3) Placental anatomy, fetal demise and therapeutic intervention in monochorionic twins and the transfusion syndrome: New hypotheses By Professor Martin van Gemert, Amsterdam; Attila L. Major, California; Sicco A Scherjon, Amsterdam Professor Martin Van Gemert, University of Amsterdam, Netherlands The following abstarct from the paper is copyright 1998 Elsevier Science Ireland Ltd. ABSTRACT Objective: Monochorionic twins with circulatory sharing have an incompletely understood response to acute hemodynamic events. We relate placental vascular anatomy with, first, the response to (a) acute fetal demise and (b) laser interrupted placental anastomoses and, second, the efficacy of current and possibly future therapeutic interventions in twin-twin transfusion syndrome. Design: Hemodynamic response to acute fetal demise and laser interrupted anastomoses is analysed using the model previously developed for monochorionic twins. Efficacy of therapeutic interventions in twin-twin transfusion syndrome is analysed by combining the estimated incidence of placental anastomotic patterns with three previously proposed pathophysiologic mechanisms. Results: Fetal demise may cause sequelae for the co-twin in all anastomotic patterns except unidirectional arteriovenous and single venovenous anastomoses which are predicted to be hemodynamically harmless. In twin-twin transfusion syndrome, laser interruption of all anastomoses mitigates further transfusion. This is of benefit for the twins in equally but not in unequally shared placentas. Analysis predicts that -75% fetal survival could be achieved interrupting only arteriovenous anastomoses. Amniocentesis may only prolong pregnancies that lack progressively increasing discordance, assuming that placental anastomoses remain patent following polyhydramnios. This proposed mechanism of action predicts current therapeutic efficacy accurately and could explain the significantly higher reported serious morbidity compared with laser ( 15/81 = 19±5% versus 4/146=3%, P=0.00004). However, if therapeutic interventions could match the syndrome's individual placental anatomy, the analysis suggests -10-15% laser related mortality (premature rupture of membranes) and <3% severe morbidity could possibly become achievable goals. Conclusion: Our predictions allow clinical testing. This information may contribute to an improved management of monochorionic twins. In previous papers, Professor Van Gemert has identified distinct placental pathologies in TTTS. His model predicts what will happen to TTTS twins given a particular placental physiology, treated with a particular therapeutic intervention. In essence, Martin predicts that if treatment is tailored to the placental type, then success rates will reach a much higher level than is possible with the current policy of applying one treatment or another to every case presented. There follows a summary of the paper's contents, containing extracts which are copyright 1998 Elsevier Science Ireland Ltd. Distinct placental types 1) AV - Unidirectional artery-to-vein connection in an equally shared placenta A predicted blood flow from donor to recipient of <1ml per day produces a steadily increasing difference in size between the babies. From other studies it is estimated that 39% of TTTS cases have this placental type, and that these have by far the highest mortality rate, being the most difficult to treat. 2) AV + VA, AA, VV - Unidirectional artery-to-vein connection with compensating anastomoses in an equally shared placenta Thought to occur in around 50% of TTTS cases.The AV anastomosis sets up fetal discordance and an increasingly high blood pressure in the Recipient, with a low blood pressure in the Donor. This continues until the compensating and AV blood flows are equal to each other. Then, a steady state of discordant growth occurs with opposing blood flows striving towards minimal transfusion. Widely varying discoedances are reported, depending on the resistance ratio of the AV and compensating anastomoses. Mortality is lower than in 1). 3) Unequal Placental Sharing + Superficial compensating anastomoses (AA, VV) Fetal growth discordance is started by the difference between the available placental cotyledonic fractions. A steady state of virtually equal growth and almost equal blood pressures establishes later on because of the compensating AA and VV anastomoses. Mortality is low. The Effectiveness of Treatment Laser ablation of all connecting vessels Currently this treatment has an overall reported success rate of live-born infants of 55%, with lower reported complications such as Cerebral Palsy than with amnioreduction. In equally shared placentas, the treatment is predicted to be hemodynamically fully protective of both twins. In unequally shared placentas (around 16% of cases), ablation of all vessels will serve to cut off some of the vessels necessary for the survival of the smaller twin, thus hastening its death. Theoretically, laser ablation of all vessels has a success rate of 92% (all of those from equally shared