Three-dimensional sonograph of a monochorionic diamniotic triplet pregnancy.

A monochorionic diamniotic triplet pregnancy was diagnosed by sonographic scan at 9 weeks of gestation. The three embryos appeared to share the same trophoblast, with two of them sharing the same amniotic sac. The two amniotic sacs were divided by a thin membrane, with no chorionic projection within it, and each amniotic sac presented a single yolk sac. Only few cases of nontrichorionic-triamniotic triplets have been reported in the literature. Although the diagnosis was reached using the two-dimensional ultrasound, the complementary use of three-dimensional ultrasound helped in confirming the diagnosis, and in offering the couple an adequate counseling.

A placebo-controlled, randomized clinical trial using testosterone undecanoate with injectable norethisterone enanthate: effect on anthropometric, metabolic and biochemical parameters.

Testosterone administered alone or in combination with progestogens in male contraception induces reversible oligo-azoospermia, but its effects on body composition and metabolism are less known. We analysed anthropometric and metabolic parameters in five groups of 10 males: four receiving testosterone undecanoate (TU: 1000 mg) plus norethisterone enanthate (NETE: 200 mg) at different intervals (every 8 weeks: NETE-8; every 12 weeks: NETE-12; every 6 weeks for 12 weeks and then every 12 weeks: NETE-6/12; every 6 weeks for 12 weeks and then TU plus placebo every 12 weeks: NETE-6/12/0) and one placebo (NETE-0/0) for a total of 48 weeks. Body mass index (BMI) and waist circumference did not change in any groups except for the NETE-8 in which BMI increased significantly (p = 0.02) at the end of the treatment period. Lean body mass (MAMC or AMA) increased significantly in the highest hormonal dose groups (p = 0.04, NETE-6/12; p = 0.004, NETE-8). No differences were observed in glucose levels, insulin sensitivity index and lipid profile as well as in biochemical and cell count parameters in any groups. In conclusion, NETE and TU for 48 weeks were not accompanied by any metabolic changes and any adverse effects. The weight gain of the highest NETE plus TU dosage was mainly because of gain in muscle mass.

Maternal cardiac function in complicated twin pregnancy: a longitudinal study.

OBJECTIVE: To evaluate longitudinally a cohort of twin pregnancies and to assess whether the occurrence of adverse pregnancy outcome may be related to specific maternal cardiac findings. METHODS: Women with twin pregnancies were enrolled prospectively and underwent serial maternal echocardiography at 20-23 weeks, 26-29 weeks and 30-33 weeks of gestation. Patients were excluded if delivery took place prior to 34 weeks. Cardiac findings were compared between patients with uneventful pregnancy outcome and those who developed one of the following complications: pre-eclampsia or gestational hypertension; small-for-gestational age (SGA) neonates (birth weight of one or both twins < 5(th) centile for gestational age). RESULTS: A group of 28 twin gestations was obtained for analysis, including eight complicated cases. At each visit, mean ± SD cardiac output (CO) was significantly higher in uncomplicated than complicated twin pregnancies (6.55 ± 0.82 vs 4.99 ± 0.67 L/min, P < 0.001 at 20-23 weeks; 7.31 ± 0.74 vs 5.66 ± 1.17 L/min, P < 0.001 at 26-29 weeks; 7.50 ± 0.89 vs 5.32 ± 0.74 L/min, P < 0.001 at 30-33 weeks), as was stroke volume (83.4 ± 12.2 vs 64.5 ± 9.2 mL, P = 0.001 at 20-23 weeks; 84.4 ± 15.6 vs 64.5 ± 12.0 mL, P = 0.003 at 26-29 weeks; 85.0 ± 19.2 vs 65.6 ± 10.7 mL, P = 0.013 at 30-33 weeks), whereas total vascular resistance (TVR) was lower (1005 ± 137 vs 1406 ± 159 dynes × s/cm(5) , P < 0.001 at 20-23 weeks; 924 ± 100 vs 1249 ± 231 dynes × s/cm(5) , P < 0.001 at 26-29 weeks; 929 ± 96 vs 1400 ± 244 dynes × s/cm(5) , P < 0.001 at 30-33 weeks). Moreover, CO, blood pressure (BP), heart rate (HR) and TVR remained stable throughout the assessed pregnancy interval in women developing a complication, whereas significant changes (rise in CO, HR and BP; fall in TVR) were noted in the uncomplicated group. CONCLUSIONS: Maternal cardiac function in twin pregnancies complicated by pre-eclampsia or SGA neonates apparently does not undergo the profound longitudinal changes that occur in uneventful twin pregnancies.

