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The vascular anastomoses in monochorionic twin pregnancies and their clinical consequences

Published:October 01, 2012DOI:https://doi.org/10.1016/j.ajog.2012.09.025
      Monochorionic twin pregnancies are at increased risk of adverse outcome because of the vascular anastomoses that connect the 2 fetal circulation systems. The shared circulation is responsible for some unique complications in monochorionic twins, such as the twin-to-twin transfusion syndrome, the twin anemia polycythemia sequence, the twin reversed arterial perfusion sequence, and monoamniotic twinning. Another consequence of the shared circulation is that the well-being of one twin critically depends on that of the other. In this review, we will describe the technique of placental injection. Further, we will discuss the role of the vascular anastomoses in each of the complications described above and provide an update on their management.

      Key words

      All twin pregnancies are at increased risk of death due to miscarriage and preterm birth. However, monochorionic twins, which constitute 20% of all twins, face the highest risks. For a monochorionic twin, the risk of death between the first trimester and 24 weeks is about 12%, which is 6 times higher than the 2% risk of a dichorionic twin pregnancy.
      • Sebire N.J.
      • Snijders R.J.
      • Hughes K.
      • Sepulveda W.
      • Nicolaides K.H.
      The hidden mortality of monochorionic twin pregnancies.
      Although most deaths occur <24 weeks, even after viability monochorionic twins remain at significantly increased risk.
      • Breathnach F.M.
      • McAuliffe F.M.
      • Geary M.
      • et al.
      Perinatal Ireland Research Consortium
      Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies.
      Complications of the shared circulation account for this excess mortality.
      • Sebire N.J.
      • Snijders R.J.
      • Hughes K.
      • Sepulveda W.
      • Nicolaides K.H.
      The hidden mortality of monochorionic twin pregnancies.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      • Acosta-Rojas R.
      • Becker J.
      • Munoz-Abellana B.
      • Ruiz C.
      • Carreras E.
      • Gratacos E.
      Catalunya and Balears Monochorionic Network
      Twin chorionicity and the risk of adverse perinatal outcome.
      During intrauterine life, dichorionic twins have completely separate circulation systems, whereas about 95% of monochorionic twins have vascular anastomoses on the placental surface that connect the 2 circulations.
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.
      For Editors' Commentary, see Contents
      The nearly ever-present blood exchange is responsible for some unique complications in monochorionic twins, such as the twin-to-twin transfusion syndrome (TTTS), the twin anemia polycythemia sequence (TAPS), the twin reversed arterial perfusion (TRAP) sequence, and monoamniotic twinning.
      • Lewi L.
      • Gucciardo L.
      • Van Mieghem T.
      • et al.
      Monochorionic diamniotic twin pregnancies: natural history and risk stratification.
      Another consequence of the shared circulation is that the well-being of one twin critically depends on that of the other. After the diagnosis of spontaneous demise of one of a monochorionic pair, the survivor has a 15% risk of death and a 25% risk of neurodevelopmental impairment
      • Hillman S.C.
      • Morris R.K.
      • Kilby M.D.
      Co-twin prognosis after single fetal death: a systematic review and meta-analysis.
      because of acute exsanguination along the anastomoses into its demised cotwin. The fact that their well-being is interrelated also poses some specific problems in the management of poor growth and imminent demise of the growth-restricted twin or if 1 twin has a severe anomaly and selective reduction is considered. In this review, we will describe the technique of placental injection. Further, we will discuss the role of the vascular anastomoses in each of the complications described above and provide an update on their management.

      Injection studies of the monochorionic placenta

      Placental injection from complicated monochorionic twin gestations often provides exceptionally useful information that would otherwise be lost on routine pathological examination. Nevertheless, placentas from pregnancies complicated with single death and delayed delivery can no longer be evaluated because of postmortem involution of the placental part of the demised twin.
      Although placental injection is time-consuming, it is basically a simple technique that can be performed by anyone with minimal surgical skills. After delivery, it is important to mark the cords of the first- and/or second-born twin with 1 and/or 2 clamps, respectively. The placenta should be stored in the refrigerator (at 4°C) until examination. The sooner the placenta is examined the better, but an interval of up to 10 days is feasible. It takes about 1 hour to inject a placenta.
      Before catheterization, it is best to cut both cords at about 5 cm from their placental insertion, because the arteries are less coiled in their distal segment, which makes it easier for catheter insertion (Figure 1). Of each cord, we catheterize both arteries and the vein and use a 22G (blue) catheter for the artery and a 16G (gray) for the vein (Insyte-W; Vialon, Becton Dickinson, Franklin Lakes, NJ). For placentas from pregnancies delivered <26 weeks, pediatric 26G and 24G catheters (BD Neoflon; Becton Dickinson) can be used for arterial and venous catheterization, respectively. Once inside the vessel, we fix each catheter to the cord with Vicryl 3/0 (Ethicon, Johnson & Johnson, New Brunswick, NJ) to prevent subsequent dislodgement. In >90%, there is an anastomosis that connects the 2 umbilical arteries at the base of the cord (Hyrtl anastomosis). To save time, only 1 artery may be catheterized, but we prefer to catheterize both from the start as it is more difficult to catheterize the other once injection is started.
      Figure thumbnail gr1
      FIGURE 1Technique of placental injection
      A, Insertion of catheters after cord is cut 5 cm from its placental insertion. B, Three catheters fixed to cord. C, Before injection with purple, blue, white, and red barium-sulphate mixtures. D, Injection of one of the arteries.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      For color injection, we always use undiluted barium sulphate (Micropaque; Guerbet, Villepinte, France), which is available in every radiology department. To have a better macroscopic view of the anastomoses, we add water-soluble color agents for each set of arteries and veins: blue (methylene blue), red (eosin), and purple (mixture of methylene blue and eosin). We inject the arteries and vein of each twin successively with a 20-mL syringe until all peripheral branches are filled and backpressure prevents further injection. We then clamp the cords again to prevent further leakage with 1 and 2 clamps to identify the first- and second-born twin, respectively. Finally, for optimal visualization, we remove the amniotic membranes from the chorionic surface and rinse the placenta under cold tap water. After injection, the number and type of anastomoses are recorded. We take a high-resolution digital photograph perpendicular to the chorionic surface to document the angioarchitecture.
      Anastomoses can be of 3 types: arterioarterial, arteriovenous, and venovenous. Arterioarterial and venovenous anastomoses are superficial and bidirectional anastomoses. “Superficial” refers to the fact that they are visible on the surface of the chorionic plate, forming direct communications between the arteries and veins. “Bidirectional” means that they allow flow in both directions depending on the relative intertwin vascular pressure gradients. An arterioarterial anastomosis functions as a flexible arteriovenous connection and thus compensates for any imbalance that occurs over the unidirectional arteriovenous anastomoses (Figure 2). Most monochorionic placentas typically have only 1 arterioarterial anastomosis. Venovenous anastomoses are more rare and seen in only about 25% of monochorionic placentas.
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.
      The function of venovenous anastomoses is less well established. Venovenous anastomoses may be associated with decreased perinatal survival
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      and cause demise because of sudden changes in venous return. However, this association has not been confirmed by other series. Nevertheless, in the absence of a venovenous anastomoses, each twin has its own placental territory defined by the venous vessels that drain oxygen-rich blood back to its owner. In contrast, in the presence of a venovenous anastomosis, there is no longer an individual but rather a common and most probably flexible venous drainage area (Figure 3).
      Figure thumbnail gr2
      FIGURE 2Typical monochorionic diamniotic placenta from an uncomplicated pregnancy
      A, Typical monochorionic diamniotic placenta from uncomplicated pregnancy. Delivery was at 35 weeks of 2 healthy neonates of 2534 g and 2440 g. Placenta is equally shared. Each twin has its own individual placental territory (veins colored blue for twin 1 and veins colored brown for twin 2) defined by venous chorionic plate vessels of each twin (dotted line). There is 1 artery-to-artery anastomosis (star); 5 arteriovenous anastomoses (from twin 1 to 2) (open circles); and 6 oppositely directed venoarterial anastomoses (dotted circles). B, Magnification of artery-to-artery anastomosis. Each artery-to-artery anastomosis functions as flexible arteriovenous anastomosis. Depending on direction of flow, it can act as arteriovenous anastomosis from twin 1 to 2 (solid arrow), or as venoarterial anastomosis from twin 2 to 1 (dotted arrows).
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Figure thumbnail gr3
      FIGURE 3Another monochorionic diamniotic placenta from uncomplicated pregnancy delivered at 37 weeks and birthweights of 2180 g and 2380 g
      This placenta has artery-to-artery (solid star and purple colored artery) and large vein-to-vein (open star and pink colored vein) anastomoses. In contrast to placenta in , it is impossible here to delineate individual venous territories accurately and to determine which twin has larger territory. Dotted lines reflect some possible placental distributions depending on where one assumes venous return is located for each twin.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      On the other hand, arteriovenous anastomoses are usually referred to as deep and unidirectional anastomoses. “Deep” refers to the fact that the anastomosis itself occurs at the capillary level within a shared placental lobule. “Unidirectional” means that they allow flow in 1 direction only. It receives its arterial supply from one twin and gives its venous (well-oxygenated) drainage to the other. The supplying artery and draining vein of the arteriovenous anastomosis are visible on the chorionic surface as an unpaired artery and vein that pierce the chorionic plate at close proximity of one other to supply the underlying, shared placental lobule. Because of the arteriovenous anastomoses, the monochorionic placenta actually consists of 3 parts: 2 that belong to each twin individually, and a third part that is shared and supplied by arteriovenous anastomoses.
      Because of their unidirectional nature, arteriovenous anastomoses can create a transfusion imbalance, unless an oppositely directed transfusion by other superficial or deep anastomoses provides adequate compensation. About 90% of monochorionic placentas have several arteriovenous and venoarterial anastomoses in combination with an arterioarterial and/or venovenous anastomosis. In about 5% of monochorionic placentas, there are only arteriovenous anastomoses and in another 5% there are no anastomoses.
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.

