Assisted reproduction and Coronavirus in Italy.

OBJECTIVE: A novel type of Coronavirus was identified in China in December 2019. The first cases of a form of pneumonia of unknown etiology were detected at the beginning of that month in Wuhan. The virus is believed to have emerged at the Wuhan Huanan Seafood Market, where transmission of a zoonotic pathogen to humans occurred. PATIENTS AND METHODS: Some studies conducted in China during the epidemic report small numbers of pregnant women infected with SARS-CoV-2 and some pregnancy complications in patients with COVID-19. However, they fail to document the transplacental passage of the virus from mother to fetus. RESULTS: Following the COVID-19 outbreak, guidelines for couples who are undergoing treatments of assisted reproduction have been issued by the International Federation for Fertility Societies (IFFS), the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE) and the Latin American Network of Assisted Reproduction (REDLARA). They recommend couples to discuss assisted reproduction with their doctors while those at risk or with SARS-CoV-2 should consider freezing oocytes or embryos and retransferring them later. CONCLUSIONS: Other than the US, Italy is the country with the highest number of cases (197675 positives, 26644 deaths) (updated on April 26). The Italian National Transplant Centre and the Higher Institute of Health advised on March 17 to complete the cycles already started and not to start new cycles. Phase 2 will begin on 4 May with an increase in freedom of action and fertilization treatments will start again. The Society that brings together embryologists (SIERR) has issued the guidelines to be followed when this happens.

Ultrasonographic evaluation of placental cord insertion at different gestational ages in low-risk singleton pregnancies: a predictive algorithm.

OBJECTIVE: To evaluate the accuracy of ultrasound in visualizing placental cord insertion (PCI) at different gestational ages in order to recommend the most feasible period during pregnancy to identify it. Secondary aim was to propose a predictive algorithm for PCI visualization. METHODS: We performed a single-center, prospective cohort study. We enrolled patients with singleton low-risk pregnancies who underwent fetal ultrasound scan at different gestational ages. We excluded patients with body mass index of 30 Kg/m2 or more, uterine fibroids larger than 5 cm, high-risk pregnancies, fetal weight lower than < 10° percentile or higher than > 90° percentile, increased ("deep pocket" > 80 mm) or decreased ("deep pocket" < 20 mm) amniotic fluid. RESULTS: Among the 468 recruited patients, the visualization of PCI was not possible in 5.77% of the cases. Furthermore, we showed that PCI visualization was lower as the gestational age increased (p = 0.049) and more difficult in case of posterior placenta (p = 0.001). CONCLUSIONS: PCI should be evaluated in the first trimester or as early as possible during the second trimester. Moreover, we propose a feasible model to predict the possibility of PCI visualization according to gestational age and uterine site of implantation.

Fetal urinoma in females without obstructive uropathy.

OBJECTIVE: Prenatal diagnosis of urinomas has long been established with underlying obstructive uropathy generally responsible for urinary extravasation. Because urinoma formation represents a pop-off mechanism in cases of posterior urethral valves, the number of affected males greatly exceeds the number of females. Fetal urinoma has rarely been reported without obstruction and in females it has only been described as a consequence of a complicated amniocentesis. METHODS: Three cases of fetal urinoma in female fetuses without any dilatation of the urinary tract are described. Since the fetus remained healthy, they were all conservatively managed. RESULTS: Two urinomas resolved after birth and 1 exhibited significant regression. In the second case, a compressed kidney was visualized with fetal MRI. Renal function was impaired in cases 1 and 3 and absent in case 2 (the kidney was no longer visualized). CONCLUSIONS: Fetal urinomas can occur even in the absence of urinary tract obstruction and in a low-pressure system as is found in female fetuses. Fetal MRI may help both visualize the ipsilateral kidney and differentiate the mass from other conditions. In a healthy fetus, fetal urinomas can be conservatively managed, but renal function after birth is often absent or impaired. Whether or not in utero aspiration may be beneficial for the preservation of renal function remains unclear.

Acute oligohydramnios: antenatal expression of VURD syndrome?

