Atosiban improves implantation and pregnancy rates in patients with repeated implantation failure

This prospective cohort study examined the effects of atosiban on uterine contraction, implantation rate (IR) and clinical pregnancy rate (CPR) in women undergoing IVF/embryo transfer. The study enrolled 71 women with repeated implantation failure (RIF; no pregnancies from an average of 4.8 previous embryo transfers with a mean of 12 top-quality embryos) undergoing IVF/embryo transfer using cryopreserved embryos. The total atosiban dose was 36.75 mg. The IR per transfer and CPR per cycle were 13.9% and 43.7%, respectively. Before atosiban, 14% of subjects had a high frequency of uterine contractions (?16 in 4 min). The frequency of uterine contractions was reduced after atosiban. This reduction of uterine contractions in all cycles was significant overall (from 6.0 to 2.6/4 min; P < 0.01), in cycles with ?16 uterine contractions/4 min at baseline (from 18.8 to 5.1; P < 0.01) and in cycles with <16 uterine contractions/4 min (from 3.9 to 2.2; P < 0.01). IR and CPR improved in all subjects, irrespective of baseline uterine contraction frequency. This is the first prospective study showing that atosiban may benefit subjects with RIF undergoing IVF/embryo transfer with cryopreserved embryos. One potential mechanism is the reduction in uterine contractility, but others may also contribute.Many women undergoing IVF/embryo transfer do not achieve the outcome that they wish for. In fact, IVF/embryo transfer repeatedly fails for a subgroup of patients. There are limited options available to help these patients with repeat implantation failure (RIF) to become pregnant. This study looks at one potential new treatment option for women who experience RIF. A drug called atosiban is already being used to delay premature labour by inhibiting contractions of the uterus. In this study, atosiban was given at the time of embryo transfer to women undergoing IVF/embryo transfer. Atosiban reduced the number of uterine contractions in these patients and also increased the implantation and pregnancy rates. The pregnancy rate went from zero to 43.7%. The beneficial effects of atosiban were observed not only in patients who had a high frequency of uterine contractions at baseline but also in those who had a low frequency. These findings suggest that atosiban may have other benefits in addition to its effect on contractions of the uterus. More studies are required to find out exactly how atosiban works and to increase the knowledge of its use in patients with RIF undergoing IVF/embryo transfer.     

Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF

This report aimed to examine the effects of atosiban on pregnancy outcome after IVF–embryo transfer. A prospective, randomized, placebo-controlled clinical study was performed. A total of 180 women undergoing intracytoplasmic sperm injection who had top-quality embryos were randomly allocated into treatment and control groups. All the patients had infertility due to tubal factor, hormonal-anovulatory disorders, male factor or unexplained reasons. The treatment group received intravenous administration of atosiban before embryo transfer with a total administered dose of 37.5 mg. In the control group, the same number of cycles was performed with placebo medication. The clinical pregnancy rate (PR) per cycle and implantation rate (IR) per transfer were 46.7% and 20.4% in the atosiban-treated group, which were significantly higher than in the control group (28.9% and 12.6%, respectively, P = 0.01). The miscarriage rates of groups 1 and 2 were 16.7% and 24.4%, respectively (P = 0.01). These results have indicated that atosiban increases the IR and PR after IVF–embryo transfer. These results suggest that atosiban treatment before embryo transfer is effective in priming of the uterus for implantation. This is the first study to investigate the possible contributions of atosiban for improving the PR after IVF–embryo transfer.     

