Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Identification of essential steps in laser procedure for twin-twin transfusion syndrome using the Delphi methodology: SILICONE study.

OBJECTIVE: To determine, by expert consensus, the essential substeps of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) that could be used to create an authority-based curriculum for training in this procedure among fetal medicine specialists. METHODS: A Delphi survey was conducted among an international panel of experts (n = 98) in FLS. Experts rated the substeps of FLS on a five-point Likert-type scale to indicate whether they considered them to be essential, and were able to comment on each substep, using a dedicated online platform accessed by the invited tertiary care facilities that specialize in fetal therapy. Responses were returned to the panel until consensus was reached (Cronbach's α ≥ 0.80). All substeps that were rated ≥ 4 by 80% of the experts were included in the evaluation instrument. RESULTS: After the first iteration of the Delphi procedure, a response rate of 74% (73/98) was reached, and in the second and third iterations response rates of 90% (66/73) and 81% (59/73) were reached, respectively. Among a total of 81 substeps rated in the first round, 21 substeps had to be re-rated in the second round. Finally, from the initial list of substeps, 55 were agreed by experts to be essential. In the third round, the 18 categorized substeps were ranked in order of importance, with 'coagulation of all anastomoses that cross the equator' and 'determination of fetoscope insertion site' as the most important. CONCLUSIONS: A total of 55 substeps of FLS for TTTS were defined by a panel of experts to be essential in the procedure. This list is the first authority-based evidence to be used in the development of a final training model for future fetal surgeons.

Congenital megalourethra: prenatal diagnosis and postnatal/autopsy findings in 10 cases.

OBJECTIVE: Congenital megalourethra is a rare urogenital malformation characterized by dilation and elongation of the penile urethra associated with absence or hypoplasia of the corpora spongiosa and cavernosa. Postnatal complications include voiding and erectile dysfunction as well as renal insufficiency and pulmonary hypoplasia. To date, only a few prenatally diagnosed cases have been reported. We report on 10 cases diagnosed prenatally and their postnatal/autopsy findings. METHODS: The study involved retrospective chart review of all cases diagnosed antenatally in three tertiary care centers over 5 years. Antenatal ultrasound images and medical records from obstetrics, genetics, urology and nephrology were reviewed. RESULTS: Ten fetuses with megalourethra were identified at a median gestational age of 19 (range, 13-24) weeks and all were confirmed postnatally or at autopsy. Three pregnancies were terminated and seven continued. All cases presented with a distended bladder and megalourethra and all cases had normal karyotype. Of seven liveborn babies, one died neonatally of pulmonary hypoplasia. All six infants alive at the time of writing had a dysfunctional urethra and three suffered from impaired or end-stage renal disease. Associated anomalies were found in half of the cases. CONCLUSION: Congenital megalourethra is caused by abnormal development or hypoplasia of the penile erectile tissue, secondary to distal urethral obstruction. When the amniotic fluid volume is normal, survival is possible. However, all liveborn infants have voiding and renal dysfunction and sexual dysfunction is expected. Megalourethra should be considered in all male fetuses presenting prenatally with megacystis and detailed fetal ultrasonography should look for an elongated and/or distended phallic structure as well as any associated anomalies.

Fetal Doppler mechanical PR interval: correlation with fetal heart rate, gestational age and fetal sex.

OBJECTIVES: To establish normal fetal values for the mechanical PR interval by pulsed-wave Doppler at 16-36 weeks of gestation, and to evaluate the influence of fetal heart rate (FHR), gestational age (GA) and fetal sex. METHODS: Fetal mechanical PR intervals were evaluated prospectively by obstetric ultrasound examination. Healthy mothers with sonographically normal fetuses from singleton pregnancies were included. Mechanical PR intervals were measured from simultaneous mitral and aortic Doppler waveforms, from the onset of left atrial contraction (mitral A-wave) to the onset of left ventricular ejection (aortic pulse wave). Simple and multiple linear regression analyses were performed to examine the correlation between PR interval and GA, FHR and fetal sex. RESULTS: We evaluated 336 fetuses at 16-36 weeks. The mean +/- SD FHR was 143.4 +/- 8.3 beats per min (bpm). The PR intervals had a typical Gaussian distribution with a mean +/- SD of 122.4 +/- 10.3 ms. Robust linear regression showed that the PR increased by about 0.40 ms (95% CI, 0.22-0.58) per gestational week (P < 0.001), and this relationship remained after adjustment for FHR and fetal sex. PR intervals diminished by 1.4 (95% CI, 0.75 to 2.0) ms for each 5 bpm increase in FHR (P < 0.001), independently of GA and fetal sex. No fetal sex differences were observed. CONCLUSIONS: We provide normal fetal values for the mechanical PR interval at 16-36 weeks of gestation. Mechanical PR intervals in normal fetuses are influenced by GA and FHR independently, and both variables should be taken into account when evaluating fetuses at risk for congenital heart block.