Maternal cardiac function in normal twin pregnancy: a longitudinal study.

OBJECTIVE: To investigate maternal cardiac function in a cohort of uncomplicated twin gestations assessed longitudinally. METHODS: Women with twin pregnancies were enrolled prospectively and underwent serial maternal echocardiography at 20-23 weeks, 26-29 weeks and 30-33 weeks of gestation. Patients were excluded if any of these complications occurred after recruitment: delivery < 34 weeks; pre-eclampsia or gestational hypertension; small-for-gestational age neonates (birth weight of one or both twins < 5(th) centile for gestational age). Cardiac findings were compared with those obtained at the same gestational age periods in a group of singleton gestations. RESULTS: A group of 20 uncomplicated twin gestations was obtained for analysis and 10 singleton pregnancies were then selected as controls. At each visit, mean ± SD cardiac output (CO) was significantly higher in twins than in singletons (6.55 ± 0.82 vs 5.62 ± 0.82 L/min, P = 0.007 at 20-23 weeks; 7.31 ± 0.74 vs 6.39 ± 0.74 L/min, P = 0.003 at 26-29 weeks; 7.50 ± 0.89 vs 6.68 ± 0.65 L/min, P = 0.015 at 30-33 weeks), whereas total vascular resistance (TVR) was lower (1005 ± 137 vs 1179 ± 199 dynes × s/cm(5) , P = 0.009 at 20-23 weeks; 924 ± 100 vs 1070 ± 138 dynes × s/cm(5), P = 0.003 at 26-29 weeks; 929 ± 96 vs 1031 ± 122 dynes × s/cm(5), P = 0.018 at 30-33 weeks). In both twins and singletons, CO showed a significant increase while TVR decreased significantly throughout the assessed pregnancy time period. CONCLUSION: In twin gestation, maternal cardiac function apparently undergoes more profound changes compared with in singleton gestation, as testified by higher CO and lower TVR values at each stage of pregnancy starting from the mid-trimester.

Accuracy of fetal gender determination in the first trimester using three-dimensional ultrasound.

OBJECTIVES: To evaluate the accuracy of three-dimensional (3D) ultrasound in fetal gender assignment in the first trimester. METHODS: A series of pregnant women attending at 11 to 13 + 6 weeks for the nuchal translucency (NT) scan were enrolled into the study. An ultrasound volume of each fetus was obtained and stored for offline analysis. On the reconstructed mid-sagittal plane, the angle between the genital tubercle and an imaginary line passing tangentially through the fetal back (genital angle) was estimated and a receiver-operating characteristics (ROC) curve was constructed to determine the best cut-off for genital angle in fetal male gender determination. Fetal gender was subsequently ascertained in all cases. To calculate the interobserver variability, a second operator repeated the measurements. RESULTS: There were 85 cases included in the study. The genital angle in males was significantly higher than that in females (51.2 ± 11.3° (n = 36) vs. 18.9 ± 4.1 (n = 49), P < 0.001). The ROC curve revealed the estimated genital angle to have a high degree of accuracy in fetal gender determination (area under the curve ± SE = 1.000 ± 0.001). The best cut-off for male gender determination was found to be between 27° and 29° (sensitivity, 100%; specificity, 98.0%). There was a high degree of correlation between the two operators (r(2) = 0.998; coefficient of variation = 5.4%). CONCLUSIONS: 3D ultrasound is a highly accurate and reproducible tool for fetal gender assignment prior to 14 weeks of gestation.

Persistence of increased uterine artery resistance in the third trimester and pregnancy outcome.

OBJECTIVE: To evaluate whether the persistence of abnormal findings in the third trimester following increased uterine artery (UtA) resistance in the second trimester is related to adverse pregnancy outcome. METHODS: Low-risk nulliparous women with increased UtA mean pulsatility index (PI) at 20-22 weeks underwent repeat Doppler interrogation at 26-28 weeks and were divided into two groups: those with persistently abnormal Doppler and those with normalized UtA findings. Pregnancy outcome was noted for all patients and compared with that of 104 controls. RESULTS: We examined 104 women with increased UtA resistance in the second trimester and in 62 (59.6%) cases the abnormal uteroplacental Doppler findings persisted to 26-28 weeks. Compared with controls and with patients with normalized Doppler at the third-trimester scan, patients with persistently abnormal Doppler results had a significantly higher risk of pre-eclampsia (10/62 vs. 1/104, P = 0.002 and 10/62 vs. 1/42, P = 0.047, respectively), small-for-gestational age (SGA) fetus (20/62 vs. 1/104, P < 0.001 and 20/62 vs. 4/42; P = 0.007, respectively) and admission of the infant to a neonatal intensive care unit (16/62 vs. 4/104; P < 0.001 and 16/62 vs. 1/42; P < 0.001, respectively). Compared with controls, cases with normalization had an increased risk of SGA (4/42 vs. 1/104, P = 0.03), but there were no significant differences for the other outcome measures. CONCLUSIONS: In low-risk nulliparous women with increased UtA resistance in the second trimester, the persistence of abnormal Doppler findings at 26-28 weeks is associated with an increased risk of obstetric complications when compared with both controls and patients with third-trimester Doppler normalization.