Subjective sexual response to testosterone replacement therapy based on initial serum levels of total testosterone

IntroductionTestosterone replacement therapy (TRT) has been shown to be beneficial for men with hypogonadism. However, it is unknown how well hypogonadal men respond to TRT based on the severity of testosterone deficiency.AimTo determine subjective sexual response rates to TRT based on initial serum testosterone values, with particular interest in men with “low-normal” levels of total testosterone (TT).Main Outcome MeasuresSubjective responses to TRT in the domains of erectile dysfunction, libido, orgasm, and morning erections.MethodsA retrospective study was performed of 211 men with sexual symptoms of hypogonadism who underwent TRT. All men had either low values of TT (<300 ng/dL) or free testosterone (FT) (<1.5 ng/dL). The cohort was divided into three groups based on initial TT levels: Group 1: 0–200 ng/dL (N = 26; 12.3%); Group 2: 201–300 ng/dL (N = 64; 30.3%); Group 3: 301 ng/dL or greater (N = 121; 57.3%). Improvement in erectile function was determined prior to addition of any other treatment (e.g., phosphodiesterase type 5 inhibitors). The mean follow-up was 9 months (range 3–36 months).ResultsThe mean age was 55.2 years. Testosterone gel was used in approximately two-thirds of each group. Improvement in libido was reported in 61.5%, 96.6%, and 29.8% for Groups 1, 2, and 3, respectively (P < 0.001). Improvement in erectile function was noted in 46.2%, 45.3%, and 73.6% for Groups 1, 2, and 3, respectively (P < 0.001). At time of last follow-up, the percentage of men continuing with TRT was 73.1%, 57.8%, and 58.7% for Groups 1, 2, and 3, respectively (P = nonsignificant).ConclusionsThese preliminary data suggest that men with sexual symptoms of hypogonadism respond well to TRT across a wide range of initial TT values, including men with low-normal TT levels. These men may have low bioavailable levels of testosterone that are not reflected in TT values. Reyes-Vallejo L, Lazarou S, and Morgentaler A. Subjective sexual response to testosterone replacement therapy based on initial serum levels of total testosterone.     

VEGF expression and the effect of NSAIDs on ascites cell proliferation in the hen model of ovarian cancer

ObjectiveTo determine if extra-peritoneal laparoscopic para-aortic (PA) lymphadenectomy allows a reliable assessment of PA nodes in patients with endometrial cancer (EC).MethodsIn October of 2005, a single surgeon began performing extra-peritoneal laparoscopic PA lymphadenectomy for patients with EC. A prospective cohort study was initiated from October 2005 through October 2007. Staging of Group A included extra-peritoneal laparoscopic PA lymphadenectomy, while Group B underwent staging via laparotomy.ResultsIn a 24 month period, 293 patients underwent surgical treatment for EC, 203 of them underwent complete staging as determined by previously published criteria. Extra-peritoneal laparoscopic PA lymphadenectomy to the renal veins was successful in 35/38 patients (92%). Mean BMI was 33.0 for Group A and 32.3 for Group B (p = NS). Mean EBL and hospital stay were lower in Group A compared to Group B (163 vs 373 cm³, p < 0.0001; median 2 vs 4 nights, p < 0.001). The total number of PA nodes harvested was not statistically different between Groups A and B (16.5 vs 19.6). Interestingly, in Group A the total number of PA nodes was greater for patients with BMI > 35, (21.6 vs 13.1), while in Group B fewer nodes were removed in obese patients (17.8 vs 20.5).ConclusionsExtra-peritoneal laparoscopy is a reliable method to routinely reach the level of the renal veins, even in obese patients. This approach was feasible in over 90% of unselected patients and well-tolerated.     

Enoxaparin and aspirin therapy for recurrent pregnancy loss due to anti-phospholipid syndrome (APS)

