1

Sonography of multiple gestations1 Jacqueline Reyesó, MD, Luís Flávio de Andrade Gonçalvesõ, MD, Sandra Rejane Silvaö, MD, Philippe Jeantyò, MD, PhD ó Santo Domingo, Dominican Republic õ Clínica Materno-Fetal, Florianópolis, Brazil ö Instituto de Medicina Fetal e Genetica Humana de Sao Paulo, Rua Felix de Sousa 321 - Campo Belo, Sao Paulo - SP – Brazil ò Women’s Health Alliance, Nashville, TN 37203-2131, USA

Introduction Multiple gestations account for 1-2% of all births2 and represent 10-14% of the overall perinatal mortality, a rate five to ten times higher than that of singletons. Because of the increase use of assisted reproductive tech-nologies, the number of high order pregnancies has steeply increased over the past 20 years. The aim of early diagnosis of multiple gestations and their associated complications is the reduction of perinatal morbidity and mortality. Sonography allows determination of zygosity, chorionicity, amnionicity, placental location and fetal presentation, as well as the detection of complications such as growth discrepancy, abnormal vascular anastomoses, amniotic fluid volume imbalance and cord entanglement3. In this chapter, we will discuss the ultrasonographic evaluation, most common complications and the role of invasive procedures in the manage-ment of multiple pregnancies.

Embryology Two mechanisms may lead to a multiple pregnancy: fertilization of two or more oocytes or early embryonic splitting of a single ovum. The most common mechanism is fertilization of several oocytes in a single menstrual cycle (2/3 of the cases). This type of twining results in genetically different individuals (also known as polyzygotic, non-identical or fraternal twins) and has a hereditary tendency. It is associated with a recurrence risk three times higher than that of the general population4. Each zygote develops its own chorion, placenta and amniotic cavity. Every fetal-placental-amniotic compartment is individualized and there are no (or very rare) vascular communica-tions between them. Circulatory complications are thus rare, unless the placentas become fused during preg-nancy. The incidence of dizygotic twin varies in different populations while the incidence of monozygotic twins is fairly constant.

0.18%

1.00% 1.20%

5.70%

0%

1%

2%

3%

4%

5%

6%

Japan USA (Caucasian) USA (Afr-Am) Nigeria

The incidence of dizygotic twin varies in different populations: from left to right: Japan, US Caucasian population, US African American population and Nigeria.

2

In one third of the cases, early embryonic splitting of a single ovum is the mechanism of twinning. Four situations may arise as a result of this process: dichorionic-diamniotic placentation (1/3 of the cases), mono-chorionic-diamniotic placentation, monochorionic-monoamniotic placentation and conjoined twins. If early embryonic splitting occurs before day three after fertilization (during the two to eight cells stage), two inde-pendent fetuses with separate placentas will result. A single placenta with two amniotic cavities occurs if splitting takes place between days four and seven (blastocyst stage). If division of the embryoblast occurs after about eight days, the twins share a single placenta and amniotic cavity (monochorionic-monoamniotic twins). Division beyond day 13 results in conjoined twins.

< 4 days

4-8 days

8-13 days

> 13 days

© '92 P hilippe J eanty

< 4 days

4-8 days

8-13 days

> 13 days

Fig: Schematic drawing demonstrating the outcome of twinning at different stages of early embryonic life. Top: Fission before the formation of the inner cell mass and any differentiation will produce two embryos with two separate chorions, amnions and placentas. Middle: Twinning at the early blastocyst stage, after formation of the inner cell mass, will cause the development of two embryos, with one placenta and one chorion but two separate amnions. Bottom: If separation occurs after the formation of the embryonic disc, the amnion has already formed, and will lead to a monoamniotic, monochorionic pregnancy. Incomplete fission at this stage or later will result in conjoined twins.

3

Less frequently, monozygotic and dizygotic twining may occur simultaneously in a pregnancy with 3 or more embryos.

Dichorionic, triamniotic pregnancy in an assisted pregnancy. Note on the left image the thick septum between the 2 embryos and on the right side the barely visible septation.

Clinical implications of zygosity and chorionicity Improving the outcome of multiple pregnancies is a major challenge for prenatal care. The mortality rate for twins is 4 to 11 times higher than that of singletons. Stillbirths account for approximately one third of the perinatal deaths. The remaining two thirds occur during the neonatal period, mainly as a result of prematurity.

0

2

4

6

8

10

12

14

Generalmortality

Stillbirths Neonatal

Compared to singletons, the rate of mortality of twins is 4-11 higher, that of stillbirths, 3-13 and that of neonatal death 6-7 times.

4

The increased mortality of twins is already apparent in the first trimester

Another normal dichorionic preg-nancy, with appropriate early growth (in spite of vaginal bleeding). The repeat examination demonstrates demise of both twins.

5

The various types of twins are described in the following table (further details are in the text). The table is organized from most dissimilar on top to most similar at the bottom.

Types of twins Dizygotic twins (1/90): Superfecondation Not the same father Many case-reports in the litera-

ture of the last century Superfetation

Not the same cycle Historically these were misinter-pretations of growth discordance, but recent DNA studies have demonstrated that the condition is occasionally possible, in particu-lar with assisted reproductive techniques

Fraternal twins

Same father, same cycle The usual twins

Monozygotic twins (1/250): DiAmniotic DiChorionic Same zygote, 2 separate sacs Early separation DiAmniotic MonoChorionic Same zygote, 2 separate amnions MonoAmniotic MonoChorionic Same zygote, same sac Late separation Conjoint Equally but incompletely divided Incomplete separation Duplicata incompleta Incompletely duplicated Ectoparasitic twin Partial fetus attached to sib Partial division Fetus-in-fetu Embedded A classification of twin from most dissimilar to most identical from top to bottom. A classification of monozygous twin according to their symmetry or lack of.

Separate Joined

Symmetrical

ExternalAcardiac (TRAP)

AttachedEcto/hetero parasitic

InternalFetus in fetu

Asymmetrical

Monozygous twins

6

Precise determination of zygosity and chorionicity is the most important step for the proper management of multiple pregnancies. Monochorionic-monoamniotic pregnancies are associated with the highest mortality rate (50%), followed by monochorionic-diamniotic pregnancies (26%) and dichorionic-diamniotic pregnan-cies (9%). Mortality is even higher before 24 weeks of gestation5. The elevated mortality rate seen in mono-chorionic placentation is caused mainly by aberrant vascular communications in the placenta leading to twin-to-twin transfusion syndrome. In monoamniotic twins, the risk is worsened by the possibility of cord acci-dents. Monochorionic twins are thus at a higher risk of prematurity, intrauterine death and neurological dam-age secondary to complications of twin-to-twin transfusion syndrome. As illustrated below from data from the Collaborative Perinatal Project, the excess mortality in twins is pre-dominantly dues to the contribution of the monochorionic twins.

2.5%3.3%

4.0%

2.4%

0.0%

1.0%

2.0%

3.0%

4.0%

Singletons Twins Monochorionic Dichorionic

Ectoparasitic twins are parts of twins implanted in another fetus. In this case what appears to be an omphalocele on the left is a fetal abdomen with lower legs on the extreme left. (Courtesy Glynis Sack, MD, www.TheFetus.net)

7

0 2 4 6 8 10 12

Times

Mortality

Prematurity

Molar Pregancy

Wilms

Crib death

SUA

Cerebral palsy

The relative risk of twins compared to singletons is not limited to mortality, but also affect morbidity Also important is the determination of the number of viable fetuses: higher order multiples have a greater risk of prematurity. A singleton gestation has an average length of 39 weeks versus 35 weeks for twins, 33 weeks for triplets, and 29 weeks for quadruplets. Early ultrasound evaluation at 9 to 12 weeks can precisely inform chorionicity, amnionicity and the number of viable fetuses. This information is important for the development of appropriate methods of surveillance and intervention during the second trimester of pregnancy aimed at reducing the excess fetal loss in twins6,7. Frequency and mortality according to the types of placentation234

DiAmniotic DiChorionic Separate placentae

DiAmniotic DiChorionic Fused placentae

DiAmniotic MonoChorionic Single placenta

MonoAmniotic MonoChorionic Single placenta

Frequency: 35% 27% 36% 2% Mortality: 13% 11% 32% 44%

3-4

2-2.5

3-6

4

6.7

3-4

2-11

8

The chorionicity and zygosity of twins is expressed in the following chart compiled from the Birmingham twin survey8. 65% of twins are like sex. Of these 28% are monozygotic and 37% are dizygotic. The chart also demonstrates that 80% of twins are diamniotic-dichorionic and that 90% of these diamniotic-dichorionic are also dizygotic. Further 43% of like sex twins are monozygotic. This helps answer the common question from patients: “If I have like-sex fetuses, what is the likelihood that they are identical ?”.

8% Same sex (genotype:

monozygotic)

37% Same sex (genotype: dizygotic)

35% Different sex (dizygotic)

20% Monochorionic

(same sex) (monozygotic)

Dichorionic twins are easier to recognize from monochorionic twins in the first trimester. The criterion is simply that dichorionic twins have a thick membrane (actually some interposing tissue) while monochorionic twins have either a very thin or barely visible membrane. This is illustrated in the figure below. Dichorionic twins Monochorionic twins

The two left images are di-chorionic twins, which are easily recognized from mono-chorionic twins on the two right images (the first trimester) by the thick intervening mem-brane.

9

Later, dizygotic twins can be suspected or identified when they have separate placenta or discordant sex.

Dizygotic twins can be suspected or identified in the second trimester when they have separate placenta or discordant sex.

The naming of twins In the pre-ultrasound days, when the obstetrician delivered a set of twin, it was traditional to call the first one out “Twin A” and the second one “Twin B”. By some twisted extrapolation this nomenclature has been ap-plied to ultrasound, although we have observed that the presenting twin is not always the same one from ex-amination to examination (figure). A much better terminology, aside from the monoamniotic twins, is to de-scribe the relative positions of the twins: Left-upper, right-lower. One of the characteristics is bound to be constant from examination to examination since the membrane prevents the twins from switching side.

The vestigial convention of naming of twins “A&B” has to be replaced by a description of the actual posi-tions.

10

Monochorionic twins

Definition Monochorionic twining is a type of gestation in which the fetuses share a single chorion (the outer membrane) and may or may not share the amnion (the inner membrane). When the amnion is shared, the twins are called monochorionic-monoamniotic (Mo-Mo) and the reader is referred to the specific topic in this chapter. When they do not share the amnion the twins are called monochorionic-diamniotic (Mo-Di). Independently from the number of amniotic sacs, all monochorionic twins are monozygotic9,10.

The implantation of two fertil-ized eggs (left side of the draw-ing) will result in two gesta-tional sacs that share neither the chorion nor the amnion. The drawing illustrates how the placenta can insert between the two sacs producing the “λ sign” (lambda sign). On the right side of the drawing, a single egg can either split early (before 4 days) into two em-bryos and the 2 embryos will then resemble the previous condition, or the fertilized egg can split between the 4th and 8th days at a time when the chorion is no longer divisible. Both embryos will then share the chorion, the placenta will not be able to infiltrate between the two gestational sacs and the membrane insertion will have the “T” appearance. The ultra-sound images underneath the drawings illustrate the mem-brane insertion in both cases.

11

Monochorionic placentation occurs in two-thirds of monozygous twins and represents approximately 0.3% of all spontaneous conceptions11. It is highly associated with the overall adverse outcome in multiple gestations. Of all intrauterine deaths in twins, 73% are associated with monochorionic placentation12, and among the live births, there is an elevated incidence of perinatal mortality, birth weight discrepancies, and intrauterine growth retardation13,14.

Sonographic features Determination of chorionicity and can be performed by transvaginal ultrasound as early as 5 weeks15,16. In early pregnancy, the separate sacs are clearly visible. In monochorionic twins, there is a single placental mass, with or without a dividing membrane. When there is a dividing membrane, it is composed of two layers repre-senting the two layers of amnion. In contrast, the inter-twin membrane of dichorionic twins is composed of a layer of chorion sandwiched between two layers of amnion. Therefore, the inter-twin membrane in dichori-onic twins is thicker, especially between 6 to 9 weeks, when a septum can be observed between the chorionic sacs. After 9 weeks, the septum becomes progressively thinner; however, it remains thick and relatively easy to identify at the insertion point into the placental mass as a triangular projection called the lambda or “twin-peak” sign17,18. Sepulveda et al19 studied 368 twin pregnancies at 10 to 14 weeks gestation, classifying them as monochorionic if there was a single placental mass in the absence of the lambda sign at the inter-twin mem-brane-placental junction and dichorionic if there was a single placental mass but the lambda sign was present or the placentas were not adjacent to each other. In 81 (22%) cases, the pregnancies were classified as mono-chorionic and in 287 (78%) as dichorionic. All pregnancies classified as monochorionic resulted in the deliv-ery of same-sex twins and all different-sex pairs were correctly classified as dichorionic. Other authors suggest counting the number of layers of fetal membranes to determine chorionicity, however this strategy is not always possible and should be used in conjunction with other sonographic crite-ria20,21,22,23,24,25. Membrane thickness is also occasionally useful to predict the type of placentation. Thick membranes suggest dichorionic placentation while thin membranes suggest monochorionic placentation26,27,28. Another important criterion of differential diagnosis is the sex of the fetuses29. If they are of different sex, the odds are that the fetuses are dichorionic. There is a small risk, however, of a cytogenetic change that could result in monozygotic twins presenting as a boy and a girl. The most common cause of this rare anomaly is the early loss (during the embryo stage) of a Y chromosome in a cell line that eventually becomes a Turner syndrome.

