Which infertile women should be indicated for sonohysterography?

OBJECTIVE: To evaluate the indications for transvaginal saline contrast sonohysterography (TV-SCSH) in endometrial screening by transvaginal sonography in infertile women. METHODS: The study involved 850 consecutive infertile women presenting to an outpatient clinic. Using transvaginal ultrasound endometrial images were evaluated in the proliferative phase. Abnormal images were classified as follows: rugged (R), hyperechoic (H), waved (W), or thick (T). Clinical symptoms such as hypermenorrhea, dysmenorrhea and abnormal uterine bleeding were also recorded. Abnormal endometrial images were further evaluated on TV-SCSH. Age-matched women with normal endometrial images underwent TV-SCSH as controls. RESULTS: The endometrial pattern was abnormal in 111 patients (13.1%). Lesions that had been identified by TV-SCSH including endometrial polyps (44 cases), submucosal myomata (29 cases), and intramural myomata with mucosal extension (24 cases) were largely associated with the R and/or the H pattern, the W or the T pattern, and the W pattern, respectively. Sensitivity and specificity of the abnormal endometrial image for any lesion were 100% and 91.5%, respectively. Sixty-four patients (59.3%) were asymptomatic despite an abnormal endometrial image. CONCLUSIONS: TV-SCSH should be performed on selected patients following assessment of endometrial images on transvaginal sonography in order to diagnose intra- and pericavitary lesions in infertile women.

Establishment of a ciliated epithelial cell line from human Fallopian tube.

Human tubal epithelial cells in primary culture were transfected with simian virus 40 (SV40) large T antigen plasmid, and an immortalized ciliated cell line, named as NT/T-S, was established without crisis. Transmission electron microscopy proved that NT/T-S cells had cilia, microvilli, junctional complexes, rough endoplasmic reticula, free ribosomes and microtubules. NT/T-S cells were evaluated preliminarily on the basis of co-culture study using surplus embryos at the 4- to 8-cell stage in our IVF and embryo transfer programme. All of the 133 embryos had >/=10% fragments (based on the surface area) and were unworthy of cryopreservation. Up to 57% (16/28) of the embryos with 10-30% fragments reached the blastocyst stage by co-culture. In contrast, blastocyst formation was observed in <10% of the control embryos, some of which were co-cultured with NFL/T cells (the immortalized human fetal liver epithelial cells) (1/16), and the others were incubated with the co-culture medium alone (1/18). Various cytokines/growth factors such as leukaemia inhibitory factor (LIF), interleukin (IL)-6, IL-8 and basic fibroblast growth factor were secreted by NT/T-S cells as well as by the tubal epithelial cells in primary culture. The establishment of a ciliated cell line will provide a valuable resource for the further studies of the Fallopian tube in the early events of pregnancy.

Biochemical markers of bone turnover during hormone replacement therapy.

OBJECTIVE: To assess the clinical usefulness of bone turnover markers, including serum osteocalcin (OC), urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), in monitoring and predicting bone response to hormone replacement therapy (HRT). METHOD: The relationships between baseline levels or changes in markers and change in lumbar bone mineral density were examined in 21 surgically-induced postmenopausal women. RESULTS: Levels of OC, Pyr and D-Pyr in the estrogen effective group (responders) significantly decreased during HRT and baseline levels of Pyr and D-Pyr in responders were significantly higher than those in premenopausal women. CONCLUSION: Bone turnover markers were useful in monitoring the bone effect of HRT and baseline levels of markers reflect subsequent bone response to HRT.

[Bone mineral content in premenopausal women treated with gonadotropin-releasing hormone analogue].