      TTTS

      TTTS is an antenatal sonographic diagnosis based on the presence of polyhydramnios (deepest vertical pocket ≥8 cm) with a distended bladder in the recipient and oligohydramnios (deepest vertical pocket ≤2 cm) with a small or empty bladder in the donor. Because amniotic fluid increases with gestation, most Europeans adhere to the gestational age-dependent cutoff of a deepest pocket ≥10 cm after 20 weeks to define the degree of polyhydramnios. “Twin-to-twin transfusion syndrome” is somewhat a misnomer, as in the overall majority there is no difference in hemoglobin concentration between donor and recipient twin.
      • Saunders N.J.
      • Snijders R.J.
      • Nicolaides K.H.
      Twin-twin transfusion syndrome during the 2nd trimester is associated with small intertwin hemoglobin differences.
      As such, the name “twin oligopolyhydramnios sequence” may be better suited.
      • Lopriore E.
      • Middeldorp J.M.
      • Oepkes D.
      • Kanhai H.H.
      • Walther F.J.
      • Vandenbussche F.P.
      Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence.
      About 1 in 10 monochorionic twins develop TTTS, usually between 16-26 weeks.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      Why certain monochorionic twins are affected and others are not remains elusive because of the lack of animal models and ethical constraints to routinely perform fetal blood sampling. Both postnatal injection studies
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      and in vivo fetoscopic observations
      • Diehl W.
      • Hecher K.
      • Zikulnig L.
      • Vetter M.
      • Hackelöer B.J.
      Placental vascular anastomoses visualized during fetoscopic laser surgery in severe mid-trimester twin-twin transfusion syndrome.
      • Bermúdez C.
      • Becerra C.H.
      • Bornick P.W.
      • Allen M.H.
      • Arroyo J.
      • Quintero R.A.
      Placental types and twin-twin transfusion syndrome.
      indicate the presence of at least 1 unidirectional arteriovenous anastomosis as an anatomical prerequisite for the development of TTTS (Figure 4). Although there is no unique pattern of anastomoses, the presence of an arterioarterial anastomosis seems to be protective. As such, an arterioarterial anastomosis is present in only 1 of 5 TTTS placentas in contrast to 4 of 5 placentas not complicated by TTTS.
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      Also, a mathematical computer model simulating TTTS demonstrated that an arterioarterial anastomosis indeed compensates more efficiently for any flow imbalance than oppositely directed venoarterial anastomoses.
      • Umur A.
      • van Gemert M.J.
      • Nikkels P.G.
      • Ross M.G.
      Monochorionic twins and twin-twin transfusion syndrome: the protective role of arterio-arterial anastomoses.
      This is due to a much lower resistance over the direct arterioarterial anastomosis than over arteriovenous anastomoses, which occur at a capillary level.
      Figure thumbnail gr4
      FIGURE 4Monochorionic diamniotic placenta from patient who developed twin-to-twin transfusion syndrome with double intrauterine demise at 24 weeks
      Placenta is equally shared. There is 1 tiny artery-to-artery anastomosis (star) that could insufficiently compensate flow over 7 arteriovenous anastomoses (open circles) from donor (twin 1, 540 g) to recipient (twin 2, 750 g).
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Although the vascular anastomoses are an anatomical prerequisite, the pathogenesis of TTTS must be more complex than a simple net transfer of red blood cells, because both twins usually have similar hemoglobin values.
      • Saunders N.J.
      • Snijders R.J.
      • Nicolaides K.H.
      Twin-twin transfusion syndrome during the 2nd trimester is associated with small intertwin hemoglobin differences.
      As mentioned above, TTTS is a problem of amniotic fluid discordance with a volume-overloaded recipient and a volume-depleted donor and not a problem of hemoglobin discordance with a polycythemic recipient and anemic donor. Therefore, endocrine factors related to fluid and pressure homeostasis are likely to be involved as well. Due to the intertwin blood exchange, one twin is exposed to the endocrine environment of the other. As such, transfer of renin-angiotensin-aldosterone effectors from the donor may partly explain the recipient's hypertensive cardiomyopathy and volume overload.
      • Mahieu-Caputo D.
      • Meulemans A.
      • Martinovic J.
      • et al.
      Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient.
      TTTS is the most important cause of death and handicap in a monochorionic twin pregnancy.
      • Ortibus E.
      • Lopriore E.
      • Deprest J.
      • et al.
      The pregnancy and long-term neurodevelopmental outcome of monochorionic diamniotic twin gestations: a multicenter prospective cohort study from the first trimester onward.
      Because TTTS occurs prior to viability, the prognosis is dismal without treatment. Polyhydramnios-related miscarriage or the preterm birth of 2 sick neonates is common, as is the intrauterine demise of one or both twins. Fetoscopic laser coagulation of all anastomoses along the equator is currently the best treatment option regardless of disease severity.
      • Roberts D.
      • Gates S.
      • Kilby M.
      • Neilson J.P.
      Interventions for twin-twin transfusion syndrome: a Cochrane review.
      For early detection and because TTTS is often difficult to predict, it is generally recommended that all monochorionic twins are scanned every fortnight, especially between 16-26 weeks. Laser aims to cure the disease by disconnecting the 2 fetal circulations. Successful interruption leads to a normalization of urine output, of amniotic fluid volumes, and of cardiac function in the recipient twin. After laser, there is a 50-60% survival of both twins and an 80% survival of survival of at least 1 twin.
      • Rossi A.C.
      • D'Addario V.
      The efficacy of Quintero staging system to assess severity of twin-twin transfusion syndrome treated with laser therapy: a systematic review with meta-analysis.
      Donor twins seem to have somewhat lower survival rates (60%) than recipient twins (70%).
      • Rossi A.C.
      • D'Addario V.
      Comparison of donor and recipient outcomes following laser therapy performed for twin-twin transfusion syndrome: a meta-analysis and review of literature.
      Of surviving infants, 11% have some form of developmental impairment. Cerebral palsy is the most common impairment, affecting 5%. Both donor and recipient are at equal risk of long-term impairment. Also, in single survivors, the risk of handicap is not increased,
      • Rossi A.C.
      • Vanderbilt D.
      • Chmait R.H.
      Neurodevelopmental outcomes after laser therapy for twin-twin transfusion syndrome: a systematic review and meta-analysis.
      supporting the concept that laser protects the survivor in case of intrauterine demise of its cotwin. The single most important predictor of adverse long-term outcome is an early gestational age at birth.
      • Lopriore E.
      • Ortibus E.
      • Acosta-Rojas R.
      • et al.
      Risk factors for neurodevelopment impairment in twin-twin transfusion syndrome treated with fetoscopic laser surgery.
      It is clear that outcome after laser surgery is far from perfect, because at best only 50-60% of parents will take home 2 healthy babies. Missed anastomoses are common and, depending on the thoroughness of the injection technique, are found in about 5-30% of cases.
      • Chmait R.H.
      • Assaf S.A.
      • Benirschke K.
      Residual vascular communications in twin-twin transfusion syndrome treated with sequential laser surgery: frequency and clinical implications.
      • Lopriore E.
      • Slaghekke F.
      • Middeldorp J.M.
      • Klumper F.J.
      • Oepkes D.
      • Vandenbussche F.P.
      Residual anastomoses in twin-to-twin transfusion syndrome treated with selective fetoscopic laser surgery: localization, size, and consequences.
      The type and size of missed anastomoses correlate with the outcome.
      • Lewi L.
      • Jani J.
      • Cannie M.
      • et al.
      Intertwin anastomoses in monochorionic placentas after fetoscopic laser coagulation for twin-to-twin transfusion syndrome: is there more than meets the eye?.
      As such, missed large arteriovenous anastomoses may lead to recurrent TTTS or double demise, unless a compensating arterioarterial anastomosis is missed as well. On the other hand, missed small arteriovenous anastomoses can result in TAPS.
      • Lewi L.
      • Jani J.
      • Cannie M.
      • et al.
      Intertwin anastomoses in monochorionic placentas after fetoscopic laser coagulation for twin-to-twin transfusion syndrome: is there more than meets the eye?.
      The latter develops usually several weeks after the procedure with mostly a recipient that becomes anemic and the former donor becoming polycythemic. TAPS is associated with missed small-caliber anastomoses (<1 mm) (Figure 5) that, owing to the polyhydramnios and increased intrauterine pressure, may not be visible at the time of surgery. However, a chronic net transfusion via these hairlike anastomoses may lead to severe hemoglobin discordances several weeks later in ongoing twin pregnancies. TAPS is usually not associated with severe amniotic fluid discordance and is only picked up by serial measurement of the middle cerebral artery (MCA)-peak systolic velocities (PSV). Connecting the dots of coagulated anastomoses with laser may decrease the chance of missing these tiny anastomoses and thereby improve outcome. The benefit of drawing a line along the entire equator from one edge of the placenta to the other is currently the subject of a multicenter randomized trial
      • Slaghekke F.
      Fetoscopic laser coagulation of the entire vascular equator for the treatment of twin-to-twin transfusion syndrome: the “Solomon” study.
      (Figure 6).
      Figure thumbnail gr5
      FIGURE 5Monochorionic diamniotic placenta from patient who developed twin anemia polycythemia sequence 3 weeks after laser treatment
      Patient was delivered at 29 weeks because of nonreassuring heart rate tracing. Twin 1 (ex-donor) and twin 2 (ex-recipient) had hemoglobin of 19 and 8.8 g/dL, respectively. Placenta is shared equally. There is a tiny missed venoarterial anastomosis from twin 2 to 1 at edge of placenta.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Figure thumbnail gr6
      FIGURE 6Monochorionic diamniotic placenta after laser coagulation of placenta at 20 weeks where line was drawn with laser on placental surface
      Coagulation line is clearly visible connecting one edge of placenta with other (dotted line). Patient delivered 2 healthy newborns of 2310 g and 2100 g, respectively.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Fetal complications because of incomplete coagulation commonly occur. We therefore recommend placental injection of all placentas that underwent laser treatment, except those with single intrauterine demise and delayed delivery as the anastomoses can no longer be documented. Placental injection is also a means of quality control and may improve the surgical technique. As such, most missed anastomoses are located near the placental edge.
      • Lopriore E.
      • Slaghekke F.
      • Middeldorp J.M.
      • Klumper F.J.
      • Oepkes D.
      • Vandenbussche F.P.
      Residual anastomoses in twin-to-twin transfusion syndrome treated with selective fetoscopic laser surgery: localization, size, and consequences.
      Finally, placental examination provides a good learning experience for any fetal medicine specialist who seeks to embark on endoscopic laser surgery.