BackgroundRecurrent miscarriage affects 1–2% of women. Thrombophilia included antiphospholipid syndrome has been identified in about 50% of women with recurrent miscarriage. Aspirin and heparin therapy is frequently prescribed for APS, yet there is no robust evidence for the most efficacious regime.ObjectiveTo determine maternal and foetal outcomes in women with APS managed with aspirin or enoxaparin plus aspirin during pregnancy.DesignProspective non randomized study.SettingHigh-risk pregnancy unit-Benha University Hospital.MethodsSeventy selected patients during pregnancy with clinical and/or serological findings of antiphospholipid syndrome were divided into two Groups: Group A (n = 47) had received aspirin (81 mg once daily orally) plus LMWH enoxaparin (40 mg subcutaneously/day) while Group B (n = 23) had received low-dose aspirin (81 mg day orally).Main outcome measuresMaternal outcomes included thromboembolic, haemorrhagic complications and pregnancy-induced hypertension. Prematurity, intrauterine growth restriction and neonatal death were considered as foetal complications.ResultsThere were significant differences between Groups A and B in the rate of miscarriages (4 in Group A (9%) versus 8 in Group B (35%); p = 0.02), number of live births (43/47(91%) versus 15/23(65%); p = 0.02), mean gestational age (37.86 ± 1.8 versus 36.13 ± 2.39 weeks; p = 0.005), neonatal birth weight (3252 ± 459 versus 2907 ± 618 g; p = 0.03) and rate of pre-eclampsia (3/43 (7%) versus 6/15 (40%); p = 0.009). Although not statistically significant, women in Group A tended to have lower rates of preterm births (6/43 (14%) versus 3/15 (20%); p = 0.89) and IUGR (5/43 (12%) versus 5/15 (33%); p = 0.13) than in Group B.ConclusionsUse of low dose aspirin and enoxaparin 40 mg subcutaneously daily in patients with RPL due to antiphospholipid syndrome resulted in higher live birth rates compared to low dose aspirin alone. Solid conclusions from this study are limited due to the small number of patients, non-randomization of groups and discrepancy in number between groups because the choice of the interventional drug was left to patient’s preference after counselling. A larger RCT is needed.     

The efficacy of converting high response – Ovulation induction cycles to in vitro fertilization in patients with PCOS

ObjectiveTo evaluate the outcomes of high response clomiphene citrate (CC)-gonadotropin ovulation induction cycles for natural unassisted conception in patients with PCOS (Polycystic Ovary Syndrome) being converted to IVF–ICSI–ET and compare them with other PCOS patients who underwent planned IVF–ICSI–ET using the GnRH-antagonist protocol.Study designProspective study with a retrospective controlled section. The study was conducted at Taiba Hospital in Kuwait during the period from January 2010 to August 2012. It included 128 infertile patients with the diagnosis of PCOS, divided into two groups. Group I comprised 64 PCOS patients who received ovulation induction, using CC-gonadotropin, in view of natural conception and were converted to IVF–ICSI–ET due to high response. Group II comprised 64 age-matched PCOS patients who underwent planned IVF using the GnRH-antagonist protocol. Primary outcomes were number of mature oocytes, number of grade 1 embryos transferred, and implantation and clinical pregnancy rates.ResultsThe implantation and clinical pregnancy rates were comparable in the two groups (in group I were 23.43% and 43.75%, respectively and in group II were 25% and 45.31%, respectively). There was no statistically significant difference between group I and group II as regards number of retrieved oocytes (7.7 ± 1.3 vs. 8.1 ± 1.4, respectively), number of mature oocytes (5.7 ± 1.1 vs. 6.1 ± 1.3, respectively), total number of embryos (4.9 ± 0.8 vs. 5.1 ± 0.5, respectively), number of cells/embryo (8.1 ± 0.8 vs. 7.9 ± 0.7, respectively).ConclusionConversion of high response CC-gonadotropin ovulation induction cycles in patients with PCOS to IVF–ICSI–ET is a safe, economic and effective strategy.     

Intravital high-frequency ultrasonography to evaluate cardiovascular and uteroplacental blood flow in mouse pregnancy

