Treatment options for the twin-twin transfusion syndrome: a review.

This article reviews the treatment options of the twin-twin transfusion syndrome (TTTS). No single therapy is associated with a uniformly improved outcome for the involved twins and success is primarily related to gestational age and severity at diagnosis. Treatment options for severe cases include digitalization, ligation of the umbilical cord, serial amniocenteses, septostomy, laser occlusion of placental vessels, and selective feticide. These modalities are associated with significant risks of complications, and variable results of fetal morbidity and mortality. Therefore, they should be considered when risks of withholding treatment clearly outweigh those associated with intervention.     

Natural history of 11 cases of twin-twin transfusion syndrome without intervention.

The natural history of 11 cases of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin pregnancies has been reviewed. Seven cases before 28 weeks and four pregnancies after 28 weeks had been followed up without intervention. Eight cases had premature uterine contractions. All seven pregnancies before 28 weeks aborted, leading to a 100% mortality rate. After 28 weeks all mothers delivered live births. The diagnosis of TTTS before 28 weeks, and with premature uterine contraction, seems to be a poor prognostic sign.     

Modeling a hydropic recipient twin in twin-twin transfusion syndrome

We developed a mathematical model of twin-twin transfusion syndrome (TTTS) that includes a hydropic recipient twin, adding interstitial and intracellular fluid compartments, fetal congestive cardiac failure, and the dynamics of renin-angiotensin system (RAS) mediators to our previous TTTS model. Ten differential equations for each twin, coupled by the net fetofetal transfusion of blood and blood components, i.e., colloids, osmoles, and RAS mediators, describe the development of fetal arterial and venous blood volumes, blood osmolality and colloid osmotic pressure (COP), interstitial fluid volume and COP, intracellular fluid volume, amniotic fluid volume and osmolality, and RAS mediator concentration. We included varying placental anastomoses, placental sharing, and amnionicity. The 20 differential equations were solved numerically from 0 to 40 wk with a 0.6-s time step. Consistent with clinical experience, model predictions are as follows. Unidirectional arteriovenous anastomoses and arteriovenous anastomoses inadequately compensated by oppositely directed anastomoses cause severe TTTS that includes a hydropic recipient. Adequately compensated arteriovenous anastomoses simulated TTTS without hydrops. The probability that oppositely directed anastomoses prevent onset of a hydropic recipient after TTTS onset, i.e., the largest interval between onset of TTTS and onset of hydrops in the recipient, was best for a venovenous anastomosis, closely followed by an arterioarterial and finally an oppositely directed arteriovenous anastomosis. Hydropic recipients have decreased amniotic fluid volume. Unequal placental sharing and amnionicity modify hydrops onset. In conclusion, our model simulates a sequence of events that results in a hydropic recipient twin in severe TTTS. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS cases that include a hydropic recipient twin.     

Early changes in vascular dynamics in relation to twin-twin transfusion syndrome.

A clearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.     

Management of twin-twin transfusion syndrome: laying the foundation for future interventional studies.

Twin-twin transfusion syndrome is the most common complication of monochorionic pregnancies affecting between 5 and 15% of such pregnancies and accounts for 15-77% of perinatal mortality in twins. The management of twin-twin transfusion syndrome is complex and various treatment modalities have been tried. This review critically evaluates the different management options available for the syndrome and recommends some guidelines for future interventional studies.     

A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations

The twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies caused by a net transfusion of blood from one twin (the donor) to the other (the recipient) through placental anastomoses. To examine the pathophysiology of TTTS evolving through clinical stages I to IV, we extended our mathematical model to include pulsating circulations propagating along the arterial tree as well as placental and cerebral vascular resistances, and arterial wall thickness and stiffness. The model demonstrates that abnormal umbilical arterial flow (TTTS stage III) in the donor twin results from increased placental resistance as well as reduced resistance in the cerebral arteries. In contrast, recipient twin abnormal umbilical arterial flow requires a significantly greater increase in placental resistance, resulting from the compressive effects of high amniotic fluid pressure. Thus simulated abnormalities of donor umbilical arterial pulsations occur in the donor more commonly and earlier than in the recipient. The "normal" staging sequence (I, II, III, IV) correlates with the presence of compensating placental anastomoses, constituting the majority of monochorionic twin placentas. However, TTTS stage III may occur before manifestations of stage II (lack of donor bladder filling), in our model correlating with severe TTTS from a single arteriovenous anastomosis, an infrequent occurring placental angioarchitecture. In conclusion, this mathematical model describes the onset and development of the four stages of TTTS, reproduces a variety of clinical manifestations, and may contribute to identifying the underlying pathophysiology of the staging sequence in TTTS.     

