**3. Complications**

The MC pregnancies have several unique and serious complications that contribute to a perinatal mortality rate of 11% [17, 18]. The pathophysiology of most of these complications is related to the placental angio-architecture [19]. Placental anastomoses are described since the 1600s. The term "third circulation" that represents an "area of transfusion" and the potential harmful effect of vascular connections between the fetuses was first described by Schatz in 1896 [20]. In 1965, Naeye [21] identified the effect of chronic nutritional deprivation on the size of organs in one twin while appreciating that transfusion to the other increased the hemoglobin concentration and hematocrit, with subsequent cardiomyopathy and hypertension. Since then, several authors have proposed diagnosis criteria and different kinds of treatments of the MC pregnancy problems. In this session, the main complications of the MC gestations will be discussed.

## **3.1. Twin to twin transfusion syndrome**

delivery [2–5] in the maternal side and higher risk of fetal anomalies, fetal demise, neonatal

It is known that monochorionic (MC) pregnancies have higher rates of fetal morbidity and mortality when compared to dichorionic (DC) ones [1, 8, 9]. Besides that, the MC pregnancies have specific complications such as the twin to twin transfusion syndrome (TTTS), the selective fetal growth restriction (sFGR), the twin anemia polycythemia sequence (TAPS), and the twin reversed arterial perfusion sequence (TRAPS). Most of these complications can be

In the last years, the rate of multiple pregnancies has raised all over the globe. In the USA, it rose from 18.9in 1980 to 33.4 twins per 1000 births in 2016. The twin birth rates were higher in black women, followed by non-Hispanic white women. The triplet and high-order multiple birth rate has decreased about 48% in the last 8 years, from 193.5 in 1998 to 101.4 twins per 100.000 births in 2016 [7]. This decrease in high-order multiple pregnancies illustrates the reproductive medicine societies' strategies for reducing the risk of high-order pregnancies,

In England, there is also an increase in multiple births. From 1998 to 2016, the multiple maternity rate rose from 14.4 to 15.9 twins per 1000 births. Since 1993, women aged 45 and over have consistently recorded the highest multiple maternity rate. These changes in the multiple pregnancy rates are due to the increase in ART. It is estimated that in vitro fertilization (IVF) conceptions are 11 times more likely to result in a multiple birth than natural conceptions. In 2014, 16% of IVF pregnancies resulted in multiple birth, with nearly 19,000 IVF babies born in the UK in 2014 [13]. This trend was largely attributed to an elevated amount of dizygotic pregnancies, without significant variations in monozygotic births over the past few decades. The dizygotic twinning rate is affected by many factors such as race, previous multiple pregnancy, maternal age and parity, lifestyle, season, use of fertility drugs and treatments, genetics, and others [14–16]. The high number of multiple births impacts directly in rate of preterm birth and low birthweight. Data from 2016 show that among twin pregnancies, 59.9% are born before complete 37 weeks of gestation, while in singletons, only 8% are preterm births. In singleton births, 6.4% were born with weight less than 2500 g. This percentage is 55.4 in twins and more than

The MC pregnancies have several unique and serious complications that contribute to a perinatal mortality rate of 11% [17, 18]. The pathophysiology of most of these complications is related to the placental angio-architecture [19]. Placental anastomoses are described since the 1600s.

death [6], and preterm birth in the fetal side [7].

126 Multiple Pregnancy - New Challenges

**2. Importance of multiple pregnancy**

95% in triplets [7].

**3. Complications**

managed and treated in order to decrease the fetal morbimortality.

like single-embryo transfer and multifetal pregnancy reduction [10–12].

One of the first suggestions of this disease in history lies in a Dutch painting from 1617 named the Early-Deceased Children of Jacob de Graeff and Aeltge Boelens that illustrates two children. One of them is pale and the other plethoric (**Figure 1**). Twin to twin transfusion syndrome is one of the main complications that occurs in about 10–15% of the MC pregnancies with an overall incidence of 3 in 10,000 pregnancies [22, 23].

If left untreated, TTTS mortality rates are about 70–100%. Perinatal mortality is the result of either miscarriage or very preterm delivery as a consequence of severe polyhydramnios and uterine distention or fetal demise due to severe cardiovascular disturbances [24, 25].

**Figure 1.** The Dutch painting the Early-Deceased Children of Jacob de Graeff and Aeltge Boelens shows two male twins: one pale and the other plethoric.