ObjectiveThe objective of this study is to define the ultrasonographic changes in the cardiovascular and uteroplacental circulation of normal pregnant mice compared to non-pregnant mice using high-frequency, high-resolution ultrasonography.MethodsTen to twelve-week-old CD-1 mice (six non-pregnant and six pregnant animals) were used for all experiments. Vevo® 2100 (VisualSonics) was used to evaluate the cardiovascular and uteroplacental circulation physiology. Cardiac echocardiogram and uterine artery Doppler studies were performed on all animals. Pregnant animals were evaluated on embryonic day 7 (E7), 13 (E13) and 18 (E18). Fetal heart rate and umbilical artery Doppler flows were obtained on pregnant animals. Three-dimensional ultrasonography imaging was utilized for quantification of placental volumes. All data are presented as median (10th–90th percentiles).ResultsIn pregnant mice on E7 compared to non-pregnant mice, there was an increase in cardiac output (p = 0.008), stroke volume (p = 0.002), ejection fraction (p = 0.02), and fractional shortening (p = 0.02). The maternal heart rate increased throughout gestation (p = 0.009). During pregnancy, a gestational sac was clearly visible on E7. Between E13 and E18, the fetal size and fetal heart rate increased (p = 0.001) and the umbilical artery peak systolic velocity increased (p < 0.001). Minimal diastolic blood flow was observed in the umbilical artery on E13, which increased slightly on day E18 (p = 0.01). There was no change in the uterine artery resistance index between non-pregnant and pregnant mice. The placental volume increased between E13 and E18 (p = 0.03).ConclusionSeveral changes noted in cardiovascular and uteroplacental systems occurring during normal murine pregnancy have striking similarities to humans and can be accurately measured using newer ultrasonographic techniques. Further studies are needed to evaluate changes in these vascular beds in mouse models of diseases such as preeclampsia and intrauterine growth restriction.     

Effect of avoiding bladder flap formation in caesarean section on repeat caesarean delivery

ObjectivesTo evaluate the effect of bladder flap formation (BFF) during caesarean section (CS) on the uterine scar, assessed during repeat CS.Study designOne hundred and fifteen women undergoing their first CS were divided into two groups: 58 women had a CS with BFF (Group 1) and 57 women had a CS without BFF (Group 2). During the repeat CS, four specimens from the uterine scar from the first CS were collected from each woman, and evaluated by light microscopy and transmission electron microscopy (TEM).ResultsAdhesions were found in 28 (48.3) women in Group 1 and 14 (24.1%) women in Group 2 (p < 0.01). Of the women with adhesions in Group 1, 20 (71.4%) had mild adhesions and eight (28.6%) had severe adhesions. Of the women with adhesions in Group 2, eight (57.1%) had mild adhesions and six (42.9%) had severe adhesions. Light microscopy revealed significant differences in submesothelial fibrosis (39.6% vs 12.2%; p < 0.01) and neo-angiogenesis of the mesothelial stroma (46.5% vs 21%; p < 0.01) in Groups 1 and 2, respectively. TEM revealed more specimens with inflammatory cells in Group 1 compared with Group 2 {mean 29.7 [standard deviation (SD) 1.3] vs 18.2 (SD 1.9) patients; p < 0.01}.ConclusionBFF during CS leads to an inflammatory and fibrotic reaction, resulting in inflammation reactive and regenerative processes, mesothelial hyperplasia and submesothelial fibrosis. CS without BFF reduces the inflammatory processes and the subsequent intraperitoneal adhesions and adhesions between the bladder and uterus.     

The association of maternal and fetal glucose homeostasis with fetal adiposity and birthweight

ObjectiveTo examine the association between maternal and fetal glucose levels and fetal adiposity and infant birthweight.Study designThis is a prospective study of 479 healthy, non-diabetic mother and infant pairs attending the National Maternity Hospital in Ireland. Fasting glucose was measured in early pregnancy (11.8 ± 2.3 weeks). At 28 weeks gestation a repeat fasting glucose was measured and 1 h glucose challenge testing (1 h GCT) was performed. At 34 weeks’ gestation (33 + 5–34 + 5 weeks) fetal growth and fetal anterior abdominal wall width, a marker of fetal adiposity, were measured. At delivery cord glucose was measured and neonatal anthropometry recorded.ResultsThere was a positive correlation between fasting glucose concentration during pregnancy and both infant birthweight and fetal anterior abdominal wall width at 34 weeks gestation. The incidence of macrosomia (birthweight > 4.5 kg) was significantly greater for maternal and cord blood glucose levels in the highest quartile compared to the lowest quartile (20.7% vs. 11.7%, p < 0.05 in the first trimester, 21.3% vs. 7.2%, p < 0.05, at 28 weeks, and 33.3% vs. 10%, p < 0.05, in cord blood). Maternal glucose concentrations at each time point, though not cord glucose, were related to early pregnancy maternal body mass index (r = 0.19, p < 0.001 in first trimester, r = 0.25, p < 0.001 at 28 weeks, r = 0.15, p < 0.01 with 1 h GCT).ConclusionMaternal glucose homeostasis is an important determinant of fetal size. We have shown that even small variations in fasting glucose concentrations can influence fetal growth and adiposity. This effect is seen from the first trimester and maintained until delivery.     