In rare instances, not only the primordial fertilized egg divides but one of the 2 daughter cells also looses genetic material (and more commonly the Y chromosome) resulting in a heterokaryotypic monozygotic twin pregnancy consisting of a boy and a Turner girl.

12

Very asymmetrical growth may occurs in heterokaryotypic twins

Associated syndromes Monochorionic twins are at risk for twin-to-twin transfusion30,31,32,33,34, twin embolization syndrome, higher rates of congenital malformations35,36, growth restriction and prematurity. Death of one twin may have serious implications for the survivor37,38,39, 40,41,42,43,44 because of the increased risk of preterm delivery as well as the risk neurological handicap secondary to hypotensive episodes caused by hemorrhage from the live fetus into the dead fetoplacental unit through vascular anastomoses45,46,47,48.

Monoamniotic twins

Definition Monoamniotic twins are those that share not only the chorion (the outer membrane) but also the amnion (the inner membrane) and thus are in the same gestational sac49. They result from splitting between 7 to 13 days after fertilization50, 51 and represent 1% of twin pregnancies52, 53,54.

Monoamniotic twins are share the chorion and the amnion and thus are in the same gestational sac

13

Sonographic features Monoamniotic twins can be suspected if the following features are observed55:

• Single placenta and same sex twins; • Close approximation of the cord insertions; • Entanglement of the cords; • Normal and identical amniotic fluid volume around both fetuses; • Unrestricted fetal movement; and • Absence of a dividing membrane demonstrated on two studies at least 12-15 hours apart56. • A single yolk sac may be a normal finding57.

Absence of a dividing membrane between two fetuses that are intimately in contact.

Close approximation of the cord insertions

14

Cord entanglement (power Doppler on top, and gray-scale bottom) Counting twins with different chorionicity by counting the number of gestational sacs is easier in the first trimester when thick layers of tissue separate the sacs. However, differentiating monochorionic diamniotic from monochorionic monoamniotic twins is not easy58. The amniotic membrane is very thin, and unless the ultrasound beam is perpendicular, it may be difficult to observe. A simple trick that is convincing when pre-sent is to roll the patient to the side and observe the passive motion of the embryos. If they both gravitate to the bottom of the gestational sac no matter what decubitus position, the suspicion of monoamniotic twin is high. If they do not, a dividing membrane is suspected. The findings however can be equivocal59. This must be an accurate diagnosis since it identifies patients at higher risk for cord accidents60.

Differential diagnosis Monoamniotic twins can easily be confused with monochorionic diamniotic twins, especially when there is twin-to-twin transfusion and one of the twins is stuck (see elsewhere in this chapter). A careful search for a membrane, in particular between the limbs and the body, is the only way to ascertain the diagnosis. The ab-sence or reduced amniotic fluid around the stuck twin should raise the suspicion of a diamniotic gestation as well.

Associated syndromes Monoamniotic twins may be affected by multiple pathological conditions including twin-to-twin transfusion (although less commonly and less severe than in monochorionic diamniotic twins)61,62,63, tangled umbilical cords64,65,66,67,68,69,70,71,72,73 and increased risk of congenital anomalies (15-20%)74,75,76,77,78,79,80,81,82. Cord entan-glement occurs in 40-70% of monoamniotic twins because of their increased mobility in the second trimester.

15

During the third trimester, the reduced space is usually no longer sufficient to allow the twins to move around.83,84 Cord entanglement appears to be a pathognomonic sign of monoamnionicity85 and can be seen as early as the first trimester. In cases of cord entanglement, in spite of apparent cord compression with absent end-diastolic velocities (AEDV), some fetuses may grow appropriately86. The significance of AEDV in monoamniotic twins may thus be less predictive than in singletons. The presence of a notch in the umbilical artery velocity waveform may reflect hemodynamic alterations in the fetal-placental circulation secondary to narrowing of the umbilical vessels involved in cord entanglement. Due to these complications the overall mortality for monoamniotic twins can be as high as 50-60%,87, 88, 89, 90, 91.

Fetal growth Intrauterine growth restriction is a pathological situation, caused in the majority of the cases by placental insufficiency. Poor maternal-fetal exchange reduces the offer of nutrients to the fetus, which grows slower than normal. This condition is seen in 25% of twin gestations, a rate ten times higher than that found in the general population. Growth rate in multiple gestations during the first and early second trimesters parallels the growth rate of singleton pregnancies, dropping off during the late second and third trimesters. Serial growth assessment is the most accurate method to diagnose intrauterine growth retardation. Some con-troversy remains concerning the use of growth nomograms derived from the general population in multiple pregnancies. The expected growth of head, limbs, and abdomen for twins is discussed below.

Twins commonly experience decreased growth after 26-28 week, and, as in this set, the effect may be more pronounced on the smaller of the twins.

Head Reece et al92 reported that the growth of the fetal head was not significantly different from that observed in singleton pregnancies. According to his findings nomograms derived from singleton pregnancies remains useful for twin gestations.

16

Limbs Another study conducted by Reece et al93 evaluated growth of the long bones in multiple and singleton gesta-tions. Although a difference in fetal growth between these two groups was found, the authors concluded it was not statistically significant to justify the generation of separate nomograms for twins.

Abdomen Neonatal differences in abdominal circumference from the normal singleton population are frequently identi-fied. It is still unclear if these differences occur due to genetic differences in growth potential of twins or if they are secondary to decrease supplies. Our personal impression is that it is better to consider twin growth with singleton measurement. Using special twin chart increases the risk that the nomograms be established on fetuses with less then adequate growth and thus mask the presence of growth restriction in the index fetus. Despite the controversies regarding the use of nomograms in twin gestations, concordant growth should be expected between fetuses.

Appropriate growth of twins with similar sized chest and abdominal areas

17

Growth discrepancies Definition Anthony Vintzileos has pointed out that the term “growth discordance” was introduced many years ago when obstetricians had no ultrasound to estimate fetal weights or gestational ages. In these dark old days they only had a scale, so they only could measure the weights after birth. Since then, the term has been used to under-line the associated increased mortality and morbidity that only affects the small (IUGR) twin. It would be inappropriate to institute fetal surveillance in the setting of discordance when one twin has an EFW at the 50% percentile and the other at the 90% percentile, because neither of these twins would have IUGR. The data has shown that there only is increased morbidity and mortality when discordance is associated with IUGR. Conversely, when both twins have IUGR, fetal surveillance is indicated because of the increased risk despite the lack of discordance. The term should thus be abandoned because it promulgates confusion, and unnecessary testing. Fetal growth discrepancy is defined as a greater than 20% difference in the inter-twin estimated fetal weight. It is generally caused by placental insufficiency resulting in growth restriction of one twin94,95,96,97,98,99,100,101, death of one twin after the 16th week or chromosomal abnormalities. The definition of growth discrepancy should be categorized with respect to gestational week since the level of discrepancy varies at different stages of pregnancy102. Most cases of growth discrepancy are diagnosed at the second half of the pregnancy. How-ever, pathology can be present as early as the first trimester103,104. Sonographic features The standard care for twin pregnancy includes serial sonographic evaluations to assess the growth of each fetus105,106. Findings suggestive of growth discrepancy include:

• Estimated fetal weights discordant by more than 20%107,108,109,110,111,112,113,114,115,116,117,118,119,120. It can be classified as mild (15-25%) or severe (>25%). Cases of pre-term twin gestations with severe dis-crepancy are associated with a higher morbidity rate121,122,123.

• Abdominal circumference diverging by 20 mm or more124, 125, 126, 127. • Difference in biparietal diameter greater than 6 mm, with the smaller biparietal diameter less than 2

standard deviations below the mean128. • Head perimeter diverging by more than 5%. • Umbilical artery S/D ratios discordant by more than 15% and elevated umbilical artery S/D ratio

(≥0.4) in one or both twins129,130,131,132,133,134,135. Differential diagnosis Twin-to-twin transfusion syndrome is the main differential diagnosis136,137,138,139. Observation of discordant sexes or dichorionic placentation excludes this possibility140. In general, twin-twin transfusion syndrome is associated with the polyhydramnios-oligohydramnios and/or anemia-polycythemia sequences141. Differences in genetic growth potential between the twins are another possibility: both twins would have normal growth but significant size discrepancy. These cases have adequate growth on serial sonographic analysis plotted in a growth chart, normal amniotic fluid volume and birth weight usually above 2500g. Females of unlike-sexed pairs are more likely to present growth discrepancy142. Associated syndromes Growth discrepancy can be associated with low amniotic fluid volume in the sac of the growth-restricted fetus143. The smaller twin is at increased risk of perinatal morbidity and mortality as well as reduced physical and mental development later in life144,145. The association with prematurity also implies a high perinatal morbidity and mortality for the affected twin. When growth discrepancy is associated with death of one of the twins, the presence of a fetus papyraceous is expected on subsequent scans. When the etiology of the condi-tion is a chromosomal abnormality, fetal structural defects might be found at sonographic evaluation. Twin pregnancies following in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) are more likely to result in birth weight discordance, as well as those with high serum alpha-fetoprotein levels146,147. Doppler evaluation Doppler assessment of uterine and umbilical blood flows may be used to evaluate fetal well-being in multiple gestations148. It has been demonstrated that fetuses with abnormal Doppler velocimetry have increased mor-

18

bidity and mortality rates149. Some have found umbilical Doppler velocimetry useful to predict discrepancy in twins150; it is certainly an important tool to diagnose congenital anomalies such as twin reversed arterial per-fusion sequence, where a retrograde perfusion in the umbilical artery of the abnormal twin is found151. Other important applications of Doppler velocimetry are the demonstration of superficial anastomoses in twin-twin transfusion syndrome and identification of cord entanglement, which is a pathognomonic sign of monoam-nionicity152, 153, 154, 155.

Chromosomal anomalies Chromosomal abnormalities are more frequent in multiple pregnancies than in the general population. In dizygotic pregnancies two oocytes are fertilized and each oocyte has an inherent risk of a chromosomal anomaly. The result is an increased rate of chromosomal abnormalities for any given maternal age. The ge-netic risk is calculated as 166% the empiric maternal age risk. Rodis and co-workers156 constructed a nomo-gram for the calculation of risk of chromosomal abnormalities in twin gestations. For example, in the United States, a 33-year-old mother with a twin gestation carries the same risk of chromosomal abnormalities as a 35-year-old woman with a singleton pregnancy. This concept has clinical implications in the management of twin gestations and the maternal age at which cytogenetic studies should be offered. When karyotyping is recommended chorionic villus sampling is an early and safe technique of prenatal diag-nosis in multiple pregnancies157,158. If the invasive procedure is performed during the second trimester, am-niocentesis should be the first choice. Fetal sex assignment can be another useful information, particularly in pregnancies at risk for severe sex-linked diseases and fetal disorders involving the genitalia159. It is worth mentioning that there have been re-ports of discordant sex in monozygous twins160,161,162,163,164,165 (see figure above). Monozygotic twins are highly concordant for minor anomalies, tend to be concordant for rare congenital defects and malformations, and are predominantly discordant for more common major malformations. In general, the smaller twin is the more severely affected166. There are reports of discordant karyotype in identi-cal twins, with the recommendation of sampling both sacs if one or both fetuses have ultrasound abnormali-ties, even if the scan is suggestive a monochorionic pregnancy167. This technique must be carefully performed making sure that each sample is properly attributed to the correspondent twin. Klinefelter syndrome with inversion of chromosome 13 in the co-twin168, trisomy 13169, aneuploidy170 and gonadal dysgenesis171, 172 are some of the discordant chromosomal abnormalities reported in twins.

Congenital anomalies Multiple gestations have approximately twice as many congenital anomalies when compared to the expected rate for the general population. Major anomalies are seen in 2.1% of twins versus 1.2% of singletons while minor anomalies are seen in 4.1% of twins versus 2.4% of singletons. Some of the anomalies reported in multiple gestations are: cloacal dysgenesis sequence173, cyclopia174, amni-otic band disruption complex175, cystic hygroma176, cerebral and ocular abnormalities177, microcephaly178 and Russel-Silver syndrome179,180 among others. According to the literature, the occurrence of malformations is higher in monozygotic than in dizygotic twins. The reported incidence of anomalies in monozygotic twins is around 16.7% for minor plus an additional 16.7% for major anomalies. If a malformation is observed in one twin, the other has a high chance of being equally affected. Concordance, however, is seen in just 10 to 20% of monozygotic twins. A careful anatomy survey is necessary to exclude a discordant anomaly, especially in monozygotic pairs. Three theories have been proposed to explain the etiology of structural anomalies in monozygotic twins.

19

1. The first theory postulates that the crowding of the uterine cavity may be associated with certain types of anomalies. This would explain the statistically significant concordance seen in muscu-loskeletal abnormalities in monozygotic twinning, predominantly clubfeet.

2. The second theory advocates the occurrence of an early defect in the process of splitting or a delay at the splitting of the embryo that should cause structural anomalies in the fetuses. The ultimate exam-ple of this theory is the conjoined twins.

3. The third theory associates fetal anomalies to a vascular compromise secondary to a shared placenta. Syndromes that relate to this etiology include twin reversed arterial perfusion, twin–twin transfusion syndrome, and twin embolization syndrome.