OBJECTIVE: Oligohydramnios (OA) is nowadays regarded as one of the best markers of renal function (RF) impairment in bladder outlet obstruction (BOO) detected in utero. As such, its onset is usually early and progressive because of decline in fetal urine production. A series of acute OA complicating pregnancies with BOO has never been reported. METHODS: Over a 7-year period, 5 fetuses with in utero suspicion of BOO exhibited an abrupt decrease of amniotic fluid after the 30th week of gestation. RESULTS: All fetuses were delivered by cesarean section: diagnosis was posterior urethral valves in 3 cases, urethral atresia in 1, and prune-belly syndrome in 1. Urologic work-up demonstrated a unilateral vesicoureteral reflux dysplasia (VURD syndrome) in all 5 fetuses. RF at 1 year was normal in 4 fetuses and impaired in 1. CONCLUSIONS: Besides obstetrical reasons, OA may also have acute onset occurring in the presence of anomalies of the urinary tract; although diagnosis is almost always BOO, functional and anatomical characteristics of the urinary tract are those of VURD syndrome with a non-functioning, refluxing renal unit. The associated acute OA/VURD syndrome may represent a milder expression of a pop-off mechanism advocated in this syndrome with a more favorable prognosis than progressive OA detected early in pregnancy.

Prenatal rectal perforation: an unsuspected cause of isolated ascites.

In fetal intestinal perforation, inflammation leads to production of ascites. Small bowel is usually involved by perforation with the distal ileum the most frequent site. We report the first case of prenatal perforation of the intraperitoneal part of the rectum, which presented as severe ascites at a 37 weeks' gestation antenatal ultrasonography. As none of the reported causes of intestinal perforation were identified in our case, its etiology remained idiopathic.

Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia.

BACKGROUND: There is considerable debate regarding the optimal management of congenital diaphragmatic hernia (CDH) in high-risk infants (those cases presenting with respiratory distress within 2 hours of birth or those diagnosed prenatally). The aim of this study was to analyze patient outcomes using a new treatment protocol for CDH in a tertiary care non-extracorporeal membrane oxygenation (ECMO) neonatal unit. METHODS: The records of 78 consecutive neonates with CDH presenting to Bambino Gesù Children's Hospital from 1996 to 2001 were analyzed retrospectively. Of these infants, 70 high-risk patients were identified (prenatal diagnosis or respiratory distress requiring intubation and assisted ventilation within 2 hours after birth), regardless of associated anomalies, medical condition on presentation, or degree of pulmonary hypoplasia. A prenatal diagnosis was made in 46 of 70 (66%) patients. Associated lethal malformations were present in 6 of the children (8.5%). The patients were placed in 3 historical groups: group 1, 19 patients from 1996 to 1997, group 2, 22 patients from 1998 to 1999, and group 3, 29 patients from 2000 to 2001. In the first 2 groups, a new protocol was introduced using inhaled nitric oxide (iNO) and high-frequency oxygen ventilation (HFOV). In the third group, gentle ventilation and permissive hypercarbia were also used routinely. Mortality and severe morbidity--defined as O2 requirement at discharge, need for a tracheostomy, neurologic impairment, or bilateral hearing loss-were evaluated when the patients were at 6 months old. Univariate analysis was performed. RESULTS: The 3 groups were comparable with respect to predictive risk factors such as side of hernia, prenatal diagnosis, polyhydramnios, stomach and liver in the thorax, associated lethal malformations, and patch. Overall survival rate significantly increased from 47% (9 of 19) in group 1 and 50% (11 of 22) in group 2 to 90% (26 of 29) in group 3 (P =.02). None of the 19 patients in group 1 had severe morbidity compared with 2 of 22 (9%) patients in group 2 and 2 of 29 (7%) patients in group 3. Hearing loss was observed in 4 patients. Mortality rate and preoperative pneumothorax significantly decreased in group 3 compared with groups 1 and 2 (P =.03 and P =.00, respectively). CONCLUSIONS: (1) The application of new treatment protocol for CDH, using gentle ventilation and permissive hypercarbia, produced a significant increase in survival with concomitant decrease in morbidity. (2) The rate of pneumothorax was significantly decreased by the introduction of permissive hypercarbia and gentle ventilation. (3) As more infants survive CDH without the use of ECMO, severe long-term sequelae of CDH can be recognized in these children.