High-quality embryos retain their implantation capability in overweight women

To assess the effect of obesity on implantation rate, pregnancy rate and course of pregnancy in young women undergoing IVF in whom only high-quality embryos were transferred, a cohort study included women attending the IVF unit in 2006–2007 with favourable parameters to achieve pregnancy (<38 years, fewer than three IVF cycles, transfer of two high-quality embryos), grouped by body mass index (BMI). Of 230 women, 160 had a BMI ?25 kg/m² (mean 21.6 ± 2.2) and 73 had BMI >25 kg/m² (mean 29.5 ± 3.7). The overweight group had a higher consumption of gonadotrophins during stimulation. There were no between-group differences in treatment protocols, duration of gonadotrophin stimulation, maximal oestradiol concentrations, endometrial thickness and number of oocytes retrieved/fertilized, or in rates of pregnancy (51.3%, 52.1%), implantation (34.5%, 37.5%), multiple pregnancy, and abortion. Rate of gestational diabetes or pregnancy-induced hypertension was higher in the overweight group (23.3%, 8.2%; P = 0.045). Within the overweight group, those with multiple pregnancies were at highest risk (31.3%, 6.9%; P = 0.031). In conclusion, implantation and pregnancy rates are not compromised in overweight women when high-quality embryos are transferred. However, in overweight women, pregnancy complications remain high, mainly in those with multiple pregnancies.     

Misoprostol for term labor induction: a randomized controlled trial

ObjectivesThe aim of this study was to compare the efficacy of vaginal misoprostol with vaginal dinoprostone for term labor induction.Material and MethodsIt was a randomized controlled trial done in the Obstetrics Department, Shifa Community Health Centre, Shifa International Hospital (Teaching Hospital of Shifa College of Medicine, Islamabad). All pregnant women at term pregnancy coming for induction of labor were enrolled. 246 women fulfilled the inclusion criteria. Out of them 208 women consented to be part of the study. These women were then randomized to receive either Treatment A (vaginal misoprostol) or Treatment B (vaginal dinoprostone). Data were completed for 200 women. These included induction labor and induction-delivery interval, fetal and maternal complications, and baby apgar score.ResultsOut of 200 women in the study, 100 were in Group A and 100 in Group B. Labor commenced in a mean of 6.67 hours (±3.63) in Group A whereas it took a mean of 8.41 hours (±5.13) in Group B (p = 0.00). Actual induction to delivery (of the baby) interval was a mean of 11.68 hours (±4.55) for misoprostol and 15.37 hours (±5.30) for dinoprostone group (p = 0.00). There were no cases of uterine rupture in both groups; however, there were 10 cases of uterine hyperstimulation in Group A and 4 in Group B (p = 0.09).ConclusionsIt is time to re-evaluate the role of misoprostol for term labor induction. It is an efficacious and cost-effective alternative to the presently licensed treatment.     

Positive correlation between the quantity of Wharton's jelly in the umbilical cord and birth weight

ObjectiveTo determine the possible protective effects of Wharton’s jelly (WJ) in umbilical cord and fetal growth by investigating the relationship between the amount of WJ and fetal birth weight.Materials and MethodsThis study enrolled 299 women who delivered after an uneventful pregnancy. After separation of the placenta, a 5 cm long section of umbilical cord was removed by scalpel. The weight of the cord section; the weight, volume, and density of its WJ; and the weight of the newborn and placenta were measured.ResultsA significant positive correlation was found between WJ quantity, birth weight (p = 0.002), and placental weight (p = 0.003), whereas a significant negative correlation was observed for WJ density, fetal growth (p = 0.035), and placental growth (p = 0.002). WJ density was 1.63 ± 0.27 g/mL. No significant correlation was found between the amount of WJ and weight gained during pregnancy (p = 0.274) or maternal age (p = 0.220).ConclusionAs the amount of WJ increases, fetal weight increases. Accordingly, the amount of WJ might be a factor that influences fetal growth.     