Unique monozygotic monochorionic syndromes

Twin-twin transfusion (Stuck twin) Definition Twin-twin transfusion syndrome is a pathological condition whereby a donor fetus bleeds into the circulation of a recipient fetus through the abnormal inter-twin placental anastomoses. The donor twin becomes anemic, hypovolemic, growth restricted, and as a consequence has a reduced urinary production. Since swallowing of the fluid is not impaired, the amniotic fluid volume progressively decreases. The recipient twin becomes hy-pervolemic. Lacking a mechanism to remove blood, the recipient twin eliminates as much fluid as possible, thus becoming hypercytemic or even hydropic in the more severe cases. The elevated urinary production from the recipient twin leads to polyhydramnios and an overdistension of the amniotic cavity, that compresses the donor and it’s vascular supply against the uterine wall, further decreasing perfusion to the donor fetus. The reduction in amniotic fluid on the donor side results in a close apposition of the inter-twin membrane that fixes the donor fetus to the uterus, a condition nicknamed “stuck twin”181. The donor twin: • Chronic blood loss: • anemic, • hypovolemic, • hypoxia • growth restricted, • decreased renal flow, • oligohydramnios • vascular

compression

The recipient twin: • Chronic blood gain: • hypervolemic • polycytemic • embolization • hypertension • cardiac failure • hydropic • polyhydramnios

In twin-twin transfusion syndrome (top drawing, note the artery to vein connection) the donor twin (on the left) becomes anemic, hypovolemic, growth restricted, and as a consequence has a reduced urinary produc-tion. Since swallowing of the fluid is not impaired, the amniotic fluid volume progressively decreases (yel-lows lines representing the interamniotic membrane. Conversely, the recipient twin (on the right) becomes hypervolemic. The elevated urinary production from the recipient twin leads to polyhydramnios and an overdistension of the amniotic cavity, that compresses the donor and it’s vascular supply against the uterine wall, further decreasing perfusion to the donor fetus. The end condition is the “stuck twin” (lower drawing)

20

Sonographic features Commonly reported criteria for the diagnosis of twin-to-twin transfusion syndrome are:

• Monochorionic placentation, with visualization of a separating membrane; • Same sex fetuses; • Mid-trimester polyhydramnios-oligohydramnios sequence (polyhydramnios at the recipient’s sac and

oligohydramnios at the donor’s sac), in the absence of other causes of abnormal amniotic fluid vol-ume;

• Size discordance, with the larger twin in the polyhydramniotic sac and the smaller stuck against the uterine wall (abdominal circumference difference or weight discrepancy > 20%)182,183,184,185,186;

• Non-visualization of the donor’s bladder with enlarged recipient’s bladder; • Abnormal Doppler S/D ratio at the umbilical cord (> 0.4). The absent end-diastolic flow in the do-

nor’s umbilical artery accompanied by venous pulsation in the recipient’s umbilical vein are usually associated with a poor prognosis187,188,189,190,191,192,193;

• Hydrops or evidence of congestive heart failure of either twin (although more common in the recipi-ent twin)194,195,196;

The difference in size of the cord is clearly visible.

The anastomosis is occasionally visible.

As the transfusion progresses, the donor twin looses more fluid and the recipient produces more. The net effect being that the membranes becomes closely apposed to the donor-twin

21

Before the donor twin becomes stuck, a typical intermediate stage is the “folding membrane” stage where the redundant membrane progres-sively folds as it wraps itself around the donor.

At some point the “folding membrane” stage could impose for an amniotic band syndrome. Awareness of the condi-tion will prevent a misdiagnosis.

The typical appearance of the “stuck twin” immobi-lized in a portion of the uterus

22

The criteria used to select cases for the open multicentric randomized trial to evaluate serial amniodrainage versus endoscopic placental surgery in the treatment of twin-to-twin transfusion syndrome are197:

• Twin pregnancy diagnosed as monochorionic during a first trimester scan and/or as having a single placental mass and concordant sex on the second trimester scan.

• Polyhydramnios in one sac with a deepest vertical pool of amniotic fluid of at least 6.0 cm at less than 20 weeks of gestation, 8.0 cm at 20 to 22 weeks, and 12.0 cm at 23 to 25 weeks. The polyhy-dramnios should be related to polyuria with a distended fetal bladder during most of the examination period.

• Oligohydramnios (stuck twin) in the other sac with a deepest vertical pool of amniotic fluid of at most 2.0 cm. The oligohydramnios should be likely related to fetal oliguria with a collapsed bladder during most of the examination period.

In the most severe forms, the diagnosis should not be difficult: a single placenta, massive polyhydramnios in the sac of the recipient twin, a stuck donor twin attached to the uterine wall with poor mobility and obvious growth discordance. Milder forms of the disease are more difficult to diagnose due to the lack of uniform criteria; however, one should suspect twin-to-twin transfusion in the presence of amniotic fluid discrepancy between the cavities, regardless of the percentage of weight discrepancy between the twins. An inter-twin hemoglobin difference >2.4 gm/dl in fetal blood obtained by cordocentesis has been shown to be consistent with stuck twin syndrome198. Prevalence Twin-to-twin transfusion complicates about 15-35% of monochorial twin gestations and is responsible for 17% of the perinatal mortality in multiple pregnancies199,200. Pathogenesis If embryonic splitting occurs before day three after fertilization, two independent fetuses with separate pla-centas will result. A single placenta with two amniotic cavities occurs if splitting takes place between days four and seven. If division of the embryoblast occurs after about eight days, the twins share a single placenta and amniotic cavity (monochorionic-monoamniotic twins). Division beyond day 12 results in conjoint twins201. When two fetuses share the same placenta, vascular anastomoses develop between their circulations. These anastomoses can be of three types: vein-to-vein, artery-to-artery, and artery-to-vein. Even when there are multiple vascular connections within a single placenta, no transfusion should occur provided the anastomoses are balanced. Placentas from pregnancies with twin-to-twin transfusion syndrome have fewer anastomoses, which are more likely to be solitary and of deep arterio-venous type than those without twin-to-twin transfu-sion syndrome202,203,204,205,206,207. When the transfusion occurs, the donor or “pump” twin becomes hypo-volemic due to blood loss. Hypoxia develops because of placental insufficiency, which is also responsible for intrauterine growth retardation. Poor renal perfusion leads to oligohydramnios. This latter feature, when se-vere, is responsible for the classical appearance of the stuck twin: the amniotic sac becomes too small, the amniotic membrane comes in close contact with the body of the “pump” twin and the fetus appears trapped to the uterine wall. Hypervolemia with increased renal perfusion leads to polyhydramnios in the sac of the re-cipient twin208. Since there is no loss of protein or cellular components from its circulation, colloid osmotic pressure draws water from the maternal compartment across the placenta, establishing a vicious cycle of hy-pervolemia, polyuria and hyperosmolarity leading to high output cardiac failure, hydrops and polyhydram-nios209. Prognosis Basically, the prognosis depends on the stage of the pregnancy at which the disease manifests and the severity of the circulatory imbalance. When signs of twin-twin transfusion syndrome are seen at mid-gestation there is a higher risk of perinatal morbidity and mortality210,211,212. Intrauterine hypoxia, pre-term delivery, and death of one fetus (usually the donor) with subsequent death or hypoxia-ischemia in the surviving twin are the most common complications to watch for in these pregnancies.

23

Management Aggressive treatment appears to be more successful than conservative medical management213. For many years, the most employed technique has been amnio-drainage of the recipient amniotic sac by serial amnio-centesis214,215,216,217,218,219,220,221. The aim of amniodrainage is to restore the normal amniotic fluid volume and thereby decreasing the pressure on the donor vasculature and improving its perfusion, and decreasing the risk of polyhydramnios-induced preterm labor and thus prolong the pregnancy. The number of amniocentesis and volume of fluid drained varies, depending on the severity of the polyhydramnios, degree of fetal compromise and maternal symptoms. Approximately one liter of amniotic fluid should be removed for every 10cm of amniotic fluid index elevation. Possible mechanisms of action for serial amniodrainage are:

• restoration of placental shape with realignment of maternal spiral artery entry points with placental lobules; and

• reopening of compensatory low-pressure veno-venous anastomoses. Amniodrainage, however, only temporarily corrects the symptoms and multiple complications and does not alter or interrupt the pathological chain of event responsible for the condition. Perinatal survival with am-niodrainage is quoted as 61% ± 22%. However, there remains a risk of serious chronic handicap in 19% ± 5% of the survivors222,223, 224,225,226,227,228,229,230,231,232,233,234,235. More recently, ablation of communicating vessels on the placental surface by neodymium YAG laser guided by fetoscopy has been pro-posed236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252. The aim of this technique is to interrupt the abnormal placental vascular communications between the twins. Although the survival rate comparing amniodrainage with fetoscopy is similar, preliminary studies suggest a significant decrease in neurological handicap among survivors submitted to fetoscopy (Table I). A multicentric randomized trial is currently being conducted by the EUROFOETUS group in order to answer this question.197 Although some authors advocate an intentional rupture of the intervening membrane (amniotic septostomy) to equalize the volume of fluid in both sacs253,254 it has been argued that artificial normalization of the fluid vol-umes with septostomy would not change the hemodynamic status of the fetuses and disruption of the mem-branes could lead to death of the fetuses from cord entanglement255. Ligation of the umbilical cord256 of the donor twin and maternal treatment with indomethacin or digoxin257, 258 have also been proposed as therapeu-tic options in selected cases. Further information on treatment can be obtained at www.fetalmd.com. Table I. Management of twin-twin transfusion syndrome by laser coagulation.

Outcome Intact survival of Author

Year Study design

N cases Technique

both twins

one twin

Death of both twins

Neurological handicap in survivors

De Lia et al.250 1995

Case series 26 Nd:YAG laser coagulation of the placental vessels crossing the interamniotic membrane

34.6% (9/26)*

34.6% (9/26)

30.8% (8/26)

4% (27/28)

Ville et al.238 1998

Case series 41 Nd:YAG laser coagulation of the placental vessels crossing the interamniotic membrane

36.5% (15/41)

41.5% (16/41)

22% (10/41)

6.5% (3/46)

Hecher et al.251 1999

Comparative study

116 Nd:YAG laser coagulation of the placental vessels crossing the interamniotic membrane (n=73; Hamburg) Serial amniocentesis (n=43; Bonn)

42% (31/73) p=1.00 42% (18/43)

37% (27/73) p=0.058 19% (8/43)

3% (2/73) p=0.003 19% (8/43)

6% (5/89) p=0.030 18% (8/44)

De Lia et al.249 1999

Case series 67 Nd:YAG laser coagulation of the placental vessels crossing the interamniotic membrane

56.7% (38/67)

25.4% (17/67)

17.9% (12/67)

4.3% (4/93)

*one triplet pregnancy

24

Differential diagnosis The differential diagnosis should mainly include twins of discordant size that do not have the transfusion syndrome as the underlying pathophysiologic mechanism for the problem. Some authors have proposed a new entity called twin oligohydramnios-polyhydramnios sequence259,260, of which twin-twin transfusion would be part. Histopathological studies of the placenta are required to differentiate twin-twin transfusion from the other conditions included in twin oligohydramnios-polyhydramnios sequence. Isolated intra-uterine growth restriction can be considered if the growth discrepancy is less than 15% and the other features of the syn-drome are not present. Dichorionic twin pregnancy with fused placentas and growth restriction of one of the fetuses is another condition that can lead to misdiagnosis. This can be excluded if the twins have different sexes or after birth, by histopathological analysis of the placenta. Other differential diagnoses to be considered are: TORCH infections restricted to one twin, asymmetrical chorionic development, feto-maternal hemor-rhage, abruption, agenesis of the ductus venosus and bilateral renal agenesis261,262,263. Associated syndromes The over-distension of the uterus caused by the polyhydramnios can cause pre-term labor, amniorrhexis, abruptio placentae, and maternal respiratory and abdominal discomfort. Death of one twin is associated with at least a 25% risk of death or neurological handicap of the surviving twin. Although the cause of neurological handicap has been usually attributed to embolization264,265,266,267,268,269, currently accepted evidence points out severe hypotension with hemorrhage from the live fetus into the dead fetoplacental unit as the causative fac-tor45,46,270.

Fetus papyraceous Papyraceous fetus is characterized by a macerated fetus, resulting from an early loss (second trimester) of one twin, and may affect both mono and dichorionic gestations. The non-viable fetus is compressed by the ex-panding sac of the co-twin and partially absorbed throughout the pregnancy271,272. The surviving twin often has sequelae of twin embolization syndrome such as aplasia cutis, a rare disorder characterized by localized absence of skin273,274.

A macerated fetus next to the live cotwin.

Twin embolization syndrome

Definition Twin embolization syndrome is a complication of monozygotic twinning following in utero demise of the co-twin 275. It results from the embolization of placentary and fetal thromboplastins or to the direct embolization of necrosed fragments of the placenta from the dead fetus, disseminated intravascular coagulation causing embolization, or even an endarteritis 276, 277. The emboli damages predominantly high vascularized organs such as the brain and kidneys, but can affect almost all organ systems. In the central nervous system these emboli can result in ventriculomegaly, porencephaly, cerebral atrophy, cystic encephalomalacia or micro-cephaly 278. Extracranial abnormalities include small bowel atresia, gastroschisis, hydrothorax, aplasia cutis and renal cortical necrosis 279, 280.

