients had moderate or severe symptoms recurrence in the goserelin group compared with, respectively, 22/103 (21.4%) and 27/74 (36.5%) in the expectant management group (P = 0.143 at 1 year and 0.082 at 2 years). Time to symptoms recurrence was significantly longer in the goserelin group according to survival analysis (Wilcoxon test, P = 0.041). Among women wanting children, few conceptions occurred in both the goserelin (8/69, 11.6%) and the expectant management group (14/76, 18.4%). There was no significant difference at survival analysis (Wilcoxon test, P = 0.427). CONCLUSION: Post-operative treatment with goserelin significantly prolonged the pain-free interval after conservative surgery for symptomatic endometriosis and did not influence reproductive prognosis.

[Use of nomegestrol acetate in the treatment of menstruation disorders. Our experience in 56 cases]. / Utilizzo del nomegestrolo acetato nella terapia delle irregolarità mestruali. Esperienza di 56 casi.

OBJECTIVE: To investigate tolerability and efficacy of nomegestrol acetate, a new 19-nor-progesterone derivative, in the treatment of oligomenorrhea and amenorrhea; to compare this drug with didrogesteron, a widely-used spatial isomer of progesterone. METHODS: 56 women, aged 22 to 50, affected by menstrual disorders or premenstrual syndrome, entered the study. They were divided in two homogeneous groups by randomization. In the first group nomegestrol acetate was administered 5 mg daily per os; in the second group patients were treated by the usual didrogesteron dose, that is 10 mg twice a day per os; both treatments were administered for 10 days from day 16, during three consecutive menstrual cycles. Efficacy, compliance and biological tolerance were evaluated. RESULTS: 24 patients in the group treated by nomegestrol acetate and 22 in the group treated by didrogesteron completed the study. After the first cycle of therapy, nomegestrol acetate showed a higher efficacy in reducing menstrual loss; results are statistically homogeneous in the two groups at the end of the study. There were no reports of pain in both the groups. Evaluation of biological and clinical parameters at the end of the study did not show significant modifications in any subject. CONCLUSIONS: Nomegestrol acetate is an innovative and efficient molecule in the treatment of menstrual disorders. A good response to the drug is evident in a short time and with very low doses; its good compliance, if compared with other progesteron-derivatives, indicates nomegestrol acetate as a first-line therapy for polymenorrhea, olygomenorrhea and premenstrual syndrome.

[Preliminary experience with a new tumor marker in obstetrics and gynecology: UGP (Urinary Gonadotropin Protein)]. / Esperienze preliminari con un nuovo marcatore tumorale in ostetricia e ginecologia: UGP.

AIM: To evaluate the use of UGP (urinary gonadotropin protein) as a tumor marker in gynaecologic and obstetric malignant diseases. MATERIALS AND METHODS: The study was carried out in the division of Gynaecology and Obstetrics of the Ospedali Riuniti in Bergamo. 63 patients, with obstetric or gynaecologic benign or malignant diseases, entered the study. 66 healthy volunteers were examined as a group-control. In both the groups UGP levels were determined in morning urine, using an immunoenzymatic commercial kit. RESULTS: Results, expressed in fmol UGP/ml of urin, show that UGP is produced by several neoplasms, but the false-positive percentage is still high; a higher precision can be obtained with an accurate choice of the cut-off value and with a standardization of the analytical technics. Besides, the contemporary determination of UGP and CA 125 levels reduces the possibility of false-positive and false-negative results. CONCLUSIONS: More studies must be carried out to confirm the value of UGP as a tumor marker in obstetrics and gynaecology. Anyway, this recently purified protein can already be useful, in combination with the usual tumor markers, in the prompt diagnosis and management of primary neoplasms or recurrences, with a higher sensibility in comparison with traditional clinical and radiological examinations.

Immunotherapy and recurrent abortion: a randomized clinical trial.

We conducted a randomized trial comparing expectant management versus immunotherapy with paternal leukocytes to improve obstetric outcome in women with unexplained recurrent abortion. Eligible for the study were women with unexplained recurrent abortion (three or more miscarriages and no live birth), negative findings of immunological screening and no inhibition of the mixed lymphocyte culture. These women were seen for the first time between October 1988 and March 1991 in a network of obstetric departments in Northern Italy. Subjects positive for HLA DR3 or with a partner positive for hepatitis virus B antigen were not eligible. A total of 44 women entered the study. Patients were randomly allocated to immunotherapy (22 women) or expectant management (22 women). Women allocated to immunotherapy were given 200 x 10(6) purified paternal lymphocytes before pregnancy. Median follow-up was 24 months (range 10-39) in the immunotherapy group and 25 months (range 11-38) in the expectant management group. Out of the 22 women randomized to immunotherapy, 16 became pregnant and the corresponding value was 14 in the expectant management group. Spontaneous abortion occurred in six out of the 16 pregnancies observed in the treated women. Among the 14 pregnancies observed in the expectant management group, two aborted and one late fetal death occurred. The cumulative proportions of women who became pregnant over 4 years were 37 and 45% in the immunotherapy and expectant management groups respectively; this difference was not significant. No adverse effect was observed in treated women.

Antiphospholipid antibodies and risk of intrauterine late fetal death.