Critical care providers' opinion on unsafe abortion in Argentina

ObjectiveTo survey the opinion of critical care providers in Argentina about abortion.MethodsAn anonymous questionnaire was distributed to critical care providers attending the 20th National Critical Care Conference in Argentina.Results149 of 1800 attendees completed the questionnaire, 69 (46.3%) of whom were members of the Argentine Society of Critical Care (ASCC). 122 (81.9%) supported abortion decriminalization in situations excluded from the current law; 142 (95.3%) in cases of congenital defects; 133 (89.3%) in cases of rape; 115 (77.2%) when women's mental health is at risk; 71 (47.7%) when pregnancy is unintended; and 61 (40.9%) for economic reasons. 126 (84.6%) supported abortion in public and private institutions, and 121 (81.2%) before 12 weeks of pregnancy. Variables independently associated with abortion support among female versus male attendees were abortion to preserve women's mental health (OR 4.47; 95% CI, 1.61–12.42; P = 0.004) and abortion before 12 weeks of pregnancy (OR 3.93; 95% CI, 1.29–11.94; P = 0.015). Abortion at request was independently associated with ASCC membership (OR 2.63; 95% CI, 1.07–6.45; P = 0.034).ConclusionCritical care providers would support abortion in situations excluded from the current abortion law and before 12 weeks of pregnancy, in both public and private hospitals.     

Maternal serum leptin concentration in gestational diabetes

ObjectiveThe aim of this study was to evaluate fasting serum leptin concentration and its relation to insulin resistance in women with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (IGT).Materials and MethodsThis case-control study, at 28 weeks of gestation, measured serum concentration of fasting leptin, insulin, and homeostatic model assessment index in three groups, GDM, IGT, and normal control, and compared them with each other.ResultsThe serum leptin level was significantly higher in women with GDM than in the two other groups (p = 0.03). In women with GDM and IGT, leptin was significantly positively related with insulin and homeostatic model assessment index (r = 0.221, p = 0.03) and (r = 0.246, p = 0.03), respectively. In all of the participants, there was a significant correlation between leptin and body mass index before pregnancy (r = 0.416, p = 0.001).ConclusionOur data showed that serum leptin level was higher in GDM and had a positive correlation with insulin resistance. Our findings suggest that high leptin levels might be a risk factor for GDM and IGT in pregnant women.     

Comparison of misoprostol-only and combined mifepristone-misoprostol regimens for home-based early medical abortion in Tunisia and Vietnam

ObjectiveTo assess the potential advantages of combined mifepristone–misoprostol versus misoprostol-only for early medical abortion.MethodsA double-blind randomized placebo controlled study was conducted that enrolled 441 pregnant women (< 63 days since last menstrual period) at 2 hospitals in Tunisia and Vietnam. The mifepristone–misoprostol group (n = 220) received 200 mg of mifepristone on day 1 and 800 μg buccal misoprostol followed by placebo 3 hours later on day 2. The misoprostol-only group (n = 221) received placebo on day 1 and 1600 μg of misoprostol (2 doses of 800 μg, given 3 hours apart) on day 2. All medications were self-administered at home with follow-up 1 week later. The primary outcome was complete uterine evacuation without surgical intervention.ResultsSuccessful uterine evacuation occurred for 78.0% (n = 170) of women with misoprostol only versus 92.9% (n = 195) of women with mifepristone–misoprostol (relative risk 0.84, 95% CI, 0.78–0.91; P < 0.001). Ongoing pregnancy occurred for 13.8% (n = 30) of women given misoprostol-only and 1.4% (n = 3) of women given mifepristone–misoprostol (relative risk 9.63, 95% CI 2.98–31.09; P < 0.001).ConclusionMifepristone plus misoprostol is significantly more effective than misoprostol-only for early medical abortion.Clinical trials.gov registration number: NCT00680394.     