#### *3.1.1. Pathophysiology*

The pathophysiology underlies in the placental angio-architecture which is characterized by individual placental territory size, cord insertion location, and the quantity, size, and direction of intertwin anastomoses which are the most important factors in the pathogenesis because when unbalanced, they may cause hemodynamic changes that end in TTTS [26].

first trimester, diagnosis is difficult, since the amniotic fluid is usually normal in both fetuses. Some sonographic markers such as discordance in nuchal translucency thickness (NT) and abnormalities in ductus venosus (DV) may be early signs of TTTS, but they have a low predictive value [29–31]. The sonographic manifestations usually may be noted as early as 16 weeks of gestation, but they can appear in the third trimester as well. TTTS manifestations are rare

Complications in Monochorionic Pregnancies http://dx.doi.org/10.5772/intechopen.83390 129

In the second trimester, the oligohydramnios in the donor twin, as well as the polyhydramnios in the recipient twin, can easily be noted by ultrasound examination. The donor becomes hypovolemic; therefore, renal perfusion decreases. This hypoperfusion activates the reninangiotensin system (RAS), producing vasoconstriction, oliguria, and oligohydramnios. As the disease progresses, the fetus becomes anuric and gets "stuck" against the uterine walls (**Figure 3**). The circulation becomes hyperdynamic with an increased vascular resistance in the fetus and in the placenta, leading to fetal growth restriction (FGR), cerebral redistribution, and abnormal arterial Doppler assessment. The recipient twin becomes hypervolemic and, by myocardial stretching, releases atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are also biomarkers associated with heart failure. Elevated levels of these biomarkers and troponin are found in the amniotic fluid of the recipient, suggesting the presence of myocardial damage [26, 32, 33]. Despite the hypervolemia, vascular resistance in the recipient twin is increased. This hypertension is attributed to vasoactive mediators such as endothelin and also a paradoxically high level of renin. The source of endothelin and renin is probably partly from the placenta and partly from the donor via the vascular communications [34, 35]. These changes in fetal hemodynamics may cause a progressive cardiomyopathy that increases the heart size, reduces the myocardial compliance, and causes atrioventricular valvar regurgitation and abnormal venous Doppler findings. Several studies show that in early Quintero stages or even before the diagnostic of TTTS, the cardiac function in the recipient twin may be impaired [36–38]. A recent study noted that in the recipient twin, left ventricular filling pressures are elevated and systolic function is decreased before abnormalities in the

**Figure 3.** Two fetal abdomens. The smaller one (short arrow) is stuck in the anterior uterine wall and has no amniotic fluid. The bigger fetus (long arrow) has polyhydramnios. Adapted from: https://radiologykey.com/complications-of-

after 28 weeks of gestation.

multiple-gestations/.

All MC placentas have intertwin anastomoses that are formed in the first trimester. They are important because they allow transfer of volume, red blood cells, vasoactive substances, and hormones. There are three type of intertwin anastomoses, and their flow may be unidirectional or bidirectional. Arteriovenous (AV) anastomoses are unidirectional but they exist in both directions (from donor to recipient or from recipient to donor). AV anastomoses end in a shared cotyledon where the arterial villous circulation of one twin links to the venous villous return of the other at the level of the intervillous space. Artery-to-artery (AA) and vein-tovein (VV) are more superficial and bidirectional anastomoses (**Figure 2**). The flow direction depends on the types of connection, vessel calibers, and the pulse pressure. TTTS results from an unbalanced chronic perfusion from donor to recipient twin across placental anastomoses. This blood transfer is more likely in those placentas with more AV anastomoses and a lack of superficial balancing AA or VV anastomoses or when these bidirectional anastomoses are unusually small [26, 28].

#### *3.1.2. Clinical manifestations of TTTS*

The principal clinical feature in TTTS is hypervolemia in the recipient and hypovolemia in the donor twin that may progress to cardiovascular impairment, hydrops, and fetal death. In the

**Figure 2.** Monochorionic placenta of not complicated twin pregnancy. The blue, white, and yellow arrows represent AA, VV, and AV anastomoses, respectively. Adapted from twin research and human genetics, Zhao et al. [27].

first trimester, diagnosis is difficult, since the amniotic fluid is usually normal in both fetuses. Some sonographic markers such as discordance in nuchal translucency thickness (NT) and abnormalities in ductus venosus (DV) may be early signs of TTTS, but they have a low predictive value [29–31]. The sonographic manifestations usually may be noted as early as 16 weeks of gestation, but they can appear in the third trimester as well. TTTS manifestations are rare after 28 weeks of gestation.

*3.1.1. Pathophysiology*

128 Multiple Pregnancy - New Challenges

unusually small [26, 28].