25

Sonographic features Dead twin associated with a surviving twin affected by:

• CNS anomalies: ventriculomegaly, porencephaly, cerebral atrophy, cystic encephalomalacia, micro-cephaly

• somatic anomalies • small bowel atresia • gastroschisis • hydrothorax • aplasia cutis • renal cortical necrosis • limb amputation

After demise of a cotwin, the survivor developed an intraparenchymal hemorrhage in the brain (echogenic area) that evolved into an area of porencephaly.

Differential diagnosis The presence of any of the above mentioned anomalies in the surviving twin with a dead co-twin should raise the suspicion 281. Only fetal death occurring during the second and third terms of pregnancy is considered 282.

Associated syndromes Twin-to-twin transfusion – if one of the fetuses dies due to twin-twin transfusion syndrome, a retrograde blood flow carrying thromboplastic material from the dead twin may reach the blood stream of the survivor through the placental anastomosis, causing disseminated intravascular coagulation. Another possibility is the emboli itself from the dead twin reaching the survivor’s circulation.

Twin-reversed arterial perfusion syndrome (TRAP or Acardiac twin)

Definition Twin-reversed arterial perfusion (TRAP) sequence is a rare condition reported at an incidence of 1% of monochorionic twin pregnancies (0.3:10,000 births), resulting in coexistence of a normal “pump” twin and an acardiac twin 283, 284, 285, 286, 287.

Sonographic features The pathognomonic feature is the presence of reversed arterial perfusion on Doppler. When imaging the um-bilical cord with Doppler, arterial waveforms are observed from the placenta towards the acardiac twin. Ve-nous blood flow takes the opposite direction 288, 289, 290, 291. This finding results from the absence of a heart

26

(pump) in the acardiac twin in association with artery-to-artery communications on the placenta, allowing the acardiac twin to get its blood supply from the normal twin 292. The abnormal fetus presents with impaired or absent development of cephalic pole, heart, upper limbs and many viscera. The lower limbs are relatively well preserved, although clubbing and abnormal toes are com-mon. The appearance is so pathognomonic that the diagnosis has been made as early as 10 weeks293. A 2-vessels cord is the rule (66%)294. The membrane development between the twins is inconsistent and varies from full sac to strips of membrane. Occasionally the umbilical artery of the acardiac twin connects to the superior mesenteric artery (instead of the iliac artery), which is the persistence of a “primitive” vitelline sup-ply.

Reverse flow on pulsed/color Doppler: arterial flow in the vessel going in (under the base line) and venous flow in the vessel going out (above the baseline).

This large mass is an acardiac twin (large cystic hygroma on the left) and ill-defined body parts on the right.

27

Two sets of acardiac twins demonstrate the range of development (or absence of development) of the cephalic end.

Pathogenesis The mechanism that has been proposed is the association of paired artery-to-artery and vein-to-vein anasto-moses through the placenta combined with delayed cardiac function of one of the twins early in preg-nancy295,296. Some authors have also suggested that aneuploidies could lead the abnormal twin to have a slower development than the healthy twin as a possible etiological factor297. Chromosomal abnormalities have been found in 33% of the acardiac twins 298,299,300. If one twin develops slower, the imbalance in the blood pressure of the twins will result in a retrograde transfer of blood from the healthy twin to the abnormal twin. The retrograde flow of poorly oxygenated blood through the developing heart of the abnormal twin interferes with the development of that twin’s heart that rarely goes beyond the stage of tubular heart causing the “acar-dia”. The upper half of the body of an acardiac twin is extremely poorly developed and, sometimes, not de-veloped at all. Head, cervical spine and upper limbs are usually absent. Edema and sonolucent areas in the upper body, consistent with cystic hygroma, are common. In contrast, the lower half of the body, although malformed, is better developed. This pattern of development may be explained by the mechanism of perfusion of the acardiac twin. Blood that enters the abdomen of the fetus is deoxygenated blood that left the normal twin. The morphological abnormalities in the acardiac twin are consistent with perfusion of tissues supplied by the common iliac and lower branches of the aorta with deoxygenated blood. Most of the oxygen available is extracted when the blood enters the acardiac twin, allowing for some development of the lower body and extremities. Lower pressure in the retrogradely perfused upper half of the body, combined with low oxygen saturation impairs the development of this area. The acardiac twin is thus, a parasite301,302. It requires blood pumped from the normal twin to keep developing, putting the pump fetus at risk of high output cardiac failure303. The risk is directly dependent on the size of the acardiac twin: the higher the weight of the acardiac twin, the higher the risk of cardiac failure and death for the normal twin. Overall only 50% of pump twins survive, and the mortality for acardius is 100%304,305,306.

28

In the twin-reversed arterial perfusion syndrome the “acardiac” twin is perfused retrogradely with poorly oxygenated blood that should have gone to the placenta. The mechanism that has been proposed is the association of paired artery-to-artery and vein-to-vein anasto-moses through the placenta combined with delayed cardiac function of one of the twins early in pregnancy. If one twin develops slower, the imbalance in the blood pressure of the twins will result in a retrograde transfer of blood from the healthy twin to the abnormal twin. The retrograde flow of poorly oxygenated blood through the developing heart of the abnormal twin interferes with the development of that twin's heart that rarely goes beyond the stage of tubular heart causing the “acardia”. The upper half of the body of an acardiac twin is poorly or not developed, while the lower half of the body, although malformed, is better developed. The acar-diac twin is thus, a parasite. It requires blood pumped from the normal twin to keep developing, putting the pump fetus at risk of high output cardiac failure.

Management The management includes conservative and invasive therapies. Conservative management includes serial cardiotocography (CTG), ultrasonography and echocardiography, and opportune delivery. Non-invasive therapies may be used supporting the cardiac function of the pump twin with digoxin and indomethacin. The more invasive management consists in termination of pregnancy or interruption of flow to the acardiac fetus, by surgical extraction (hysterotomy with selective delivery of the acardiac twin) and ligation of the acardiac twin’s umbilical cord307,308 ultrasound-guided embolization of the cardiac twin’s umbilical artery with abso-lute alcohol309, platinum coils or thrombogenic coils, laser vaporization310,311. Large numbers are not available to compare the various techniques.

Nomenclature Authors have had a field day at creating a nomenclature for each variant (table). This is of little significance, since the disorder is invariably fatal, and the only concern is the preservation of the pump twin. Name Malformation Acephalus No cephalic structure present312 Anceps Some cranial structure and or neural tissue present313 Acormus Cephalic structure but no truncal structures Amorphus No distinguishable rostral or caudal structure314

Differential diagnosis Few entities can resemble an acardiac twin. Occasionally a twin-to-twin transfusion could impose for a TRAP. These can be differentiated by the recognition of a membrane (even in a stuck twin), and of course,

29

cardiac activity in the smaller fetus. A fetal demise in a twin pregnancy could also look like an acardiac, how-ever, there should be no Doppler signal in the dead fetus.

Associated syndromes None.

Conjoined twins

Definition Conjoined twins are monochorionic-monoamniotic twins fused at any portion of their body as a result of an incomplete division of the embryonic disk, which occurs after the 13th day of conception315,316,317,318,319,320. The term “conjoined” is actually a misnomer, since most authors consider the pathogenesis of the condition to result from failure of complete separation, instead of fusion of twin321.

Sonographic features The minimal sonographic criterion for the prenatal diagnosis of conjoined twins is the visualization of fused portion of the bodies of monozygotic-monoamniotic twins. Aside from this basic criterion, several sono-graphic signs (listed below) can be observed in this condition. Careful search for these features and serial scans for confirmation are recommended to prevent misdiagnosis322. The following sonographic criteria can also be observed in conjoined twins:

• Bifid appearance of the first-trimester fetal pole (“V” or “Y” shaped twin pregnancy), continuous skin contours at the same anatomic level320

• Absence of a interamniotic membrane between the twins • Inability to separate fetal bodies • Presence of fetal anomalies • Abnormal number of vessels (more than three) in the umbilical cord • The heads and bodies of both twins are seen at the same level 323 • Unusual extension of the spines • Unusual proximity of the extremities320 • Permanent position of the fetus relative one to another, even after external stimulation or maternal

movement • Presence of a single heart

One unusual case of conjoined twins that only shared a part of the cord has also been described324.

The presence of more than 3 vessels in a cord is a strong marker of conjoint twins.

30

The heads are seen in an unnatural position at the same and constant level.

Conjoint abdomen in frontal position. Note the stomach bubbles in diagonal positions.

A shared heart is a sign of non-operability. The presence of these signs varies according to the different types of conjoined twins. These must be consid-ered whenever a monochorionic and monoamniotic pregnancy is suspected. Discordant presentation does not exclude conjoined twins. Although the diagnosis of conjoined twins is easier during the first trimester, the type and severity of the condition is better achieved during the second trimester, when a more precise evalua-tion of the shared organs can be done325,326,327. The diagnosis with 3D-transvaginal sonography during the first trimester has also been described328,329. If diagnosis is made before viability, termination of pregnancy can be offered330,331,332,333,334.

31

Prevalence This is a rare condition and the reported frequency varies from 0.1-0.35:10,000 births320. If stillborns are ex-cluded the estimate is 0.05:10,000. Females are more commonly affected with a male to female ratio of 1.6-3:1. No association with maternal age, race, parity or heredity has been observed. The recurrence risk is neg-ligible320,335.336.

Prognosis Most of the conjoined twins are born prematurely, 40% are stillborn, and 35% die within 24 hours337. Among the survivors, the prognosis as well as attempts of surgical separation will depend on the type of conjunction, degree of involvement of the shared organs, and the presence of associated anomalies320,338. The most omi-nous prognosis is among those twins who share liver and or heart. Attempts of separation in cases of a com-mon liver can be done as long as two biliary tracts are seen. In the presence of a shared heart, separation is only attempted if two normal hearts coexist in a single pericardium339,340.

Management The method of choice for delivery is C-section to maximize survival and prevent maternal and fetal trauma341,342.

Classifications Conjoined twins are classified according to the area of the bodies where the fusion takes place and the in-volvement of internal organs. The symmetrical and equal forms, in which the twins have equal or nearly equal duplication of structures, are called duplicata completa. When there is an unequal duplication of structures they are called duplicata incompleta, and this category includes the most severe types of conjoined twins in which just few organs systems are duplicated. The most frequent varieties of conjoined twins are thoraco-pagus (40-74%), omphalopagus (10-33%), pygopagus (18%), ischiopagus (6%) and craniopagus (1-6%). The classification of conjoined twins is described in the table.

Classification of conjoined twins Duplicata incompleta: duplication occurring in only one part or region of the body.

Examples: Diprosopus: one body, one head, two faces 343, 344 Dicephalus: one body, two heads Dipygus: one head, thorax and abdomen with two pelvis, and/or external genitalia 345

32

Duplicata completa: two complete conjoined twins Terata catadidyma: conjunction in the lower part of the body

Examples: Ischiopagus: joined by inferior portion of coccyx and sacrum Pygopagus: joined by lateral and posterior portion of coccyx and sacrum Terata anadidyma: conjunction in the upper part of the body

Examples: Syncephalus: joined by the face Craniopagus: joined at homologous portion of the cranial vault Terata anacatadidyma: conjunction in the midpart of the body

Examples: Thoracopagus: joined at the thoracic wall 320 Xiphopagus: joined at xiphoid process 346 Omphalopagus: joined in the area between the xiphoid cartilage and the umbilicus315 Rachipagus: joined at he level of the spines above the sacrum Adapted from: Romero, R., Pilu, G., Jeanty, P., Ghidini, A. and Hobbins, J.C.(1988). Prenatal Diagnosis of Congenital Anomalies, p 405. In one attempt to universalize the current nomenclature, a new classification was proposed recently based on the theoretical site of union: Ventral union: twins united along the ventral aspect Cephalopagus: fused from the top of the head down to the umbilicus. Two rudimentary (fused) faces, four arms and four legs. Lower abdomen and pelvis are separated347. The cephalothoracopagus Janiceps type is a rare variety of conjoined twins in which the fetuses are joined face to face, the face of each fetus being split in the midline and in half turned outward, so that each observed face is made up of the right face of one fetus and the left face of the other. The name originates from Janus, in Roman mythology, the god of gates and doorways, his statue with two faces, facing east and west for the beginning and ending of the day; and caput, head348,349.

33

Thoracopagus: united face-to-face from the upper thorax down to the umbilicus, with heart involvement always. Four arms, four legs, two pelvises. Omphalopagus: joined face-to-face primarily in the area of the umbilicus, and sometimes involving the lower thorax, but always preserving two distinct hearts. There is not even a cardiac vessel in common. Two pelvis, four arms and four legs350,351. Ischiopagus: united ventrally from the umbilicus to a large conjoined pelvis with two sacrums and two sym-physes pubis. They appear more frequently joined end-to-end with the spine in a straight line, but they can also present face-to-face with a joined abdomen. Four arms, four legs, and in general, a single external genita-lia and a single anus. Lateral union: twins joined side-by-side with shared umbilicus, abdomen, and pelvis. Parapagus: twins that share a conjoined pelvis, one symphysis pubis and one or two sacrums. When the union is limited to the abdomen and pelvis (does not involve the thorax) it is called dithoracic parapagus. If there is one trunk with two heads it is called dicephalic parapagus. If there is a single trunk and a single head with two faces they are diprosopic parapagus. Two, three or four arms, and two or three legs. Dorsal union: twins joined at the dorsal aspect of the primitive embryonic disc. There is no involvement of thorax and abdomen Craniopagus: united on any portion of the skull, except the face or foramen magnum. They share bones of the cranium, meninges, and occasionally brain surface. Two trunks, four arms and four legs352. Pygopagus: they share dorsally the sacrococcygeal, perineal regions and occasionally the spinal cord. There is one anus, two rectums, four arms and four legs. Rachipagus: twins fused dorsally above the sacrum, involving different segments of the column. This type is extremely rare.

