Differentiation between TTTS Stages I vs II and III vs IV does not affect probability of double survival after laser therapy.

OBJECTIVE: To compare the perinatal outcome of monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS), according to the disease severity, defined using Quintero staging, after treatment with fetoscopic laser surgery. METHODS: This was a single-center study of 1020 consecutive cases with severe TTTS, which were treated with fetoscopic laser surgery. During the study period from January 1995 to March 2013, the participants were included at a mean ± SD gestational age of 20.8 ± 2.2 weeks. Perinatal survival analysis, including the rates of double survival and survival of at least one fetus, was undertaken according to the Quintero staging system. For blockwise comparisons of data, the whole population was divided into five chronologically consecutive study subgroups of 200 patients in each of the first four subgroups and 220 in the last one. RESULTS: For the entire study population with known outcome (n = 1019), the rate of pregnancy with double fetal survival was 69.0% (127/184) in Stage-I, 71.4% (257/360) in Stage-II, 55.4% (236/426) in Stage-III and 51.0% (25/49) in Stage-IV TTTS cases. At least one twin survived in 91.3% (168/184) of pregnancies with Stage-I, 89.7% (323/360) of those with Stage-II, 83.1% (354/426) of those with Stage-III and 77.6% (38/49) of those with Stage-IV TTTS. The rates of double survival and survival of at least one fetus were both significantly higher in Stage-II TTTS compared with those in Stage-III TTTS cases (P < 0.001 and P = 0.011, respectively). Survival rates between pregnancies with Stage-I vs Stage-II TTTS and between those with Stage-III vs Stage-IV TTTS were not significantly different. Therefore, we combined pregnancies with Stage-I or Stage-II TTTS, and those with Stage-III or Stage-IV TTTS. The double survival rate was 70.6% (384/544) in combined Stage-I and Stage-II vs 54.9% (261/475) in combined Stage-III and Stage-IV TTTS cases (P < 0.001). At least one twin survived in 90.3% (491/544) of pregnancies with Stage-I or Stage-II TTTS vs 82.5% (392/475) in those with Stage-III or Stage-IV TTTS (P < 0.001). The double survival rate increased between the first and the last consecutive study subgroups from 59.8% (55/92) to 75.0% (96/128) (adjusted odds ratio (aOR)linear trend , 1.26 (95% CI, 1.01-1.56); P = 0.037) in pregnancies with Stage-I or Stage-II TTTS and from 41.7% (45/108) to 62.0% (57/92) (aORlinear trend , 1.21 (95% CI, 0.98-1.50); P = 0.082) in those with Stage-III or Stage-IV TTTS. Double survival rate was the lowest for Stage-III cases in which the donor twin was affected by severely abnormal Doppler findings (45.4% (64/141)). CONCLUSIONS: Double survival and survival of at least one fetus in monochorionic twin pregnancies with TTTS were related significantly to Quintero stage. However, our data show that the differentiation between Stages I vs II and Stages III vs IV does not have any significant prognostic implication for perinatal survival. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetoscopic laser coagulation in 1020 pregnancies with twin-twin transfusion syndrome demonstrates improvement in double-twin survival rate.