*3.1.2. Clinical manifestations of TTTS*

The pathophysiology underlies in the placental angio-architecture which is characterized by individual placental territory size, cord insertion location, and the quantity, size, and direction of intertwin anastomoses which are the most important factors in the pathogenesis because

All MC placentas have intertwin anastomoses that are formed in the first trimester. They are important because they allow transfer of volume, red blood cells, vasoactive substances, and hormones. There are three type of intertwin anastomoses, and their flow may be unidirectional or bidirectional. Arteriovenous (AV) anastomoses are unidirectional but they exist in both directions (from donor to recipient or from recipient to donor). AV anastomoses end in a shared cotyledon where the arterial villous circulation of one twin links to the venous villous return of the other at the level of the intervillous space. Artery-to-artery (AA) and vein-tovein (VV) are more superficial and bidirectional anastomoses (**Figure 2**). The flow direction depends on the types of connection, vessel calibers, and the pulse pressure. TTTS results from an unbalanced chronic perfusion from donor to recipient twin across placental anastomoses. This blood transfer is more likely in those placentas with more AV anastomoses and a lack of superficial balancing AA or VV anastomoses or when these bidirectional anastomoses are

The principal clinical feature in TTTS is hypervolemia in the recipient and hypovolemia in the donor twin that may progress to cardiovascular impairment, hydrops, and fetal death. In the

**Figure 2.** Monochorionic placenta of not complicated twin pregnancy. The blue, white, and yellow arrows represent AA,

VV, and AV anastomoses, respectively. Adapted from twin research and human genetics, Zhao et al. [27].

when unbalanced, they may cause hemodynamic changes that end in TTTS [26].

In the second trimester, the oligohydramnios in the donor twin, as well as the polyhydramnios in the recipient twin, can easily be noted by ultrasound examination. The donor becomes hypovolemic; therefore, renal perfusion decreases. This hypoperfusion activates the reninangiotensin system (RAS), producing vasoconstriction, oliguria, and oligohydramnios. As the disease progresses, the fetus becomes anuric and gets "stuck" against the uterine walls (**Figure 3**). The circulation becomes hyperdynamic with an increased vascular resistance in the fetus and in the placenta, leading to fetal growth restriction (FGR), cerebral redistribution, and abnormal arterial Doppler assessment. The recipient twin becomes hypervolemic and, by myocardial stretching, releases atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are also biomarkers associated with heart failure. Elevated levels of these biomarkers and troponin are found in the amniotic fluid of the recipient, suggesting the presence of myocardial damage [26, 32, 33]. Despite the hypervolemia, vascular resistance in the recipient twin is increased. This hypertension is attributed to vasoactive mediators such as endothelin and also a paradoxically high level of renin. The source of endothelin and renin is probably partly from the placenta and partly from the donor via the vascular communications [34, 35]. These changes in fetal hemodynamics may cause a progressive cardiomyopathy that increases the heart size, reduces the myocardial compliance, and causes atrioventricular valvar regurgitation and abnormal venous Doppler findings. Several studies show that in early Quintero stages or even before the diagnostic of TTTS, the cardiac function in the recipient twin may be impaired [36–38]. A recent study noted that in the recipient twin, left ventricular filling pressures are elevated and systolic function is decreased before abnormalities in the

**Figure 3.** Two fetal abdomens. The smaller one (short arrow) is stuck in the anterior uterine wall and has no amniotic fluid. The bigger fetus (long arrow) has polyhydramnios. Adapted from: https://radiologykey.com/complications-ofmultiple-gestations/.

right heart become apparent. They also described an improvement after fetoscopic laser photocoagulation (FLPC) in these fetuses [38].

In the third trimester, fetal discordance in amniotic fluid and growth may occur, increasing uterine distension and causing shortened cervical length and preterm birth. Also, the mirror syndrome, a rare condition that presents itself as a sudden maternal edema, loss of renal and cardiac function, hypertension, and fetal hydrops, may appear in women with TTTS [26, 39, 40].

There is another rare form of TTTS described as "acute peripartum TTTS" which is defined as the intertwin hemoglobin difference at birth >8 g/dl. Since it is a rare condition (2.5% of all the MC pregnancies), there are a few studies and the pathogenesis remains unclear. Some studies says that in theory, acute fetal blood loss from the donor twin into the circulation of the recipient twin may occur as a result of variations in blood pressure due to uterine contractions or fetal positions [41].

> There are some critics about it because this staging system is not progressive (e.g., stage I can go to stage IV without passing through stages II and III) [45], and it does not correlate well with survival chance in twins treated with FLPC [48]. Nevertheless, these criteria are the most

> Before 20 weeks the universal cutoff is 8 cm, and between 21 and 26 weeks, the cutoff is 8 cm in the USA and 10 cm in

\*\*Absent-reverse diastolic flow in the umbilical artery and/or absent/reverse flow in the ductus venosus or pulsatile flow

and < 2 cm in the donor twin

Complications in Monochorionic Pregnancies http://dx.doi.org/10.5772/intechopen.83390 131