Differential diagnosis Conjoined twins have a unique presentation and the few differential diagnoses could include lymphangioma, teratoma, or cystic hygroma.

Associated syndromes Congenital anomalies of organs other than the shared ones are present in 50% of the cases of conjoined twins. Cardiac defects are the most common association (20-30%) and thus echocardiography is recommended in all cases. Neural tube defects and midline fusion defects, orofacial clefts, imperforate anus and diaphragmatic hernia are also frequently seen. Polyhydramnios is observed in 50-75% of the cases.

Fetus-in-fetu

Definition A fetus-in-fetu is an encapsulated, pedunculated vertebrate tumor. It represents a malformed monozygotic, monochorionic diamniotic parasitic twin included in a host (or autosite) twin (see Etiology below). Character-istically the fetus-in-fetu complex will be composed of a fibrous membrane (equivalent to the chorioamniotic complex) that contains some fluid (equivalent to the amniotic fluid) and a fetus suspended by a cord or pedi-cle. The presence of a rudimentary spinal architecture is used to differentiate a fetus-in-fetu from a teratoma, since teratomas are not supposed to develop through the primitive streak stage (12-15 days). This last criterion has been considered too stringent by many authors who regard a rudimentary body architecture (metameric segmentation, craniocaudal and lateral differentiation, body coelom, “gestational sac”), or the presence of an associated fetus-in-fetu as equivalent criteria. Although teratomas can achieve striking degrees of differentia-tion by the inductive effect of adjacent tissues on one another, they do not present the criteria mentioned above.

34

Synonyms As for any unusual anomalies, several descriptive terms have been used. These include: cryptodidymus (κριπτο = hidden, διδυµος = twin), dermocyme (δερµα = skin, κυµα = fetus), double monster, endocyme fetus (ενδον = inside, κυµα = fetus) [note that the word fetus is redundant], fetiform teratoma, fetal inclusion, included heteropagus twin (ετερος = other, παγος = which is fixed) and suppressed twin.

Prevalence The prevalence is unknown. About 70 cases353,354,355,356,357,358,359,360,361,362,363,364,365,366,367,368,369,370,371,372,373,374,

375,376,377,378,379,380,381,382,383,384,385,386,387,388,389,390,391,392,393,394,395,396,397,398,399,400,401,402,403,404,405,406,407 ,408,409,410,411,

412,413,414,415,416,417 have been reported but this number varies according to how strictly identification criteria are used (see Definition above). Several cases have been formally recognized by some as fetus-in-fetu, while categorically rejected by others. Seven cases have been detected in utero. An estimated frequency of 0.02:10,000 is commonly reported in the literature, but this number is based on the unsubstantiated assump-tion that fetus-in-fetu represents 5% of conjoined twins. Further, (see Etiology) the current trend is to consider that fetus-in-fetu does not represent a form of conjoined twins. The male-to-female ratio in the 39 reports that we reviewed was M1.3:F1. This is in contrast with conjoined twin, which occurs predominantly in girls.

Historical review Several cases of fetus-in-fetu were reported in the past, and no distinction from teratoma was done until the first quarter of this century. For this reason, those reports that did not clearly identify the presence of a spine are subject to caution. Further, because of possible confusion with abdominocyesis, cases in women of child-bearing age should be interpreted cautiously. The most credible old cases are those reported by Young, Highmore and Taylor. Only the first two reports include figures. Young reports the case of an 18-week-old boy examined for vomiting. On physical examination, a smooth, round tumor was palpated in the left upper quadrant. The patient was lost to follow-up but returned 5 months later, emaciated. The tumor had grown and extended to the scrobiculus cordis (the epigastric fossa), and the child poorly tolerated breast-feeding. Young describes episodes of enlargement and decrease of the abdominal perimeter, which he attributes to accumula-tion of fluid in the cyst. The child died at 9 months. On autopsy, a large mass occupying most of the abdomen was found. Opening the cyst revealed the fetus-in-fetus. Young gives a remarkably complete description of the findings. The case reported by Highmore368 is even more extraordinary in that it occurred in a teenage boy. This 15-year-old boy had a 7-year history of abdominal complaints and mass. As in the previous case, the child died of malnutrition. At autopsy, a large tumor containing a fetus was discovered.

Drawing from the case reported by Highmore.

Etiology Several etiologies have been proposed. A primordial organizer defect was once thought to explain dermoids, teratoma and embryoma. Another theory suggested that the fetus-in-fetu derived from germ cells from the host that evolved on their own. This appears to be supported by the occasional localization in an ectopic testicle. However, that localiza-

35

tion can also result from migration of the fetus-in-fetu along with the germ cells, when the germ cells of the host return from the yolk sac into the retroperitoneal cavity on their way to the gonads. A parthenogenetic origin has also been suspected. In this theory, germ cells from the retroperitoneal region (where they normally are located) are parthenogenetically stimulated and evolve into a rudimentary fetus. Histocompatibility studies and gene markers do not support parthenogenesis as a likely etiology. In the continuum theory of monozygous twin, a progression from normal twin to conjoined symmetrical twins into asymmetrical twin (acardiac twins) and then into parasitic twins, included twins and then teratoma is hypothesized. As mentioned under Prevalence, the incidence is about equally divided among sexes (with a slight male predominance in this review), which is an argument against the continuum theory and the highly differentiated sacrococcygeal teratoma theory since conjoint twins and sacrococcygeal teratomas are more common in females. Willis considered that the fetus-in-fetu did not represent a monoamniotic twin but instead an included monozygotic diamniotic parasitic twin within the host twin: “It is, I believe, a mistake to suppose that a gentle series of gradations exists between double monsters and malformed twins on one hand and teratomas on the other—a mistake widely promulgated because of the prevalent view that teratomas are included monsters or malformed twins. The sooner this misconception is abandoned, the better”418. His postulate explains why in all extracranial locations the fetus-in-fetu is embedded in a gestational sac. If the fetus-in-fetu was a conjoined twin, it would have to be monoamniotic and thus would not have its own gestational sac. This theory has been widely accepted.

Pathogenesis The currently accepted mechanism is the embedding of a twin due to vitelline circulation anastomoses. Vas-cular anastomoses between twins have variable repercussions, depending on the vessels anastomosed and the location of the anastomoses. The most benign anastomoses are superficial connections of similar vessels on the surface of the placenta. These connections between artery and artery or vein and vein are common and of limited significance when they occur after the first few weeks of gestation. When they occur early, and one fetus has a slight developmental delay, they result in the twin reversed arterial perfusion syndrome. Ana-stomoses that are between dissimilar vessels and occur in the placenta are responsible for the twin-to-twin transfusion syndrome.

Anastomoses between vitelline vessels is believed to cause the common form of fetus-in-fetu Finally, anastomoses between vitelline vessels —only possible when the twins are monochorionic—are as-sumed to cause fetus-in-fetu by a mechanism similar to that which produces acardiac twins. The cardiac de-velopment of the affected twin is impaired by the reversal of the flow in its heart. This stunts the growth of the affected fetus, and as the host grows it progressively embeds the smaller twin around the third week. A few intracranial cases have been described. The location in the skull results from a different embryological mechanism. To be imbedded in the ventricle, a fetus-in-fetu has to separate at a much latter date than those that are imbedded in the retroperitoneum. At 15 days, when the embryo is at the bilaminar disc level, the primitive streak develops. At the cephalic end of the streak, a depression, the primitive knot or Hensen's node, forms and extends cranially. The invagination of the cells into the depression is at the origin of the mesoderm and forms the notochordal process (or blastopore). The blastopore extends to become the notochord, which elongates towards the cranial end. If a second differentiation focus occurs in the bilaminar embryo and grows

36

at the same rate as the primary focus, it will form a craniopagus conjoint twin. If the second differentiation focus grows slower than the primary focus, it will be engulfed in the invagination of cells and may arrest in what will ultimately become the ventricles. A fetus-in-fetu might thus also arrest along the central canal of the spinal cord. In intracranial fetus-in-fetu, one does not expect to find a gestational sac (amnion or chorion equivalent), and indeed none of the intracranial cases have described any surrounding membranes.

Primitive streakPrimitive groove

Primitive knotNotochordalprocess

Amnioticcavity

Yolk sac

Secon d d if fe ren t ia t io n fo cusSecond d iffe ren t ia t ion fo cus

The cause of intracranial and spinal fetus-in-fetu is probably due to the presence of a second differentiation focus in the bilaminar embryo.

Localization The majority of fetus-in-fetu are retroperitoneal, but some have been found in the mesentery adrenal, cranial cavity, lateral ventricles, pelvis, coccyx, inguinal region, testicles and scrotum. Thus, most of the resting places are retroperitoneal or on the path that the germ cells follow on their way back from the yolk sac to the retroperitoneum and onto the gonads. When located on ectopic testes, they may be intraperitoneal. The af-fected testicle is usually ectopic or undescended, probably because the added bulk impairs the migration of the cells.

Vascularization As expected from the etiologies, most fetus-in-fetu are connected to the host by vessels originating from or around the superior mesenteric artery, a derivative of the right vitelline artery in mammals. The artery of the fetus-in-fetu derives from the vitelline artery and thus is the equivalent of a superior mesenteric artery. In the host, if the superior mesenteric artery is not directly involved, the connection is usually with direct branches from the aorta, small retroperitoneal or diaphragmatic vessels. In a testicular location, spermatic vessels or even renal and adrenal vessels may be involved. In only a few cases, a definite vascular connection can be recognized between the fetus-in-fetu and the host. In other cases, a capillary system exists between the two circulations. Since the fetus-in-fetu does not have a cardiac system, the severe hypoxia is responsible for the lack of evolution.

Age at detection Only a few cases have been detected prenatally. Most cases are discovered in newborns or small children.

Weight The weight varies from a few grams up to 2000 or even 4000g. There is some inexactitude in the report of the weights since some reports mention the weight of the whole tumor, while others report the weight of the fe-tus-in-fetu alone.

37

Presenting symptoms in children Aside from a few fortuitous discoveries, the disorder usually becomes apparent from its compression of adja-cent organs, principally the gastrointestinal tract.

Number Usually one fetus is found, but several instances of two, three, five or even more have been described. When several fetuses are present, they usually share a same sac, but some may have their own sacs.

Zygosity Studies of gonads 419, blood types, chromosomes, and red cell antigens (ABO, Rh, M, N, S, P1, K, Fy and Jk)

have shown the fetus-in-fetu to be monozygotic to the host. It is not surprising, however, that the fetus-in-fetu has the same blood type as the host, since it is perfused by the host. There have been no recorded cases of dizygosity. However, as in acardiac twins, the combination of a normal twin with a twin that has lost a gono-somic chromosome and thus appears as a 45,X0 could potentially be found.

Macroscopic appearance At surgery, the fetus-in-fetu appears as a well-circumscribed mass bound by a fibrous membrane. Inside the mass the fetus-in-fetu is suspended in straw-colored fluid by a pedicle. Two vessels (an artery and a vein) travel along the pedicle. The fluid is generally not abundant and has been described as containing sebaceous material. The origin of this fluid is uncertain. Several authors have pointed out that the membranes of a nor-mal embryo are not responsible for the production of amniotic fluid. They would more likely act as semiper-meable membrane. In fetuses past 12 weeks, the urinary system produces the fluid and the gastrointestinal system reabsorbs it. Since no fetus-in-fetu has ever been described to contain a urinary system, and the seg-ments of gastrointestinal tract that are found are too incomplete to have any reabsorptive capabilities, the fluid is probably in communication with the extra-cellular fluid of the fetus-in-fetu and maintained in the amniotic cavity solely by osmotic and oncotic pressure. The presence of chorionic villi has only been reported in one case. Except for one quote of a 15-year old-saying “Mother, do come to me, I have something alive in my body”, and the mother being quoted as saying that she felt something resembling “the motion of a child during gestation”, no fetal movements have ever been recorded in a fetus-in-fetu. The above record of movement is somewhat doubtful since striated muscles have rarely been found around joints. Yet this host is one of the older hosts described.

What is included Fetus-in-fetu resemble poorly formed acardiac twins. Most every organ has been recognized in various stages of development. The notable exception is the urinary tract, which does not appear to have been recognized in any of the cases that we reviewed. Some structures such as ribs, intrathoracic organs (lung, heart, thymus) and retroperitoneal organs (liver, spleen, kidneys, adrenal glands, pancreas, gonads) are rarely described. An in-complete heart has been found. In one instance, a rudimentary 2-chamber heart was found with the atrium in the caudal position and the ventricle in the cranial position. This is the stage normally reached in a 22-day embryo420. Facial and cranial structures also are uncommonly seen, yet eyes, ears, mouth and poorly organ-ized brain and cerebellum have been observed. The cord that connects the fetus to the membrane has different characteristics than a normal cord: it contains vasa vasorum and nerve fibers. The evolution of the fetus-in-fetu is usually arrested at the first trimester, and further evolution is by mass accretion more than by development. Overall structures derived from the ectoderm are better represented than structures derived from the other two layers. The mesoderm contributes the musculoskeletal system, which is usually well represented, but the other derivatives (the vascular and urogenital system, the spleen and adrenal glands) are uncommonly found. The most commonly represented derivative from the endodermal layer is the gastrointestinal tract, but the liver and pancreas are also often recognized.