      TAPS

      In contrast to TTTS, which is essentially an amniotic fluid discordance, TAPS is characterized by a severe hemoglobin discordance caused by a chronic net transfusion over minuscule and usually unidirectional anastomoses. TAPS can be diagnosed antenatally based on discordant MCA-PSV measurements. One twin typically has an elevated MCA-PSV (>1.5 multiples of the median) and in the other twin the MCA-PSV is decreased (<1 multiples of the median).
      • Slaghekke F.
      • Kist W.J.
      • Oepkes D.
      • et al.
      Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome.
      The anemic twin often has decreased amniotic fluid whereas the recipient twin may have increased fluid, but the discordance is not as severe as is required for the diagnosis of TTTS.
      • Gucciardo L.
      • Lewi L.
      • Vaast P.
      • et al.
      Twin anemia polycythemia sequence from a prenatal perspective.
      TAPS can also be defined by postnatal criteria. Here, the hemoglobin discordance should be at least 8 g/dL. Also, to differentiate chronic TAPS from an acute intrapartum transfusion, there should be an increased reticulocyte count in the anemic twin and a decreased count in the polycythemic twin with a ratio of >1.7 or placental injection should demonstrate only tiny (<1 mm) anastomoses.
      • Slaghekke F.
      • Kist W.J.
      • Oepkes D.
      • et al.
      Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome.
      Spontaneous TAPS occurs in about 5% of previously uncomplicated monochorionic twin pregnancies,
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      whereas iatrogenic TAPS after incomplete laser treatment for TTTS occurs in up to 13% of ongoing twin pregnancies.
      • Robyr R.
      • Lewi L.
      • Salomon L.J.
      • et al.
      Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome.
      In contrast to TTTS that typically presents in the previable period between 16-26 weeks, spontaneous TAPS usually occurs >26 weeks and thus in the viable period.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      On the other hand, iatrogenic TAPS usually develops within 1-5 weeks after the procedure.
      • Robyr R.
      • Lewi L.
      • Salomon L.J.
      • et al.
      Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome.
      The placentas of spontaneous and iatrogenic TAPS show some striking similarities
      • Lewi L.
      • Jani J.
      • Cannie M.
      • et al.
      Intertwin anastomoses in monochorionic placentas after fetoscopic laser coagulation for twin-to-twin transfusion syndrome: is there more than meets the eye?.
      • Lopriore E.
      • Deprest J.
      • Slaghekke F.
      • et al.
      Placental characteristics in monochorionic twins with and without twin anemia-polycythemia sequence.
      (Figure 7). In contrast to TTTS, the anastomoses in TAPS are smaller and fewer in number, supporting the hypothesis that TAPS is a pure chronic net transfusion of red blood cells, whereas in TTTS with its larger anastomoses there is a more elaborate plasma exchange so endocrine factors may play a role as well. Similar to TTTS, an arterial anastomosis seems to protect against the development of TAPS. As such, an arterioarterial anastomosis is present in only 1 of 5 TAPS placentas in contrast to 4 of 5 placentas not complicated by TAPS. If present, the diameter of the arterioarterial anastomoses is also smaller in TAPS and always <1 mm, so it can inadequately compensate for any flow imbalance.
      • Lopriore E.
      • Deprest J.
      • Slaghekke F.
      • et al.
      Placental characteristics in monochorionic twins with and without twin anemia-polycythemia sequence.
      • de Villiers S.
      • Slaghekke F.
      • Middeldorp J.M.
      • et al.
      Arterio-arterial vascular anastomoses in monochorionic twin placentas with and without twin anemia-polycythemia sequence.
      Figure thumbnail gr7
      FIGURE 7Monochorionic diamniotic placenta complicated by spontaneous twin anemia polycythemia sequence delivered at 35 weeks
      Growth had been concordant throughout pregnancy. At birth, there was growth discordance of 30%. Twin 2 weighed 2445 g with hemoglobin of 22 g/dL requiring partial exchange transfusion. Twin 1 weighed 1720 g with hemoglobin of 12 g/dL. Placenta is equally shared. There was 1 tiny arterioarterial anastomosis (star), 4 tiny arteriovenous anastomoses from twin 1 to 2 (open circles), and 1 tiny oppositely directed venoarterial connection (dotted circle).
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      As compared to TTTS, spontaneous TAPS usually presents in the viable period, so its mortality and morbidity is much lower. TAPS is in fact the TTTS of the neonatologist. As prenatal medicine specialists, we stole this term to denote a condition that occurs in the previable period when no neonatologist is involved yet. In our series of 202 monochorionic pairs, only 1 intrauterine death was attributable to TAPS.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      Neonatal complications are mainly hematological and include the need for transfusion and partial exchange transfusion of the anemic and polycythemic twin,
      • Lopriore E.
      • Slaghekke F.
      • Oepkes D.
      • Middeldorp J.M.
      • Vandenbussche F.P.
      • Walther F.J.
      Clinical outcome in neonates with twin anemia-polycythemia sequence.
      respectively. Nevertheless, the need for a severe preterm birth to manage the problem may complicate the outcome. Also, rarely, antenatal cerebral lesions may occur due to severe anemia-polycythemia, such as cerebellar hemorrhage or cerebral infarction. Because iatrogenic TAPS is a common complication if both twins survive, a weekly to fortnightly measurement of the MCA-PSV is an essential part of the postlaser follow-up. Further, because in previously uncomplicated twins, TAPS may cause late intrauterine demise, we measure the MCA-PSV routinely every fortnight from 20 weeks until birth. Especially in pairs with worsening growth discordance >24 weeks, one should be suspicious of TAPS.
      • Lewi L.
      • Gucciardo L.
      • Huber A.
      • et al.
      Clinical outcome and placental characteristics of monochorionic diamniotic twin pairs with early- and late-onset discordant growth.
      The management will mainly depend on gestational age and accessibility of the equator. However, due to its rarity and the lack of comparative studies, there is no firm guidance on what is best. If TAPS is suspected, we always reevaluate the MCA-PSV in 2-3 days. If the discordance persists prior to 30 weeks or if there is hydrops in the anemic twin, then our next step would be a cordocentesis and intrauterine transfusion (IUT). A second IUT may be considered to prolong gestation. However, if there is rapid recurrence of the anemia after 2 IUTs and depending on the gestational age, the condition of the twins, and the accessibility of the equator, the options are an elective delivery, a selective reduction, or a (re)laser of the vascular anastomoses. In rapid recurring anemia, there is a significant risk of hyperviscosity-related complications in the receiving twin, so usually only up to 2 IUTs are attempted. A fetoscopic laser procedure for TAPS is more difficult than for TTTS, because of the lack of polyhydramnios, the minuscule anastomoses, and the more advanced gestational age. After 30 weeks and administration of steroids, an elective delivery seems a reasonable option.

      TRAP sequence

      In TRAP sequence, blood flows from an umbilical artery of the pump twin in a reversed direction into the umbilical artery of the perfused twin, via an arterioarterial anastomosis and usually returns via a venovenous anastomosis back to the pump twin. The perfused twin is thus a true parasite. The perfused twin's blood supply is by definition deoxygenated and results in variable degrees of deficient development of the head, heart, and upper limb structures. Usually, the perfused twin does not have any functional cardiac activity, hence also the name “acardiac twin.”
      Two criteria seem to be necessary for the development of a TRAP sequence. The first is the presence of an arterioarterial anastomosis and the second a discordant development
      • Van Allen M.I.
      • Smith D.W.
      • Shephard T.H.
      Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardiacus.
      or an intrauterine demise of one of the monochorionic twins,
      • Gembruch U.
      • Viski S.
      • Bagamery K.
      • Berg C.
      • Germer U.
      Twin reversed arterial perfusion sequence in twin-to-twin transfusion syndrome after the death of the donor co-twin in the second trimester.
      allowing for reversal of blood flow (Figure 8). In dichorionic twin pregnancies, intrauterine demise of 1 twin in the first trimester invariably leads to a “vanishing twin,” whereas in monochorionic twins, existing anastomoses may actually prevent vanishing and sustain further cell growth and some degree of differentiation of the demised twin. Whenever a single intrauterine demise is diagnosed in a monochorionic twin pregnancy in the first trimester, the possibility of TRAP sequence should be kept in mind, which can be easily diagnosed by demonstrating the reversed blood flow in the umbilical artery with color Doppler flow.
      Figure thumbnail gr8
      FIGURE 8Placenta of monochorionic monoamniotic triplet complicated by twin reversed arterial perfusion sequence and miscarriage at 15 weeks
      Cords were entangled. Placenta shows 1 arterioarterial anastomosis (solid star) from cord of smaller triplet 1 (open arrow) and venovenous anastomosis (open star) to larger triplet 2 (open arrow). Triplet 1 was therefore pump triplet, whereas triplet 2 was draining triplet.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      TRAP is a rare condition and complicates probably only about 1% of monochorionic twin pregnancies. The condition is associated with a high risk of perinatal death caused by a combination of high-output cardiac failure and polyhydramnios-related preterm birth.
      • Moore T.R.
      • Gale S.
      • Benirschke K.
      Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning.
      The outcome may be improved by an intervention to arrest the circulation of the acardiac twin. The type of technique will depend on the clinical presentation and may consist of a coagulation of the umbilical cord and/or placental anastomoses or of intrafetal laser or radiofrequency ablation (RFA).
      • Hecher K.
      • Lewi L.
      • Gratacos E.
      • Huber A.
      • Ville Y.
      • Deprest J.
      Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord.
      • Lee H.
      • Wagner A.J.
      • Sy E.
      • et al.
      Efficacy of radiofrequency ablation for twin-reversed arterial perfusion sequence.
      With the widespread introduction of the first-trimester scan, TRAP is increasingly being diagnosed in the first trimester. However, intrauterine intervention can only safely be performed >16 weeks, after fusion of amnion and chorion. We offer all our patients a prophylactic intervention at 16 weeks, because pump twin demise is difficult to predict in the early second trimester and it precludes the difficulty of achieving arrest of flow in the larger and often hydropic mass later on in pregnancy. However, in a series of 24 TRAP cases diagnosed in the first trimester, 1 of 3 had an intrauterine demise of the pump twin at the time of the planned intervention at 16-18 weeks.
      • Lewi L.
      • Valencia C.
      • Gonzalez E.
      • Deprest J.
      • Nicolaides K.H.
      The outcome of twin reversed arterial perfusion sequence diagnosed in the first trimester.
      Of those undergoing prophylactic surgery, 90% survived. Because of the high mortality of TRAP in the first trimester, small case series have been reported on the outcome of intrafetal coagulation in first trimester.
      • O'Donoghue K.
      • Barigye O.
      • Pasquini L.
      • Chappell L.
      • Wimalasundera R.C.
      • Fisk N.M.
      Interstitial laser therapy for fetal reduction in monochorionic multiple pregnancy: loss rate and association with aplasia cutis congenita.
      • Scheier M.
      • Molina F.S.
      Outcome of twin reversed arterial perfusion sequence following treatment with interstitial laser: a retrospective study.
      Although these show promising results, larger series are necessary to demonstrate that a first-trimester intervention is safe and will improve the survival rate in TRAP sequence.