OBJECTIVE: To investigate the growing experience and learning curve of fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin-twin transfusion syndrome (TTTS) and its influence on perinatal outcome in a single-center setting. METHODS: Between January 1995 and March 2013 we performed laser therapy in 1020 consecutive pregnancies with TTTS between 15.1 and 27.4 weeks' gestation. We compared perinatal outcome in blocks of five sequential groups of 200 cases, taking into account several covariates in order to adjust for case mix and to demonstrate learning curves and success rates. RESULTS: The percentage of pregnancies with survival of both fetuses increased from 50.0% (n = 100) in the first 200 cases to 69.5% (n = 153) in the last 220 cases (P = 0.018 for trend) and the overall survival rate for both fetuses in the complete series of 1019 cases with known outcome was 63.3% (n = 645). The survival rate of at least one fetus increased from 80.5% (161/200) in the first group to 91.8% (202/220) in the last group (P = 0.072 for trend) and the overall survival rate of at least one fetus in the complete series was 86.7% (883/1019). In the total population, the mean gestational age at delivery of pregnancies with at least one liveborn neonate was 33.7 ± 3.2 weeks, with a mean interval of 12.9 ± 4.0 weeks between intervention and delivery. Among the first two groups, 124 pregnancies had anterior placentae and were treated with a 0° fetoscope. These cases had the poorest overall outcome, with a double-twin survival rate of 44.4% (55/124), which increased to 65.1% (207/318; P = 0.001) after the introduction of a 30° fetoscope for cases with anterior placenta. The success rate for double-twin survival reached a plateau of 69% at 600 procedures, a rate equalled by a new operator who was trained hands-on and performed 174 of the last 400 procedures. CONCLUSIONS: We report the largest single-center experience of laser coagulation in TTTS. We observed a continuous increase in double-twin survival rate owing to the growing experience based on the learning curve and refinements in fetoscopic instruments and techniques. These data provide strong arguments for the centralization of minimally invasive intrauterine surgery in specialized high-volume centers. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Time-interval analysis of ductus venosus flow velocity waveforms in twin-to-twin transfusion syndrome treated with laser surgery.

OBJECTIVES: To investigate time-interval variables of ductus venosus (DV) flow velocity waveforms (FVWs) in twin-to-twin transfusion syndrome (TTTS), comparing the results with reference ranges from normal singleton fetuses. The impact of laser surgery and the effect of prognostic factors were also evaluated. METHODS: In 107 TTTS cases, DV-FVWs of both recipients and donors were recorded 1 day before and 2 days after laser therapy. Time intervals for systolic (S) and early diastolic (D) peaks were analyzed retrospectively with regard to acceleration time (acc-S and acc-D for S and D, respectively) and deceleration time (dec-S and dec-D for S and D, respectively). For each variable, Z-scores were calculated with respect to previously reported normal reference ranges. RESULTS: Z-scores for all variables showed statistically significant differences from those observed previously in normal fetuses, with the exception of dec-S of donors. The most striking differences were observed in longer dec-S of recipients (P < 0.001) and longer dec-D of donors (P < 0.001). Laser therapy showed significant impact on dec-S and acc-D in recipients and on all variables in donors. Regarding the short-term prognosis, acc-S and dec-S showed significant differences for the prediction of intrauterine fetal demise in donors (P = 0.009 and P = 0.011, respectively). CONCLUSION: This study demonstrates that time-interval variables of DV-FVWs may differentiate the characteristic hemodynamic changes caused by unbalanced blood volume between recipients and donors.

[Peripartum cardiomyopathy: interdisciplinary challenge]. / Peripartale Kardiomyopathie: Interdisziplinäre Herausforderung.

Peripartum cardiomyopathy (PPCM) is a rare type of heart failure which presents towards the end of pregnancy or in the first 5 months after delivery. Depending on the geographical location the incidence is reported in the literature as 1:300 up to 1:15,000. There are a number of known risk factors, such as multiparity and age of the mother over 30 years. The symptoms of PPCM correspond to those of idiopathic cardiomyopathy. The diagnosis is mainly carried out using echocardiography which shows a clear reduction of systolic left ventricular function. The therapeutic approach is the same as for idiopathic cardiomyopathy and in this context it is absolutely necessary to show caution concerning the state of pregnancy and the resulting contraindications for therapeutic drugs. The prognosis is dependent on recovery from the heart failure during the first 6 months postpartum. The lethality of the disease is high and is given in the literature as up to 28 %. Because of its complexity PPCM is an interdisciplinary challenge. In the peripartum phase a close cooperation between the disciplines of cardiology, cardiac surgery, neonatology, obstetrics and anesthesiology is indispensable. For anesthesiology the most important aspects are the mostly advanced unstable hemodynamic condition of the mother and the planning and implementation of the perioperative management. This article presents the case of a patient in advanced pregnancy with signs of acute severe heart failure and a suspected diagnosis of PPCM. The patient presented as an emergency case and delivery of the child was carried out using peridural anesthesia with a stand-by life support machine.