38

Ultrasound appearance The few cases detected prenatally all presented as a complex mass. The general appearance is a well-delineated capsule, with an echogenic mass suspended in fluid or partially surrounded by fluid. Occasionally, the diagnosis can be suggested by the recognition of a rudimentary spine.

A fetus in fetu, with a rudimentary spinal organization (Courtesy Caldwell K and Dix P)

Differential diagnosis When discovered in a newborn child during physical examination, the differential diagnosis includes all the common masses such as Wilms' tumor, hydronephrosis, and neuroblastomas. Prenatally, the main differential diagnosis is with teratoma. Teratomas are disorganized congregations of pluripotential cells from all three primitive tissue layers. By differentiation and induction, they can achieve striking organization, with exam-ples of several organs being well formed. However, teratomas do not have vertebral segmentation, craniocau-dal and lateral differentiation, body coelom or systemic organogenesis. Thus the presence of a mass with a spinal organization and surrounded by fluid suggests the correct diagnosis. When spinal structures are not present, most authors have considered that the diagnosis of fetus-in-fetu can still be made when the alternate criteria described under Definition are found. These criteria are sufficiently restrictive that even well organ-ized teratomas cannot fulfill all of them. Teratomas have a definite malignant potential, a feature that has not been reported in fetus-in-fetu. Teratomas occur predominantly in the lower abdomen, not the upper retroperi-toneum. Yet, the coexistence of a fetus-in-fetu and a teratoma as well as the occurrence of a teratoma 14 years after removal of a twin fetus-in-fetu have been reported, supporting the older hypothesis of a continuum be-tween twin and teratoma. Cases of sacrococcygeal fetus-in-fetu should probably be regarded and treated as teratoma, because of the high incidence of teratoma in this region421. Ectopic testicles have a higher incidence of germ cell tumors422, and the differentiation between fetus-in-fetu and teratoma is particularly important. Although the characteristics of intracranial teratoma differ from those of intracranial fetus-in-fetu, Wakai found, in a large review of 245 intracranial teratomas, that there are some transitions between certain teratoma and fetus-in-fetu423. In the older literature, several descriptions of fetus-in-fetu were too vague to be acceptable by current criteria. For example, the case reported by Phillips does not unequivocally suggest the criteria described above and therefore should probably be considered a teratoma. Some have argued that fetus-in-fetu should be considered as teratomas since they do not evolve into lithopedion like fetuses of abdominocyesis. That argument is probably not valid since in abdominocyesis the antigen complements of the host and fetus are different, which contrasts with fetuses in fetu.

Associated anomalies Every organ of the fetus-in-fetu has undergone hypoxic growth and is deformed. Most cases are anencephalic. Usually the body is closed, but ventral wall defects such as omphalocele are common, and a case that suggests a limb-body wall complex has also been described. The host rarely presents any anomalies, except those re-

39

lated to the presence of a space-occupying lesion. Those manifestations have rarely been severe, even in the case of intracranial fetus-in-fetu, although in rare cases, severe hydrocephalus was responsible for the death of the host. One case of Meckel diverticulum and another of skin hemangioma have been described. A malignant degeneration has never been reported, even in the cases that have been allowed to evolve for several years.

Evolution If conservative management is opted for, the fetus-in-fetu do not seem harmful to the host, but in every case in which the fetal mass was not removed at the time of discovery, a slow growth has been described.

Prognosis In the literature of the past century, fetus-in-fetu was fatal to the host because of the compression imposed to adjacent organs. In the more recent literature, the outcome for the host twin is usually favorable. Only a few cases of spontaneous or postsurgical deaths are recorded.

Recurrence risk There is no report of recurrence.

Management Aside from a few attempts, in the first half of this century, to marsupialize fetus-in-fetu, surgical removal is the treatment of choice. The membranous capsule can usually be enucleated from the host with minimal prob-lems. In only a few cases, removal is difficult due to adhesions and this difficulty may precipitate the end of the operation, or even be the reason of the postoperative death of the host. Leaving the capsule, or part of it, has not led to complications, except in very rare cases in which fluid reaccumulated in it.

Heterotopic gestation

Definition An heterotopic pregnancy is the occurrence of a multiple pregnancy in which one or more gestational sacs are implanted outside the uterine cavity (ectopic pregnancy) associated with a single or multiple intrauterine pregnancy (eutopic pregnancy)424,425 ,426 ,427 ,428. It occurs in 1-2.9% of pregnancies after in-vitro fertilization and embryo transfer429,430,431,432,433.

An heterotopic pregnancy is the combination of an ectopic pregnancy with an intrauterine pregnancy.

40

Sonographic features Visualization of one or more intra-uterine gestational sacs associated with one or more ectopic pregnancies, which are classified depending on the site of implantation in:

• Tubal434,435 • Cervical436 • Cornual437,438,439,440 • Abdominal441,442 • Ovarian443,444,445

The diagnosis can be made by transvaginal ultrasound during the first trimester. This diagnosis should par-ticularly be considered in cases with abdominal pain, (vaginal bleeding may be absent446) and those a failed pregnancy with rising β-hCG.

Differential diagnosis The presence of a small pelvic mass associated with an early intrauterine pregnancy is also suggestive of heterotopic pregnancy. The differential diagnosis can be made by the identification of the heartbeat. Patients with diagnosis of ectopic pregnancy, in particular the ones who have undergone infertility treatment, must have the uterine cavity investigated to exclude heterotopic pregnancy. The presence of an intrauterine gesta-tion sac in a patient without symptoms should not exclude the diagnosis of a concomitant extrauterine preg-nancy until the pelvis is carefully visualized447,448. Heterotopic pregnancies can occur even in patients without risk factors.

Associated syndromes This condition is particularly associated with infertility cases that have undergone assisted reproductive tech-niques449,450,451,452,453,454,455,456.

Molar gestation with a concurrent pregnancy The recognition of twin pregnancies that include a complete hydatidiform mole and coexisting fetus have a greater malignant potential and thus should be differentiated from simple partial hydatidiform moles457,458,459,460.

Vanishing twin The three common forms of spontaneous fetal loss in multiple gestation are

1. “the vanishing twin syndrome” which occurs inn the first trimester 2. “the fetus papyraceous” in the second trimester, and 3. “stillbirth” in the third trimester.

Definition First trimester loss of a member of a twin gestation461,462. The incidence of twinning has been reported to be 3.29% and of these, 21.2% demonstrated the “vanishing twin” phenomenon463. The vanishing twin is simply reabsorbed.

Sonographic features Small gestational sac with a fetus whose development lags compared to the other fetus, with any detectable fetal heart activity. The spectrum varies from a crescent-shaped sac adjacent to a normal early gestation (up to 10-14 weeks) to a well-formed but dead fetus (fetus papyraceous / second trimester). Early vanishing twins should be distinguished from implantation bleeds that are not surrounded by a trophoblastic ring464. Sono-graphic evaluation of early gestational bleeds frequently leads to the diagnosis of a vanishing twin, and this is apparently the single complication associated to the disappearance of a twin at this stage465,466. A vanishing

41

twin does not adversely affect the development of a coexisting singleton pregnancy, and therefore the exact distinction from implantation bleed versus vanishing twin may be academic.

At 5-6 weeks 2 gestational sacs are seen. Two weeks later a single fetus is visible and the sac of the other is already partially resorbed at the lower aspect of the image.

In this sequence of images, the first im-age demonstrates the 2 main gestational sacs. The upper fetus is visible but with a questionable/slow heart beat. The lower fetus appears normal. A repeat scan 10 days later (seond image) demonstrates some growth of the first fetus but cessa-tion of cardiac activity. The other fetus (third image) has grown appropriately.

42

In those 4 images, a vanishing twin was suspected in the early examination (image 1). Both embryos had heartbeats but of different rhythms (99 and 141 bpm). A repeat examination 10 days later demonstrates re-sorption of the vanishing twin with normal growth of the co-twin.

Differential diagnosis The differential diagnosis includes implantation bleeds in the early pregnancy, artifactual error (rectus muscle artifact), incomplete scanning technique, and poor quality ultrasound equipment as well as placental cysts after the second trimester. Tomko and Baltarowich have shown that a synechia could also impose for a van-ishing twin467

43

Although a implantation bleed can occasionally impose for a vanishing twin, the lack of trophoblastic ring allows the distinction.

Associated syndromes Fetus papyraceus (see above). This is a macerated fetus delivered with a normal co-twin, and usually embed-ded in the placental membranes468,469,470.

Multifetal pregnancy reduction Multifetal pregnancy reduction is the elective termination of a variable number of fetuses, preferably done between the 10th and the 13th week of gestation, attempting to improve the perinatal outcome of the remaining fetuses471,472,473,474,475,476,477,478,479,480,481,482. It is well known that high order multiple gestations have increased risks for both maternal and fetal complications, and the most common are the entire pregnancy loss, maternal high blood pressure, intrauterine growth retardation, premature rupture of membranes, and pre-term delivery. The occurrence of any of these events increase the risk of perinatal death and that of sequelae, such as inter-ventricular hemorrhage, cerebral palsy, retinopathy, respiratory diseases, and more483,484. The procedure may improve maternal and fetal conditions, thus reducing the risk of prematurity and its associated complica-tions485,486,487,488,489. Although it confers unequivocal benefits to the pregnancy when successful, fetal reduc-tion itself carries risks. The risk of loss of the entire pregnancy is the major concern and occurs in approxi-mately 12% of the cases. Basically the procedure consists of a transabdominal needle injection of potassium chloride into the fetal thorax490,491. If reduction of both fetuses of a monochorionic pair is desired, the procedure may be success-fully accomplished with a single injection in one of the pair492. A special attention should be given to the appropriate use of the terminology selective termination and elective fetal reduction. Although both are pro-cedures applied only in multiple gestations, there are some differences between them. Selective termination is a procedure in which an anomalous fetus in a multifetal pregnancy is terminated to improve the prognosis of the normal co-twin493,494,495,496,497,498,499. It is usually a second trimester procedure that follows the same routine of a first trimester reduction. The term elective fetal reduction is employed to describe reduction of triplets or higher order fetuses to a smaller set (in general, to twins) for medical, psychological, and socio-economic reasons, improving the out-come of the remaining fetuses and reducing the maternal risks as well. Some controversy still persists regard-ing the impact of fetal reduction from triplets to twins. Some authors state that triplet to twin fetal reduction significantly reduces the risk for prematurity and low birth weight, and may be even associated with a reduc-tion at the overall pregnancy loss rate, suggesting thus that it is a medically justifiable procedure, and should

44

be offered in these cases500,501,502,503. Others who recommend the maintenance of the entire pregnancy, state that bed rest starting at the 20th week of gestation, associated with special diet and close prenatal care reduces the prematurity rate and optimize fetal growth, improving the outcome to the levels of a twin pregnancy. Selective termination can be performed any time in pregnancy with good outcome in around 90% of cases, and a total pregnancy loss rate of 11.7%504,505.

Amniocenteses in twins

Diagnostic amniocentesis Although amniocentesis is a well-known safe technique employed in prenatal diagnosis for many years, the risks and benefits should be considered when a multiple gestation is involved. The risk of pregnancy loss when amniocentesis is performed in twins is higher than in singletons. Some authors attribute this increased loss rate to the natural tendency of miscarriage observed in multiple gestations 506, 507, 508. In the past, the most common technique employed the injection of dye in one of the amniotic cavities to dif-ferentiate one sac from the other. Since 1990, the avoidance of methylene dye in prenatal diagnosis has been recommended because of its fetotoxity and a small association with intestinal atresia509, 510, 511.

1 2

3 4

In the double stick technique, a needle is inserted in one sac, the fluid sampled (1) and blue dye injected (2). The fluid equilibrates for a few minutes (3). The second sample is then obtained (4) hopefully clear of the dye. More recently Jeanty et al. have successfully used a single needle puncture with no need of dye injection and the advantages of being less invasive and less painful512. Their results were reproduced by others 513, 514, 515.

45

1 2 3

4

56

7

In the single insertion technique, the needle is inserted near the membrane attachment at a location where both sacs are visible (1). The fluid is then obtained and transferred to the appropriate containers (2). The plastic tubing disconnected and the stylet of the needle reinserted. The needle is then advanced through the membrane (3) under ultrasound guidance. A few cc of fluid from the second sac are aspirated (4) and then the whole assembly (Syringe, and tubing discarded (5) to prevent contamination of the second sample by cells from the first sample. The proper sample is then obtained (6) and transferred to the containers.

Therapeutic amniocentesis Amniocentesis may also have therapeutic applications particularly in acute polyhydramnios, a common com-plication in twin pregnancies, with elevated perinatal mortality if not treated. The overdistension of the uterus provokes maternal discomfort, premature labor, and premature rupture of membranes. The treatment consists of serial amniocenteses to normalize the intrauterine pressure, prevent premature labor, and relieve maternal symptoms. (See twin-to-twin transfusion syndrome, above).

Cervical cerclage Cervical cerclage in multiple gestations remains a controversial matter in prenatal care. Some authors demon-strate a satisfactory fetal survival rate with minimal incidence of maternal complications post cerclage and thus recommend the routine use of the procedure in multiple pregnancies516. Other groups show a higher risk for premature rupture of membranes with no evident benefit for the pregnancy outcome517,518,519,520,521. We believe the twin pregnancy by itself does not justify the procedure. In multiple pregnancies with sets of trip-lets or more, the cerclage should be discussed with the patient, considering risks, and benefits on each case. If there is a history of cervical incompetence, the procedure must be offered independently of the number of fetus.