      Monoamniotic twin pregnancies

      Monoamniotic twins not only share a single placenta but also the amniotic sac. Diagnosis is made reliably in the first trimester by the presence of a single amniotic sac surrounding the 2 twins and the lack of an intertwin septum. Transvaginal ultrasound scan can help to demonstrate the lack of intertwin septum. As both twins are in the same amniotic sac, cord entanglement is usually already demonstrable in the first trimester by the simultaneous recording of 2 different heart rates within the same pulsed-wave sampling gate. Contrary to previous belief, several recent case reports indicate that the number of yolk sacs does not accurately predict amnionicity. As such, a minority of monoamniotic twins has 2 yolk sacs, whereas a minority of diamniotic twins has only a single yolk sac.
      • Shen O.
      • Samueloff A.
      • Beller U.
      • Rabinowitz R.
      Number of yolk sacs does not predict amnionicity in early first-trimester monochorionic multiple gestations.
      • Murakoshi T.
      • Ishii K.
      • Matsushita M.
      • Shinno T.
      • Naruse H.
      • Torii Y.
      Monochorionic monoamniotic twin pregnancies with two yolk sacs may not be a rare finding: a report of two cases.
      Monoamniotic twins are rare and about 1 in 20 monochorionic twins are monoamniotic. They are thought to arise from a late cleavage of the inner cell mass. The cords typically insert close to one another on the chorionic plate with large-caliber anastomoses connecting the stem vessels of both twins (Figure 9). Nearly all monoamniotic placentas have an arterioarterial anastomosis as compared to 80% of monochorionic diamniotic placentas.
      • Umur A.
      • van Gemert M.J.
      • Nikkels P.G.
      Monoamniotic-versus diamniotic-monochorionic twin placentas: anastomoses and twin-twin transfusion syndrome.
      TRAP sequence is not uncommon and also all conjoined twins are by definition monoamniotic. Both are readily detectable in the first trimester, but prognosis is determined primarily by these complicating features rather than by the monoamnionicity itself. Nevertheless, even in the absence of TRAP and conjoined twinning, monoamniotic twins are at increased risk of adverse outcome as compared to their diamniotic counterparts. First, discordant structural anomalies are more common, affecting up to 20% of monoamniotic twin pregnancies
      • Baxi L.V.
      • Walsh C.A.
      Monoamniotic twins in contemporary practice: a single-center study of perinatal outcomes.
      as compared to 6% of diamniotic twin pregnancies.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      Late embryonic cleavage and imbalances across the large-caliber anastomoses possibly account for this increased prevalence. Second, monoamniotic twins are at increased risk of unexpected and mostly double intrauterine demise. In the largest series on monoamniotic twins, 15% and 4% of ongoing pregnancies were complicated by intrauterine demise >20 and >32 weeks, respectively.
      • Hack K.E.
      • Derks J.B.
      • Schaap A.H.
      • et al.
      Perinatal outcome of monoamniotic twin pregnancies.
      In comparison, in a large prospective series of monochorionic diamniotic twins, 6% and 1.2% were complicated by intrauterine demise >20 and >32 weeks, respectively. In monochorionic diamniotic twins, TTTS is the most important cause of death.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      In contrast, in monoamniotic twins, because of the nearly ever-present arterioarterial anastomoses, TTTS is a rarer occurrence. The main cause of death in a monoamniotic pair is probably an acute fetofetal hemorrhage across the large-caliber anastomoses that is triggered by cord compression.
      Figure thumbnail gr9
      FIGURE 9Monoamniotic placenta with short distance between 2 marginal cord insertions
      Delivery was elective at 32 weeks with birth of 2 healthy neonates of 1510 g and 1570 g, respectively. Placenta is unequally shared. There is 1 large arterioarterial anastomosis from twin 1 to 2 (star). There is no individual placental part for twin 1 that is entirely supplied through at least 8 arteriovenous anastomoses from twin 2.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Although death is usually unexpected, careful surveillance and planned preterm birth seem to improve survival rates to 80%.
      • Heyborne K.D.
      • Porreco R.P.
      • Garite T.J.
      • Phair K.
      • Abril D.
      Obstetrix/Pediatrix Research Study Group
      Improved perinatal survival of monoamniotic twins with intensive inpatient monitoring.
      If a severe anomaly is detected in 1 twin, selective feticide can be performed by ultrasound-guided bipolar cord coagulation and subsequent fetoscopic laser transection of the cord. Release of the entanglement is important to prevent demise of the healthy twin later on in pregnancy. Cord transection is technically challenging, therefore although the survival rates seem comparable to those of cord coagulation in diamniotic twins, the preterm premature rupture of membrane rates are somewhat higher and gestational age at birth lower in monoamniotic than in diamniotic twin pregnancies.
      • Valsky D.V.
      • Martinez-Serrano M.J.
      • Sanz M.
      • et al.
      Cord occlusion followed by laser cord transection in monochorionic monoamniotic discordant twins.
      There is no firm evidence to guide management, but as would most fetal medicine specialists, we would recommend inpatient monitoring from ≥28 weeks, and an elective preterm birth at 32-33 weeks after the administration of antenatal corticosteroids for lung maturation.
      • Desai N.
      • Lewis D.
      • Sunday S.
      • Rochelson B.
      Current antenatal management of monoamniotic twins: a survey of maternal-fetal medicine specialists.