placentas, and half of those from unequally shared placentas). The discrepancy between this theoretical success of 92%, and the actual success rate of 55% is put down to procedural and methodological faults in the procedure. It appears, therefore, that the efficiency of laser treatment can be improved. Firstly, laser ablation along the placental vascular equator instead of the interfetal membrane septum may reduce early fetal deaths to around 16%, the assumed incidence of unequal placental sharing. Interestingly, Dr. Julian De Lia's second series of 33 cases has a success rate of 67%. Secondly, if the placental anatomy could be derived from fetal growth patterns and anastomotic flow measurements, additional single fetal deaths in cases of unequal placental sharing might be prevented. This, however, would require selective coagulation of the AV anasomoses, leaving either AA or VV anastomoses alone (if present). This could increase the 67% success rate by an additional 8% to reach about 75%. If this were the case, premature rupture of the membranes would be the major cause of treatment failure, most likely due to the combined effects of polyhydramnios and fetoscopic intervention. It is believed that the use of smaller fetoscopes could reduce this type of intervention related mortality. Serial Amniocentesis Currently this treatment has an overall reported success rate of live-born infants of 60%. Based on the available number of reported cases, the difference in success rates between laser and amnio treatments is considered statistically not significant. However, as amnioreduction is simple, and carries limited procedural related complications, it is the treatment of choice for most obstetricians. On the other hand, it is a purely symptomatic intervention - not preventing the continuing transfusion. Furthermore, the twins may experience inadequate physiologic recovery following the treatment, as suggested by the reported incidence of handicapped babies. Therefore, it just might be that the most important function of serial amnioreduction is to prevent untimely rupture of the membranes. The hypothesis, therefore, is that this treatment prolongs all pregnancies except cases of unidirectional AV anastomoses. Because these may occur in about 39% of cases, it is predicted that amnioreduction will result in two live babies in 61% of cases treated. Laser versus Amnioreduction: is there an optimal intervention in TTTS? It is proposed that selective application of either laser ablation or amnioreduction could provide optimal intervention in TTTS. Laser procedure, with coincidental amnioreduction to prevent premature rupture of the membranes, should be applied in cases where both fetuses are thought most likely to die or where severe morbidity can be expected. It is proposed that this is if the discordance between the twins is significant due to placental types 1) and 2). Amnioreduction should be used alone in those cases where discordance remains limited. This is the case in placental type 2) if the discordance is limited, specifically when the steadty state of minimal transfusion has ensued, and in type 3) where discordance tends to disappear spontaneously. It is speculated that amnioreduction, applied alone in type 2) may be associated with a high incidence of severly handicapped babies. On the other hand, laser ablation of all vessels in type 3) - unequal placental sharing - may cause the demise of the smaller twin. Obviously, any application of treatments that match the underlying placental anatomy requires a precise diagnosis of the placental physiology. It has been suggested that this might be achieved by serial ultrasound measurement of fetal growth patterns and anastomotic flow. Even under such circmstances, however, a 10% to 15% mortality could still be expected due to premature rupture of membranes.  Conclusion This analysis produces theoretical predictions that allow straightforward clinical testing. Further progress, therefore, requires careful documentation of clinical presentation, the response to therapeutic intervention and, most importantly, the corresponding placental anatomical details in the monochorionic twin pregnancies involved. Notes From twin2twin: Having had the above paper explained in person by Professor Van Gemert, the theories are certainly logical and attractive. Some disagreement, however, would come from proponents of Amnioreduction Therapy - who would state that that therapy has been shown to have beneficial effects to the condition, and not simply be a method of prolonging the pregnancy. See Geoff Machin's paper. Research currently underway at Queen Charlotte's Hospital in London is constantly helping to improve diagnosis of placental physiology via ultrasound techniques, and it may be that through this research Martin's theories can be more effectively and clinically tested. The current Eurofetus Project at http://www.eurofoetus.org hopes to collect much of the data that Martin has requested - again this should provide valuable clinical data to support his theories