Mati Zolti

Granulosa cells as a source and target organ for tumor necrosis factor-α

Tumor necrosis factor (TNF‐α), a 17 kDa cytokine, is a product of activated macrophages which was recently shown to be produced by rat and bovine granulosa cells. In the present work, human granulosa cells derived from preovulatory follicles were used. It was demonstrated that human granulosa cells produce TNF‐α (5–10 units/300 000 cells per 15 h). This production was increased by addition of follicle‐stimulating hormone or by a combination of human chorionic gonadotrophin and CSF to the culture media. TNF was also found in bovine follicular fluid and the concentration was higher in the periovulatory than mid‐cycle follicles. TNF‐α was found to increase prostaglandin F‐2α production by human granulosa cells (P < 0.001). We conclude that granulosa cells are both a source and target organ for TNF‐α.

Combined gonadotropin releasing hormone agonist/human menopausal gonadotropin therapy (GnRH-a/hMG) in normal, high, and poor responders to hMG

Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatment were classified into normal, high, or poor responders. They were routinely offered another cycle with a combination of a gonadotropin releasing hormone agonist and gonadotropin therapy (in order to evaluate whether this combined therapy could improve their response). The gonadotropin-induced cycle was compared with the combined therapy cycle. With the combination treatment, in the normal responders the phase of ovarian stimulation was significantly (P<0.001) prolonged, and the number of follicles and oocytes collected (5.7±0.7 vs 3.1±0.4) was increased, without any change in serum estradiol level compared to the control cycle. In high responders the number of oocytes was not modified by the combined treatment compared with the control cycle. However, serum estradiol level was significantly (P<0.005) decreased. The combined therapy did not modify any parameter of response in poor responders. We conclude that the response to combined agonist/gonadotropin therapy is dependent on the patients own basal response. No improvement in response was expected in poor responders.

Sonohysterography for the diagnosis of residual trophoblastic tissue.

To assess the efficacy, safety, and associated complications of sonohysterography for the diagnosis of residual trophoblastic tissue.

Follicular and luteal cysts after treatment with gonadotropin-releasing hormone analog for in vitro fertilization

Ovarian cysts are a common complication of GnRH-a administration. We followed 98 patients who were suppressed with GnRH-a before ovarian stimulation with hMG for IVF treatment. Approximately 20% of the patients receiving GnRH-a during the follicular or luteal phase had developed ovarian cysts. However, the number of cysts per patient was significantly higher in the follicular phase compared with luteal phase. Systematic aspiration of those cysts under local anesthesia permitted the start of ovarian stimulation with hMG as scheduled on day 16 after GnRH-a administration. Follicular fluid content of the cysts revealed similar levels of steroids to those in normal follicles. These cysts contained few cells and no egg. In vitro fertilization treatment was more successful in patients whose cysts were aspirated during the luteal phase than in those with cysts during the follicular phase. We concluded that luteal phase cysts are more benign than follicular phase cysts, and it is possible that they represent an enlargement of pre-existing corpora lutea.

Endometrial resectoscopic ablation in patients with menometrorrhagia as a side effect of anticoagulant therapy

OBJECTIVE The study was conducted to examine the effect of endometrial ablation therapy for patients suffering from coagulation abnormalities and presenting with failed medical treatment for menometrorrhagia. STUDY DESIGN Eleven patients with a mean age of 42 years (range 39-45) and with coagulation disorders in whom medical therapy for abnormal uterine bleeding was unsuccessful, were treated by the ablation procedure under video monitoring. Complications, length of hospitalisation and long-term follow-up were noted. The age of the patients ranged from 39-45 years. Menstrual characteristics were scored, but blood loss before and after the procedure was not quantified. RESULTS Uterine fibroids were found in two patients. The duration of the ablation procedure was 20 min and was prolonged for 30 to 40 min when fibroids were diagnosed. During the operation, no excessive bleeding was noted in ten patients and postoperative recovery was rapid in all. After a one-year follow-up the overall satisfaction of the patients was high (10/11). CONCLUSIONS Our initial experience with a selected group of patients suffering from coagulation abnormalities is promising. Bearing in mind the risks of a major operation in this group of patients, endometrial ablation should be seriously considered.

Oxytocin or saline injected intra-umbilically did not influence the third stage of labor.

The injection of varying volumes of normal saline solution, alone or with oxytocin, into the umbilical vein immediately after delivery was studied in 125 normal women delivered at term. Thirty seconds after cord clamping, either 20 ml (group 1, n = 25 women), 30 ml (group 2, n = 25) or 40 ml (group 3, n = 25) of normal saline solution alone, or oxytocin 10 units in 20 ml saline solution (group 4, n = 25) or ozytoxin 10 units in 40 ml saline solution (group 5, n = 25) were injected into the umbilical vein 1 cm from the introitus just proximal to the umbilical clamp. The mean (± SD) duration of placental expulsion was similar in the five study groups. We conclude that neither the volume of the solution nor the oxytocin injected intra‐mumbilically has any effect on the duration of the third stage of normal labor.

Estradiol valerate as a possible endocrine reproductive disruptor: evidence from an in vivo rat model

We used an in vivo rat model to demonstrate that low-dose intradermal exposure to E(2) valerate has an inverse effect on the females estrus cycle pattern and can significantly reduce litter size. These results suggest that, under certain circumstances, environmental exposure to exogenous estrogens may play a role as an endocrine disruptor and adversely affect reproductive outcome.

Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone

The effect of dexamethasone (DEX) (9 α -Fluro-16 α -methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program. Patients were treated with DEX 0.5mg/d until the day of human chorionic gonadotropin administration. The cells were cultured for 24 hours in the presence of androstenedione (10 −7 M). After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours. The medium was then harvested and assayed for estradiol (E 2 ) and progesterone (P). Results were compared with those of a control group who was not treated with DEX. Estradiol production by cells was significantly lower in the study group treated with DEX. Progesterone production was not influenced by DEX. Follicular fluid levels, E 2 , and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment. These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function.