Selective feticide in monochorionic pregnancies: toys for the boys or standard of care?

In monochorionic pregnancies when only one fetus is affected by a severe abnormality that can either lead to the birth of an abnormal baby or affect the development of the normal fetus, selective feticide is an option that is frequently sought. However, conventional feticide techniques involving the injection of potassium chloride (KCl) or xylocaine into the fetal circulation are unsuitable. Indeed, monochorionic placentae are characterized by a certain degree of sharing of one or more cotyledons by the two fetal circulations, which constitutes functional vascular anastomoses between them. Hemodynamic instability in one fetus in its most extreme form (intrauterine fetal death) leads to an absolute and permanent drop in blood pressure, and this will trigger siphoning of blood from the co-twin. The subsequent exsanguination into the dead fetus may occur to such an extent that the resulting acute anemia and hypotension cause fetal death; if the fetus survives, ischemic damage of varying severity, particularly in the brain, occurs in up to 30% of cases. This follows the basic physics principle of communicating vessels and can involve all anastomotic vessels on the chorionic plate irrespective of their histological and directional characteristics1. Beyond ethical considerations, the crux of the problem is technical, in that total and permanent circulatory confinement of the sacrificed twin is crucial to the fate of the healthy co-twin. Although a consensus has been reached on these pathophysiological aspects, the best technique to use is still under debate; this issue of the Journal contributes to the debate with a report of one center's experience of selective feticide in monochorionic twin pregnancies2. Over the past 15 years, a wide range of techniques and management strategies have been proposed and supported, mainly through case reports or small series. These have included conventional feticide by intracardiac injection of potassium chloride, fetectomy following maternal laparotomy and hysterotomy for removal of the abnormal fetus, intrafunicular insertion of stenting systems or coils, and injection of either fibrin glue into the umbilical cord or absolute alcohol into the systemic circulation of the affected fetus. However, subsequent to their description, these techniques either disappeared from the literature or were declared unsuitable by their initial proponents3. Indeed, the results obtained were largely inconsistent and could not demonstrate adequate protection for the healthy twin. The main reasons for the illusion spread about the efficacy of these techniques are (1) reporting bias towards mainly successful attempts of rare procedures; (2) statistically non-significant small series; (3) a bias in the indication for performing the procedure. The latter point covers mainly acardiac twins: the acardiac fetus/tumor usually shares very little with the normal pump twin other than a direct artery-to-artery and vein-to-vein anastomosis and is often characterized by a low-flow circulation. This allows for alternative and uncontrolled techniques to appear successful because often the outcome of the normal pump twin is favorable. Indeed, when delivery occurs several weeks after the procedure, histology cannot be informative on the completeness of vascular occlusion. Furthermore, even in selective feticide involving fetuses with fully developed systemic and placental vasculature, the co-twin will survive and remain unaffected in as many as 50% of the cases, without any form of vascular protection for the healthy twin. Tan and Sepulveda, in a recent issue of this Journal, reviewed the specific situation of acardiac twinning and occlusive disconnection of the acardiac tumor4. In contrast to what they, quoting Healey et al.5, reported, our experience, along with that of most reported cases, is that the amount of fluid within the acardiac sac is minimal bordering on anhydramnios. This implies that access to the umbilical cord and/or the placental surface will often require amnioinfusion to be performed prior to cord coagulation using either laser, bipolar forceps or a suturing device. This systematic review4, although reporting on more than 70 cases, examined 32 reports of 1–13 cases. Conclusions drawn on the best technique to choose therefore rely on very little evidence due to the reporting biases to which I have already alluded. Indeed the praise for intrafetal ‘ablation’ techniques covers four different techniques all performed before 25 weeks' gestation. In 6/31 cases, the pregnancy was lost within 2 weeks of the procedure. Reviewing each technique individually, the use of absolute alcohol failed in two of five cases, and that of interstitial laser in one of only four cases, all of which were before 20 weeks. More recently, coagulation or mechanical occlusion of the umbilical cord have been developed by applying endoscopically derived surgical techniques such as self-tying knotting systems6 or small bipolar forceps7. The cases reported by Gallot et al.2 on cord compression should probably remain anecdotal since the technique which involves the use of two different ports and the extra-abdominal suture tied on the maternal abdomen may facilitate the development of intrauterine infection. According to the review of Tan and Sepulveda4, all monopolar coagulation procedures but two (7/9), and aiming at the main intrafetal vessel, were unsuccessful. The apparently good overall outcome in this ill-defined group of heterogeneous procedures and techniques is due mainly to a single series of 13 cases of acardiac twins in which coagulation of the main systemic vessel was achieved using radiofrequency8. This may be seen as encouraging but clearly awaits confirmation with larger numbers from different groups. Tan and Sepulveda4 also put various techniques under the single umbrella of cord occlusion although most of these have disqualified themselves over the poor results initially reported. This applies to the use of coils and fibrin glue, alcohol and monopolar coagulation. In particular, Denbow et al.3 discouraged the further use of embolization after 12 attempts with a success rate of only 33%. However, three different techniques of cord occlusion deserve closer and individual assessment: laser coagulation, bipolar forceps coagulation and cord ligation. The technique of laser coagulation of the umbilical cord was derived from that used to coagulate chorionic plate vessels in twin-to-twin transfusion syndrome9. Overall 12 cases involving