STUDY OBJECTIVE: Goal of the study was to analyze the relationship between anticardiolipin antibodies, lupus anticoagulant and the risk of intrauterine late fetal death. DESIGN: A case-control study was conducted in a network of general and teaching hospitals in northern Italy. Cases studied were 99 women (median age 27 years), without clinical evidence of systemic lupus erythematosus or other immunological disorders who had an 'unexplained' intrauterine fetal death at or after the 20 weeks of gestation. The control subjects were 85 women (median age 28 years) who gave birth at term (> 37 weeks gestation) to healthy infants on randomly selected days at the same hospitals where cases had been identified. RESULTS: The presence of lupus anticoagulant was detected in four of the 99 cases (4%, 95% confidence interval 2%-15%) and none of the 85 controls. A total of 10 out of the 89 cases (11%, 95 confidence interval 6%-23%), but none of the 79 controls for whom anticardiolipin antibodies value was available had elevated anticardiolipin antibodies; this difference was statistically significant (chi 2(1) = 9.38, p < 0.01).

Buserelin acetate versus expectant management in the treatment of infertility associated with minimal or mild endometriosis: a randomized clinical trial.

OBJECTIVE: We performed a randomized clinical trial to evaluate the efficacy of intranasal 400 micrograms buserelin three times daily for 6 months versus expectant management in the treatment of infertile women with pelvic endometriosis stage I or II of the revised American Fertility Society classification. STUDY DESIGN: Seventy-one consecutive patients (mean age 32 years) were studied at the First Department of Obstetrics and Gynecology, University of Milan, and the Department of Obstetrics and Gynecology, Ospedali Riuniti, Bergamo, between February 1988 and June 1989. Thirty-five women were randomly allocated to buserelin treatment and 36 to expectant management. The baseline distribution of subjects for age, disease stage, and reproductive history was similar in the two groups. All patients were followed regularly; median follow-up was 17 months in the buserelin group and 18 months in the women given expectant management. If pregnancy did not occur within 12 months of randomization, cycles were monitored by ultrasonography and hormone measurements, and when abnormalities were detected clomiphene citrate and human chorionic gonadotropin were administered. RESULTS: A total of 17 pregnancies were observed both in the buserelin-treated patients and in the expectant management group. The 1- and 2-year actuarial overall pregnancy rates were similar in the two groups, 30% and 61% in the former and 37% and 61% in the latter group, respectively. Spontaneous abortion occurred in five of the 17 pregnancies in the women treated with buserelin and in one of the 17 in those managed expectantly; this difference was, however, not statistically significant (chi 1(2) adjusted for disease stage and use of clomiphene citrate and human chorionic gonadotropin treatment = 3.01, p = 0.08). No fetal death or stillbirth was observed. CONCLUSIONS: Our findings suggest that treatment with gonadotropin-releasing hormone agonists is unlikely to have a marked influence on the reproductive outcome of infertile women with minimal or mild endometriosis.

Effects of clomiphene citrate on cervical mucus: analysis of some influencing factors.

A multicenter study was performed to investigate the effects of a standard dose of clomiphene citrate (100 mg/day from day 5 of the cycle for five days) on the quality of cervical mucus. A total of 82 cervical mucus samples from 60 infertile patients (15 with secondary amenorrhea, 16 with delayed ovulation, 15 with anovulatory cycles, 14 with oligomenorrhea) was examined on the day of maximum follicular diameter. As a control we studied 54 cervical mucus samples from 47 patients with documented tubal sterility or infertile partners, who had spontaneous cycles with normal rhythm. Cervical mucus was unfavorable in 59% of the treatment cycles compared with 11% of the control cycles. Clomiphene citrate's antiestrogenic effect on cervical mucus was found to be related to the length of time between the last drug administration and the day of maximum follicular diameter (delta days), since cervical mucus was favorable in 64% of the cycles with a delta days more than 6 and in only 16% of the cycles with a delta days of 6 or less. Clomiphene citrate thus seems able to decrease cervical mucus quality. This could be one of the causes of the discrepancy between the rates of ovulation and pregnancy reported in patients treated with this drug.

Antiphospholipid antibodies in early repeated abortions: a case-controlled study.

The relation among lupus anticoagulant (LAC), anticardiolipin antibodies (ACA), and repeated abortions was evaluated in a case-controlled study of 49 women with two or more unexplained spontaneous abortions (cases) compared with 141 control subjects, who had had one or more normal pregnancies and no previous spontaneous abortion. The women were admitted to the same hospital where the cases had been identified for acute conditions other than immunologic neoplastic, gynecologic or cardiovascular. LAC was detected in 7 out of 49 cases (14%, 95% confidence limits 8% to 26%) but in none of the 141 controls. Similarly, ACA were detected in four cases (8%, 95% confidence limits 0.3% to 30%) but no controls. These differences in frequency were statistically significant. These findings confirm that LAC and ACA are associated with a history of repeated abortions in clinically asymptomatic patients for immunologic conditions.

HLA sharing in Italian recurrent abortion couples.

We performed HLA typing in 96 couples affected by recurrent abortion "sine causa". We matched these patients with 124 fertile couples and 204 individuals random paired. No significant difference in HLA sharing was demonstrated in the three study groups. The statistical analysis denoted significant differences in regard to HLA A3, A24, B12, and DR- comparing patients and normal members of fertile couples. The frequencies of HLA Cw5, Cw6 and DR2 were different in patients when compared with their partners.