Prenatal diagnosis and outcome of partial agenesis and hypoplasia of the corpus callosum.

OBJECTIVE: To present antenatal sonographic findings and outcome of fetuses with hypoplasia or partial agenesis of the corpus callosum. METHODS: The database of our ultrasound laboratory was searched retrospectively for cases of hypoplasia or partial agenesis of the corpus callosum suspected at antenatal neurosonography between 1998 and 2008 and confirmed by pathology or postnatal neuroimaging. In surviving infants, clinical follow-up had been arranged to assess neurodevelopmental outcome. RESULTS: Nineteen fetuses with callosal underdevelopment were identified at a median gestational age of 22 (range, 21-33) weeks and confirmed at follow-up, including 14 with partial agenesis and five with hypoplasia. Among the 14 fetuses with partial agenesis, there were additional brain findings in 10, including two with absent cavum septi pellucidi, four with mild isolated ventriculomegaly and four with cerebellar abnormalities, two of which also had ventriculomegaly. Pregnancy was terminated electively in seven of the cases with partial agenesis and there was one neonatal death. Among the six surviving infants, neurodevelopmental outcome was appropriate for age in three at follow up, including two cases with isolated partial agenesis of the corpus callosum. Among the five fetuses with prenatally diagnosed callosal hypoplasia, additional anomalies were present in four. Two cases were terminated electively and three were alive at the time of writing, with a median age of 3 years. Among them, apparently normal neurological development was observed in only one case. CONCLUSIONS: An antenatal diagnosis of callosal underdevelopment is possible by expert sonography. There is often association with other major anomalies. However, even in fetuses with apparently isolated findings, the prognosis is uncertain.

Diagnosis of station and rotation of the fetal head in the second stage of labor with intrapartum translabial ultrasound.

OBJECTIVE: To investigate the ability of intrapartum translabial sonography to diagnose fetal station in the second stage of labor. METHODS: Patients with uncomplicated pregnancies at term gestation with fetuses in vertex presentation in the second stage of labor underwent serial translabial sonography and digital examinations. In a sagittal section of the maternal pelvis, the direction of the head was noted and categorized as downward, horizontal or upward. By rotating the transducer in the transverse plane the cerebral midline echo was also visualized and the rotation of the head was noted. Clinical and ultrasound data were compared using Somer's d-test. RESULTS: Sixty patients underwent a total of 168 clinical and sonographic examinations. When on the sonogram the fetal head was directed downward, the station assessed clinically was most frequently or= + 3 cm (46/52 (88.5%) cases). Failure to visualize the cerebral midline or a rotation >or= 45 degrees were associated with a station of + 2 cm or less in 98/103 (95.1%) examinations. Conversely, a rotation of < 45 degrees was associated with a station of + 3 cm or more in 45/65 (69.2%) examinations. All comparisons between clinical and sonographic findings demonstrated a statistically significant relationship (P < 0.0001). The probability of a station + 3 cm or more was particularly high when an upward direction of the head was seen in combination with a rotation of < 45 degrees (40/42 (95.2%) examinations). The interobserver variability (Cohen's kappa 0.795 and 0.727 for station and rotation, respectively; P < 0.001) and intraobserver variability (0.845 for both station and rotation, P < 0.001) suggested good reproducibility of the method. CONCLUSIONS: Translabial sonography allows a diagnosis of fetal station with an accuracy comparable to that of digital examination and may provide useful information for diagnosing obstructed labor in the second stage as well as assisting in the choice of instrumental delivery.

Cervical length and risk of antepartum bleeding in women with complete placenta previa.