complicated monochorionic twins have been reported from 16 weeks' onwards, using a double needle loaded with a 1-mm fetoscope and a 400-µm laser fiber10. The procedure allows direct visualization and was successful before 20 weeks but appeared to be inappropriate later in gestation due to the thickness of the cord's Wharton's jelly9. Another limitation is stained amniotic fluid, which impairs endoscopic vision of the target. The reported rate of preterm premature rupture of membranes (PPROM) in such cases is around 10%. Because of the failure of laser coagulation of the cord at later gestational ages, the use of bipolar energy was explored7. Bipolar forceps cannot reliably coagulate the umbilical cord of a fetus lying in the other amniotic sac without disrupting the membranes. Although not restricted to acardiac twins, the papers quoted by Tan and Sepulveda4 involve more cases of bipolar cord coagulation in complicated monochorionic twin pregnancies and are worth reviewing to assess the technique. They discuss 27 cases altogether to which can be added the five cases of Gallot et al.2. Of these 32 cases, a successful outcome with a healthy co-twin was obtained in 26 (81%). There was an overall 30% PPROM rate of which half were only transient and associated with a good outcome. The average operating time was 20 min. Cord ligation has been reported in 22 cases, including those discussed by Tan and Sepulveda4 and those of Gallot et al.2. Although in at least two cases the learning process caused the cord of the healthy twin to be ligated11, 12, the procedure was associated with a good outcome for the healthy twin in 14 of the 22 (64%) cases. The reported PPROM rate was also around 30%. The evaluation of cord occlusion techniques is not an easy task. Although it is often quoted to demonstrate the success of these procedures, color Doppler assessment is clearly unsuitable. The disappearance of blood flow in the umbilical cord should not lead to the assumption that the procedure was successful; a simple injection of KCl would lead to the same result. Likewise, any major alteration of blood flow within the cord could achieve fetal death; this is not the same as complete occlusion of all cord vessels. Similarly, a few cases, including the recent report by Sepulveda et al.13-15, of intra-aortic monopolar coagulation using a monopolar coagulation needle or electrode have been reported to be successful. However, this was true only in cases of acardiac twins treated before 20 weeks' gestation, exposing this still poorly explored procedure to the same criticisms as those raised above regarding later gestations or fetuses with normal systemic circulation. Furthermore, intrafetal coagulation leaves the cord patent. This raises the possibility that exanguination of the survivor, which may still occur, will be more extensive because blood can accumulate in the body of the dead fetus and surrounding placental territory. The expected benefit for the normal twin of prolongation of the pregnancy, which can be by hours to more than 20 weeks, makes such procedures questionable after 26–27 weeks when the abnormal twin is not viable (anencephaly, hypoplastic left heart syndrome or acardiac twins) when compared with lung maturation and timed elective delivery of a preterm healthy twin. Gallot et al.2 reported that in 4/11 cases PPROM and premature delivery occurred within 8 days and in a further two cases this occurred in less than 4 weeks, but in the remaining five the pregnancy was prolonged by more than 8 weeks. They suggest, albeit without conclusive evidence, that complications may be related to the size of the instrument they used. Maternal safety should remain the priority. This is why general anesthesia and fluid overload should be discouraged. Indeed, this could also mask placental abruption symptoms. Gallot et al. had to perform an emergency Cesarean section for ‘severe maternal extra-amniotic bleeding’. However, acute abdominal pain and fluid collection often reflects amniotic fluid leakage, which can cause acute excruciating pain. Although spectacular, this resolves rapidly following the administration of morphine-like pain killers. Morbidity and mortality in the survivor may occur through acute anemia and hypotension at the time of its co-twin's demise1. Screening for fetal anemia in the survivor by measuring the middle cerebral artery mean velocity is a non-invasive technique that has proved reliable for this indication16. This helps to refine the risk for these survivors and may also pave the way for future intrauterine transfusion therapy. It is currently impossible to be definite about the best single method for selective feticide in monochorionic pregnancies. Although specific data are lacking, we recommend the use of formal cannulas, i.e. ports that remain throughout the procedure and through which instruments and scopes can be introduced and exchanged as often as required. This allows adaptation of the best strategy to a given situation that often will only reveal itself during the procedure. However, an algorithm could be proposed that involves the best evaluated techniques to date. Fetoscopically guided laser coagulation of the cord and/or the vessels at the root of the cord allows optimal visual control of the procedure and should be the first thing that is attempted for complete cord occlusion. Procedures could be attempted from 16 weeks' gestation onwards using local injection of non-adrenalinized xylocaine down to the level of the myometrium along the proposed path of entry, which should aim to enter the sac of the affected fetus. Failure due to cord thickness or stained amniotic fluid should indicate the use of bipolar coagulation. Cord ligation could be reserved as a third solution, for cases of a massively edematous cord or difficult access to the cord for the bipolar forceps. To summarize, selective feticide in a monochorionic fetus has indisputable indications. When counseling the couple, one should not forget to mention the fact that there is fetal loss in 10 to 15% of cases. The three best standardized techniques should be used in a rational way, bearing in mind that safety and efficacy do not always go hand in hand with simplicity. These procedures should be carried out in specialized units and the surviving twin should be closely followed up throughout the pregnancy. These procedures should ideally be reported and gathered in a registry17, 18 so that safety and efficacy can be assessed more objectively in the near future, thus avoiding publication biases of small series of mostly successful procedures.