Tocolysis with atosiban: experience in the management of premature labor before 24 weeks of pregnancy.

OBJECTIVE: Atosiban has been shown to be an effective tocolytic agent with a low rate of side effects during 24 to 33 weeks of gestation. Atosiban acts through selective, competitive inhibition of both oxytocin and vasopressin, so that there are reasons to assume that a tocolytic effect can also be achieved earlier in the pregnancy. STUDY DESIGN: In this prospective, randomized pilot study, 20 women in the 18th through 24th week of gestation who presented at our hospital with preterm labor were treated with atosiban. In the control group 20 women received saline infusions. All patients received antibiotic therapy. A cervical cerclage was performed when indicated as was correction of the vaginal pH. RESULTS: The tocolytic effect began after 3-10 min (median: 6.5 min). Treatment time until the complete absence of contractions was 3-12 h (median: 7.5 h). Pregnancies were prolonged between 11.1 and 21.7 weeks (median: 15.6 weeks) in the atosiban group vs. 10.5-19.1 weeks in the control group. If well tolerated, atosiban was continued. There were no significant alterations in the routine laboratory parameters, circulation parameters, and fluid balance. CONCLUSION: In summary, atosiban showed itself to be effective for tocolytic treatment for premature labor, even during 18 and 24 weeks of pregnancy, while exhibiting its known, favorable profile of side effects.

Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis.

INTRODUCTION: As a cytotoxic product of activated monocytes, macrophages, and lymphocytes, tumor necrosis factor alpha (TNF-alpha)--together with other cytokines and growth factors--is an important component in the immune response of the human organism. In addition, TNF-alpha plays a central role in neoangiogenesis. Because of its cytotoxicity with regard to several tumor cells and its motility-hindering effect on human sperm, TNF-alpha is considered to be a significant pelvic mediator of female sterility. OBJECTIVE: The goal of our study was to determine as to whether or not an increased TNF-alpha secretion by peritoneal macrophages (PM) can be measured in female patients with endometriosis compared with healthy subjects, and if TNF-alpha secretion can be correlated with the activity of endometriosis. METHODS: During infertility work-up, 100 female patients underwent a diagnostic laparoscopy. In accordance with the rAFS classification as well as from the macroscopic aspect of the degree of activity of the endometriosis, the patients were divided as follows: an endometriosis-free control group with a completely normal pelvic status (n=35) and three groups with increasing stages of endometriosis (n=65). In the control group (Group 1), the TNF-alpha concentrations (median values with minimum / maximum) were 6.2 pg/ml (1.9/10.2), in Group 2 with rAFS stage I/II less active endometriosis 56.33 pg/ml (39.5/71.2), in Group 3 with rAFS stage I/II but highly active endometriosis 81.41 pg/ml (68.4/98.7), while in Group 4 with rAFS stage III/IV 200,15 pg/ml (182.6/226.8), respectively. CONCLUSION: In conclusion, we were able to show that the TNF-alpha secretion of PM was significantly higher in patients with proven endometriosis compared to the control group. These results were found to be statistically significant and were in accordance with the histological findings. Thus, due to its immunomodulating potential, TNF-alpha may be a marker of both activity and stage of endometriosis.

Immunohistochemical reactivity of myometrial oxytocin receptor in extracorporeally perfused nonpregnant human uteri.

INTRODUCTION: In the pregnant uterus oxytocin and the oxytocin receptor play a major part for uterine contractility and the induction of labor. Clinical evidence implicates that with regard to contractility associated disorders like for example dysmenorrhea also in the nonpregnant and very early pregnant myometrium oxytocin and the oxytocin receptor seem to be more important than believed at the moment. However, little is known about the mutual dependence of the oxytocin receptor, oxytocin and 17-beta-estradiol in the nonpregnant myometrium and about the distribution of the oxytocin receptor in the nonpregnant uterus. Therefore, in the present study we investigated in the nonpregnant myometrium if oxytocin receptor expression can be affected by 17-beta-estradiol and oxytocin stimulation. METHODS: We used a previously established experimental perfusion system for the human uterus. We perfused 10 uteri for 27 h under physiological conditions without 17-beta-estradiol (group A, n=5) or with high 17-beta-estradiol stimulation (group B, n=5) followed by oxytocin stimulation in both groups in the last 3 h of the experiment. The expression of the myometrial oxytocin receptor in both groups was compared immunohistochemically. RESULTS: In comparison to the negative controls the immunohistochemical reactivity demonstrated increasing oxytocin receptor concentrations with maximum levels under 17-beta-estradiol and oxytocin stimulation in the uterine fundus (40% of positive stained cells, p<0.01). However, oxytocin receptor levels did not reach concentrations comparable to specimen of third trimester of pregnancy, which were used as positive controls. CONCLUSIONS: Taken together, our data demonstrate that the dynamics of oxytocin receptor expression can be affected by stimulation with 17-beta-estradiol and oxytocin not only in the pregnant uterus, but also in the nonpregnant uterus. Therefore, dyscontractile phenomena of the nonpregnant myometrium also may be mediated via 17-beta-estradiol, oxytocin and the oxytocin receptor.