Twin anemia-polycythemia sequence in a case of monoamniotic twins.

Twin anemia-polycythemia sequence (TAPS) complicates up to 6% of monochorionic diamniotic twin pregnancies, typically in the late second or third trimester. The presence of only a few and very small arteriovenous vascular anastomoses characterizes the underlying angioarchitecture at the chorionic plate in cases of TAPS. In monoamniotic twins, large vascular anastomoses can usually be seen at the placental vascular equator, and therefore one would not expect the development of TAPS in monoamniotic twins. We report a case of TAPS in a monoamniotic pregnancy at 26 + 5 weeks' gestation which responded favorably to fetoscopic laser coagulation of the small placental anastomoses, resolving severe anemia in one twin and polycythemia in the other. The pregnancy continued until 32 + 5 weeks, when worsening cord entanglement with increased resistance and the development of postsystolic notches in the umbilical artery of one twin prompted delivery by Cesarean section. There was only a moderate difference in neonatal hemoglobin concentrations, with the former polycythemic twin needing a single partial volume exchange transfusion. The postnatal course of the neonates was uneventful, according to their gestational age at birth. To our knowledge this is the first case report describing successful laser therapy for TAPS in monoamniotic twins.

Laser therapy of twin-to-twin transfusion syndrome in triplet pregnancies.

OBJECTIVE: Laser coagulation of placental anastomoses in twin pregnancies complicated by severe twin-to-twin transfusion syndrome (TTTS) has been shown to be superior to serial amniodrainage, and has emerged as the standard therapy for this condition. We report the outcome of triplet pregnancies treated with laser therapy for severe TTTS. METHODS: From a database containing information on all multiple pregnancies referred to our center we identified 20 triplet pregnancies with severe TTTS. Sixteen of them were dichorionic, four monochorionic and all cases were triamniotic. Perinatal outcome was obtained in all cases. RESULTS: Fetoscopy was performed in 18 out of 20 cases at a median gestational age of 19.7 (range, 17.0-23.3) weeks. Delivery occurred at a median of 31.9 (range, 24.7-36.4) weeks with an overall fetal survival rate of 65%, at least one surviving fetus in 83% of cases and all three fetuses surviving in 39%. CONCLUSION: Laser coagulation is an effective treatment for severe TTTS in triplets. However, survival rates are lower than in twin pregnancies.

Selective cord coagulation in acardiac twins.

The twin reverse arterial perfusion (TRAP) sequence is a serious complication of monochorionic multiple pregnancies in which the affected twin is reversely perfused from the healthy co-twin, resulting in severely abnormal or absent cardiac development, severe malformations, and massive hydrops fetalis. The acardiac twin threatens the survival of the pump twin either by increasing the risk of congestive cardiac failure or by the development of polyhydramnios, preterm premature rupture of membranes, preterm labour and premature delivery. A wide spectrum of surgical interventions has been applied in the management of TRAP; however, because of the rarity of this condition and the heterogeneity of its presentation, no single technique has been shown to be unequivocally optimal. In our experience, fetoscopic laser coagulation of the placental vascular anastomoses or the umbilical cord of the acardiac twin, with the possibility of applying bipolar forceps as an additional minimally invasive surgical technique, offers an effective treatment option in the management of the TRAP sequence; this treatment has a survival rate of 80%, and 67% of pregnancies with surviving pump twins go beyond 36 weeks of gestation without further complications.

Perinatal outcome in monochorionic twin pregnancies complicated by amniotic fluid discordance without severe twin-twin transfusion syndrome.