First report of prenatal diagnosis of genetic congenital deafness in a routine prenatal genetic test.

OBJECTIVE: We aimed to screen for connexin26 gene (GJB2) mutations associated with autosomal recessive non-syndromic neurosensory deafness (NSRD) in a general risk population. METHODS: Screening for the most common connexin26 gene mutations was offered to all women undergoing a second-trimester amniocentesis for fetal karyotype analysis in our Center. After rapid DNA extraction from amniotic fluid, PCR amplification was performed and products analysed to detect mutations of GJB2 gene by a sequencing technique. In particular, we searched for the 20 most frequently reported mutations (out of the approximately 90 so far described) and for which there are commercially available tests. RESULTS: From a total of 4819 consecutive amniotic fluids examined, the following five different heterozygous mutations were detected: 35delG in 80 cases, 167delT in 3 cases and 1 occurrence of each of the following mutations: M34T, 35insG and W77R. From these data, a prevalence of 1 : 56 (1.78%) for the heterozygous condition can be estimated in the Mediterranean general risk population. The striking predominance of 35delG mutation is confirmed. In addition, we detected a homozygous 35delG mutation condition in a foetus of no risk parents. In this case, the early diagnosis permitted prompt application of an acoustic prosthesis allowing for cochlear implantation in due time, with significant improvement of the prognosis. CONCLUSIONS: In a general risk population, a carrier status for congenital deafness can be observed in 1 : 56 (1.78%) amniotic fluids; this is mostly due to the presence of a 35delG mutation of the connexin26 gene. Occasional identification of homozygous states, although rare, allows the best therapeutic approach.

[Prenatal diagnosis of congenital diaphragmatic hernia: an update]. / Aggiornamento in tema di diagnosi prenatale di ernia diaframmatica congenita.

Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1:4000 live births. Most frequently the diaphragmatic defect is a left and posterolateral (Bochdalek) one. Prenatal diagnosis is made at ultrasonography; the relevant sonographic features will be described in the paper. Cystic adenomatoid malformation of the lung (CAML), pulmonary sequestration, bronchogenic cysts, pulmonary hypoplasia/agenesia need to be considered in differential diagnosis. In some cases, diagnosis of CDH is not possible "in utero": in such cases, herniation of abdominal viscera into the thorax takes place presumably just at delivery through a small diaphragmatic defect. CDH may be associated with intrauterine growth retardation (IUGR), chromosomal abnormalities (3%) and/or other malformations (10-50%): such as Central Nervous System, digestive, cardiac and urogenital anomalies. Therefore, search of associated malformations and amniocentesis with analysis of fetal karyotype are mandatory, whenever a CDH is diagnosed. CDH is still at present characterised by a high mortality (reportedly, about 45%). Many prognostic factors have been correlated to postnatal outcome of CDH: some of them are valuable prenatally by ultrasonography. However, the role of sonography in the prediction of neonatal outcome is still controversial: in particular, although many ultrasonographic parameters have been proposed, prenatal evaluation of pulmonary hypoplasia (a crucial factor related to postnatal survival) has not proved to be very accurate so far. Nevertheless, it is undisputable that prenatal diagnosis itself represents a crucial prognostic factor for CDH, since it allows birth of the affected fetuses in 3d level Perinatologic Centres provided with a Neonatal Intensive Care Unit and Neonatal Surgery.

The impact of cystic fibrosis on neonatal intestinal obstruction: the need for prenatal/neonatal screening.

To determine the incidence of cystic fibrosis (CF) in neonates with intestinal obstruction (NIO) secondary to meconium ileus (MI), jejunoileal atresia (JA), meconium plug syndrome (MPS), volvulus (V), and meconium peritonitis (MP) and analyze the correlation of ultrasonographic (US) signs with CF in NIO with a prenatal diagnosis of intestinal anomaly, a prospective analysis of different types of NIO from 1990 to 1998 was undertaken. Immunoreactive trypsin measurement, genetic studies, and sweat tests were performed to confirm or rule out CF. Cases with prenatal diagnosis were analyzed for gestational age, dilated bowel, ascites, hyperechoic bowel, and calcifications. Of 80 neonates, 19 (24%) had CF: 2/33 (6%) JA, 6/14 (43%) MPS, 1/14 (7.1%) MP, 10/10 (100%) MI, and 0/9 V. Thirty (37.5%) had a prenatal diagnosis of an intestinal anomaly. The overall incidence of CF in NIO with a prenatal diagnosis of intestinal anomaly was 4/30 (13%), or 333 times the estimated risk of CF in the general population. A hyperechoic pattern with dilated bowel was associated with higher specificity for CF: 3/3 cases (100%), followed by hyperechoic bowel with ascites: 3/4 cases (75%). All babies with any type of NIO should thus be screened for CF. Prenatal screening for CF should be indicated in all pregnancies with US patterns of specific intestinal disorders.

