Luigi de Cecco

Transcervical selective salpingography: a diagnostic and therapeutic approach to cases of proximal tubal injection failure *

OBJECTIVE Evaluation of selective salpingography for diagnosis and treatment of tubal injection failure during hysterosalpingography (HSG). DESIGN Prospective study. SETTING Obstetrics and Gynecology Department, University of Genoa (Italy)--tertiary care. PATIENTS One hundred eighty infertile women with unilateral or bilateral proximal tubal injection failure during HSG were submitted to the procedure. INTERVENTION Under fluoroscopy, a 4.5-F nylon catheter (3-F tip) was inserted into the ostium with or without the aid of a J-shaped, coaxial, angiographic guide wire, and 2 to 3 mL of contrast medium were injected. The procedure lasts 20 to 30 sec/tube. MAIN OUTCOME MEASURES Of 155 tubal ostia, 145 (94.2%) were catheterized. RESULTS Of the 146 catheterized tubes, 110 (75%) were rendered patent. Of the others, 21 (14.3%) presented hydrosalpinx or distal obstructions, and isthmic obstruction was present in 5 (3.4%). Patency of at least one tube was achieved in 82 (81.2%) of the 101 catheterized women; 8 conceived spontaneously and 11 after gamete intrafallopian transfer to the recanalized tube. CONCLUSIONS During HSG, selective salpinography can be performed when proximal injection failure is observed to determine its cause or to restore patency.

Treatment of endometriosis with goserelin depot, a long-acting gonadotropin-releasing hormone agonist analog: endocrine and clinical results

Thirty-two patients with laparoscopic diagnosis of endometriosis were treated for 6 months with the gonadotropin-releasing hormone agonist goserelin depot. Hormonal and clinical evaluations were conducted during treatment and for a 6-month follow-up period. Serum 17 beta-estradiol levels were sharply suppressed. Luteinizing hormone was also decreased, whereas follicle-stimulating hormone, after an initial fall, gradually rose to pretreatment levels. Ovarian androgenic production was less inhibited, total testosterone being the only significantly suppressed hormone. There was a marked improvement of signs and symptoms of endometriosis and a 47.3% reduction of laparoscopic score. The results of this study suggest that goserelin depot provides a very good suppression of ovarian estrogen production and is highly effective in decreasing the symptoms of endometriosis with an acceptable compliance by the patient.

Endocrine, metabolic, and clinical effects of gestrinone in women with endometriosis

The effect of oral gestrinone, 2.5 mg twice weekly for 6 months, was studied in 11 women with mild or moderate endometriosis laparoscopically confirmed. The mean laparoscopic score decreased from 17.18 to 9.09 (P greater than 0.005). Painful symptoms were relieved in all patients within 2 months from start of therapy. Gonadotropins, prolactin (PRL) 17 beta-estradiol (17 beta-E2), estrone (E1), progesterone (P), androstenedione (A), and dehydroepiandrosterone sulfate (DHEA-S) remained in the follicular phase range. Total testosterone (TT) and sex hormone-binding globulin (SHBG) decreased, whereas free testosterone (FT) slightly increased. Metabolic studies showed a decrease of total triglycerides, very low-density lipoprotein (VLDL) triglycerides, and high-density lipoprotein (HDL) and VLDL cholesterol, parallel to the decrease of associated apoproteins. Low-density lipoprotein cholesterol and apoprotein B increased during therapy. The results suggest that gestrinone possesses antiestrogenic, androgenic, and progestigenic effects at therapeutic dosages both by acting on central and peripheral steroid receptors. For its efficacy and good tolerance, gestrinone may be considered an option for treating endometriosis.

Luteinizing hormone-releasing hormone analog therapy of uterine fibroid: analysis of results obtained with buserelin administered intranasally and goserelin administered subcutaneously as a monthly depot

From January 1987 to February 1988 patients affected by uterine fibroid were offered medical treatment with luteinizing hormone-releasing hormone analogs as an alternative to surgery. The aim was to compare results obtained with two different analog formulations. 42 patients were randomly assigned to receive either intranasal buserelin, preceded by a short period of subcutaneous injections (500 micrograms thrice daily for 10 days) or subcutaneous goserelin. Treatment was always started in the luteal phase. Response to therapy was evaluated through periodic clinic, endocrine and echotomographic controls. There were no significative differences in fibroid reduction between the two treatment groups. After 6 months of treatment, a fibroid reduction of more than 30% of the initial volume was observed in 16 patients in the buserelin group and in 18 patients in the goserelin group. The fibroid regrowth observed in all patients during the follow-up period severely limits the usefulness of this medical approach to selected clinical cases.