OBJECTIVES: To assess the natural history and perinatal outcome in monochorionic diamniotic twin pregnancies with discordant amniotic fluid volume without signs of severe twin-twin transfusion syndrome (TTTS). METHODS: This was an observational study of 84 consecutive monochorionic twin pregnancies which did not meet the criteria for severe TTTS and endoscopic laser coagulation of placental anastomoses at initial presentation. The population was subdivided into two groups. Group 1 consisted of 64 pregnancies (median gestational age, 20.1 (range, 15.6-24.7) weeks) with amniotic fluid discordance and no signs of congestive heart failure in the twin with the larger amniotic fluid volume (Twin 1) and positive end-diastolic flow in the umbilical artery of the twin with the smaller amniotic fluid volume (Twin 2). Group 2 (median gestational age, 19.1 (range, 16.0-24.4) weeks) consisted of 20 pregnancies with amniotic fluid discordance and intrauterine growth restriction (IUGR) (abdominal circumference < 5th percentile) in combination with absent or reversed end-diastolic (ARED) flow in the umbilical artery of Twin 2. After exclusion of one patient from Group 1, who opted for termination of pregnancy, nine patients in Group 1 and one in Group 2 developed severe TTTS, and laser coagulation was offered. The remaining 54 pregnancies of Group 1 were compared with the remaining 19 pregnancies of Group 2. RESULTS: Fetuses in Group 1 showed significantly higher survival rates (overall survival, 100/108 (92.6%) vs. 23/38 (60%), P < 0.0001; survival of both fetuses, 49/54 (90.7%) vs. 9/19 (47.4%), P = 0.0002) and median gestational age at delivery (33.6, (range, 27.6-37.8) weeks vs. 32.0 (range, 26.9-36.3) weeks, P = 0.0457). Overall, there was a significantly higher incidence of complications, defined as necessity for intrauterine intervention, fetal or neonatal death or delivery prior to 32 weeks, in Group 2 (Group 1: 30/63 (47.6%); Group 2: 16/20 (80%), P = 0.0188). CONCLUSIONS: Our data suggest that amniotic fluid discordance in monochorionic diamniotic twin pregnancies in combination with IUGR and umbilical artery ARED flow in one fetus represents an extremely high-risk constellation for adverse pregnancy outcome.

Ontogenetic change in relative performance of allozyme genotypes influences detection of heterosis in the earthworm Eisenia andrei.

The effect of ontogeny on relationships between allozyme genotypes and fresh weight was measured weekly throughout the life history of the earthworm Eisenia andrei to test the hypothesis that there is an ontogenetic component to variation in such relationships. Two of six allozyme loci showed a significant increase in apparent heterosis with ontogeny, while one locus showed a significant decrease in apparent heterosis. Three loci showed a significant decrease in the performance of common homozygotes with ontogeny. Patterns of relative genotypic performance varied among loci, but the cumulative effect was an increase in apparent allozyme heterosis later in ontogeny coinciding with a series of positive relationships between multilocus heterozygosity and fresh weight. The results could not be used to determine whether these patterns were caused by selection acting on the loci directly or on loci tightly linked to allozyme loci. However, because the same individuals were used throughout this study and thus allele frequencies and heterozygote deficiency were constant, the presence of both ontogenetic effects and differences in such patterns among loci is not compatible with a general inbreeding effect. Examining relative genotypic performance repetitively using the same individuals through ontogeny or in different environments is a very powerful experimental design for testing the effects of inbreeding or other populational factors.

Placental vascular anastomoses visualized during fetoscopic laser surgery in severe mid-trimester twin-twin transfusion syndrome.

The aim of this study was to describe the type and number of placental vascular anastomoses identified during fetoscopic laser coagulation in severe mid-trimester twin-twin transfusion syndrome (TTS). In 126 patients with severe TTS, undergoing fetoscopic laser coagulation between 16 and 25 weeks of gestation, the different types of placental anastomoses [arterio-venous (AV), arterio-arterial (AA) and veno-venous (VV)] were counted. In cases of AV anastomoses their direction was identified and four groups were defined: in group 1 there were only anastomoses shunting from donor to recipient. Group 2 consisted of placentae with more anastomoses shunting from donor to recipient than in the opposite direction, group 3 showed an equal number in both directions and in group 4 there were more anastomoses shunting from recipient to donor than in the opposite direction. In 9 cases (7 per cent) the anastomoses could not be clearly identified due to impaired visualization, leaving 117 cases for analysis. The median number of anastomoses found was 5 with a range from 1-14. In all cases AV anastomoses from donor to recipient were present, 36 cases (31 per cent) had also AA anastomoses and 14 cases (12 per cent) showed VV anastomoses. Regarding the direction of AV anastomoses, the results were as follows: there were 35 cases (30 per cent) in group 1, 52 cases (44 per cent) in group 2, 14 cases (12 per cent) in group 3 and 16 cases (14 per cent) in group 4. In 54 (46 per cent) placentae there was at least one thin anastomosis whose type was unclassifiable. There were no placentae showing AV anastomoses only from the recipient to the donor fetus. This study demonstrates that AV anastomoses are the prerequisite for the development of TTS in monochorionic placentae. The majority (74 per cent) of cases showed a higher number of AV anastomoses from donor to recipient than in the opposite direction. In approximately one third of placentae there are also AA anastomoses and the overall number of anastomoses seen and coagulated during fetoscopy is higher than reported in postnatal studies.