      Single intrauterine death

      Unequal placental sharing, placental insufficiency, or hemodynamic imbalances such as in TTTS or TAPS may cause intrauterine death of 1 twin. Furthermore, because of the shared circulation single death may lead to double demise or antenatal brain damage, because of acute exsanguination of the surviving cotwin into its demised twin's circulation. A recent systematic review demonstrated that in monochorionic twins, single demise will result in a double death in about 15%, and neurodevelopmental impairment in another 25% due to acute perimortem exsanguination, in addition to a 68% risk of preterm birth.
      • Hillman S.C.
      • Morris R.K.
      • Kilby M.D.
      Co-twin prognosis after single fetal death: a systematic review and meta-analysis.
      Antenatal brain damage is often detectable on prenatal ultrasound examination, but does not become apparent until several weeks after the insult. Magnetic resonance imaging may detect brain lesions earlier and with better definition.
      • Levine D.
      • Barnes P.D.
      • Madsen J.R.
      • Abbott J.
      • Mehta T.
      • Edelman R.R.
      Central nervous system abnormalities assessed with prenatal magnetic resonance imaging.
      • Righini A.
      • Kustermann A.
      • Parazzini C.
      • Fogliani R.
      • Ceriani F.
      • Triulzi F.
      Diffusion-weighted magnetic resonance imaging of acute hypoxic-ischemic cerebral lesions in the survivor of a monochorionic twin pregnancy: case report.
      Initially, thromboembolic phenomena with passage of thromboplastin from the demised to the surviving twin were thought to be responsible for these lesions.
      • Benirschke K.
      Intrauterine death of a twin: mechanisms, implications for surviving twin, and placental pathology.
      A variety of studies have failed to provide such evidence. On the other hand, perimortem exsanguination is well documented.
      • Fusi L.
      • McParland P.
      • Fisk N.
      • Nicolini U.
      • Wiggleworth J.
      Acute twin-twin transfusion: a possible mechanism for brain-damaged survivors after intrauterine death of a monochorionic twin.
      Fetal blood sampling within 24 hours of the demise has consistently revealed a decreased hematocrit in surviving twins whereas coagulation profiles were normal.
      • Okamura K.
      • Murotsuki J.
      • Tanigawara S.
      • Uehara S.
      • Yajima A.
      Funipuncture for evaluation of hematologic and coagulation indices in the surviving twin following co-twin's death.
      The outcome of the surviving cotwin may depend on the type and direction of vascular anastomoses and the fetoplacental mass of the demised twin. The presence of arterioarterial anastomoses may be associated with higher rates of death and neurologic damage.
      • Bajoria R.
      • Wee L.Y.
      • Anwar S.
      • Ward S.
      Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta.
      However, significant anemia and cotwin death may occur, even in the absence of arterioarterial anastomoses as the survivor may also exsanguinate across artery-to-vein or vein-to-vein anastomoses.
      • Tanawattanacharoen S.
      • Taylor M.J.O.
      • Letsky E.A.
      • Cox P.M.
      • Cowan F.M.
      • Fisk N.M.
      Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.
      Treatment of TTTS by laser coagulation more frequently results in single demise as compared to amniodrainage, but it consistently less often leads to double demise.
      • Quintero R.A.
      • Dickinson J.E.
      • Morales W.J.
      • et al.
      Stage-based treatment of twin-twin transfusion syndrome.
      Also, anemia in the survivor is rare in the event of single demise after laser,
      • Senat M.V.
      • Loizeau S.
      • Couderc S.
      • Bernard J.P.
      • Ville Y.
      The value of middle cerebral artery peak systolic velocity in the diagnosis of fetal anemia after intrauterine death of one monochorionic twin.
      and the neurological morbidity appears less than after amniodrainage.
      • Lopriore E.
      • Nagel H.T.
      • Vandenbussche F.P.
      • Walther F.J.
      Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome.
      • Quarello E.
      • Stirnemann J.
      • Nassar M.
      • et al.
      Outcome of anemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome.
      These findings provide further evidence that the anastomoses are responsible for most of the adverse outcomes associated with single demise in monochorionic twins.
      From ≥10-14 weeks, single demise occurs in about 4% of monochorionic twin pregnancies, whereas double demise occurs in at least 6%.
      • Sebire N.J.
      • Snijders R.J.
      • Hughes K.
      • Sepulveda W.
      • Nicolaides K.H.
      The hidden mortality of monochorionic twin pregnancies.
      Perimortem exsanguination of the survivor occurs during or soon after the demise of its cotwin. Therefore, a preemptive preterm delivery seems inappropriate, as it will only worsen the outcome of the surviving twin by adding the complications of preterm birth. MCA-PSV measurements are an effective means to predict fetal anemia.
      • Senat M.V.
      • Loizeau S.
      • Couderc S.
      • Bernard J.P.
      • Ville Y.
      The value of middle cerebral artery peak systolic velocity in the diagnosis of fetal anemia after intrauterine death of one monochorionic twin.
      If fetal anemia is excluded, then a major exsanguination is unlikely and the prognosis is most likely favorable.
      • Tanawattanacharoen S.
      • Taylor M.J.O.
      • Letsky E.A.
      • Cox P.M.
      • Cowan F.M.
      • Fisk N.M.
      Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.
      • Senat M.V.
      • Loizeau S.
      • Couderc S.
      • Bernard J.P.
      • Ville Y.
      The value of middle cerebral artery peak systolic velocity in the diagnosis of fetal anemia after intrauterine death of one monochorionic twin.
      However, if anemia is present, there is currently insufficient evidence that a rescue IUT improves outcome. Whereas it may prevent cotwin death, it may come too late to prevent brain injury
      • Quarello E.
      • Stirnemann J.
      • Nassar M.
      • et al.
      Outcome of anemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome.
      and careful follow-up of these fetuses with detailed brain scans and prenatal magnetic resonance imaging is indicated. Placental injection may still reveal useful information provided the delivery occurred within 2 weeks after the event. If only a few small unidirectional anastomoses are detected, then the outcome for the surviving twin is likely to be favorable, since this precludes a major exsanguination. On the other hand, the presence of large bidirectional anastomoses explains the occurrence of brain damage or later demise of the surviving cotwin (Figure 10).
      Figure thumbnail gr10
      FIGURE 10Monochorionic diamniotic placenta at 28 weeks from pregnancy that was complicated by early-onset type III discordant growth
      There was intrauterine demise of smaller twin at 25 weeks. Survivor was anemic (hemoglobin of 7.6 g/dL) and was given intrauterine transfusion. Three weeks later, surviving twin was noted to have infarction of entire brain, except for cerebellum and brain stem. Patient went into preterm labor and twin 2 died intrapartum. Twin 1 was polycythemic. Placenta is unequally shared. Smaller twin 1 has velamentous cord insertion and no individual placental part. There were 2 large arterioarterial (solid stars), 1 venovenous (open star), several arteriovenous (open circles), and several venoarterial (dotted circles) anastomoses. Large artery-to-artery anastomoses explain anemia in larger twin, because of exsanguination into body of demised twin.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.