To assess bone metabolism during treatment with gonadotropin-releasing hormone analogue (GnRHa), serum osteocalcin (BGP), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcitonin (CT), calcium (Ca) and phosphorus (P) were determined before and after 6 months of GnRHa treatment in 15 premenopausal women with clinically diagnosed endometriosis. The bone mineral content (BMC) of the lumbar spine (L3) was measured by single energy quantitative computed tomography in 9 women, and in 6 of these 9 women microdensitometry was performed simultaneously during the treatment. BMC decreased significantly to 92.5 +/- 6.8% (mean +/- SD) of the pretreatment value after 6 months of treatment. On the other hand, microdensitometry revealed no significant change during treatment. Serum BGP and ALP were significantly higher after 6 months of treatment than before treatment, indicating an increase in bone formation. These data indicate that the GnRHa treatment induces an increase in bone turnover and a significant bone loss.

[Bone mass and biochemical parameters in metabolic bone diseases].

We studied the relationship between the bone mass and biochemical parameters in 175 normal premenopausal, 72 normal postmenopausal and osteoporotic postmenopausal women, between 20 and 88 years old, and in 40 patients with hyperthyroidism, and 23 patients with primary hyperparathyroidism, between 13 and 64 years old. The bone mineral density (BMD) of the spine (L2-L4) and proximal femur (femoral neck) was measured by dual-energy X-ray absorptiometry using a QDR-1000, Hologic. The bone mineral content (BMC) of the radius was measured by single photon absorptiometry (SPA) using a model 2780, Norland. Serum PTH, BGP and calcitonin (CT) were determined by radioimmunoassay. The BMD of the spine (L2-L4), and the proximal femur in postmenopausal women were negatively correlated with age. The mean BMD in patients with postmenopausal osteoporosis was significantly lower than that in normal postmenopausal women. In postmenopausal women, age was positively correlated with BGP, PTH, CT and negatively correlated with P. In patients with osteoporosis, the BMD of the spine was negatively correlated with serum BGP. The BMC of radius in patients with hyperthyroidism decreased significantly compared with that in the controls, and was negatively correlated with F-T3. The BMC of the radius in patients with primary hyperparathyroidism was significantly lower than that in the controls, and was negatively correlated with serum BGP and serum calcium. The measurements of biochemical parameters such as serum BGP, ALP and PTH may be useful in the assessment of metabolic bone diseases.

[Lumbar bone density and serum osteocalcin in pre- and postmenopausal women].

The bone mineral density of the lumbar spine (L3) and serum osteocalcin (OC) were measured in 31 pre- and 25 postmenopausal women. Bone density was measured by single energy quantitative computed tomography (QCT value). A significant inverse correlation between the QCT value and age was demonstrated in postmenopausal women but no correlation was found in premenopausal women. Mean QCT value was significantly lower in postmenopausal women than in premenopausal women. Serum OC increases with advancing age and mean serum OC was significantly higher in postmenopausal women than in premenopausal women. A significant inverse correlation between the QCT value and serum OC was demonstrated. These data suggest that there is an association between menopause and accelerated loss of lumbar bone density and that the serum OC level may be useful in evaluating the bone mass.

[Pilomatrix carcinoma--report of the second case in Japan and a review of the literature].

A 53-year-old man had a rapidly growing tumor, measured 3 cm in diameter, on his left temporal region of 2 months' duration. The lesion showed histological resemblance to pilomatricoma but differed by the presence of irregular nests of atypical basophilic cells (basaloid cells) with focal squamoid differentiation and a large number of atypical mitoses. A review of 16 cases of pilomatrix carcinoma documented since the year of 1980 indicated that this tumor occurs in males three times more frequently than in females. 75% of all patients were over forty years old. Recurrences were seen in 6 of the 10 patients whose tumor had been resected simply, but there was no evidence of recurrence in the 4 patients with a wide resection of tumor.

[Effects of maternal exercise using bicycle ergometer on maternal heart rate, blood pressure, oxygen consumption and fetal heart rate].