The natural history of TTTS shows high rates of fetal morbidity and mortality. The perinatal death in some series of cases is about 70–100%, depending on the stage of disease [26]. In stage I, it is known that nearly 70% of the pregnancies remain stable or regress, but in 5% of cases of stages I or II, there is fetal death of one or both twins without warning. Besides that, only 30% of pregnancies managed expectantly have double survivors. In the other stages, mortality increases and treatment is necessary [49]. There are several ways to manage TTTS, which

The FLPC is the preferred option because its outcomes are better when compared to serial amnioreduction [50, 51]. For stage I, there is no consensus regarding the use of FLPC, so the cases should be individualized [52]. For stages II to IV, FLPC of placental anastomoses is the primary treatment between 16 and 26 weeks of gestation. In 2004, Senat et al. have shown that the mortality rate of fetuses treated with FLPC when compared with serial amnioreduction is significantly lower (RR 0.71; 95% CI 0.55; 0.92). This study also showed a decreased risk of intraventricular hemorrhage and neurological impairment in the laser group. Probably it is because there is a higher rate of prematurity in the amnioreduction group [51]. The procedure consists in inserting a fetoscope in the amniotic sac of the recipient, locating the donor twin and the intertwin membrane, coagulating (with Nd:YAG or diode laser) the intertwin anastomoses along the placental vascular equator, and, after that, removing amniotic fluid from

The quality of fetoscopy images in the early 1990s, when the first FLPC for TTTS was performed, was not good; therefore, the vascular anastomoses were not so easy to identify. The so-called nonselective technique for vessel coagulation was proposed [53]. This technique

include FLPC, amnioreduction, selective reduction, and pregnancy termination.

used to classify TTTS.

\*

Europe.

in the umbilical vein.

*3.1.4. Management of TTTS*

**Stage Sonographic findings** I DVP > 8 cm in the recipient\*

IV Hydrops of either fetus

II Absent bladder filling in the donor

V Intrauterine fetal demise of either fetus

III Critically abnormal Doppler studies of either fetus\*\*

**Table 1.** TTTS staging system. Adapted from Journal of Perinatology, Quintero et al. [44].

the recipient sac [26, 51].

#### *3.1.3. Diagnostic criteria and staging*

In the past, TTTS was diagnosed at the time of birth based on neonatal criteria that included a growth discordance of 15–20% associated with discordant cord or neonatal hemoglobin concentrations of ≥5 g/dl [42]. In 1992, another study showed that these criteria are present in other conditions such as uteroplacental insufficiency, infection, and malformations and therefore should not be used as diagnostic criteria for TTTS [43].

The screening for TTTS should begin with an early ultrasound in order to confirm the chorionicity. The first trimester scan should be performed to look for morphology abnormalities and discordance in the NT measurement, abnormalities in the DV, and even crown-rump length discordances [44]. Unlike dichorionic pregnancies, where ultrasound can be performed every 4 weeks until the end of the second trimester, monochorionic pregnancies should be examined by ultrasound every 2 weeks beginning in the 16th week. An analysis of fetal growth, amniotic fluid deepest vertical pocket (DVP), umbilical artery pulsatility index (UA-PI), medium cerebral artery pulsatility index (MCA-PI), and peak systolic velocity (MCA-PSV) should be obtained [45, 46]. Besides that, a fetal echocardiography should be performed, since cardiac abnormalities are the most common defect in MC pregnancies. The fetal growth and the MCA-PSV are important parameters in the differential diagnosis of sFGR and TAPS, respectively. The early diagnosis is extremely important, since it allows timely treatment with FLPC.

In 1999, Quintero et al. standardized the diagnostic criteria and classification system of TTTS (**Table 1**) [47]. The diagnosis is made when a discordance in the DVP of the twins is visualized. The DVP of the donor twin should be <2 cm; meanwhile the DVP of the recipient, before 20 weeks, should be >8 cm, and after 20 weeks, it should be >10 cm in the European criteria and > 8 cm in the US criteria. The fetal bladders should also be evaluated since there might be a discordance in the size of the fetal bladders (larger in the recipient and smaller in the donor). It is worth reminding that weight discordance is not a diagnostic criterion for TTTS, but it also can be noted in the ultrasound examination.


\* Before 20 weeks the universal cutoff is 8 cm, and between 21 and 26 weeks, the cutoff is 8 cm in the USA and 10 cm in Europe.

\*\*Absent-reverse diastolic flow in the umbilical artery and/or absent/reverse flow in the ductus venosus or pulsatile flow in the umbilical vein.

**Table 1.** TTTS staging system. Adapted from Journal of Perinatology, Quintero et al. [44].

There are some critics about it because this staging system is not progressive (e.g., stage I can go to stage IV without passing through stages II and III) [45], and it does not correlate well with survival chance in twins treated with FLPC [48]. Nevertheless, these criteria are the most used to classify TTTS.

