Masoumeh Rezapour

Seven-year follow-up of the tension-free vaginal tape procedure for treatment of urinary incontinence.

OBJECTIVE: To evaluate the long-term cure rates and late complication rates after treatment of female urinary stress incontinence with the minimally invasive tension-free vaginal tape operation. METHODS: Prospective observational, 3-center cohort study originally of 90 women requiring surgical treatment for primary urinary stress incontinence. Assessment variables included a 24-hour pad weighing test, a stress test, visual analog scale for assessing the degree of bother, and a questionnaire assessing the subjective perception of the women on their continence status. RESULTS: The follow-up time was a mean of 91 months (range 78–100 months). Both objective and subjective cure rates were 81.3% for the 80 women available for follow-up. Asymptomatic pelvic organ prolapse was found in 7.8%, de novo urge symptoms in 6.3%, and recurrent urinary tract infection in 7.5% of the women. No other long-term adverse effects of the procedure were detected. CONCLUSION: The tension-free vaginal tape procedure for treatment of female urinary stress incontinence is effective over a period of 7 years. LEVEL OF EVIDENCE: II-3

Identification of two further gap-junctional proteins, connexin40 and connexin45, in human myometrial smooth muscle cells at term

The powerful synchronous contractions of the uterus in labor depend on electrical coupling of myometrial smooth muscle cells by gap junctions. In humans and other mammals, gap junctions are scarce in the myometrium of the non-pregnant uterus, but become abundant at term and/or with the onset of labor. Previous work has shown that the gap-junctional protein (connexin) expressed by human myometrial smooth muscle cells is connexin43, the same connexin type that predominates in cardiac muscle. Here we show that two further gap junctional proteins, connexin40 and connexin45, are expressed by the myometrial smooth muscle cells of the human uterus at term. Transcripts encoding the human isoforms of these connexins were demonstrated by Northern blot analysis, and immunoconfocal microscopy enabled precise localization of the corresponding proteins to punctate contact points (i.e., gap junctions) between interacting smooth muscle cells. Double labeling demonstrated that, while some fluorescent spots comprise only connexin43, both connexin40 and connexin45 predominantly colocalize to connexin43-positive fluorescent spots. Triple labeling revealed that where all three connexin types were expressed, they frequently localized to the same gap junction spot. As gap-junctional channels composed of different connexin types have been demonstrated in vitro to have different functional properties, multiple connexin expression may contribute to modulation of gap junction function in human myometrial smooth muscle cells in vivo.

Expression of estrogen receptor-α and -β in anterior vaginal walls of genuine stress incontinent women

Our objective was to study the expression of estrogen receptor (ER) isoforms, ER-α and ER-β, in the anterior vaginal wall of menopausal and fertile women with genuine stress incontinence (SI) by immunohistochemistry and Western blot analysis. Eighteen menopausal women with SI who either were or were not taking estrogen/progestin replacement therapy and 14 fertile women with SI who either were or were not taking contraceptives were enrolled in the study. Biopsies from the suburethral anterior vaginal wall were obtained at tension-free vaginal tape (TVT) operation. Monoclonal antibody to ER-α and polyclonal antibody to ER-β were used to stain frozen sections of vaginal tissue. The receptor expressions were scored based on percentage of positive cells. ER-α was detected in vaginal epithelial, stromal and smooth muscle cells. In menopausal SI women ER-α was detected significantly more frequently in the vaginal walls of estrogen/progestin-treated patients than in those who were untreated. Fertile SI women had significantly higher expression of ER-α than menopausal SI women. ER-α was not observed in vaginal blood vessels. ER-β was detected in epithelial and vascular smooth muscle cells of the vagina. No significant difference in ER-β expression was observed between different groups of patients. The expression of ER-α was not correlated with that of ER-β. Both ER-α and -β were detected, indicating a potential role for both types of estrogen receptor in the human vaginal wall. The expression of ER-α, but not of ER-β, in menopausal SI women was regulated by estrogen/progestin replacement therapy. The presence of ER-β in vaginal vascular smooth muscle cells raises the possibility of vascular effects of estrogen on the human vaginal wall.

Sex steroid receptors and human parturition

Objective To investigate the correlation between sex steroid hormones and their receptors during normal and dysfunctional labor. Methods Myometrial and decidual biopsies along with maternal and cord blood samples were taken from women with or without labor activity. Estrogen and progesterone receptor contents in myometrum and decidua were determined by enzyme immunoassay, and hormone concentrations were analyzed by radioimmunoassay. Results In the lowere segment of the uterus, the prosgesterone receptor concentrations of myometrum were significantly lower in oxytocin-resistant dystocia compared with those of normal labor and before labor (P < .04, P < .005. respectively). No significant difference was found in the estrogen receptors of myometrum from the upper segment showed higher concentrations in active labor compared with those before labor and oxytocin-resistant labor (P < .01, P < .05, respectively). Estrogen receptors from the upper segment showed no significant difference in these regards. The was no difference in peripheral and myometrial sex hormone levels in the groups studied. Conclusion These data suggest that, in the human, 1) oxytocin-resistant labor is associated with low levels of progesterone receptors, 2) estrogen receptors, 2) estrogen receptors content in myometrium might have no or little relation to labor, and 3) functional labor seems not to be related to a decreased progesterone activity in the myometrium.