      Discordant growth

      Discordant growth (discordance ≥25%) without TTTS is not more common in monochorionic than in dichorionic twins and occurs in about 10-15%.
      • Sebire N.J.
      • Snijders R.J.
      • Hughes K.
      • Sepulveda W.
      • Nicolaides K.H.
      The hidden mortality of monochorionic twin pregnancies.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      • Acosta-Rojas R.
      • Becker J.
      • Munoz-Abellana B.
      • Ruiz C.
      • Carreras E.
      • Gratacos E.
      Catalunya and Balears Monochorionic Network
      Twin chorionicity and the risk of adverse perinatal outcome.
      The degree of discordance, expressed in percentage, is determined as (A – B) * 100/A, where A is the estimated weight of the heavier and B is the weight of the lighter twin. Monochorionic twins are by definition monozygotic and thus have the same genetic growth potential. Growth in monochorionic twins is determined by the division of the single placenta between the twins
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.
      • Fick A.L.
      • Feldstein V.A.
      • Norton M.E.
      • Wassel Fyr C.
      • Caughey A.B.
      • Machin G.A.
      Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins.
      as well as by the vascular anastomoses.
      • Denbow M.L.
      • Cox P.
      • Taylor M.
      • Hammal D.M.
      • Fisk N.M.
      Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome.
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.
      These 2 factors determine the venous return upon which the fetus depends for its oxygen and nutritional supply.
      Unequal placental sharing appears to be the most important determinant of discordant growth in monochorionic twins.
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.
      • Fick A.L.
      • Feldstein V.A.
      • Norton M.E.
      • Wassel Fyr C.
      • Caughey A.B.
      • Machin G.A.
      Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins.
      Although it remains impossible to assess the functional placental territory for each individual twin antenatally, the umbilical cord insertion sites may provide a good estimate. As such, the combination of a velamentous and central cord insertion is more common in monochorionic twins. Additionally, nearly a quarter of these twins have a birthweight discordance of ≥20%.
      • Fick A.L.
      • Feldstein V.A.
      • Norton M.E.
      • Wassel Fyr C.
      • Caughey A.B.
      • Machin G.A.
      Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins.
      The site of cord insertion can be reliably detected on a prenatal ultrasound examination in the second
      • Sepulveda W.
      • Rojas I.
      • Robert J.A.
      • Schnapp C.
      • Alcalde J.L.
      Prenatal detection of velamentous insertion of the umbilical cord: a prospective color Doppler ultrasound study.
      and even in the first
      • Sepulveda W.
      Velamentous insertion of the umbilical cord: a first-trimester sonographic screening study.
      trimester. Although we cannot assess the degree of sharing with prenatal ultrasound, we may well use a discordant cord insertion as a substitute for unequal placental sharing and thus identify a group of monochorionic twins at high risk for discordant growth.
      Vascular anastomoses also influence growth in monochorionic twins. As such, an unbalanced net arteriovenous transfusion–as in TTTS and TAPS–may restrict and improve the growth of the donor and recipient twin, respectively.
      • Acosta-Rojas R.
      • Becker J.
      • Munoz-Abellana B.
      • Ruiz C.
      • Carreras E.
      • Gratacos E.
      Catalunya and Balears Monochorionic Network
      Twin chorionicity and the risk of adverse perinatal outcome.
      • Lopriore E.
      • Deprest J.
      • Slaghekke F.
      • et al.
      Placental characteristics in monochorionic twins with and without twin anemia-polycythemia sequence.
      Successful laser coagulation has been shown to reduce any existing growth discordance, probably by improving the growth of the donor
      • Chmait R.H.
      • Korst L.M.
      • Bornick P.W.
      • Allen M.H.
      • Quintero R.A.
      Fetal growth after laser therapy for twin-twin transfusion syndrome.
      and/or restricting the recipient's growth.
      • Moreira de Sa R.A.
      • Salomon L.J.
      • Takahashi Y.
      • Yamamoto M.
      • Ville Y.
      Analysis of fetal growth after laser therapy in twin-to-twin transfusion syndrome.
      • Maschke C.
      • Franz A.R.
      • Ellenrieder B.
      • Hecher K.
      • Diemert A.
      • Bartmann P.
      Growth after intrauterine laser coagulation for twin-twin transfusion syndrome.
      On the other hand, growth discordance may reverse after laser, in cases with unequal placental sharing where the recipient has the smaller placental share (Figure 11).
      Figure thumbnail gr11
      FIGURE 11Placenta of monochorionic diamniotic twin pregnancy after successful laser treatment for twin-to-twin transfusion syndrome
      At 23 weeks before laser surgery, recipient (twin 2) was larger with estimated fetal weight of 578 g vs donor 442 g. At 31 weeks at time of birth, recipient was much smaller with birthweight of 810 g as compared to donor 1560 g. Recipient has smaller part of placenta, reflecting lower birthweight (dotted line). There were no missed anastomoses.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Unequally shared placentas have larger arterioarterial anastomoses, a larger net flow over arteriovenous anastomoses, and a larger diameter of all anastomoses taken together than equally shared placentas, which may reduce the impact of their placental territory discordance and result in reduced birthweight discordance. This elaborate intertwin blood exchange fulfills a beneficial and often lifesaving role by increasing the availability of oxygen and nutrients to the twin on the smaller placental share.
      • Lewi L.
      • Cannie M.
      • Blickstein I.
      • et al.
      Placental sharing, birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas.
      As a consequence, inappropriate use of laser coagulation of the vascular anastomoses as a treatment for severe discordant growth will cause the demise of the twin with the smaller share, where both twins may have survived, had they remained unseparated. On the other hand, a tightly linked interfetal circulation, and especially the large arterioarterial anastomosis, may result in sudden and unpredictable intertwin transfusion imbalances and intrauterine demise, of which in about 50% are a demise of both twins.
      • Gratacós E.
      • Antolin E.
      • Lewi L.
      • et al.
      Monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic flow (type III): feasibility and perinatal outcome of fetoscopic placental laser coagulation.