Administration of pure follicle-stimulating hormone during gonadotropin-releasing hormone agonist therapy in patients with clomiphene-resistant polycystic ovarian disease: Hormonal evaluations and clinical perspectives

Nine women with chronic anovulation caused by polycystic ovarian disease, which was unresponsive to clomiphene citrate therapy, were given a gonadotropin-releasing hormone agonist (buserelin) to induce pituitary desensitization. After 4 weeks induction of ovulation was attempted with a step-up administration of urinary follicle-stimulating hormone. Buserelin treatment was discontinued only in the presence of a positive pregnancy test result. Different responses were observed between the first and subsequent cycles. Whereas estradiol production and follicular growth were closely correlated in the first attempt, we recorded a dissociation between these two parameters of ovarian response during subsequent stimulations. Four clinical pregnancies occurred in these nine patients, and there was one abortion. This therapeutic approach can be successfully used to induce ovulation; however, prolonging pituitary suppression between treatment cycles changes the type of ovarian response and is not followed by better results.

Endometrial response in sequential cyclic therapy assessed with associated hysteroscopy and histology

A morphologic study was performed on the endometrium in 37 asymptomatic postmenopausal women under effects of cyclically administered oestrogens. Eighty-seven postmenopausal women were taken as control group. Medroxyprogesterone acetate (MPA), 10 mg daily, was administered in association with two types of oestrogen replacement therapy: conjugated equine oestrogens 0.625 mg (CEE) or transdermal 17 beta-oestradiol 0.05 mg (E2-TTS). Endometrial biopsies were taken under hysteroscopic control before treatment and on days 8-12 of combined therapy at the 6th month. Follow-up at 12 and 18 months was only performed in 8 and 5 patients, respectively, with transdermal 17 beta-oestradiol treatment. Various types of endometrial response were identified from atrophy to hyperplasia and secretory patterns. No atypical hyperplasia was found. All cases of simple or complex hyperplasia showed a regression after increased MPA dosage treatment (20 mg). This work is aimed at investigating the endometrial response during sequential cyclic therapy by using morphologic criteria based on hysteroscopy and histology. A large number of patients with hyperplasia can be detected with target biopsy under hysteroscopy, thus playing an important role in the management of patients during replacement therapy in research protocols.

Steroid Therapy and the Endometrium: Biological and Clinical Implications

The benefits of estrogen replacement therapy in postmenopausal women include increased quality of life, relief from specific symptoms, and the prevention of osteoporosis, genitourinary atrophy, and cardiovascular diseases. Despite these advantages, this therapy has been reported to be associated with an increased frequency of endometrial hyperplasia and adenocarcinoma. In order to evaluate a possible relationship between the histological findings and stroma-derived growth regulators, 19 endometrial samples obtained from women undergoing both percutaneous (n = 11) and oral (n = 8) steroid replacement therapy were processed for histological and immunocytochemical evaluation of estrogen receptor (Er), progesterone receptor (Pr), and epidermal growth factor receptor (EGFr). Transdermal estradiol was given for 21 days and 10 mg medroxyprogesterone acetate (MAP) were added to the last 12 days; conjugated equine estrogens were given for 21 days and 10 mg MAP added to the last 12 days. Endometrial samples were obtained between days 17-18 of the sixth month of therapy. Proliferative and hyperplastic endometria showed immunoreactivity against Er, Pr, and EGFr. Atrophic endometria were always negative by immunocytochemistry. Our results suggest: 1) a relationship between histological findings and the receptor examined; 2) a crucial role for EGF in the regulation of endometrial proliferation.

Use of combined exogenous gonadotropins and pulsatile gonadotropin-releasing hormone in patients with polycystic ovarian disease

We previously tested a combined regimen based on the administration of gonadotropin in the early follicular phase followed by pulsatile gonadotropin-releasing hormone (GnRH) until complete follicular maturation in patients suffering from polycystic ovarian disease. Despite good clinical results, a high rate of premature luteinization was observed with this approach. We therefore evaluated in this study whether starting pulsatile GnRH therapy before gonadotropin administration might reduce premature luteinization. Eight women underwent induction of ovulation with both combined therapy and pure exogenous follicle-stimulating hormone alone using a crossover scheme. No premature luteinization and a single follicular growth were recorded with the modified combined regimen. Clinical results (8/8 versus 3/7 ovulatory cycles; 3/8 versus 1/7 pregnancies) favor the combined approach over gonadotropin alone.

Unexpected pregnancies after tubal recanalization failure with selective catheterization**Supported by a grant from National Research Council (Consiglio Nazionale Ricerche), Targeted Project “Prevention and Control of Disease Factors,” subproject 05, “Human Fertility Control,” contract no. 01.00108.8F41, Chieti, Italy.

OBJECTIVE To evaluate selective salpingography sensitivity. DESIGN Retrospective study. SETTING Obstetrics and Gynecology Department, University of Genoa, Italy. PATIENTS One hundred seventeen patients previously submitted to selective salpingography because of unilateral or bilateral proximal tubal injection failure. RESULTS Seven pregnancies, one of which was ectopic, were obtained in 17 patients who had only recanalized tubes available for conception; 15 pregnancies were obtained in 39 patients who had one tube recanalized and one already patent; 3 tubal pregnancies were obtained in 12 patients who had only one tube already patent; 4 pregnancies, one of which was ectopic, were obtained in 19 patients who had neither patent nor recanalized tubes. CONCLUSIONS Selective salpingography can give false-positive results; therefore, it is possible to obtain a pregnancy even after selective salpingography failure.