Prognostic role of the recepteur d'origine nantais (RON) expression in ovarian cancer patients

ObjectiveThe aim of the study was to investigate the potential clinical relevance of immunohistochemically assessed RON expression in a large, single institution series of primary untreated advanced ovarian cancer patients.MethodsImmunohistochemical analysis was performed by using the polyclonal rabbit anti-RON-β antibody (C-20, clone sc-322, Santa Cruz, California). Results were expressed as the total proportion of immunostained tumor cells (RON positivity), or the percentage of cells showing strong staining of RON expression (H-RON positivity).ResultsIn the overall series RON positive immunoreaction was observed in 103/141 cases, while H-Ron positivity was detected in 577141 (40.4%) cases. No association between RON and H-RON expression with response to first-line treatment was documented. During the follow up period, progression and death of disease were observed in 111 (78.7%) and 76 (53.9%) cases, respectively. Cases with strong H-RON expression has a shorter overall survival (median = 35 months) than cases with low RON levels (median = 59 months) (X² = ? 2.1, p value = 0.032). In multivariate analysis, only platinum resistance, and extent of residual tumor retained an independent negative prognostic role for OS, with the percentages of H-RON positively immunostained cells showing a borderline statistical significance (p value = 0.0643). The unfavourable role of elevated percentages of H-RON expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients (X² = 3.89, p value = 0.048) compared to the platinum sensitive ones (X² = 1.98, p value = 0.16).ConclusionsThe assessment of RON expression deserves further attention as a parameter helpful to identify poor prognosis ovarian cancer patients potentially candidates to investigational agents.     

Comparison of the effect of two different doses of recombinant gonadotropin for ovarian stimulation on the outcome of intrauterine insemination

ObjectiveThe aim of this study was to identify an optimal stimulation protocol for intrauterine insemination (IUI) to obtain an acceptable pregnancy rate and low frequency of multiple pregnancies.Materials and MethodsIn total, 340 patients, who received intrauterine insemination because of ovulation dysfunction, were enrolled in this study. Group I consisted of 203 patients who received recombinant FSH (r-FSH) 150 U every other day as an ovulation induction agent. Group II consisted of 137 patients who received r-FSH 100 U every other day as an ovulation induction agent. All patients in both groups also received clomiphene citrate 100 mg/day for consecutive five days from the fifth day of the cycle. Only patients with at least two follicles >18 mm on the human chorionic gonadotropin injection days were included in this study.ResultsThe clinical pregnancy rate was 14.8% (30/203) in Group I compared with 20.4% (28/137) in Group II, p > 0.05. The incidence of multiple pregnancy was 41.7% (10/24) in Group I compared with 12.5% (3/24) in Group II, p < 0.05.ConclusionsThe concurrent use of low-dose r-FSH and clomiphene citrate would seem not only to be cost-effective but also highly satisfactory in that it prevents high-order multiple pregnancies.     

Robotically assisted laparoscopic hysterectomy versus total abdominal hysterectomy and lymphadenectomy for endometrial cancer