The effect of early versus delayed postcaesarean feeding on women's satisfaction: a randomised controlled trial.

OBJECTIVE: To evaluate the effect of early versus delayed feeding after caesarean section on the woman's satisfaction. DESIGN: Randomised, controlled trial. SETTING: Tertiary care hospital. POPULATION: Healthy pregnant women were enrolled for the study during antenatal care visits. METHODS: Uncomplicated singleton pregnancies undergoing a planned or intrapartum caesarean section performed under regional anaesthesia were randomly assigned to either (1) a 'delayed feeding' group who started oral fluids 4 hours after surgery with diet introduced at 24 hours; or (2) an 'early feeding' group who were offered a regular diet within the first 8 hours. MAIN OUTCOME MEASURES: Primary outcome was the woman's satisfaction measured with a visual analogue scale (VAS) before their hospital discharge. The secondary outcomes were: pain, anorexia, abdominal distension, persistent nausea and/or vomiting, time to the first bowel movement and passage of flatus. RESULTS: Two hundred women were recruited, with 103 randomised to delayed feeding and 97 to early feeding. The woman's satisfaction (mean VAS +/- SD) was similar in both groups; 73 +/- 17 mm in the delayed feeding group and 77 +/- 13 mm in the early feeding group (P= 0.12). A statistically significant difference was observed in mean postoperative pain: 29 +/- 13 mm in the delayed feeding group versus 24 +/- 11 mm in the early feeding group (P= 0.008). No other significant differences in postoperative variables were recorded, and there were no major postoperative complications observed in either group. CONCLUSION: Early feeding after uncomplicated caesarean in low-risk women is equivalent in terms of the woman's satisfaction and the reduced perceived pain.

Veno-venous anastomoses in twin-twin transfusion syndrome: A multicenter study.

INTRODUCTION: The aim of this study is to evaluate the prevalence of veno-venous (VV) anastomoses in a large cohort of monochorionic (MC) twin placentas with twin-twin transfusion syndrome (TTTS) compared to a control group of MC placentas without TTTS. METHODS: All TTTS placentas not treated with fetoscopic laser surgery (TTTS group) and examined at five international fetal therapy centers were included in this study and compared with a control group of MC placentas without TTTS (non-TTTS group). MC placentas were routinely injected with colored dye. We recorded the presence of VV and arterio-arterial (AA) anastomoses. RESULTS: A total of 414 MC placentas were included in this study (TTTS group, n = 106; non-TTTS group, n = 308). The prevalence of VV anastomoses was significantly higher in the TTTS group than in the non-TTTS group, 36% (38/106) and 25% (78/308), respectively (p = .04; odds ratio (OR) 1.65; 95% confidence interval (CI): 1.03-2.64). In the subgroup of MC placentas without AA anastomoses, the prevalence of VV anastomoses in the TTTS group and non-TTTS group was 32% (18/57) and 8% (2/25), respectively (p = .03; OR: 5.31; 95% CI: 1.13-24.98). DISCUSSION: VV anastomoses are detected more frequently in TTTS placentas than in MC placentas without TTTS and may thus play a role in the development of TTTS.

Chromosome rearrangements among couples with pregnancy losses and other adverse reproductive outcomes.