#### *3.1.4. Management of TTTS*

right heart become apparent. They also described an improvement after fetoscopic laser pho-

In the third trimester, fetal discordance in amniotic fluid and growth may occur, increasing uterine distension and causing shortened cervical length and preterm birth. Also, the mirror syndrome, a rare condition that presents itself as a sudden maternal edema, loss of renal and cardiac function, hypertension, and fetal hydrops, may appear in women with

There is another rare form of TTTS described as "acute peripartum TTTS" which is defined as the intertwin hemoglobin difference at birth >8 g/dl. Since it is a rare condition (2.5% of all the MC pregnancies), there are a few studies and the pathogenesis remains unclear. Some studies says that in theory, acute fetal blood loss from the donor twin into the circulation of the recipient twin may occur as a result of variations in blood pressure due to uterine contractions

In the past, TTTS was diagnosed at the time of birth based on neonatal criteria that included a growth discordance of 15–20% associated with discordant cord or neonatal hemoglobin concentrations of ≥5 g/dl [42]. In 1992, another study showed that these criteria are present in other conditions such as uteroplacental insufficiency, infection, and malformations and

The screening for TTTS should begin with an early ultrasound in order to confirm the chorionicity. The first trimester scan should be performed to look for morphology abnormalities and discordance in the NT measurement, abnormalities in the DV, and even crown-rump length discordances [44]. Unlike dichorionic pregnancies, where ultrasound can be performed every 4 weeks until the end of the second trimester, monochorionic pregnancies should be examined by ultrasound every 2 weeks beginning in the 16th week. An analysis of fetal growth, amniotic fluid deepest vertical pocket (DVP), umbilical artery pulsatility index (UA-PI), medium cerebral artery pulsatility index (MCA-PI), and peak systolic velocity (MCA-PSV) should be obtained [45, 46]. Besides that, a fetal echocardiography should be performed, since cardiac abnormalities are the most common defect in MC pregnancies. The fetal growth and the MCA-PSV are important parameters in the differential diagnosis of sFGR and TAPS, respectively. The early diagnosis is extremely important, since it allows

In 1999, Quintero et al. standardized the diagnostic criteria and classification system of TTTS (**Table 1**) [47]. The diagnosis is made when a discordance in the DVP of the twins is visualized. The DVP of the donor twin should be <2 cm; meanwhile the DVP of the recipient, before 20 weeks, should be >8 cm, and after 20 weeks, it should be >10 cm in the European criteria and > 8 cm in the US criteria. The fetal bladders should also be evaluated since there might be a discordance in the size of the fetal bladders (larger in the recipient and smaller in the donor). It is worth reminding that weight discordance is not a diagnostic criterion for TTTS, but it also

therefore should not be used as diagnostic criteria for TTTS [43].

tocoagulation (FLPC) in these fetuses [38].

TTTS [26, 39, 40].

130 Multiple Pregnancy - New Challenges

or fetal positions [41].

*3.1.3. Diagnostic criteria and staging*

timely treatment with FLPC.

can be noted in the ultrasound examination.

The natural history of TTTS shows high rates of fetal morbidity and mortality. The perinatal death in some series of cases is about 70–100%, depending on the stage of disease [26]. In stage I, it is known that nearly 70% of the pregnancies remain stable or regress, but in 5% of cases of stages I or II, there is fetal death of one or both twins without warning. Besides that, only 30% of pregnancies managed expectantly have double survivors. In the other stages, mortality increases and treatment is necessary [49]. There are several ways to manage TTTS, which include FLPC, amnioreduction, selective reduction, and pregnancy termination.

The FLPC is the preferred option because its outcomes are better when compared to serial amnioreduction [50, 51]. For stage I, there is no consensus regarding the use of FLPC, so the cases should be individualized [52]. For stages II to IV, FLPC of placental anastomoses is the primary treatment between 16 and 26 weeks of gestation. In 2004, Senat et al. have shown that the mortality rate of fetuses treated with FLPC when compared with serial amnioreduction is significantly lower (RR 0.71; 95% CI 0.55; 0.92). This study also showed a decreased risk of intraventricular hemorrhage and neurological impairment in the laser group. Probably it is because there is a higher rate of prematurity in the amnioreduction group [51]. The procedure consists in inserting a fetoscope in the amniotic sac of the recipient, locating the donor twin and the intertwin membrane, coagulating (with Nd:YAG or diode laser) the intertwin anastomoses along the placental vascular equator, and, after that, removing amniotic fluid from the recipient sac [26, 51].