The effects of maternal exercise on pregnant women and fetal well-being are largely unknown. Forty-eight pregnant women between 16 and 39 weeks' gestation were exercised on a bicycle ergometer. We studied the oxygen consumption, blood pressure, maternal and fetal heart rate (FHR) at rest, during and after the exercise. The mean maternal heart rate and blood pressure were increased to 166.1 +/- 12.2/min (mean +/- S.D., n = 48) and 161.1 +/- 20.1/82.7 +/- 15.2 mmHg, respectively, at maximal exercise. The absolute oxygen consumption (1/min) was increased with advancing pregnancy at rest and maximal exercise, but the functional oxygen consumption (ml/kg/min) was not changed during pregnancy. The mean FHR was increased about 4 and 9 bpm in the 2nd and 3rd trimesters, respectively. Abnormal FHR patterns after the exercise were observed in 8 cases (16.7%), mild tachycardia: 6 cases, deceleration: 2 cases. Increasing the maternal heart rate at maximal exercise, increased the frequency of the abnormal FHR pattern. When the maternal heart rate was below 160/min, there was no abnormal FHR pattern. These results suggest that several medical checks should be done not only for the mother but also for her fetus during exercise and the maternal heart rate should not exceed 160/min.

A case of solitary mastocytoma suggesting a divided form of mast cell nevus.

The case of a 10-week-old boy with a solitary mastocytoma is reported. The lesion, noticed at birth, was located in an area extending from the dorsum of the left hand to the proximal phalanx of the ring and little fingers. It appeared as a coin-sized, flattened dome-shaped, round tumor with occasional blistering. The web between the two fingers was free of cutaneous changes. The diagnosis was confirmed by the histological characteristics: a densely mastocytic infiltration into the dermis. The present case of solitary mastocytoma, referred to as "mast cell nevus", is unique because of its previously undescribed divided form.

Effects of pregnancy, delivery and lactation in hyperprolactinemia with prolactin producing pituitary adenoma.

The effects of pregnancy, delivery and lactation on changes in serum prolactin (PRL) values were investigated in patients with hyperprolactinemia. Thirty-seven patients with hyperprolactinemia who wished to become pregnant were treated by transsphenoidal surgery, bromocriptine therapy, or a combination of the two. In 33 patients whose pre-pregnancy serum PRL concentration exceeded 30ng/ml, only in two did serum PRL return to the normal range below 30ng/ml after pregnancy, delivery and lactation. However, the serum PRL concentration was decreased in 28 patients. When classified according to the pre-pregnancy serum PRL concentrations, PRL less than or equal to 100 (Group A), 100 less than PRL less than or equal to 200 (Group B) and 200 less than PRL (Group C), patients with the greatest pre-pregnancy serum PRL concentration showed the greatest reduction. The ratios of post-pregnancy serum PRL to pre-pregnancy PRL in group A, B and C were 91.4 +/- 22.1%, 81.5 +/- 7.0% and 65.0 +/- 6.5% (Mean +/- SE), respectively. Group C with the highest pre-pregnancy serum PRL concentration consisted almost entirely of patients with macroadenoma. Thus, the reduction in serum PRL after pregnancy, delivery and lactation was considered to be the result of a decrease in the size of the adenoma due to adenoma enlargement over the sella turcica through the estrogen effects during pregnancy, and from impairment of pituitary circulation.

[Clinical assessment of body hair growth in Japanese women. The relationship between a grade of hirsutism and the menstrual status].

Three hundred and sixty-nine volunteer women and 308 outpatients were studied to clarify the criteria of hirsutism and the relationship between a grade of hirsutism and menstrual status in Japanese women. The body hair growth was assessed according to the modified score system described by Ferriman and Gallway. The menstrual status was classified into six groups based on basal body temperature. The hair growth score calculated in volunteers tended to be lower than that of western women in most sites. Therefore one criterion of hirsutism in Japanese women should be a score of more than 6 points in our system. There was a close correlation between body hair growth and menstrual status. As a result, it can be considered that the systematic assessment of body hair growth is useful in diagnosing and treating some irregular menstrual patients.

Serum CA 125 levels in patients with endometriosis: changes in CA 125 levels during menstruation.