Influence of maternal obesity and metabolic and vascular mediators in twin-twin transfusion syndrome

Obesity is a risk factor for complications in singleton and twin pregnancies; however, there are limited data regarding maternal body mass index (BMI) in the setting of twin-twin transfusion syndrome (TTTS). We hypothesized that increased BMI in TTTS is associated with adverse perinatal outcomes and vascular pathology. A retrospective study of twin reversed arterial perfusion (n = 4), selective intrauterine growth restriction (n = 10) and TTTS (n = 33) was conducted. Treatment included fetoscopic laser photocoagulation (FLP) (n = 35) or Solomon technique (n = 12). Ex vivo placental intravascular injections, immunohistochemistry, and perinatal outcomes were compared by maternal BMI. In pregnancy complicated by TTTS, 16/33 women were obese (BMI > 30 kg/m²) and 11/33 were overweight (BMI 25–29.9 kg/m²). Women who were overweight or obese had an increased rate of premature rupture of membranes (PPROM), cesarean delivery, and/or concomitant co-morbidities when compared to the normal weight group. Duration of neonatal intensive care unit (NICU) admission was longer in neonates of overweight/obese women versus normal weight. Placental examination of FLP sites in the obese group showed larger infarcts, increased adipose triglyceride lipase, and a proangiogenic phenotype. Increased BMI is common in our TTTS cohort and it is associated with higher rate of co-morbidity, PPROM, prolonged NICU stay, and an imbalance of placental metabolic and vascular mediators.     

Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin-twin transfusion syndrome

We developed a mathematical model of monochorionic twin pregnancies and twin-twin transfusion syndrome (TTTS), combining both fetal fluid dynamics and fetoplacental growth and circulation alterations and assuming that transplacental fluid flow from mother to fetus accounts for normal fetal and amniotic fluid volumes. Ten coupled differential equations, describing fetal total body and amniotic fluid volumes, their osmolalities, and fetal blood colloid osmotic pressure, for both donor and recipient twins, were solved numerically. Amniotic flows are controlled by fetal plasma osmolality and hydrostatic and colloid osmotic pressures. We included varying placental anastomoses and placental sharing of the circulations. Consistent with clinical experience, model predictions are: fetofetal transfusion from unidirectional arteriovenous anastomoses cause oligo-polyhydramnios, a normal size recipient but hypovolemic donor; compensating oppositely directed deep and superficial anastomoses moderate discordant development; and anhydramnios results from mild and severe TTTS, where milder forms may even present earlier in gestation than severe TTTS. Unequal placental circulatory sharing may exacerbate discordant development. In conclusion, our model simulates a wide variety of realistic manifestations of amniotic fluid volume and fetal growth in TTTS related to placental angioarchitecture. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS.     

Rejoinder to meta-analysis of twin-twin transfusion by Skupski et al.

Assessment of treatment options in twin-twin transfusion should involve a detailed interrogation of the placenta and fetuses prior to treatment, stratification according to response to amnioreduction and careful analysis of quality of survival. Amnioreduction and laser coagulation are not alternative and equivalent modalities for the treatment of twin-twin transfusion. Randomized trials may not be ethical without prior therapeutic/diagnostic amnioreduction.     

The effect of various adjuncts on the surgical treatment of carpal tunnel syndrome secondary to chronic tenosynovitis.

A series of 22 patients with carpal tunnel syndrome secondary to chronic tenosynovitis was divided into two groups. The first group was treated by transverse carpal ligament release alone. The second group was treated by transverse carpal ligament release, external neurolysis of the median nerve, flexor synovectomy, and intraoperative corticosteroid instillation. Both groups were comparable preoperatively as to symptoms, signs, and electrophysiological data. At two years postoperatively there were no statistically significant differences in the symptoms, signs, and electrophysiological data in the two groups. The only difference was that patients undergoing release alone were able to return to work earlier than those patients who had the adjunctive procedures.     