46

Membranous insertion of placenta Membranous insertion of placenta is a complication that mainly affects higher order gestations (triplets or higher). In such pregnancies a centrally located fetus may have a trophoblast developing predominantly on the uterine tissue between the gestational sacs of the other embryos. As the sac grows that trophoblast will trans-form into a placenta that is predominantly over the membranes of the other embryos. Even with trophotropism (the tendency of the placenta to preferentially develop where maternal exchanges are best) this embryo is at great risk of growth restriction. Should a fetal reduction be considered, this embryo would be a prime candi-date.

This triplet’s placenta is inserted on the membrane with the left-sided twin. Although part of this placenta is in contact with the myometrium (bottom right) this was insufficient for adequate growth of this fetus that was several weeks smaller then the other 2.

References 1 Originally published on www.TheFetus.net ©2000 Philippe Jeanty, MD, PhD, Jacqueline Reyes, MD, Luís Flávio de Andrade Gonçalves, MD, Sandra Rejane Silva, MD. Some images courtesy Gianluigi Pilu, MD. A few drawings adapted from Lifeart from Techpool studio. 2 Sebire NJ, Nicolaides KH. Screening for fetal abnormalities in multiple pregnancies. Baillieres Clin Obstet Gynaecol 1998 Mar;12(1):19-36. 3 Benson CB, Doubilet PM. Sonography of multiple gestations. Radiol Clin North Am 1990 Jan;28(1):149-61. 4 Moore KL, Persaud TVN. The placental and fetal membranes in The Developing Human – Clinical Oriented Embriol-ogy – 5th Edition – 1993 W. B. Saunders Company - Philadelphia 5 Sebire NJ, Snijders RJM, Hughes K, Sepulveda W, Nicolaides KH. The hidden mortality of monochorionic twin preg-nancies. Br J Obstet Gynaecol 1997;104:1203–7. 6 Van Heteren CF, Nijhuis JG, Semmekrot BA, Merkus JM. Discordant fetal growth in multiple pregnancy: intervention should be based on chorionicity. Ned Tijdschr Geneeskd 1999 May 15;143(20):1017-21. 7 Nicolaides KH, Sebire NJ, Snijders RJM. The 11-14 Week Scan: The Diagnosis of Fetal Abnormalities. London: Par-thenon Publishing, 1999. 8 Cameron AH The Birmingham twin survey. Proc R Soc Med 1968 Mar;61(3):229-34

47

9 Benirschke K. The biology of the twinning process: how placentation influences outcome. Semin Perinatol 1995 Oct;19(5):342-50. 10 Husby H, Holm NV, Gernow A, Thomsen SG, Kock K, Gurtler H. Zygosity, placental membranes and Weinberg’s rule in a Danish consecutive twin series. Acta Genet Med Gemellol 1991;40(2):147-52. 11 Denbow ML, Fisk NM. The consequences of monochorionic placentation. Baillieres Clin Obstet Gynaecol 1998 Mar;12(1):37-51. 12 Thigpen J. Discordant twins: a case report. Neonatal Netw 1996 Dec;15(8):35-9. 13 McCulloch K. Neonatal problems in twins. Clin Perinatol 1988 Mar;15(1):141-58. 14 Minakami H, Honma Y, Matsubara S, Uchida A, Shiraishi H, Sato I.Effects of placental chorionicity on outcome in twin pregnancies. A cohort study. J Reprod Med 1999 Jul;44(7):595-600. 15 Malinowski W. Very early and simple determination of chorionic and amniotic type in twin gestations by high-frequency transvaginal ultrasonography. Acta Genet Med Gemellol 1997;46(3):167-73. 16 Monteagudo A, Timor-Tritsch IE, Sharma S. Early and simple determination of chorionic and amniotic type in multife-tal gestations in the first fourteen weeks by high-frequency transvaginal ultrasonography. Am J Obstet Gynecol 1994 Mar;170(3):824-9. 17 Finberg HJ. The “twin peak” sign: reliable evidence of dichorionic twinning. J Ultrasound Med 1992 Nov;11(11):571-7. 18 Rode ME, Jackson M. Sonographic considerations with multiple gestation. Semin Roentgenol 1999 Jan;34(1):29-34. 19 Sepulveda W, Sebire NJ, Hughes K, Odibo A, Nicolaides KH. The lambda sign at 10-14 weeks of gestation as a predic-tor of chorionicity in twin pregnancies. Ultrasound Obstet Gynecol 1996 Jun;7(6):421-3. 20 Kurtz AB, Wapner RJ, Mata J, Johnson A, Morgan P. Twin pregnancies: accuracy of first trimester abdominal US in predicting chorionicity and amnionicity. Radiology 1992 Dec;185(3):759-62. 21 Hertzberg BS, Kurtz AB, Choi HY, Kaczmarczyk JM, Warren W, Wapner RJ, Needleman L, Baltarowich OH, Pasto ME, Rifkin MD et al. AJR Am J Roentgenol 1987 Jan;148(1):151-3. 22 Ayala Mendez JA, Jimenez Solis G, Fernandez Martinez LR, Lopez Rangel JA. Determination by ultrasound of chori-onicity in twin pregnancy. Ginecol Obstet Mex 1997 Mar;65:111-3. 23 Vayssiere CF, Heim N, Camus EP, Hillion YE, Nisand IF. Determination of chorionicity in twin gestations by high-frequency abdominal ultrasonography: counting the layers of the dividing membrane. Am J Obstet Gynecol 1996 Dec;175(6):1529-33. 24 D’Alton ME, Dudley DK. The ultrasonographic prediction of chorionicity in twin gestation. Am J Obstet Gynecol 1989 Mar;160(3):557-61. 25 Townsend RR, Simpson GF, Filly RA. Membrane thickness in ultrasound prediction of chorionicity of twin gestations. J Ultrasound Med 1988 Jun:7(6):327-32. 26 Cheung A, Wan M, Collins RJ. Differentiation of monochorionic and dichorionic twin placentas by antenatal ultrasonic evaluation. Aust N Z J Obstet Gynaecol 1990 May;30(2):134-6. 27 Uccello N, Daniele F, Sannino F, Dell’Isola A, Di Lieto A, Catalano D. Ultrasonic criteria for the evaluation of placen-tation in twin pregnancies. Minerva Ginecol 1989 Feb;41(2):75-7. 28 Winn HN, Gabrielli S, Reece EA, Roberts JA, Salafia C, Hobbins JC. Ultrasonographic criteria for the prenatal diagno-sis of placental chorionicity in twin gestations. Am J Obstet Gynecol 1989 Dec;161(6):1540-2. 29 Bajoria R, Kingdom J. The case for routine determination of chorionicity and zygosity in multiple pregnancy. Prenat Diagn 1997 Dec;17(13):1207-25. 30 Zondervan HA, Stoutenbeek P, Arabin B, van Binsbergen CJ, Hasaart TH, Nijhuis JG, Sollie-Szarynska KM. Third circulation: twin transfusion syndrome. Ned Tijdschr Geneeskd 1999 May 15;143(20):1022-7. 31 Van Heteren CF, Nijhuis JG, Semmekrot BA, Mulders LG, van den Berg PP. Risk for surviving twin after fetal death of co-twin in twin-twin transfusion syndrome. Obstet Gynecol 1998 Aug;92(2):215-9. 32 Brackley KJ, Kilby MD. Twin-twin transfusion syndrome. Hosp Med 1999 Jun;60(6);419-24. 33 Brown DL, Benson CB, Driscoll SG, Doubilet PM. Twin-twin transfusion syndrome: sonographic findings. Radiology 1989 Jan;170(1):61-3. 34 Mari G, Detti L, Levi-D’Ancona R, Kern L. “Pseudo” twin-to-twin transfusion syndrome and fetal outcome. J Perinatol 1998 Sep-Oct;18(5):399-403. 35 Weston PJ, Ives EJ, Honore RL, Lees GM, Sinclair DB, Schiff D. Monochorionic diamniotic minimally conjoined twins: a case report. Am J Med Genet 1990 Dec;37(4):558-61. 36 Law KS, Chang SD, Chen FP, Soong YK. Acardiac acephalus: a case report and implications on expectant manage-ment. Chang Keng I Hsueh Tsa Chih 1999 Jun;22(2):334-8. 37 Benirschke K. Intrauterine death of a twin:mechanisms, implications for surviving twin, and placental pathology. Semin Diagn Pathol 1993 Aug;10(3):222-31. 38 Ries M, Beinder E, Gruner C, Zenker M. Rapid development of hydrops fetalis in the donor twin following death of the recipient twin in twin-twin transfusion syndrome. J Perinat Med 1999;27(1):68-73. 39 Lin IJ, Chen CH, Wang TM, Fu LS, Chi CS. Infants of twin pregnancies with one twin demise in the uterus: a retro-spective study. Chung Hua Min Kuo Hsiao Erh Ko I Hsueh Hui Tsa Chih 1999 Mar-Apr;40(2):92-6.

48

40 Krayenbuhl M, Huch A, Zimmermann R. Single intrauterine fetal death in twin pregnancy. Z Geburtshilfe Neonatol 1998 Mar-Apr;202(2):60-3. 41 Kilby MD, Govind A, O’Brien PM. Outcome of twin pregnancies complicated by a single intrauterine death: a com-parison with viable twin pregnancies. Obstet Gynecol 1994 Jul;84(1):107-9. 42 Chen CD, Ko TM, Hsieh FJ, Huang SF. Intrauterine death of co-twin in the third trimester: a case report of twin-to-twin transfusion syndrome and cord accident. J Formos Med Assoc 1993 Jul;92(7):665-7. 43 Gold F, Saliba E, Grangeponte MC, Paillet C, Pourcelot D, Toutain A, Pierre F, Fignon A, Body G, Laugier J. Cerebral lesions observed in a twin after the in utero death of the other twin. Fetal anoxia-ischemia can be the possible mechanism (3 cases). Arch Fr Pediatr 1992 Jun-Jul;49(6):529-33. 44 Choulot JJ, Fescharek R, Saint Martin J, Lippa A. In utero death of one twin and cerebral complications in the surviving twin. Presse Med 1985 May 11;14(19):1077-80. 45 Fusi L, MacParland P, Fisk N, Nicolini U, Wigglesworth J. Acute twin–twin transfusion: a possible mechanism for brain damaged survivors after intrauterine death of a monozygotic twin. Obstet Gynecol 1991;78:517–22. 46 Jou HJ, Ng KY, Teng RJ, Hsieh FJ. Doppler sonographic detection of reverse twin–twin trans fusion after intrauterine death of the donor. J Ultrasound Med 1993;12:307–9. 47 Pharoah PO, Cooke RW. A hypothesis for the aetiology of spastic cerebral palsy-the vanishing twin. Dev Med Child Neurol 1997 7May;39(5):292-6. 48 Perlman JM, Burns DK, Twickler DM, Weinberg AG. Fetal hypokinesia syndrome in the monochorionic pair of a triplet pregnancy secondary to severe disruptive cerebral injury. Pediatrics 1995 Sep;96(3):521-3. 49 Fleischer AC, Romero R, Manning F, et al, eds. Principles and practice of Ultrasonography in Obstetrics and Gyne-cology.4th ed. Norwalk, Conn: Appleton & Lange;1991. 50 Baldwin, VJ. Pathology of multiple pregnancies. New York: Springer-Verlag.1994. 51 Rumack CM, Wilson SR, Charboneau JW, eds. Diagnostic Ultrasound. St Louis; Mosby-Year Book;1991;745-758. 52 Overton TG, Denbow ML, Duncan KR, Fisk NM. First-trimester cord entanglement in monoamniotic twins. Ultra-sound Obstet Gynecol 1999 Feb;13(2):140-2. 53 Lumme R, Saarikoski S. Monoamniotic twin pregnancy. Acta Genet Med Gemellol. 1986;35:99-105. 54 Filly RA, Goldstein RB, Callen PW. Monochorionic twinning: sonographic assessment. AJR. 1990;154:459-469. 55 Aisenbrey GA, et al. Monoamniotic and pseudomonoamniotic twins: sonographic diagnosis, detection of cord entan-glement, and obstetric management. Obstet Gynecol. 1995 Aug; 86(2): 218-222. 56 Tannirandorn Y, Phaosavasdi S.Accuracy of ultrasonographic criteria for the prenatal diagnosis of placental amnionic-ity and chorionicity in twin gestations.J Med Assoc Thai 1993 Apr;76(4):190-5. 57 Levi CS, et al. Yolk sac number, size and morphologic features in monochorionic monoamniotic twin pregnancy. Can Assoc Radiol J. 1996 Apr; 47(2): 98-100. 58 Carlan SJ, Angel JL, Sawai SK, Vaughn V. Late diagnosis of nonconjoined monoamniotic twins using computed tomo-graphic imaging: a case report. Obstet Gynecol 1990 Sep;76(3):504-6. 59 Strohbehn K, Dattel BJ. Pitfalls in the diagnosis of nonconjoined monoamniotic twins. J Perinatol 1995 Nov-Dec;15(6):484-93. 60 Blane CE, DiPietro MA, Johnson MZ, White SJ, Louwsma GI, Hamman JE. Sonographic detection of monoamniotic twins. JCU J Clin Ultrasound 1987 Jul-Aug;15(6):394-6. 61 Bajoria R. Abundant vascular anastomoses in monoamniotic versus diamniotic monochorionic placentas. Am J Obstet Gynecol 1998 Sep;179(3):788-93. 62 Ritossa M, et al. Monoamniotic twin pregnancy and cord entanglement: a clinical dilemma. Aust N Z J Obstet Gynae-col. 1996 Aug; 36(3): 309-312. 63 D'Alton ME, et al. Syndromes in twins. Semin Perinatol. 1995 Oct; 19(5): 375-386. 64 Arabin B, Laurini RN, van Eyck J. Early prenatal diagnosis of cord entanglement in monoamniotic multiple pregnan-cies. Ultrasound Obstet Gynecol 1999 Mar;13(3):181-6. 65 Sherer DM, Anyaegbunam A, Prenatal ultrasonographic morphologic assessment of the umbilical cord: a review. Part I. Obstet Gynecol Surv 1997 Aug;52(8):506-14. 66 Sherer DM, Anyaegbunam A. Prenatal ultrasonographic morphologic assessment of the umbilical cord: a review. Part II. Obstet Gynecol Surv 1997 Aug;52(8):515-23. 67 Peek MJ, et al. Medical amnioreduction with sulindac to reduce cord complications in monoamniotic twins. Am J Ob-stet Gynecol. 1997 Feb; 176(2): 334-336. 68 Westover T, Guzman ER, Shen-Schwartz S. Prenatal diagnosis of an unusual nuchal cord complication in monoamni-otic twins. Obstet Gynecol 1994 Oct;84(2):689-91. 69 Krussel JS, von Eckardstein S, Schwenzer T. Double umbilical cord knot in mono-amniotic twin pregnancy as the cause of intrauterine fetal death of both twins. Zentralbl Gynakol 1994;116(8):497-9. 70 Hod M, Merlob P, Friedman S, Ovadia J. Single intrauterine fetal death in monoamniotic twins due to cord entangle-ment. Clin Exp Obstet Gynecol 1988;15(3):63-5. 71 Beck R. Monoamniotic twin pregnancy with knotted umbilical cords. Zentralbl Gynakol 1985;107(11):688-92. 72 McLeod FN, McCoy DR. Monoamniotic twins with an unusual cord complication. Case report. Br J Obstet Gynaecol 1981 Jul;88(7):774-5.