During the years 1975-1987, 1,364 cytogenetic studies were performed in 682 couples with history of adverse pregnancy outcome. Thirty-six balanced translocations were detected, 24 (3.5%) in women and 12 (1.7%) in men. Before 1982, all 234 couples studied had 2 or more spontaneous abortions with unknown pedigrees, with an incidence of 6.8% of balanced translocations. During 1982-1987, complete pedigree analysis was performed on a subset of 448 couples, who were then classified into 3 groups. Group I; 321 couples with 2 or more spontaneous abortions, but no other adverse outcome; group II; 37 couples with at least one or more spontaneous abortions plus a malformed child or stillbirth; and group III; 90 couples with one or more spontaneous abortions plus a sib having at least a malformed child or repetitive spontaneous abortions. The incidence of balanced translocations in these 3 groups was 2.8%, 5.4%, and 10.0%, respectively. When group III was compared with group I, the frequency of translocations was significantly different (P less than 0.02). Robertsonian translocations were predominantly detected in women, raising the possibility that prezygotic failure producing primary sterility may occur in men with such translocations.

Therapeutic management of epithelial ovarian cancer during pregnancy.

Epithelial ovarian cancer (EOC) during pregnancy is a rare condition. The diagnosis and treatment strategies are therefore not well defined. The evidence is scarce and limited to small case reports or case series. In this review we describe the safety, utility and limitations of each diagnostic tool and surgical procedure in pregnant women with ovarian cancer. We also discuss the role of chemotherapy for ovarian cancer during pregnancy. Finally, we delineate different strategies of treatment according to the stage of the disease at diagnosis and gestational age. Due to the complexity of the management of EOC during pregnancy, patients should be referred to specialized centers. Gestational age at diagnosis, the initial surgical procedure, disease stage and patient's preferences are the key factors in the decision-making process to establish the best treatment strategy for each individual case.

Congenital malformations.

Obstetricians' epidemiological knowledge and their awareness of associated risk factors are essential for the primary prevention of birth defects. Screening and early diagnosis of congenital malformations is an expanding field in general obstetrics. Cardiac defects are the most frequent type of congenital malformation, and early detection is possible.

Previous miscarriage and stillbirth as risk factors for other unfavourable outcomes in the next pregnancy.

OBJECTIVE: To look for associations between previous fetal loss and fetal malformation or low birthweight in a subsequent pregnancy. DESIGN: A case-control study with place of birth, time and sex matched controls. SETTING: 72 South American maternity hospitals. SUBJECTS: 18,534 malformed, 1150 non-malformed babies of low birthweight and 16,394 controls. All babies were from mothers with at least one previous pregnancy. MAIN OUTCOME MEASURES: Frequency of stillbirths and miscarriages in the previous pregnancy and outcome of the index pregnancy. RESULTS: Multiple malformation, Down's syndrome, anencephaly, spina bifida, pes equinovarus, congenital dislocation of the hip and low birthweight are associated with previous fetal loss. CONCLUSION: A miscarriage or a stillbirth in a previous pregnancy should be taken into account when the risk of malformations or low birthweight in a subsequent pregnancy is assessed.

Association between first trimester absence of fetal nasal bone on ultrasound and Down syndrome.

OBJECTIVES: To evaluate the association between absence of nasal bone on ultrasound and Down syndrome in fetuses at 11-14 weeks of pregnancy. METHODS: One hundred and ninety-four consecutive fetuses from singleton pregnancies undergoing chorionic villi sampling (CVS) were evaluated by transabdominal ultrasound. A sagittal view of the fetal face was obtained and the absence or presence of nasal bone was recorded and correlated with the fetal karyotype. RESULTS: A successful view of the fetal profile was possible in 183 of 194 (94%) fetuses. The nasal bone was absent in three of five fetuses with Down syndrome, and in one of 175 (0.6%) chromosomally normal fetuses. CONCLUSION: Absence of nasal bone by first trimester ultrasound was significantly associated with Down syndrome. When a proper view of the fetal face was obtained, the nasal bone was visible in more than 99% of karyotypically normal fetuses.

Growth disadvantage of 45,X and 46,X,del(X)(p11) fibroblasts.

We have previously shown that cell generation time (CGT) is prolonged in 45,X and certain X-deletion fibroblast lines (Simpson & Le Beau 1981). A consequence of that finding should be that cells with 45,X or an X-structural abnormality are at a competitive disadvantage when cocultivated with 46,XX cells. To test this hypothesis we prepared 15 minutes of cells from combinations of 9 different cell lines: four 45,X; one 46,Xdel(X)(p11); and four 46,XX. Each culture was monitored cytogenetically at frequent passage intervals for the percentage of the two cell lines. Significant differences were found between normal and abnormal lines in culture predominance, in the order predicted by our hypothesis (p less than 0.01). The specific mechanism by which absence of an X chromosome confers growth disadvantage is unknown, but is consistent with prolongation of CGT. Prolongation of CGT could also be responsible for the embryonic lethality, intrauterine growth retardation, short stature, and somatic anomalies commonly observed in individuals with absent or aberrant X chromosomes.