OBJECTIVE: To evaluate if cervical length predicts prepartum bleeding and emergency Cesarean section in cases of placenta previa. METHODS: Between September 2005 and September 2007, cervical length was measured by transvaginal ultrasound in women with complete placenta previa persisting into the third trimester of pregnancy. A complete follow-up of pregnancy was obtained in all cases. RESULTS: Overall, 59 women were included in the study group. The mean +/- SD gestational age at ultrasound was 30.7 +/- 2.7 weeks and the cervical length was 36.9 +/- 8.8 mm. Cesarean delivery was performed in all cases, at a mean gestational age of 34.7 +/- 2.3 weeks. Twenty-nine (49.1%) of the women presented prepartum bleeding and 12 (20.3%) required an emergency Cesarean section prior to 34 completed weeks due to massive hemorrhage. Cervical length did not differ significantly between cases with and those without prepartum bleeding (35.3 +/- 9.3 mm vs. 38.4 +/- 8.2 mm; P = 0.18), but was significantly shorter among patients who underwent emergency Cesarean section < 34 weeks due to massive hemorrhage compared with patients who underwent elective Cesarean section (29.4 +/- 5.7 mm vs. 38.8 +/- 8.5 mm; P = 0.0006). CONCLUSIONS: Transvaginal sonographic cervical length predicts the risk of emergency Cesarean section < 34 weeks in women with complete placenta previa.

Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid.

BACKGROUND: The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. AIM: To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. MATERIALS AND METHODS: Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. RESULTS: Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P < 0.001 and P < 0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P < 0.01). MRP4 did not show significant differences between the groups. CONCLUSIONS: Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.

Current status and future perspectives in male contraception.

Contraception is a crucial human right for its role on health, development and quality of life. Since the introduction of hormonal female contraception the burden of family planning has fallen mostly on women. The few methods of family planning available for men--namely condoms, vasectomy, periodic abstinence and withdrawal--are hundred year old in concept, are based on preindustrial practices and have low efficacy or are difficult to reverse. In spite of the shortcomings of currently available male contraceptives, 1/3 of the couples that use contraception worldwide rely on male methods suggesting that development of a safe, effective, reversible and affordable contraceptive method for men would meet a critical need. Recent surveys have shown that men want to know more about reproductive health and want to support their partner more actively. In recent decades, there have been exceptional advances in the development of safer and more effective contraceptives. Currently, several methods of contraception for men are under development. This paper summarises the efforts performed over the past decades to develop an effective, safe and reversible male contraceptive.

Pharmacokinetics of testosterone undecanoate injected alone or in combination with norethisterone enanthate in healthy men.

Long-acting injectable testosterone undecanoate (TU) is a promising androgen for male hormonal contraception. As a prerequisite for a planned multicenter male contraceptive efficacy study, we studied the pharmacokinetics of 2 doses of TU alone or in combination with norethisterone enanthate (NETE) in a prospective 2-center study, randomized for TU dose in each center. Twenty healthy male volunteers in each center were administered intramuscular injections of 750 or 1000 mg TU alone or in combination with 200 mg of NETE IM every 8 weeks for 3 injections. There were no significant differences in maximum concentration and area under the curve (AUC) for serum total and free testosterone (T) between the TU 750 and 1000 mg groups, irrespective of whether TU was administered with 200 mg of NETE. TU 1000 mg IM alone or with NETE at 8-weekly intervals resulted in linear increases in average concentration and AUC of serum total and free T with each injection. Accumulation ratios of serum total and free T levels (calculated as 8 weeks post- to preinjection levels) for each period showed significant increases in the TU+ NETE groups. Serum gonadotropins levels and sperm concentration were more consistently suppressed in the TU 1000 mg + NETE group. We conclude that despite some accumulation of T, TU 1000 mg + NETE 200 mg administered every 8 weeks may be preferable for the future contraceptive efficacy study because of more complete suppression of gonadotropins and spermatogenesis.

Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals on spermatogenesis, reproductive hormones, testis, and prostate.

The goal of this study was to find the most favorable injection interval of norethisterone enanthate (NETE) plus testosterone undecanoate (TU) in terms of gonadotropin, sperm suppression, and prostatic effects. Fifty normal men were randomly assigned to receive NETE 200 mg plus TU 1000 mg every 8 wk (n = 10), every 12 wk (n = 10), every 6 wk for 12 wk and then every 12 wk (n = 10), and every 6 wk for 12 wk and thereafter TU 1000 mg plus placebo every 12 wk (n = 10), and placebo plus placebo every 6 wk for 12 wk and then every 12 wk (n = 10) for 48 wk. Semen analyses, blood drawings, physical examinations, and prostate ultrasounds were performed throughout the study. Of the men in the 8-wk injection group, 90% (nine of 10) achieved azoospermia, compared with 37.5% (three of eight) in the 12-wk injection group (P = 0.019). TU plus placebo injected every 12 wk did not maintain sperm suppression. Prostate volumes did not change significantly in either group. In conclusion, these data suggest that the combined administration of NETE and TU at 8-wk intervals represents an effective hormonal contraceptive regimen.