The effect of interstimulus interval on somatosensory point localization

Somatosensory point localization is a clinical test evaluating spatial accuracy of the somatosensory system. Possible effects of the interstimulus interval (ISI) on point localization threshold have not been previously examined. In the present set of experiments the effect of time delay on somatosensory point localization was studied using ISIs of 1, 3, 5, 7, and 9 s, and applying a newly developed computer-controlled application method of a Semmes-Weinstein monofilament. It was found that the point localization threshold was not significantly affected by the ISI length. However, the response time was shorter and response accuracy better at the shorter (1 and 3 s) than at the longer (5, 7, and 9 s) ISIs, suggesting a change in the mechanism underlying point localization decision criteria in ISIs longer than 3 s.     

The effect of endometrial biopsy on ovulatory interval in mares

Luteolysis with subsequent shortening of diestrus has been reported to follow equine endometrial biopsy performed early in the luteal phase of the estrous cycle, but a comprehensive study of the effect of endometrial biopsy on cycle length at different times of the cycle has not been reported. In this study, endometrial biopsies were obtained from four different pony mares on each of Days 0, 4, 8, 12, 16 and 20 after ovulation as determined by serial palpation per rectum. Compared with control cycles in the same mares, the ovulatory interval was shortened in mares from which biopsies were obtained on Days 4 and 8, it was lengthened in from which samples were taken on Days 16 and 20 and it remained unchanged by biopsies performed on Days 0 and 12. Although the changes were less consistent and smaller than those observed in cows, our findings are similar to those reported for effects of endometrial manipulation or uterine infusion on the estrous cycle of cows.     

The effect of an imprecise map on interval mapping QTLs

The statistical analysis of quantitative trait locus (QTL) experiments relies on the use of a linkage map of the markers genotyped. Such a map is, at best, a good estimate of the true map. Resources might be diverted into developing better marker maps or improved maps become available after the analysis, raising concerns over the original analysis. It is therefore important to understand the sensitivity of QTL analysis to map inaccuracy. We have used simulation methods to investigate the consequences of an incorrect map on the results of a QTL analysis using interval mapping. Backcross data sets were generated with a particular map and then analysed with both the correct map and incorrect maps. If the incorrect maps maintained the true linkage groups (i.e. no markers were incorrectly assigned to another linkage group), the accuracy of the map had little or no impact on the ability to detect QTLs, the true significance levels of the tests or the relative placement of QTLs. When a marker was incorrectly placed on another linkage group, there was a small increase in the level of the test. After adjusting for this increase, there was a decrease in power to detect a QTL near the misplaced marker. This decrease was of a similar magnitude to that found when using a single-marker analysis compared with interval mapping. These results mean that QTL analyses can proceed without the need for very accurate marker maps, and that estimated QTL positions can be translated onto updated maps without the need for reanalysis.     

The effect of rest interval length on bench press performance with heavy vs. light loads

The purpose of the current study was to compare the effect of 3 different rest intervals on multiple sets of the bench press exercise performed with heavy vs. light loads. Sixteen resistance-trained men performed 2 testing sessions each week for 3 weeks. During the first testing session each week, 5 consecutive sets of the bench press were performed with 80% of 1 repetition maximum (1RM) and with a 1-, 2-, or 3-minute rest interval between sets. During the second testing session each week the same procedures were repeated with 50% of 1RM. The total repetitions completed and the sustainability of repetitions were compared between rest conditions and between loads. For each load, resting 3 minutes between sets resulted in significantly greater total repetitions vs. resting 2 minutes (p = 0.000) or 1 minute (p = 0.000) between sets. However, the sustainability of repetitions was not significantly different between loads (p = 0.849). These results can be applied to weekly bench press workouts that undulate between heavy (i.e., 80% 1RM) and light (i.e., 50% 1RM) intensities. When the training goal is maximal strength development, 3 minutes of rest should be taken between sets to avoid significant declines in repetitions. The ability to sustain repetitions while keeping the intensity constant may result in a higher training volume and consequently greater gains in muscular strength.