Fetal monolateral urinoma and neonatal renal function outcome in posterior urethral valves obstruction: the pop-off mechanism.

The "fetal urinoma" is a clinical and diagnostic entity due to urinary extravasation, early diagnosed in fetal and/or neonatal period. Both urinoma and urinary ascites, whose pathogenesis is not clear, are recognized associations of uterero-pelvic junction obstruction (UPJO) and neonatal posterior urethral valves (PUV) related with a protected fetal and neonatal renal function. Clinical and experimental studies have demonstrated that fetal urinary tract obstruction results in severe renal parenchymal injury. The so called "pop-off" valve mechanism has been advocated to justify the upper tract function preservation. Protective "pop-off" mechanisms, such as a unilateral reflux and dysplasia, urinary extravasation and congenital bladder diverticula are present in about 30% of patients with PUV. Their presence correlates with better overall long-term renal function. This mechanism has been justified as a sort of self derivation, to explain the renal function preservation in fetal and neonatal period. In the last two years we observed three cases of fetal monolateral urinoma, prenatally detected in fetuses with diagnosis of PUV. All three cases did well for that concerning renal function despite some current opinions suggesting the necessity of a bilateral urinary extravasation in order to preserve upper urinary tract function.

Prenatal measurement of testicular diameter by ultrasonography: development of fetal male gender and evaluation of testicular descent.

Prenatal ultrasonography has evolved through advancements in imaging technology and observer experience. The purpose of the present study was to evaluate fetal testicular descent and diameter in relation to gestational age. A prospective cross-sectional study on 331 fetuses from an unselected population underwent a detailed assessment of testicular descent and diameter at 20-40 weeks' gestation by means of transabdominal sonography (91.2%) and transvaginal sonography (8.8%) when necessary. Fetal gender was identified in the transverse and sagittal planes and maximum testicular diameter was measured. The mean testicular diameter (in millimeters) per week and the 95% confidence interval (CI) were defined. Testicular descent was not observed prior to 23 weeks' gestation, with 6.6% of the fetuses having one testis descended at 23 weeks and 98.2% after 32 weeks. A linear relationship between testicular diameter and gestational age was observed. The present results chart the time course for testicular descent and provide a centile chart for fetal testicular diameter from 25 to 40 weeks' gestation. These findings may aid prenatal diagnosis of associated abnormal conditions as well as investigations into the clinical finding of abnormal testicular size.

Prenatal diagnosis of a bronchogenic cyst in an unusual site.

We report a rare case of a subdiaphragmatic cyst, diagnosed prenatally during routine ultrasound screening at 25 weeks' gestation. Serial ultrasonographic evaluation demonstrated a slight increase in the size of the cyst during pregnancy. On the basis of the anatomic site and the sonographic features of the lesion, four diagnostic hypotheses were postulated: cystic neuroblastoma, adrenal hemorrhage, duplication of the inferior third of the esophagus and retroperitoneal cystic lymphangioma. A healthy baby, weighing 3300 g and with Apgar scores of 8 and 9, was delivered vaginally at term. He underwent successful surgery at the age of 3 months. The post-operative course was uneventful and the baby is currently doing well. Histology revealed a bronchogenic cyst.

Cystic adenomatoid malformation of the lung: clinical evolution and management.