      Monochorionic pairs with discordant growth from early on in pregnancy (≤20 weeks) have different placental characteristics and different clinical outcomes than those where discordant growth arises later on. Twin pregnancies with early-onset discordant growth typically have an unequally shared placenta with large anastomoses. Intrauterine demise occurs in about 20% of cases and most have an abnormal umbilical artery Doppler evaluation from ≥16 weeks (Figure 12). On the other hand, pregnancies with progressively increasing growth discordance >26 weeks have more equally shared placentas with smaller anastomoses. Doppler examination in the umbilical artery of the smaller twin is always normal and the survival rate is nearly 100%. Nevertheless, about 1 in 3 pregnancies with late-onset discordant growth have severe hemoglobin differences at the time of birth and these placentas typically have few small and mostly unidirectional arteriovenous anastomoses as seen in TAPS placentas. Late-onset discordant growth in a monochorionic twin pair should therefore raise the suspicion of TAPS and is an indication for MCA-PSV measurements.
      • Lewi L.
      • Gucciardo L.
      • Huber A.
      • et al.
      Clinical outcome and placental characteristics of monochorionic diamniotic twin pairs with early- and late-onset discordant growth.
      Figure thumbnail gr12
      FIGURE 12Placenta of monochorionic diamniotic twin pregnancy with early-onset type III discordant growth (36%)
      Birth was by emergency caesarean section because of abnormal heart rate tracing in smaller twin. Birthweights were 1075 g (twin 1) and 670 g (twin 2). Smaller twin was diagnosed with coarctation, which was treated by stent placement on day 26 and coarctectomy at 9 months of age. Larger twin had peripheral pulmonary artery stenosis requiring no treatment. Placenta is unequally shared. There is little individual territory for smaller twin (dotted line). There is large arterioarterial (star) and several arteriovenous (open circles) and venoarterial (dotted circles) anastomoses.
      Lewi. Vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol 2013.
      Next to a classification based on gestational age at first presentation, growth-discordant monochorionic pairs can also be classified according to the Doppler characteristics of the umbilical artery of the smaller twin.
      • Gratacós E.
      • Lewi L.
      • Munoz B.
      • et al.
      A classification system for selective intrauterine growth restriction in monochorionic pregnancies according to umbilical artery Doppler flow in the smaller twin.
      If a large arterioarterial anastomosis is present, as in cases with early-onset discordant growth, then this may result in a cyclical variation in the diastolic flow component and thus in an intermittent absent or reversed end-diastolic flow pattern in the umbilical artery of the smaller twin. The smaller twin of a growth-discordant monochorionic pair may thus have a normal flow pattern (type I), a persistent absent or reversed end-diastolic flow (type II), or an intermittent absent or reversed end-diastolic flow (type III). Each of these types has distinct placental features and different clinical outcomes. Large arterioarterial anastomoses (>2 mm) are present in 70%, 18%, and 98% of type I, type II, and type III, respectively. Pregnancies with normal umbilical artery Doppler measurements in the smaller twin (type I) have the most favorable outcome with a low risk of deterioration or unexpected demise and a survival rate of nearly 100%. On the other hand, a persistent absent end-diastolic flow (type II) carries the worst prognosis as 90% eventually show signs of deterioration and imminent death and survival rates are only 60%.
      • Ishii K.
      • Murakoshi T.
      • Takahashi Y.
      • et al.
      Perinatal outcome of monochorionic twins with selective intrauterine growth restriction and different types of umbilical artery Doppler under expectant management.
      Pregnancies with an intermittent absent end-diastolic flow pattern (type III) have an intermediate prognosis with an 85% survival, but are the most unpredictable. Because of the large arterioarterial anastomoses, unexpected death of the smaller twin without any signs of deterioration occurs in about 15% of pregnancies. In about half of these cases, there is also a cotwin demise of the larger twin. In type III, especially the larger twin seems to be at increased risk of antenatally acquired brain injury. Probably because of the large arterioarterial anastomosis, short episodes of bradycardia and hypotension in the smaller twin may lead to large volume shifts from the larger to the smaller twin, increasing the risk of ischemic brain lesions.
      Clearly, the natural history and outcome of discordant growth is much better than that of untreated TTTS. Outcome will be primarily determined by the onset and severity of the discordance, the degree of growth restriction, by the interval growth, and by the amniotic fluid of the smaller twin. As such, a discordancy of >40% that is present from 16 weeks with a smaller twin that is well below the 5th centile and that shows little growth and oligohydramnios (<2 cm deepest pocket) at 19 weeks is likely to have a poor outcome. Nevertheless, prospective series of unselected monochorionic pairs are needed to document the pregnancy and especially the long-term neurodevelopmental outcome according to the different Doppler patterns and to refine the current classification system, as better criteria are necessary to distinguish the discordant growth cases with favorable outcome from those with a high risk of death and handicap.
      The optimal management of discordant growth in monochorionic twin pairs is not well established. In our institutions, we follow up pregnancies with early-onset discordant growth and an abnormal umbilical artery Doppler evaluation (type II and III) on a weekly basis. In the previable period, we may offer a selective reduction by umbilical cord coagulation to pregnancies with signs of imminent fetal death of the smaller twin, such as growth stop and anuria with anhydramnios.
      • Ishii K.
      • Murakoshi T.
      • Hayashi S.
      • et al.
      Ultrasound predictors of mortality in monochorionic twins with selective intrauterine growth restriction.
      From ≥28 weeks, these patients are usually hospitalized for inpatient monitoring, and are candidates for elective preterm birth at 32-33 weeks after the administration of antenatal corticosteroids for lung maturation. Pairs with late-onset discordant growth and a normal umbilical artery Doppler evaluation in the smaller twin are also monitored on a weekly basis with measurement of the MCA-PSV to exclude evolution of TAPS and are usually delivered around 34-35 weeks.
      We do not routinely offer laser coagulation of the vascular anastomoses as a treatment for discordant growth with an abnormal umbilical artery Doppler evaluation, because most do well without treatment. Also, due to unequal placental sharing, demise of the smaller twin occurs in 50-70% of cases. As such, laser improves neither the survival rates, nor the neurologic outcome.
      • Gratacós E.
      • Antolin E.
      • Lewi L.
      • et al.
      Monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic flow (type III): feasibility and perinatal outcome of fetoscopic placental laser coagulation.
      • Quintero R.A.
      • Bornick P.W.
      • Morales W.J.
      • Allen M.H.
      Selective photocoagulation of communicating vessels in the treatment of monochorionic twins with selective growth retardation.
      Furthermore, the procedure is technically more challenging due to the absence of polyhydramnios and entry is always in the sac of the appropriately grown twin with the best chances of survival. Also, in type III cases, the procedure will be hampered by the multiple and large anastomoses.