The quality of fetoscopy images in the early 1990s, when the first FLPC for TTTS was performed, was not good; therefore, the vascular anastomoses were not so easy to identify. The so-called nonselective technique for vessel coagulation was proposed [53]. This technique consisted in coagulating all of the vessels that crossed the intertwin membrane. It did not attempt to differentiate anastomotic from non-anastomotic vessels but rather to catch as many anastomoses as possible (**Figure 4**). With the development of new techniques and advance in fetoscopy technology, another approach was proposed: the selective fetoscopic laser photocoagulation (SFLP) [54, 55]. In this method, the vascular equator is visualized and only intertwin anastomoses are coagulated. This technique differs from the "nonselective" FLPC because the equator does not always coincide with the membrane; therefore, not all the vessels that cross the intertwin membrane should be coagulated; thus, theoretically, more placental tissue will be available for the donor twin after the procedure (**Figure 4**). In 2000, Quintero et al. compared the SFLP with the "nonselective" FLPC and found that the selective method yielded superior results, with survival of at least 1 infant in 83% of patients against 61% in the "nonselective" group [56]. The order of anastomoses coagulation was also studied. Some authors claim that the sequential method, which is a technique where the AV (donor to recipient) are coagulated before the VA, improves the survival rate of both fetuses [57–59] and the survival rate of at least on fetus [58–60]. A recent meta-analysis showed that there may be an improved double neonatal survival as well as a decreased donor and recipient fetal demise with the use of the sequential technique, although all the studies are small and underpowered to confirm the hypothesis [61]. Although the SFLP improved neonatal outcomes, there is about 18% of surgical failure, defined as postoperative symptomatic patent anastomoses (**Figure 5**) [62–65], which could result in several complications such as recurrent TTTS (7–9%) [61, 65], TAPS (13–16%) [66, 67], and fetal death. This is a very delicate situation, because

repeating the procedure is more difficult for several reasons such as the size of the uterus and the fetuses. Furthermore, it is associated with an overall perinatal survival rate of 50% [67].

**Figure 5.** Digitally modified image of placenta with recurrent TTTS with missed AV and VA anastomoses. Adapted from

Complications in Monochorionic Pregnancies http://dx.doi.org/10.5772/intechopen.83390 133

Recently, a new fetoscopic technique in which superficial coagulation of microvasculature on the chorionic plate between ablated anastomotic sites following SFLP was described [68] (**Figure 4**). Some authors compared the SFLP with this new technique in cohort studies and showed a trend toward the latter group [69, 70]. A subsequent randomized trial by Slaghekke et al. compared this new approach called the Solomon technique *versus* the SFLP and found no difference in the overall survival rates. However, a decrease in recurrent TTTS and TAPS

The main early complications of laser photocoagulation are unintentional septostomy in 8–12%, premature rupture of membranes (PROM) in about 1–9%, and amnion dehiscence

The time of delivery in cases of laser photocoagulation varies between 31 and 34 weeks and most of them (60–80%) are not elective. The most common indication is the onset of labor followed by nonreassuring fetal testing and PROM. The mode of delivery is usually by cesarean

Unfortunately, in low-income countries, the laser therapy is not widely known and there are no teaching facilities. One Brazilian study showed the initial experience of a single center and found a single twin and both twins' survival rate 1 month after birth is 87.5 and 45.8%, respectively. These reported data are in line with those obtained in major centers worldwide, considering the learning curves and infrastructures [71]. In order to extend the range of the laser therapy to all the MC pregnancies, more teaching centers should be opened, and telemedicine should be used to aid low-income places to achieve the excellence in fetoscopy techniques.

The perinatal outcomes after the use of SFLP or Solomon technique are very satisfactory. Baschat et al. [70] found that the double survival rates at 6 months of age were 68% in the Solomon group and 50% in the SFLP. Ruano et al. [69] showed an overall neonatal survival rate from 61.8% in the SFLP group to 86.5% when Solomon technique was used. This difference

after the procedure was observed in the Solomon group (4 vs. 21%) [66].

(membrane separation) in 5–10% of cases.

Am J Obstet Gynecol. Lewi et al. [62].

section, in 57–70% of cases [26, 51, 60, 69, 70].

*3.1.5. Perinatal outcomes after treatment*

**Figure 4.** Types of fetoscopic laser techniques in the treatment of TTTS. The nonselective method coagulates all vessels crossing the intertwin membrane. SFLP occlude anastomoses where they occur, sparing placental tissue of the donor. The equatorial laser dichorionization or Solomon technique separates the fetal circulations by coagulating the vascular equator. Adapted from Am J Perinatol. Benoit et al. [26].

**Figure 5.** Digitally modified image of placenta with recurrent TTTS with missed AV and VA anastomoses. Adapted from Am J Obstet Gynecol. Lewi et al. [62].

repeating the procedure is more difficult for several reasons such as the size of the uterus and the fetuses. Furthermore, it is associated with an overall perinatal survival rate of 50% [67].