Birth of two infants with normal karyotype after intracytoplasmic injection of sperm obtained by testicular extraction from two men with nonmosaic Klinefelter's syndrome.

OBJECTIVE: To report two births of a healthy male and a healthy female baby after use of testicular spermatozoa from two patients with nonmosaic Klinefelter's syndrome. DESIGN: Case report. SETTING: General academic hospital with IVF center and university institute of human genetics. PATIENT(S): Two couples with primary infertility in which the men had secretory azoospermia and nonmosaic 47,XXY karyotype. Both women had a normal karyotype and no gynecologic abnormalities. INTERVENTION(S): ICSI was performed using testicular spermatozoa after ovarian stimulation and transvaginal ultrasonography-guided oocyte pick-up. MAIN OUTCOME MEASURE(S): Normal fertilization, embryo cleavage, clinical pregnancy outcome, and peripheral blood karyotype of the newborn. RESULT(S): In each case, 13 metaphase II oocytes were injected, of which 7 fertilized normally. Three good-quality embryos (4-cell stage) were transferred into the uterine cavity. Both women conceived, and normal pregnancies followed. Genetic analysis of the neonates revealed normal 46,XX and 46,XY karyotypes. CONCLUSION(S): These case reports reaffirm that patients with nonmosaic Klinefelter's syndrome produce normal spermatozoa with fertilization potential. Although it is premature to make conclusions about the rate of transmission of this aneuploidy because of the low number of the published cases, this report substantiates the idea that rates of transmission of this gonosomal aneuploidy are low.

Advanced breast biopsy instrumentation (ABBI) and management of nonpalpable breast abnormalities: a community hospital experience.

A range of diagnostic techniques have been in use for determining the nature of non-palpable mammographic abnormalities over the last decade, these include stereotactic and ultrasound guided cytology, core biopsy and vacuum assisted core biopsy techniques as well as open surgical breast biopsy. Recently, a less invasive alternative has been investigated; the Advanced Breast Biopsy Instrumentation (ABBI) technique (U.S. Surgical Corporation, Norwalk, CT). ABBI employs computer-guided stereotactic localization to target and excise mammographic lesions under local anesthesia, without the need for an operating theatre. We conducted a prospective review of all cases involving the use of the ABBI system during the first 17 months' of its use in a community hospital. One hundred and twenty six patients were referred for an ABBI procedure. One hundred fourteen ABBI procedures were performed on 113 patients (average age, 53 years; range, 33-82). The lesion was removed successfully in 113 of the 114 cases. Of the 114 lesions removed with the ABBI system, 88 were microcalcifications and 26 were masses. Cancer was diagnosed in 21 patients (18%). Of the patients who had carcinoma, 11 (52%) had ductal carcinoma in situ, 9 (43%) had infiltrating ductal carcinoma, and 1 (5%) had infiltrating lobular carcinoma. Postprocedural complications occurred in 7 patients (6%); 4 had small haematomas, 2 had superficial wound infections, and 1 had an abscess. We conclude that the ABBI system, is an excellent alternative (to open biopsy after needle localization or large-core biopsy) for nonpalpable breast abnormalities. It has a relatively low complication rate and should be considered as part of the surgical armamentarium for the diagnosis of indeterminate nonpalpable mammographic lesions.

Heterosis in two closely related species of earthworm (Eisenia fetida and E. andrei).