We investigated serum CA 125 levels in 120 patients with benign gynecologic disease, and examined variations in CA 125 levels during the menstrual cycle in six normally cycling women. CA 125 levels were elevated transiently during menstruation, suggesting that blood samples taken during menstruation can give a false-positive result. Whereas the CA 125 values during the nonmenstrual part of the cycle were significantly higher in the patients with adenomyosis and advanced endometriosis (stages III and IV) than in those with a normal pelvis, there was no difference between the patients with mild endometriosis (stages I and II) and the normal-pelvis group. CA 125 levels during menstruation were significantly elevated, not only in women with adenomyosis and advanced endometriosis, but also in those with mild endometriosis, compared with those with a normal pelvis. These data suggest that the measurement of serum CA 125 during menstruation may increase the rate of detection of endometriosis over that in studies done during other phases of the cycle.

[Intra-arterial cis-platinum in the treatment of squamous cell carcinoma of the cervix].

Three patients with advanced cervical carcinoma were treated with two courses of cis-platinum (CDDP) intra-arterial administration. Histology of all patients revealed squamous cell carcinoma, keratinizing type, and all patients had stage IIIb diseases. CDDP at a dose of 50 mg was infused through each catheter of which tips were fixed in the bilateral internal iliac arteries via the opposite femoral arteries. The course of therapy was repeated at an interval of three to four weeks, so the total dose of CDDP in each patient was 200 mg. The bleeding from lesions, which occurred intermittently before therapy in all patients, was reduced after the primary course of therapy and completely stopped after the second one. Marked reduction of lesion on computed tomograph (CT) was confirmed in all patients. The reduction in the product of perpendicular diameters of measurable lesions on CT ranged from 40 to 50%. Adverse effects such as nephrotoxicity, myelosuppression and gastrointestinal toxicity were mild as compared with patients receiving intravenous administration of CDDP. The excellent clinical effects and tolerance observed in this study indicated that an intra-arterial administration of CDDP has a highly therapeutic efficacy in the treatment of squamous cell carcinoma of the cervix.

Contracture caused by sodium removal in the pregnant rat myometrium.

The contracture produced by removal of the external Na was studied in the pregnant rat myometrium and this was compared with that of the non-pregnant myometrium. The Na-free contracture was small compared with spontaneous phasic contractions in the circular muscle of non-pregnant rat, but the contracture increased during pregnancy. On the other hand, in the longitudinal muscle, the contracture was large in both non-pregnant and pregnant myometria. The change in circular muscle did not seem to result from an increased sensitivity to the external Ca. Since the contracture induced by 40 mM K had properties similar to those of the Na-free contracture, it is likely that weak tension development in non-pregnant circular muscle is either due to a limited Ca influx or due to a low efficiency of the excitation-contraction coupling for the sustained contraction compared with the phasic contraction. A small contraction which was independent of the external Ca was observed in Na-free solution in the both layers of non-pregnant myometrium, but this was not observed in the longitudinal muscle of pregnant myometrium.

Role of sex-hormone-binding globulin and free sex steroid hormones in hyperandrogenic anovulation.

To clarify the mechanism of hyperandrogenic anovulation, the binding capacity of sex-hormone-binding globulin (SHBG-BC), the levels of free steroid hormones, and the levels of basal serum testosterone (T), estradiol (E2), estrone (E1) and gonadotropins were determined in 42 hyperandrogenic anovulatory women. The mean levels of basal T (0.74 +/- 0.04 ng/ml, p less than 0.001), free T (3.07 +/- 0.51 ng/dl, p less than 0.01) and free E2 (2.26 +/- 0.27 pg/ml, p less than 0.05), basal luteinizing hormone (LH) (33.4 +/- 2.7 mIU/ml, p less than 0.001), responsiveness of LH (180.7 +/- 21.5 mIU/ml, p less than 0.001) after luteinizing hormone releasing hormone (LHRH) administration, and the basal LH/basal follicle stimulating hormone (FSH) ratio (3.42 +/- 0.25, p less than 0.001) in the patients were significantly higher, the SHBG-BC level (1.76 +/- 0.33 micrograms DHT bound/dl, p less than 0.05) significantly reduced, and basal levels of E2 (38.0 +/- 3.2 pg/ml) and E1 (110 +/- 13 pg/ml) unchanged compared to the controls. These findings suggest that increased T in hyperandrogenic anovulatory women results in decreased SHBG-BC and increased free T and E2 which might be the cause of inappropriate gonadotropin secretion followed by chronic anovulation.

