Fabio Ghezzi

A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition

OBJECTIVE There is no evidence for the participation of the human fetus in the mechanisms responsible for the onset of preterm labor. We propose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and/or maternal host response to microbial invasion. The objective of this study was to determine whether a systemic fetal inflammatory response, defined as an elevation of fetal plasma interleukin-6 concentrations, has a temporal relationship with the commencement of labor. STUDY DESIGN After informed consent was obtained, amniocentesis and cordocentesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for both aerobic and anaerobic bacteria, as well as for mycoplasmas. Fetal plasma interleukin-6 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and survival analysis with time-dependent Cox regression hazard modeling. RESULTS Microbial invasion of the amniotic cavity was present in 58.5% (24/41) of patients. Fetuses with fetal plasma interleukin-6 concentrations > 11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interleukin-6 levels < or = 11 pg/mL (88% vs 29% and 88% vs 35%, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-6 values > 11 pg/mL than patients delivered > 48 hours (58% [7/12] vs 8% [1/13], respectively; P < .05). Survival analysis indicated that fetuses with elevated fetal plasma interleukin-6 levels had a shorter cordocentesis-to-delivery interval than those without elevated fetal plasma interleukin-6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [range 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regression hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of pregnancy after we adjusted for gestational age, amniotic fluid interleukin-6 level, and the microbiologic state of the amniotic cavity (P < .01). CONCLUSION A systemic fetal proinflammatory cytokine response is followed by the onset of spontaneous preterm parturition in patients with preterm premature rupture of membranes.

Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia

Abstract OBJECTIVE: Our purpose was to test the hypothesis that neonates who develop bronchopulmonary dysplasia have higher amniotic fluid concentrations of proinflammatory cytokines than those who do not develop bronchopulmonary dysplasia. STUDY DESIGN: The relationship between amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8 and the occurrence of bronchopulmonary dysplasia in the neonate was examined in 69 patients who were delivered of preterm neonates (≤33 weeks) within 5 days of amniocentesis. Cytokines were measured by specific immunoassays. RESULTS: Bronchopulmonary dysplasia was diagnosed in 19% (13/69) of newborns. Median amniotic fluid concentrations of interleukin-6, tumor necrosis factor-α, interleukin-1β, and interleukin-8 concentrations were significantly higher in mothers whose infants had bronchopulmonary dysplasia than in mothers whose infants did not have bronchopulmonary dysplasia ( p p CONCLUSIONS: (1) Antenatal exposure to proinflammatory cytokines is a risk factor for the development of bronchopulmonary dysplasia; (2) the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth. (Am J Obstet Gynecol 1997;177:825-30.)

Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation

OBJECTIVE To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief, pregnancy rate, and disease recurrence. DESIGN Prospective, randomized clinical trial. SETTING Tertiary care hospital. PATIENT(S) Sixty-four patients with advanced stages of endometriosis. INTERVENTION(S) Patients were randomly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma (group 1) or drainage of the endometrioma and bipolar coagulation of the inner lining (group 2). MAIN OUTCOME MEASURE(S) Pain relief and pregnancy rate. RESULT(S) Thirty-two patients were enrolled in each group. The 24-month cumulative recurrence rates of dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain were lower in group 1 than in group 2 (dysmenorrhea: 15.8% versus 52.9%; deep dyspareunia: 20% versus 75%; nonmenstrual pelvic pain: 10% versus 52.9%). The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 (19 months [range, 13.5-24 months] versus 9.5 months [range, 3-20 months]). The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 (66.7% versus 23.5%). CONCLUSION(S) For the treatment of ovarian endometriomas, a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation.

Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome

Objective: To determine whether there is a relationship between the presence of histological signs of inflammation in the extraplacental membranes and umbilical cord and the concentrations of fetal plasma interleukin-6 (IL-6). Methods: The study examined a cohort of patients who were admitted with preterm labor or preterm premature rupture of the membranes (PROM) and who underwent cordocentesis. Inclusion criteria included fetal plasma available for IL-6 determination, histological examination of the umbilical cord and placenta, and delivery within 48 h of the procedure. This last criterion was used to preserve a meaningful temporal relationship between fetal plasma IL-6 and the results of histological examination of the placenta. Fetal plasma IL-6 was determined by a high sensitivity ELISA. Forty-five patients were available for study: 18 patients had preterm labor with intact membranes and 27 had preterm PROM. Results: The incidence of funisitis was 44.4% (20/45): 27.8% (5/18) in patients with preterm labor and intact membranes and 55.6% (15/27) in patients with preterm PROM. The median values of fetal plasma IL-6 in patients with funisitis, chorioamnionitis without funisitis, and non-inflamed membranes were 51.4, 18.4 and 5.2 pg/ml, respectively. After log transformation of the fetal plasma IL-6 concentration, the means differed significantly from each other (ANOVA, p < 0.02). There was no difference in log fetal plasma IL-6 concentration between patients with funisitis and those with chorioamnionitis without funisitis. The difference in mean concentration of log fetal plasma IL-6 between patients with funisitis or chorionic vasculitis and those without inflammation was highly significant (post-hoc test, p = 0.01 and p < 0.01, respectively). Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of histological signs of inflammation in the extraplacental membranes and umbilical cord than those with fetal plasma IL-6 < 11 pg/ml (funisitis: 55.6% (15/27) vs. 27.8% (5/18), p < 0.05; chorionic vasculitis: 55.6% (15/27) vs. 12.5% (2/16), p < 0.01; chorioamnionitis only: 25.9% (7/27) vs. 16.7% (3/18), p < 0.05; no inflammation: 18.5% (5/27) vs. 55.6% (10/18), p < 0.05, respectively). Fetuses with funisitis had significantly higher rates of clinical and histological chorioamnionitis, and neonatal infectious morbidity (proven + suspected sepsis) than fetuses without funisitis (40% (8/20) vs. 8% (2/25), 90% (18/20) vs. 36% (9/25), and 40% (8/20) vs. 4% (1/25), respectively; p < 0.01 for each). Fetuses with chorionic vasculitis had significantly higher rates of clinical and histological chorioamnionitis as well as neonatal infectious morbidity (proven + suspected sepsis) than fetuses without chorionic vasculitis (100% (17/17) vs. 42.3% (11/26), p < 0.01; 82.4% (14/17) vs. 50.0% (13/26), p = 0.05; and 41.2% (7/17) vs. 7.7% (2/26), p = 0.01). Conclusion: Fetal plasma IL-6 concentration is significantly associated with the presence of inflammatory lesions in the extraplacental membranes and umbilical cord. Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of funisitis and/or chorionic vasculitis than fetuses with fetal plasma IL-6 < 11 pg/ml. These findings suggest that funisitis/chorionic vasculitis is the histological manifestation of the fetal inflammatory response syndrome.

Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia

OBJECTIVE To determine if an intrauterine sub-clinical inflammatory process is a risk factor for the development of bronchopulmonary dysplasia. METHODS A cohort study was conducted in patients who met the following criteria: (1) Singleton gestation; (2) preterm labor or preterm premature rupture of the membranes; (3) amniocentesis for microbiologic studies of the amniotic fluid and (4) delivery between 24 and 28 weeks of gestation. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen for 28 days or longer after birth, associated with compatible chest radiographic findings. Amniotic fluid interleukin-8, was measured using a specific immunoassay. Logistic regression analysis and bootstrap procedure were used for statistical purposes. RESULTS Forty-seven patients met the inclusion criteria for this study. Among these patients, the prevalence of bronchopulmonary dysplasia was 23.4% (11/47). Amniotic fluid culture was positive in 21 out of 47 (44.7%) patients. Median (range) amniotic fluid interleukin-8 concentration was higher in patients whose neonates subsequently developed bronchopulmonary dysplasia than in those who did not (17 [9.8-583.7] ng ml(-1) versus 9.6 [0.91-744] ng ml(-1), P=0.057). An amniotic fluid IL-8 level greater than 11.5 ng ml(-1) was far more common in mothers whose fetuses went on to develop bronchopulmonary dysplasia than in those who did not (10/11 [90.9%] versus 17/36 [47%]; P=0.01). This relationship remained significant even after correcting for the effect of gestational age and birthweight (Odds ratio: 11.9; P<0.05). CONCLUSION Sub-clinical intrauterine inflammation is a risk factor for the subsequent development of bronchopulmonary dysplasia. We propose that in utero aspiration of fluid with high concentration of pro-inflammatory mediators may contribute to the lung injury responsible for the development of bronchopulmonary dysplasia.

Female Sexual Function during Pregnancy and after Childbirth

INTRODUCTION Healthy sexual function during pregnancy and after childbirth is one of the cornerstones for couples to evolve from partners to parents. AIM The aim of our review is to evaluate the available evidence and define present knowledge about female sexual function during pregnancy and after childbirth. METHODS PubMed was searched for articles on sexual function during pregnancy and after childbirth, published from 1960 up to date. The most relevant articles have been reviewed and included. MAIN OUTCOME MEASURES The main outcome is the review of the effect of pregnancy, delivery, and postpartum on female sexuality. RESULTS A total of 48 articles which specifically addressed this topic were included. Sexual function was found to have a significant global decline during pregnancy, particularly in the third trimester and this persisted for 3-6 months following delivery. The lack of adequate information about sex in pregnancy and concerns about the possible adverse obstetric outcomes are the most relevant factors responsible for the avoidance of sexual activity during pregnancy. Breast-feeding, dyspareunia, and postpartum pelvic floor dysfunction were reported as possible causes for the delay in resuming sexual intercourses after childbirth. CONCLUSIONS Couples should be informed about the decline of libido, desire and orgasm, commonly encountered during pregnancy, particularly in the last trimester, and puerperium which may lead to reduction in sexual intercourse frequency.