ObjectiveTo compare surgical morbidity and clinical–pathologic factors for patients with endometrial cancer (EC) undergoing robotic-assisted laparoscopic hysterectomy (RALH) versus total abdominal hysterectomy (TAH) with aortic and/or pelvic lymphadenectomy (LA).MethodsDuring the first 14 months of a robotics surgical program, 56 patients with EC were scheduled to undergo RALH with LA. Cases were analyzed for operative (op) time, estimated blood loss (EBL), transfusion, intra- and post-op complications, surgical–pathologic data, patient demographics and length of stay (LOS). Data was compared to 106 serially treated patients with EC who underwent TAH with LA immediately prior to initiation of our robotics program.ResultsThree robotic cases (5.4%) were converted to TAH secondary to intra-op factors. FIGO stages for RALH vs. TAH were: stage I (82 vs. 69%), stage II (7 vs. 7.5%) and stage III (11 vs. 21.5%). Patients' mean age was 59 ± 10 vs. 63 ± 11 years (p = 0.05) and body mass index (BMI) was 29 ± 6.5 vs. 34 ± 9 kg/m² (p = 0.0001) for the robotic and open groups, respectively. Severe medical co-morbidities affected 5.4% of robotic patients compared to 8.5% of open cases (p > 0.05). Comparing RALH and TAH, mean op time was 177 ± 55 vs.79 ± 17 min (p = 0.0001), EBL was 105 ± 77 vs. 241 ± 115 ml (p < 0.0001), transfusion was 0 vs. 8.5% (p = 0.005), and LOS was 1.0 ± 0.5 vs. 3.2 ± 1.0 days (p < 0.0001). Robotic patients incurred a 3.6% major peri-operative complication rate while women undergoing open procedures had an incidence of 20.8% (p = 0.007). Total lymph node count was 19 ± 13 nodes for robotic cases vs. 18 ± 10 nodes obtained from open hysterectomy patients.ConclusionsPatients with EC who underwent RALH with LA during the first year of our robotics program were younger, thinner and had less cardio-pulmonary illness than patients previously treated with TAH and LA. LOS, EBL and peri-op complication rates were significantly lower for the robotic cohort.     

Nitric oxide as an early marker of human embryo metabolic cleavage in ART using fresh or thawed oocytes

ObjectiveTo study a possible role of nitric oxide (NO) as a marker of development in the early phases of human embryo cleavage during assisted reproduction.Study design179 women having ART were included. 123 women used fresh oocytes and 56 oocyte thawing cycles in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, between July 2005 and June 2006; 57 patients had IVF and 122 patients had ICSI. NO concentrations in IVF or ICSI embryo culture media were assessed by monitoring levels of NO stable oxidation products (nitrites/nitrates). Analysis of embryo quality was performed. Student’s t-test or Mann–Whitney and logistic regression model tests were applied to the data.ResultsIn patients using fresh oocytes, there were greater NO production in embryos derived from ICSI than from IVF after 52 h of culture (38.64 μmol/L vs 11.2 μmol/L, p < 0.05). No correlation with embryo quality was observed. Embryos derived from fresh oocytes produce more NO than embryos from thawed oocytes both after 48 and 52 h of culture (16.12 μmol/L vs 6.83 μmol/L and 25.93 μmol/L vs 2.98 μmol/L respectively, p < 0.05).Conclusion(s)NO in embryo culture media is not a metabolic cleavage marker or a marker of embryo quality in ART. However, it could be an important parameter in the investigation of metabolism in frozen/thawed oocytes.     

Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers A Gynecologic Oncology Group study

ObjectiveThe Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC).MethodsWomen were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel + carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide + cisplatin vs. paclitaxel + cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and mutant p53-isoforms. p53 overexpression was defined as ≥ 10% tumor cells exhibiting nuclear staining.Resultsp53 was overexpressed in 51% (73/143) and 66% (90/136) of cases in the GOG-157 and GOG-111 cohorts, respectively. In the GOG-157 cohort, p53 overexpression was not associated with any clinical characteristics or overall survival (OS) but was associated with worse progression-free survival (PFS) (logrank test: p = 0.013; unadjusted Cox modeling: p = 0.015). In the GOG-111 cohort, p53 overexpression was associated with GOG performance status (p = 0.018) and grade (p = 0.003), but not with age, stage, cell type or with tumor response and disease status after primary chemotherapy, PFS or OS. Adjusted Cox regression modeling demonstrated that p53 overexpression was not an independent prognostic factor for PFS or OS in either cohort.Conclusionsp53 overexpression assessed by DO-7 immunostaining is common in early and advanced stage EOC, but has limited prognostic value in women treated with surgical staging and platinum-based combination chemotherapy.