The importance of heterosis, and in particular allozyme-associated heterosis, in natural populations remains unclear. Much of the scepticism that surrounds allozyme-associated heterosis comes from inconsistent and unreliable detection of the relationship. Thus, evaluating the genetic mechanisms that may cause allozyme-associated heterosis in natural populations has proven difficult. The most prevalent hypotheses that have been put forward to explain the genetic basis of heterosis are the general dominance and the local overdominance hypotheses. A factorial crossing design was used to survey eight polymorphic allozyme loci in the parent and offspring generations of two species of earthworms in order to evaluate possible mechanisms of allozyme-associated heterosis for growth rate. Significant heritable variation for growth rate was detected only within a single cross. Allozyme-associated heterosis for growth rate was detected only within this cross. This relationship did not persist after the effects of interfamily variation were removed. These results indicate that simple heritability of a fitness-related trait may be necessary for predictive power and repeatability of allozyme-associated heterosis, and that the allozyme-associated heterosis detected in this study was the result of general dominant genetic effects.

Autocrine regulation of interleukin-8 production in human monocytes.

Interleukin (IL)-8 is a C-X-C chemokine that plays an important role in acute inflammation through its G protein-coupled receptors CXCR1 and CXCR2. In this study, we investigated the role of IL-8 as an autocrine regulator of IL-8 production and the signaling mechanisms involved in human peripheral blood mononuclear cells (MNCs). Sepharose-immobilized IL-8 stimulated a sevenfold increase in IL-8 production within 2 h. IL-8 induced the expression of its own message, and IL-8 biosynthesis was inhibited by cycloheximide and actinomycin D, indicating de novo RNA and protein synthesis. In contrast to MNCs, polymorphonuclear neutrophils did not respond to the immobilized IL-8 with IL-8 production despite cell surface expression of CXCR1 and CXCR2. Melanoma growth-stimulatory activity/growth-related protein-alpha (MGSA/GROalpha), which binds CXCR2 but not CXCR1, was unable to either stimulate IL-8 secretion in MNCs or desensitize these cells to respond to immobilized IL-8. The involvement of mitogen-activated protein kinase (MAPK) in IL-8-induced IL-8 biosynthesis was suggested by the ability of PD-98059, an inhibitor of MAPK kinase, to block this function. Furthermore, IL-8 induced a significant increase in extracellular signal-regulated kinase 2 phosphorylation, whereas MGSA/GROalpha was much less effective. These findings support the role of IL-8 as an autocrine regulator of IL-8 production and suggest that this function is mediated by CXCR1 through activation of MAPK.

Endoscopic laser coagulation of placental anastomoses in 200 pregnancies with severe mid-trimester twin-to-twin transfusion syndrome.

OBJECTIVE: To investigate perinatal outcome after endoscopic laser coagulation of the placental vascular anastomoses in severe mid trimester twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: In a prospective study between January 1995 and September 1999, we performed laser therapy in 200 consecutive pregnancies with TTTS between 16 and 25 weeks of gestation. We compared outcome of the first group of 73 pregnancies whose outcome has been reported previously in a study comparing laser surgery and serial amniodrainages [Am J Obstet Gynecol 1999;180:717-24], with the following group of 127 patients. RESULTS: The overall survival rate increased from 61% (89/146) in group 1 to 68% (172/254) in group 2. The percentage of pregnancies with survival of both fetuses was 42% (31/73) in group 1 and increased to 54% (69/127) in group 2 (P=0.142). The survival rate for at least one fetus was 81% (103/127) in group 2. The median gestational age at delivery of liveborn babies was 33.7 weeks in group 1 and 34.4 weeks in group 2 with a median interval of 13 weeks between the intervention and delivery. CONCLUSION: This study of a large population of pregnancies with severe second trimester twin-to-twin transfusion syndrome confirms the improvements of outcome after laser therapy as compared to serial amniodrainages reported previously. Furthermore, it shows a trend towards an increase in survival rates with growing experience in this technique, most likely attributable to a more selective identification and efficient coagulation of the placental vascular anastomoses.