Matrix metalloproteinases-9 in preterm and term human parturition.

OBJECTIVE Spontaneous rupture of the fetal membranes occurs after the commencement of labor in 90% of cases. Recent evidence indicates that the process of parturition requires not only an increase in myometrial contractility and cervical ripening, but also degradation of extracellular matrix in fetal membranes (i.e., leakage of fibronectin into cervico-vaginal secretions). This study was undertaken to determine if parturition is associated with in vivo evidence of increased bioavailability of matrix metalloproteinases-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinases-1(TIMP-1). METHODS A cross-sectional study was conducted with women in the following categories: 1) midtrimester (n = 25); 2) preterm labor and intact membranes in the absence of intraamniotic infection (n = 78); 3) term not in labor (n = 25); and 4) term with intact membranes in labor (n = 25). MMP-9, and TIMP-1 were measured using sensitive and specific immunoassays. RESULTS 1) Spontaneous labor at term was associated with a significant increase in MMP-9 but not in TIMP-1.2) Women with preterm labor who delivered prematurely had significantly higher concentrations of MMP-9 but not TIMP-1 in amniotic fluid than those with preterm labor who delivered at term. 3) The concentrations of TIMP-1 decreased with advancing gestational age. In contrast, MMP-9 concentrations did not change with advancing gestational age. CONCLUSIONS Spontaneous human parturition is associated with specific changes in the enzymatic machinery responsible for extracellular matrix degradation.

Tension-free Vaginal Tape for the Treatment of Urodynamic Stress Incontinence: Efficacy and Adverse Effects at 10-Year Follow-Up

BACKGROUND One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings. OBJECTIVE To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up. DESIGN, SETTING, AND PARTICIPANTS This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. INTERVENTION Standard retropubic TVT. MEASUREMENTS Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes. RESULTS AND LIMITATIONS A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p>0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9cm H(2)O (hazard ratio [HR]: 16.2; p=0.01) and maximum detrusor pressure during the voiding phase ≤29cm H(2)O (HR: 8.0; p=0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p=0.01) and of USI (HR: 8.9; p=0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred. CONCLUSIONS The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up.

Vaginal extraction of pelvic masses following operative laparoscopy.

Objective: To investigate the clinical outcome of patients undergoing operative laparoscopy for a benign pelvic mass followed by vaginal extraction of the surgical specimen. Methods: Patients presenting with a suspected benign mass greater than 5 cm or an extrauterine pregnancy undergoing operative laparoscopy were considered eligible. Patients with endometriosis, pelvic inflammatory disease, and previous hysterectomy were excluded. In all cases the surgical specimen was removed through a colpotomy performed in laparoscopy at the level of the posterior vaginal fornix. Additionally, a review of the literature has been conducted to specifically address the incidence of colpotomy-related complications. Results: Sixty-three patients were included in the study. The median (range) time required to extract the freed mass to the complete suture of the colpotomy was 15 min (5–31). This time was significantly longer in patients with myomas than for others [median 21 min (range: 10–31) vs median 10 min (5–13), p<0.05]. No intra- and postoperative colpotomy related complications occurred. No patients complained dyspareunia at follow-up visits. A total of 23 studies were reviewed for a total of 501 patients and only one (0.2%) complication (severe vaginal bleeding) was directly attributable to the colpotomy. Conclusion: Removal of a pelvic mass through a laparoscopic colpotomy is feasible, safe, and offers better cosmetic results than transabdominal extraction of the surgical specimen.

Vaginal cuff closure after minimally invasive hysterectomy: our experience and systematic review of the literature

OBJECTIVE To determine the incidence of vaginal cuff dehiscence after minimally invasive hysterectomy, we reported our series of total laparoscopic hysterectomies with transvaginal colporraphy. STUDY DESIGN We then conducted a systematic search of PubMed to retrieve published series of laparoscopic and robotic hysterectomies, in which different techniques for vaginal cuff closure were used. RESULTS In our study group, vaginal cuff dehiscence occurred in 2 of 665 (0.3%) patients. Our literature search identified 57 articles, for a total of 13,030 endoscopic hysterectomies. Ninety-one postoperative vaginal separations were reported (0.66%). The pooled incidence of vaginal dehiscence was lower for transvaginal cuff closure (0.18%) than for both laparoscopic (0.64%; odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12-0.65) and robotic (1.64%; OR, 0.11; 95% CI, 0.04-0.26) colporraphy. Laparoscopic cuff closure was associated with a lower risk of dehiscence than robotic closure (OR, 0.38; 95% CI, 0.28-0.6). CONCLUSION Current evidence indicates that transvaginal colporraphy after total laparoscopic hysterectomy is associated with a 3- and 9-fold reduction in risk of vaginal cuff dehiscence compared with laparoscopic and robotic suture, respectively.