      Discordant anomalies

      Major congenital anomalies are more common in monochorionic twin pregnancies and occur in about 6% of pairs.
      • Lewi L.
      • Jani J.
      • Blickstein I.
      • et al.
      The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
      • Sperling L.
      • Kiil C.
      • Larsen L.U.
      • et al.
      Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins.
      Concordance (both twins similarly affected) for a structural anomaly is rare (<20%). Several hypotheses exist to explain this increased incidence. Possibly the zygotic splitting itself is teratogenic, resulting in abnormalities, such as midline defects.
      • Machin G.A.
      Some causes of genotypic and phenotypic discordance in monozygotic twin pairs.
      Furthermore, in monochorionic twin gestations, transfusion imbalances through the anastomoses during embryogenesis or during later fetal life may account for at least part of the cardiac or brain anomalies observed in these pregnancies. As such, the prevalence of congenital cardiac anomalies in monochorionic twins has been reported to be 2.3% in those without TTTS and 7% in those with TTTS, compared to 0.6% in the general population. Pulmonary valve stenosis in recipients accounted for all the additional congenital heart defects detected in TTTS cases, suggesting a causative role for the hemodynamic imbalance of TTTS in its development.
      • Karatza A.A.
      • Wolfenden J.L.
      • Taylor M.J.
      • Wee L.
      • Fisk N.M.
      • Gardiner H.M.
      Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: prospective case-control study of 136 monochorionic twin pregnancies.
      Furthermore, severe ischemic brain lesions because of exsanguination of the surviving twin into the fetal-placental unit of the demised twin are a well-known phenomenon in monochorionic pairs.
      The vascular anastomoses are not only implied in the etiology of major congenital anomalies in monochorionic gestations, they also influence their management. Because of the anastomoses, the conventional technique of potassium chloride injection as a means of selective feticide cannot be used. Double intrauterine demise may occur because of transfusion of the potassium chloride to the nonaffected twin or because of acute exsanguination of the healthy twin in the fetoplacental unit of the dead twin.
      As such, minimal invasive techniques have been proposed to produce complete circulatory confinement of the affected twin. At present, ultrasound-guided bipolar cord coagulation and intrafetal RFA are the preferred approaches. RFA is especially indicated in cases with oligohydramnios or anhydramnios, with a short umbilical cord in the target twin, and at an earlier gestational age or smaller fetal tissue volume. Ideally, fetal therapy centers have access to both cord and intrafetal coagulation techniques, so that the choice of technique can be tailored to the specific demands of each case. Fetal loss rates are higher as compared to selective feticide by potassium chloride in multichorionic pregnancies. The overall survival rate is about 70-80% with normal developmental outcome in >90% of surviving infants. About half of the losses are attributable to intrauterine demise of the healthy cotwin usually within the first 2 postoperative weeks and about half to postnatal losses due to very preterm birth.
      • Lewi L.
      • Gratacos E.
      • Van Schoubroeck D.
      • et al.
      Pregnancy and infant outcome of 80 consecutive cord coagulations in monochorionic multiple pregnancies: a prospective follow-up study.
      • Lanna M.M.
      • Rustico M.A.
      • Dell'avanzo M.
      • et al.
      Bipolar cord coagulation for selective feticide in complicated monochorionic twin pregnancies: 118 consecutive cases at a single center.
      • Bebbington M.W.
      • Danzer E.
      • Moldenhauer J.
      • Khalek N.
      • Johnson M.P.
      Radio frequency ablation vs bipolar umbilical cord coagulation in the management of complex monochorionic pregnancies.
      Neurodevelopmental impairment is largely due to an early gestation at birth.

      Conclusion

      In summary, the vascular anastomoses are responsible for some unique complications in monochorionic twin pregnancies. They also account for the increased mortality and morbidity as compared to dichorionic twins, which have separate circulations. As long as the twins are connected to this shared circulation, intertwin transfusion imbalances may occur and each twin is exposed to the hormonal environment of its cotwin. The shared circulation is also responsible for the fact that the well-being of each twin critically depends on the well-being of the other one. Placental injection studies are vital for our understanding of these complications and also for the choice of the best management.

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