Myometrial steroid concentration and oxytocin receptor density in parturient women at term

The aim of this study was to measure oxytocin receptor concentration in myometrial tissue from term pregnant women with normal and dysfunctional labor and to relate this concentration to the progress of labor and to the levels of estradiol and progesterone in the same myometrium. Myometrial biopsies were obtained from 50 term pregnant women undergoing cesarean section. The patients were categorized as follows: not in labor, normal labor, successful oxytocin-augmented labor, and oxytocin-resistant labor. Specific binding of [3H]oxytocin to high-affinity sites in membrane preparations from myometrial tissues was determined. Estradiol and progesterone were assayed using tritiated steroids with a sensitive radioimmunoassay technique. Oxytocin receptor density was significantly lower in oxytocin-resistant labor compared to successful oxytocin-augmentated labor (P < 0.04) and to spontaneously active normal labor (P < 0.02). Oxytocin receptor concentration was also significantly lower in non-labor patients compared to normal spontaneous labor (P < 0.01), and successful oxytocin-augmented labor (P < 0.02). There was a positive relationship between the progress of cervical dilatation (cm/h) and oxytocin receptor density in the myometrium (r = 0.408, P < 0.025). The concentration of progesterone and estradiol in the pregnant myometrium did not differ in patients with different types of labor or with the state of uterine contractile activity. Our results suggest that individual myometrial sensitivity is an important determinant of the response to administered oxytocin in humans. Furthermore, myometrial oxytocin receptor expression in vivo seems not be related to ovarian steroid concentration in the myometrium. The low oxytocin receptor density in oxytocin-resistant dystocia needs further investigation.

Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro

Objective: To determine whether progesterone causes any changes in the action of oxytocin on the contractile activity of term human myometrium in vitro. Methods: Myometrial biopsies from 13 term pregnant women undergoing cesarean delivery were immediately immersed in Hepes buffer or buffer containing 5 &mgr;g/mL progesterone. In the laboratory under a stereomicroscope, the specimens were dissected into 1 × 7.5‐mm muscle strips. These were mounted into six tissue baths and superfused with Hepes buffer and buffer containing 5 &mgr;g/mL progesterone, 5 &mgr;g/mL progesterone plus 10 mU/mL oxytocin, 5 &mgr;g/mL progesterone plus 100 mU/mL oxytocin, 10 mU/mL oxytocin, and 100 mU/mL oxytocin. Isometric tension was recorded constantly for at least 3 hours. Results: The frequency of myometrial contractions and tonus increased by superfusion with progesterone, progesterone plus oxytocin, and oxytocin alone compared to buffer. In addition, a gradual decrease in frequency was observed after 60 minutes of contractions with oxytocin alone, whereas progesterone plus oxytocin had no such decrease. The activity area of contractions was greater with 10 mU/mL oxytocin and decreased with progesterone, progesterone plus both concentrations of oxytocin, and 100 mU/mL oxytocin alone, compared to buffer. Conclusion: Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin. (Obstet Gynecol 1993;82:532‐8)

Effects of progesterone and oxytocin on intracellular elemental composition of term human myometrium in vitro

OBJECTIVE To study the effects of progesterone and oxytocin on contractile activity related to the intracellular elemental composition of human pregnant myometrium. STUDY DESIGN Myometrial strips were mounted in tissue baths and superfused with plain buffer, oxytocin or progesterone. Progesterone was initially added to the tissue bath or at the onset of spontaneous contraction of the strips. The myometrial contractile activities were recorded isometrically and the results were analyzed by a specific computer program. The effects of oxytocin and progesterone on the intracellular elemental composition were studied by X-ray microanalysis in an electron microscope. RESULTS The contractile activity in terms of frequency and tonus of the muscle strips was increased by oxytocin and progesterone. This increase was more pronounced if progesterone was added to the bath at the start of the experiment. After 120 min of incubation with oxytocin and progesterone the total intracellular concentration of calcium was significantly higher (P < 0.0001 and P < 0.002, respectively) compared to buffer. CONCLUSIONS (i) Oxytocin increases total intracellular calcium concentration concomitant with an increase in uterine contractile activity. (ii) Progesterone increases the myometrial tone and frequency of contractions, simultaneously with an increase in total intracellular calcium.

Morphometric analysis of gap junction density in human myometrium at term

In the human myometrium. the formation of gap junctions in the various stages of labor and, in correlation with the concentration of progesterone in the maternal blood, has not been described adequately. The accepted hypothesis that raised concentrations of progesterone in maternal blood in animals prevent the formation of gap junctions was scrutinized in human niyometrium. Myometrial tissue was examined by electron microscopy for the presence of gap lunctions and analyzed morphometrically in 17 women who had an elective or emergency cesarean operation at the 38th or 39th week of pregnancy. The concentrations of progesterone and estradiol in the maternal and cord blood was measured by means of radioimiiiunoassay. The frequency and area of gap junctions varied in relation to the presence or absence of labor. In the myometrium of women in labor, gap junctions were most frequent (5.2/1000 μm of cell membrane), their area largest (0.32 μ2/1000 μm of cell membrane) and their fractional area greatest (0.20%). When the women were not in genuine labor or when contractions were weak, the percentage fractional areas of gap junctions were low (0.020‐0 090) and the gap junctions very small. In the pre‐ and active phases of labor, the concentration of progesterone in maternal blood was significantly higher (p <0.025 and 0.03 respectively) than in women who were not in labor.