UNLABELLED: Cystic adenomatoid malformation of the lung (CAML) is a rare pulmonary maldevelopment resulting from an abnormal growth of the terminal bronchial structures. This study proposes a possible management of prenatally diagnosed CAML. A group of nine cases of CAML diagnosed prenatally between January 1990 and December 1995 was studied retrospectively. The evolution of lesions was followed in utero by serial ultrasound monitoring. Chest X-ray was performed at birth in all neonates and CT only in the symptomatic ones. CAML was macrocystic in three cases and microcystic in six. No polyhydramnios, hydrops or associated malformations were seen. In four cases, CAML was confirmed at birth and required surgery. The lesion decreased in size prenatally in five fetuses, of whom only one underwent surgery. In two further cases a prenatal diagnosis of CAML was changed to diaphragmatic hernia. CONCLUSION: Given the possible clinical disappearance or resolution of cystic adenomatoid malformation of the lung, we believe that surgery is justified at birth only in symptomatic and radiologically positive neonates. It could be safely delayed in those asymptomatic patients with either positive or negative chest X-ray. The former need computed tomography at birth, whereas, in the latter, it should be performed at 6 months of age for a more definitive assessment of the patient.

Persistent cloaca: are we ready for a correct prenatal diagnosis?

Cloacal malformations are rare and can present in variable aspects. The importance of ultrasound in detecting these anomalies is well known. Sonographic features vary in accordance with the type of malformation and the gestational age. A positive diagnosis is not possible because of the lack of specific ultrasound findings, which can show similar aspects to other abnormalities. We present 3 cases of prenatal diagnosis of this malformation, emphasizing that in the presence of a plurilobed cystic pelvic fetal mass with associated malformations, such as cardiac, renal, and vertebral anomalies, a persistent cloaca can reasonably be suspected.

Spermatozoa with chromosomal abnormalities may result in a higher rate of recurrent abortion.

OBJECTIVE: To determine whether sperm aneuploidy can lead to abortion. DESIGN: Clinical study. SETTING: Couples with reproductive problems evaluated in a private diagnostic laboratory. PATIENT(S): Two men whose wives had histories of multiple abortions. INTERVENTION(S): Whole and Percoll-processed semen samples were analyzed. MAIN OUTCOME MEASURE(S): The results of fluorescence in situ hybridization. RESULT(S): Aneuploidy rates in Percoll-processed samples were higher than those found in whole specimens. Aneuploid spermatozoa also displayed greater motility. CONCLUSION(S): Sperm aneuploidy should be studied before and after Percoll capacitation in all couples with unexplained infertility.

Non-invasive early prenatal molecular diagnosis using retrieved transcervical trophoblast cells.

Fetal DNA was recovered from 17 of 39 (44%) transcervical cell (TCC) samples obtained between 7 and 9 weeks of gestation by endocervical canal flushing. Trophoblast retrieval was adequate for polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences and detection of paternal-specific microsatellite alleles. The fetal sex predicted by PCR in TCCs was confirmed in all cases by karyotype analysis of chorionic villi at 10 weeks of gestation. The absence of the disease-associated paternal alleles in TCC samples from two pregnancies at risk for spinal muscular atrophy and myotonic dystrophy predicted unaffected fetuses in agreement with subsequent results on chorionic villi and newborns' leukocytes. A trisomy 21 fetus was diagnosed in TCCs using fluorescent in situ hybridization (FISH) and semi-quantitative PCR analysis of superoxide dismutase-1 (SOD 1). Present experience indicates that TCC sampling is a promising technique for early prenatal monitoring of Mendelian disorders and chromosome aneuploidy.

Blood contamination of amniotic fluid after amniocentesis in relation to placental location.

The aim of the present study was to evaluate blood contamination of the amniotic fluid collected in 20 patients undergoing a second amniocentesis performed 2 weeks after a first procedure that had failed due to Pseudomonas aeruginosa contamination of the cell cultures. Red blood cell and haemoglobin concentrations in the amniotic fluid were significantly higher in patients who had undergone a transplacental procedure compared with patients in whom the placenta was not traversed with the needle. For both groups, blood contamination of the amniotic fluid was significantly higher compared with a control group of 20 patients undergoing amniocentesis for the first time. Significant blood contamination of the amniotic fluid after amniocentesis occurs in every instance if evaluated at a "second-look' procedure; the blood contamination is higher when an anterior placenta is traversed with the needle. The clinical significance of these findings needs to be further evaluated.