Recently, a new fetoscopic technique in which superficial coagulation of microvasculature on the chorionic plate between ablated anastomotic sites following SFLP was described [68] (**Figure 4**). Some authors compared the SFLP with this new technique in cohort studies and showed a trend toward the latter group [69, 70]. A subsequent randomized trial by Slaghekke et al. compared this new approach called the Solomon technique *versus* the SFLP and found no difference in the overall survival rates. However, a decrease in recurrent TTTS and TAPS after the procedure was observed in the Solomon group (4 vs. 21%) [66].

The main early complications of laser photocoagulation are unintentional septostomy in 8–12%, premature rupture of membranes (PROM) in about 1–9%, and amnion dehiscence (membrane separation) in 5–10% of cases.

The time of delivery in cases of laser photocoagulation varies between 31 and 34 weeks and most of them (60–80%) are not elective. The most common indication is the onset of labor followed by nonreassuring fetal testing and PROM. The mode of delivery is usually by cesarean section, in 57–70% of cases [26, 51, 60, 69, 70].

Unfortunately, in low-income countries, the laser therapy is not widely known and there are no teaching facilities. One Brazilian study showed the initial experience of a single center and found a single twin and both twins' survival rate 1 month after birth is 87.5 and 45.8%, respectively. These reported data are in line with those obtained in major centers worldwide, considering the learning curves and infrastructures [71]. In order to extend the range of the laser therapy to all the MC pregnancies, more teaching centers should be opened, and telemedicine should be used to aid low-income places to achieve the excellence in fetoscopy techniques.

#### *3.1.5. Perinatal outcomes after treatment*

consisted in coagulating all of the vessels that crossed the intertwin membrane. It did not attempt to differentiate anastomotic from non-anastomotic vessels but rather to catch as many anastomoses as possible (**Figure 4**). With the development of new techniques and advance in fetoscopy technology, another approach was proposed: the selective fetoscopic laser photocoagulation (SFLP) [54, 55]. In this method, the vascular equator is visualized and only intertwin anastomoses are coagulated. This technique differs from the "nonselective" FLPC because the equator does not always coincide with the membrane; therefore, not all the vessels that cross the intertwin membrane should be coagulated; thus, theoretically, more placental tissue will be available for the donor twin after the procedure (**Figure 4**). In 2000, Quintero et al. compared the SFLP with the "nonselective" FLPC and found that the selective method yielded superior results, with survival of at least 1 infant in 83% of patients against 61% in the "nonselective" group [56]. The order of anastomoses coagulation was also studied. Some authors claim that the sequential method, which is a technique where the AV (donor to recipient) are coagulated before the VA, improves the survival rate of both fetuses [57–59] and the survival rate of at least on fetus [58–60]. A recent meta-analysis showed that there may be an improved double neonatal survival as well as a decreased donor and recipient fetal demise with the use of the sequential technique, although all the studies are small and underpowered to confirm the hypothesis [61]. Although the SFLP improved neonatal outcomes, there is about 18% of surgical failure, defined as postoperative symptomatic patent anastomoses (**Figure 5**) [62–65], which could result in several complications such as recurrent TTTS (7–9%) [61, 65], TAPS (13–16%) [66, 67], and fetal death. This is a very delicate situation, because

132 Multiple Pregnancy - New Challenges

**Figure 4.** Types of fetoscopic laser techniques in the treatment of TTTS. The nonselective method coagulates all vessels crossing the intertwin membrane. SFLP occlude anastomoses where they occur, sparing placental tissue of the donor. The equatorial laser dichorionization or Solomon technique separates the fetal circulations by coagulating the vascular

equator. Adapted from Am J Perinatol. Benoit et al. [26].

The perinatal outcomes after the use of SFLP or Solomon technique are very satisfactory. Baschat et al. [70] found that the double survival rates at 6 months of age were 68% in the Solomon group and 50% in the SFLP. Ruano et al. [69] showed an overall neonatal survival rate from 61.8% in the SFLP group to 86.5% when Solomon technique was used. This difference could be due to the increased experience with fetoscopic laser in general and not to the use of the Solomon technique. In the only randomized trial, the single twin and both twins' survival rates after 1 month in the SFLP were 87% and 60%, while in the Solomon group these rate were 85% and 64%, respectively [66].

combine their results, or to establish robust evidence-based management. The pathophysiology in sFGR in MC and DC twins seems to be different. While DC sFGR have conventionally been managed as FGR in a singleton pregnancy, MC twin pregnancies sFGR is thought to result mainly from an unequal placental share. In most cases the origin is in the placental territory discrepancy (**Figure 6**). Vascular anastomoses between both fetuses intrinsically justify

Complications in Monochorionic Pregnancies http://dx.doi.org/10.5772/intechopen.83390 135