Conservative surgery of infertile patients with pelvic endometriosis--factors affecting the pregnancy rate and expectancy.

Conservative surgery was used in the treatment of 95 infertile patients with endometriosis who desired to have a child; of these 95 patients, 44 (46.3%) became pregnant after treatment. We studied the postoperative pregnancy rate and the expectancy value for pregnancy and the factors affecting them. The postoperative pregnancy rate was significantly lower in the patients with an infertility period of more than 5 years. As the age of the patients at the time of operation increased, the pregnancy rate decreased; the expectancy value was also significantly lower in patients over 30 years of age. Endometriotic lesions were, in the ovary (77.9%), in the peritoneum (42.1%), and in the uterosacral ligament (42.1%). The rates of pregnancy in patients in Beecham's stages II (43.2%) and III (53.3%) were not statistically significant. The rate was significantly lower in stage IV. Intrapelvic complications were usually myoma of the uterus and cystoma of the ovary. Both pregnancy rate and expectancy value were significantly lower in the patients with pelvic complications. Hormonal therapy combined with conservative surgery gave a higher rate of pregnancy and expectancy value than surgery alone. Thus, the duration of infertility, the age of the patient at the time of operation, intrapelvic complications, and the mode of treatment were key factors affecting the postoperative rate of pregnancy and expectancy.

Determination of serum delta 5-3 beta-hydroxysteroid sulphates by combined high-performance liquid chromatography and immobilized 3 beta,17 beta-hydroxysteroid dehydrogenase in column form.

We studied the use of an immobilized enzyme, covalently bound to aminopropyl-CPG, in the analysis of individual delta 5-3 beta-hydroxysteroid sulphates. A microcolumn with immobilized 3 beta,17 beta-hydroxysteroid dehydrogenase was prepared and used together with high-performance liquid chromatography (HPLC). The reduced nicotinamide-adenine dinucleotide produced from delta 5-3 beta-hydroxysteroids by this enzyme was fluorimetrically determined. The immobilized enzyme was sufficiently stable for at least one month or for 180 tests when used repeatedly. A clinical trial demonstrated that this HPLC-immobilized enzyme method is superior to the soluble enzyme method, giving reliable and reproducible results at a low cost.

Spironolactone therapy for hyperandrogenic anovulatory women--clinical and endocrinological study.

Seventeen patients with irregular menstrual periods and androgenic symptoms such as excessive hair growth, acne, and oily skin were treated with spironolactone. The basal levels of serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and luteinizing hormone (LH) were significantly higher in the patients than in the controls. After a 4-week treatment with spironolactone, serum T and DHT showed significant decreases. Before treatment, the serum sex hormone binding globulin (SHBG) levels were significantly lower in the patients than in the controls. After initiation of the spironolactone treatment, the SHBG levels tended to increase but not significantly. Spironolactone treatment resulted in the improvement or disappearance of acne in 4 of 5 patients who suffered from this ailment. Improvement of hirsutism was obtained in 2 of 10 patients. Although 4 oligomenorrheic patients and 6 amenorrheic patients showed anovulatory bleeding but did not ovulate, 2 patients in the amenorrheic group ovulated. Two patients complained of tiredness and weakness, and 2 others of polyuria and polydipsia. Both groups showed only temporary symptoms, so treatment was not interrupted. Spironolactone has beneficial effects on ovarian function and few side effects, so it may prove to be an effective anti-androgen, especially for hyperandrogenic anovulatory patients.

Cyclic therapy resulted in pregnancy in premature ovarian failure.

A successful pregnancy in a patient with premature ovarian failure is described. Increased serum gonadotropin titers, decreased serum estrogen levels, and lack of ovarian follicles on histologic examination confirmed the state of ovarian failure. The patient conceived after several courses of cyclical treatment with estrogen-progestin. A possible relationship between the estrogen treatment and subsequent pregnancy is discussed.