Disgenesia gonadal: aspectos genéticos / Gonodal dysgenesis: genetic factors

La disgenesia gonadal producto de una anomalía en la diferenciación de la gónada primitiva puede estar asociada tanto a factores genéticos como ambientales. En los últimos años el aumento en el conocimiento del primero de estos mecanismos etiológicos así como del proceso normal de diferenciación, desarrollo y mantenimiendo de la gónada, junto con una mayor precisión diagnóstica de este cuadro, ha posibilitado establecer el origen del mismo en la mayoría de los casos, permitiendo evaluar el pronóstico y posibles recursos terapéuticos. Inicialmente la disgenesia gonadal fue considerada prácticamente sinónimo de síndrome de Ullrich-Turner, asociado con la ausencia de un cromosoma X (pese a que la primera ilustración de una gónada acintada fue realizada por Bauks en 1805). Actualmente la aplicación sistemática de las distintas técnicas de estudio citogenético permitieron establecer la frecuencia real de esta anomalía tanto en su forma única como cuando se asocia con otras líneas celulares. Pese a que las anomalías estructurales del cromosoma X son menos frecuentes, el análisis de la relación fenotipo cariotipo ha posibilitado establecer la existencia y localización de las determinantes gonadales. La aplicación de las nuevas técnicas de genética molecular permitirá aclarar aún más estos mecanismos. Uno de los más importantes adelantos en el conocimientos etiológico de la disgenesia gonadal fue también la demostración de su asociación con la mutación de un gen único con mecanismo de herencia mendeliana. Esto fue resultado del análisis genealógico en pacientes con disgenesia gonadal cuyo motivo de consulta en muchos casos, era amenorrea secundaria, retardo puberal o irregularidad menstrual junto con otras anomalías fenotípicas comprobándose así la expresividad variable y heterogeneidad genética del cuadro y enfatizando la importancia de ampliar el estudio a nivel familiar. El complemento sexual en estos casos es normal con cariotipo 46,KX o 46,XY,...

Tratamiento del factor autoinmune en el aborto recurrente y en el retardo de crecimiento intrauterino con anti-agregantes plaquetarios / Treatment of autoimmunity factor in recurrent abortion and in intrauterine growth retardation with platelets anti-aggregation

Objetivo: Describir los resultados del tratamiento anti-agregante plaquetario en un grupo de pacientes con auto-anticuerpos y antecedentes de aborto recurrente (AR) y/o retardo de crecimiento intrauterino (RCIU). Material y Métodos: Diecisiete pacientes que consultaron por AR y/o RCIU, mala historia obstétrica o antecedentes de VDRL falso positivo, en cuyo estudio inmunológico se detectaron autoanticuerpos, constituyen el material del presente trabajo. A las pacientes que tenían como antecedente un RCIU, una vez descartados todos los cuadros clínicos que pudieran ocasionarlo, se les efectuó determinación de anticuerpos. Las parejas que consultaban por AR eran sometidas a estudio para descartar un factor uterino, infeccioso, endocrinológico, metabólico, genético, innmunológico y espermático. En algunas pacientes se realizó una laparoscopia para descartar endometriosis. Todas las pacientes fueron tratadas con Acido Acetilsalicílico (AAS) 80 mg diarios, a partir del momento de la detección de autoanticuerpos. A una sola paciente se le administró además heparina subcutánea durante dos embarazos. Resultados: De las diecisiete pacientes en las que se detectaron autoanticuerpos, catorce embarazaron, algunas de ellas en más de una oportunidad, sumando un total de 24 embarazos. De ellos, 5 concluyeron en aborto espontáneo y dieciocho concluyeron en el tercer trimestre con recién nacido vivo. De éstos, siete presentaron un crecimiento fetal normal, mientras que los once restantes desarrollaron RCIU. La vía de terminación fue vaginal en seis casos y abdominal en los doce restantes. Un embarazo se encuentra en evolución al momento de la presente comunicación