Since many authors have proposed different diagnostic criteria, in 2017, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published a guideline for the sFGR diagnostic. It is defined as a condition in which one fetus has estimated fetal weight (EFW) < 10th centile and the intertwin EFW discordance is >25%. EFW discordance is calculated by the following formula: (weight of larger twin – weight of smaller twin) × 100)/weight of larger twin [45]. This weight discordance was proposed by an expert consensus, mainly based on data that show that an 18% EFW discordance reflects poorer outcomes both in DC and MC pregnancies [88]. Curiously, the charts used to monitor the fetal growth should be the same as those used in singleton pregnancies [45, 89], although specific multiple pregnancy charts are available [90]. However, there is a reduction in fetal growth in twin compared with singleton pregnancy, particularly in the third trimester. The key question for clinicians is whether this difference in growth represents adaptation or restriction [91]. Once the diagnosis is made, a detailed anomaly scan and screening for viral infections (cytomegalovirus, rubella, and toxoplasmosis) should be made. Amniocentesis

may also be required to exclude chromosomal abnormalities as a cause of FGR [45, 92].

**Figure 6.** Macroscopic photograph demonstrates the measurement of the vascular anastomoses. There is a 2-mm arterioarterial anastomosis (dashed arrow) and 5 AV anastomoses (arrows). A macroscopic placental surface discordance

is also visible (green dashed line: Vascular equator). Adapted from Am J Obstet Gynecol. Lewi et al. [86].

IUGR, and one twin receives better oxygenated blood [87].

*3.2.1. Diagnostic criteria and staging*

The neurologic outcomes in the neonatal period following laser procedures, such as intraventricular hemorrhage, periventricular leukomalacia, cerebral white matter cysts, ventricular dilatation, and cerebral atrophy, range from 8 to 18% [51, 72, 73]. The long-term neurodevelopmental outcomes vary between 3 and 12% for cerebral palsy and 4 and 18% for neurodevelopmental impairment [73]. In one study, the neurodevelopmental scores in preterm-born children treated with laser therapy for TTTS were similar in preterm-born DC children, suggesting that prematurity has the main role in the neurologic impairment in fetus treated with laser photocoagulation [74]. Other authors have suggested risk factors for poorer neurodevelopmental outcomes [75, 76]. Lopriore et al. analyzed 212 pregnancies treated with fetoscopic laser surgery and found that advanced gestational age at laser surgery, low gestational age at birth, low birthweight, and high Quintero stage are risk factors of poor neurological development at 2 years of age [76].

Several studies report a rapid cardiac function recovery in the recipient and in the donor twin [36, 38, 77–80]. The coagulation of vascular anastomoses stops the volume exchange, as well as the vasoactive mediators, allowing cardiac output, cardiac size, valvular regurgitation, and ventricular inflow to normalize in the recipient twin in about half of the cases [38, 77]. The donor twin shows an increase in left ventricular filling pressure and cardiac output, which can temporarily cause a relative volume overload. It can worsen the cardiac function and cause ductus venosus alterations and even hydrops; however, these changes tend to disappear by 2 to 4 weeks after the laser procedure [79, 81, 82].

There are other types of treatment, such as septostomy. This procedure increases the risk of severe complications like cord entanglement and disruption of the membrane. This procedure has generally been abandoned [64, 83]. The selective reduction is another therapeutic option that tries to improve the outcome of the surviving twin whenever there is an imminent risk of spontaneous intrauterine death of one fetus. It can be performed either by ultrasound-guided vascular embolization or cord clamping through fetoscopy. A maximum of 50% survival is reached and most services have not supported this technique [68].

The fetoscopic laser coagulation is the gold standard treatment in stage II to stage IV TTTS affected pregnancies; the SFLP and Solomon technique are the best options for lowering the mortality and morbidity in theses fetuses. For Quintero stage I, there is not enough data that favors laser surgery, and more powered studies should be done comparing it to other kinds of treatment; therefore, the treatment for this stage has to be individualized.

#### **3.2. Selective intrauterine growth restriction**

Selective intrauterine growth restriction happens in 10–25% of MC gestations and it considerably increases perinatal morbidity and mortality [84–86]. The diagnostic criteria for sFGR differ among clinicians; therefore, it is hard to compare the findings of existing studies, to combine their results, or to establish robust evidence-based management. The pathophysiology in sFGR in MC and DC twins seems to be different. While DC sFGR have conventionally been managed as FGR in a singleton pregnancy, MC twin pregnancies sFGR is thought to result mainly from an unequal placental share. In most cases the origin is in the placental territory discrepancy (**Figure 6**). Vascular anastomoses between both fetuses intrinsically justify IUGR, and one twin receives better oxygenated blood [87].