Testosterone undecanoate maintains spermatogenic suppression induced by cyproterone acetate plus testosterone undecanoate in normal men.

In this study we evaluated whether testosterone undecanoate (TU), alone or combined with low dose cyproterone acetate (CPA), can maintain spermatogenic suppression induced by higher doses of CPA plus TU. Twenty-four men received for 12 wk 20 mg/d CPA plus 1000 mg/6 wk TU and then 1000 mg/8 wk TU plus 20 mg/d CPA (n = 8), 2 mg/d CPA (n = 8), or plus placebo (n = 8) for 32 wk. Blood samples, physical examinations, hormones, chemistry, hematology, semen analysis, and sexual/behavioral assessments were performed throughout the study. Sperm counts decreased to less than 1 million/ml in all subjects by wk 12, and 54% of them achieved azoospermia. Suppression of sperm counts was maintained until wk 44. Serum LH and FSH levels were suppressed by wk 12 of hormone administration and remained suppressed until wk 44. No significant changes in any biochemical parameters were detected at wk 44 in any group. There was a slight increase in total prostate volume to within the normal range at wk 44 that returned to baseline 1 yr after stopping hormone administration. In conclusion, TU alone or combined with lower doses of CPA maintains sperm suppression induced by higher dose CPA plus TU for 32 wk. This prototype regimen represents a promising male contraceptive regimen.

Benign ovarian tumors.

The aim of this study was to analyze whether, in a series of benign ovarian tumors, the diagnosis could be reliably established and whether the surgical treatment was appropriate. All patients underwent the preoperative evaluation and laparotomy was performed in all cases. The patients were followed for up to 3-8 years after surgery. Demolition surgery (mono or bilateral adnexiectomy with hysterectomy) was more frequently performed in postmenopausal women, while conservative surgery (enucleation, monolateral adnexiectomy) was done in fertile women. Evaluation of the treatment in our series shows that the surgical approach was more aggressive than necessary with respect to the histological diagnosis. Although in the serous and mucinous form tumors on can not rule out the possibility of malignancy in the remaining part of the ovary, the current approach should be more conservative, with enucleation of the mass and preservation of the ovary.

Brenner tumor of the ovary: a correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation.

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuron-specific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

Increased placental production of leukotriene B4 in gestational hypertension.

Production of some lipoxygenase and cyclooxygenase derivatives of arachidonic acid was measured in placental tissue obtained from women with gestational hypertension and with normal pregnancies. The levels of leukotriene B4 were about five times higher in placentas from hypertensive women and also raised thromboxane A2 and reduced prostaglandin E2 levels were observed. Prostacyclin production was lowered only in women with more severe hypertension, in association with the highest measured levels of leukotriene B4 and thromboxane A2. It is suggested that increased placental levels of leukotriene B4 and thromboxane A2 appear already in mild gestational hypertension, while depression of prostacyclin may occur only at more severe stages of gestational hypertensive disease.

AgNOR protein quantity of cervical smears correlates with that of histological sections in cervical intraepithelial neoplasia.

The quantitative distribution of AgNOR proteins has been determined by image cytometry in 52 cervical smears obtained from normal cervix (n = 20), grade I CIN (cervical intraepithelial neoplasia) (n = 3), grade II CIN (n = 5) and grade III CIN (n = 24). No significant difference was demonstrated in the mean AgNOR protein area values between normal cervix, CIN I and CIN II, while AgNOR protein scores of CIN III were significantly greater than those of normal cervix (p < 0.05). AgNOR protein quantity was also determined in 17 colposcopic directed biopsies of patients with CIN lesions (3 CIN II and 14 CIN III) already studied by cytological analysis. When AgNOR protein values of histological sections and corresponding cytological smears were compared by linear regression analysis, a significant correlation was found (r = 0.74, p < 0.05). Our results demonstrate that AgNOR protein quantity of cervical smears actually reflects that of the cervical epithelium in situ and may therefore be useful for the cytological diagnosis of cervical lesions.