49

73 Foglmann R. Monoamniotic twins. Acta Genet Med Gemellol 1976;25:62-5. 74 Hansen LM, Donnenfeld AE. Concordant anencephaly in monoamniotic twins and an analysis of maternal serum mark-ers. Prenat Diagn 1997 May;17(5):471-3. 75 McCoy MC, Chescheir NC, Kuller JA, Altman GC, Flannagan LM. A fetus with sirenomelia, omphalocele, and menin-gomyelocele, but normal kidneys. Teratology 1994 Aug;50(2):168-71. 76 Cilento BG Jr, Benacerraf BR, Mandell J. Prenatal and postnatal findings in monochorionic monoamniotic twins dis-cordant for bilateral renal agenesis-dysgenesis (perinatal lethal renal disease). J Urol 1994 Apr;151(4):1034-5. 77 Langer JC, Brennan B, Lappalainen RE, Caco CC, Winthrop AL, Hollenberg RD, Paes BA. Cloacal exstrophy: prenatal diagnosis before rupture of the cloacal membrane. J Pediatr Surg 1992 Oct;27(10):1352-5. 78 Neal GS, Hankins GD. Left microtia in one monozygotic twin. A case report. J Reprod Med 1992 Apr;37(4):375-7. 79 Berry SA, Johnson DE, Thompson TR. Agenesis of the penis, scrotal raphe, and anus in one of monoamniotic twins. Teratology 1984 Apr;29(2):173-6. 80 Vaughn TC, Powell LC. The obstetrical management of conjoined twins. Obstet Gynecol 1979 Mar;53(3):67S-72S. 81 James WH. The sex ratio of monoamniotic twin pairs. Ann Hum Biol 1977 Mar;4(2):143-53. 82 Myrianthopoulos NC. Congenital malformations in twins: epidemiologic survey. Birth Defects Orig Artic Serv 1975;11(8):1-39. 83 Entazami M, Ragosch V, Hopp H, Weitzel HK, Runkel S. Notch in the umbilical artery Doppler profile in umbilical cord compression in a twin. Ultraschall Med 1997 Dec;18(6):277-9. 84 Carr SR, Aronson MP, Couston DR. Survival rates of monoamniotic twins do not decrease after 30 weeks gestation. Am J Obstet Gynecol 1990;163:719-22. 85 Townsend RR, Filly RA. Sonography of nonconjoined monoamniotic twin pregnancies. J Ultrasound Med 1988 Dec;7(12):665-70. 86 Rosemond RL, Hinds NE. Persistent abdominal umbilical cord Doppler velocimetry in a monoamniotic twin with cord entanglement. J Ultrasound Med 1998 May;17(5):337-8. 87 Tessen JA, Zlatnik Fj. Monoamniotic twins: a retrospective study controlled study. Obstet Gynecol 1991 Jun;77(6):832-4. 88 Dorum A, Nesheim BI. Monochorionic monoamniotic twins-the most precarious of twin pregnancies. Acta Obstet Gynecol Scand 1991;70(4-5):381-3. 89 Fraser RB, Liston RM, Thompson DL, Wright JR Jr. Monoamniotic twins delivered liveborn with a forked umbilical cord. Pediatr Pathol Lab Med 1997 Jul-Aug;17(4):639-44. 90 ACOG Technical Bulletin. Multiple gestation. Number 131 August 1989. 91 Benirschke K, Kim CK. Multiple pregnancy. N Engl J Med 1973;228:1276-84. 92 Reece EA, Yarkoni S, Abdalla M, Gabrielli S, Holford T, O'Connor TZ, Hobbins JC. A prospective longitudinal study of growth in twin gestations compared with growth in singleton pregnancies. I. The fetal head. J Ultrasound Med 1991 Aug;10(8):439-43. 93 Reece EA, Yarkoni S, Abdalla M, Gabrielli S, Holford T, O'Connor TZ, Bargar M, Hobbins JC. A prospective longitu-dinal study of growth in twin gestations compared with growth in singleton pregnancies. II. The fetal limbs. J Ultrasound Med 1991 Aug;10(8):445-50. 94 Rode ME, Jackson M. Sonographic considerations with multiple gestation. Semin Roentgenol 1999 Jan;34(1):29-34. 95 Sherer DM, Divon MY. Fetal growth in multifetal gestation. Clin Obstet Gynecol 1997 Dec;40(4):764-70. 96 Caravello JW, Chauhan SP, Morrison JC, Magann EF, Martin JN Jr, Devoe LD. Sonographic examination does not predict twin growth discrepancy accurately. Obstet Gynecol 1997 Apr;89(4):529-33. 97 Talbot GT, Goldstein RF, Nesbitt T, Johnson JL, Kay HH. Is size discordancy an indication for delivery of preterm twins?. Am J Obstet Gynecol 1997 Nov;177(5):1050-4. 98 Bajoria R. Vascular anatomy of monochorionic placenta in relation to discordant growth and amniotic fluid volume. Hum Reprod 1998 Oct;13(10):2933-40. 99 Sonntag J, Waltz S, Schollmeyer T, Schuppler U, Schroder H, Weisner D. Morbidity and mortality of discordant twins up to 34 weeks of gestational age. Eur J Pediatr 1996 Mar;155(3):224-9. 100 Rizzo G, Arduini D, Romanini C. Cardiac and extracardiac flows in discordant twins. Am J Obstet Gynecol 1994 May;170(5):1321-7. 101 Eberle AM, Levesque D, Vintzileos AM, Egan JF, Tsapanos V, Salafia CM. Placental pathology in discordant twins. Am J Obstet Gynecol 1993 Oct;169(4):931-5. 9 Yalcin HR, Zorlu CG, Lembet A, Ozden S, Gokmen O. The significance of birth weight difference in discordant twins: a level to standarize?. Acta Obstet Gynecol Scand 1998 Jan;77(1):28-31. 10Tadmor O, Nitzan M, Rabinowitz R, Skomorovsky Y, Aboulafia Y, Diamant YZ. Prediction of second trimester intrau-terine growth retardation and fetal death in a discordant twin by first trimester measurements. Case report and review of the literature. Fetal Diagn Ther 1995 Jan-Feb;10(1):17-21. 11Weissman A, Achiron R, Lipitz S, Blickstein I, Mashiach S. The first trimester growth discordant twin: an ominous prenatal finding. Obstet Gynecol 1994 Jul;84(1):110-4.

50

12Chitkara U, Berkowitz GS, Levine R, Riden DJ, Fagerstrom RM Jr, Chervenak FA, Berkowitz RL. Twin pregnancy: routine use of ultrasound examinations in the perinatal diagnosis of intrauterine growth retardation and discordant growth. Am J Perinatol 1985 Jan;2(1):49-54. 13Divon MY, Weiner Z. Ultrasound in twin pregnancy. Semin Perinatol 1995 Oct;19(5):404-12. 107 Blickstein I, Goldman RD, Smith-Levitin M, Greenberg M, Sherman D, Rydhstroem H. The relation between inter-twin birth weight discrepancy and total twin birth weight. Obstet Gynecol 1999 Jan;93(1):113-6. 108 Lemery DR, Santolaya-Forgas J, Serre AF, Besse GH, Jacquetin B. Fetal serum erythropoietin in twin pregnancies with discordant growth. A clue for prenatal diagnosis of monochorionic twins with vascular communications. Fetal Diagn Ther 1995 Mar-Apr;10(2):86-91. 109 Hsieh TT, Chang TC, Chiu TH, Hsu JJ, Chao A. Growth discordancy, birth weight, and neonatal adverse events in third trimester twin gestations. Gynecol Obstet Invest 1994;38(1):36-40. 110 Chauhan SP, Washburne JF, Martin JN Jr, Roberts WE, Roach H, Morrison JC. Intrapartum assessment by house staff of birth weight among twins. Obstet Gynecol 1993 Oct;82(4):523-6. 111 Sayegh SK, Warsof SL. Ultrasonic prediction of discordant growth in twin pregnancies. Fetal Diagn Ther 1993 Jul-Aug;8(4):241-6. 112 Mordel N, Benshushan A, Zajicek G, Laufer N, Schenker JG, Sadovsky E. Discordancy in triplets. Am J Perinatol 1993 May;10(3):224-5. 113 Jakobovits AA. The significance of birth weight discrepancy in twins. Acta Med Hung 1992-93;49(3-4):195-200. 114 Chamberlain P, Murphy M, Comerford FR. How accurate is antenatal sonographic identification of discordant birth weight in twins?. Eur J Obstet Gynecol Reprod Biol 1991 Jul 1;40(2):91-6. 115 Blickstein I, Shoham-Schwartz Z, Lancet M. Growth discordancy in appropiate for gestational age, term twins. Obstet Gynecol 1988 Oct;72(4):582-4. 116 Blickstein I, Shoham-Schwartz Z, Lancet M, Borenstein R. Characterization of the growth-discordant twin. Obstet Gynecol 1987 Jul;70(1):11-5. 117 Philip AG. Term twins with discordant birth weights: observations at birth and one year. Acta Genet Med Gemellol 1981;30(3):203-12. 118 Devoe LD, Ware DJ. Antenatal assessment of twin gestation. Semin Perinatol 1995 Oct;19(5):413-23. 119 Fraser D, Picard R, Picard E, Leiberman JR. Birth weight discordance, intrauterine growth retardation and perinatal outcomes in twins. J Reprod Med 1994 Jul;39(7):504-8. 120 Storlazzi E, Vintzileos AM, Campbell WA, Nochimson DJ, Weinbaum PJ. Ultrasonic diagnosis of discordant fetal growth in twin gestations. Obstet Gynecol 1987 Mar;69(3):363-7. 121 Blickstein I, Manor M, Levi R, Goldchmit R, Weissman A. The intrauterine ponderal index in relation to birth weight discrepancy in twin gestations. Int J Gynaecol Obstet 1995 Sep;50(3):253-5. 122 Cheung VY, Bocking AD, Dasilva OP. Preterm discordant twins: what birth weight difference is significant?. Am J Obstet Gynecol 1995 Mar;172(3):955-9. 123 Blickstein I. The definition, diagnosis, and management of growth-discordant twins: an international census survey. Acta Genet Med Gemellol 1991;40(3-4):345-51. 124 Blickstein I, Manor M, Levi R, Goldsmith R. Is intertwin birth weight discrepancy predictable?. Gynecol Obstet Invest 1996;42(2):105-8. 125 Divon MY, Girz BA, Sklar A, Guidetti DA, Langer O. Discordant twins-a prospective study of the diagnostic value of real-time ultrasonography combined with umbilical artery velocimetry. Am J Obstet Gynecol 1989 Sep;161(3):757-60. 126 Blickstein I, Friedman A, Caspi B, Lancet M. Ultrasonic prediction of growth discordancy by intertwin difference in abdominal circumference. Int J Gynaecol Obstet 1989 Jun;29(2):121-4. 127 Brown CE, Guzick DS, Leveno KJ, Santos-Ramos R, Whalley PJ. Prediction of discordant twins using ultrasound measurement of biparietal diameter and abdominal perimeter. Obstet Gynecol 1987 Nov;70(5):677-81. 128 Crane JP, Tomich PG, Kopta M. Ultrasonic growth patterns in normal and discordant twins. Obstet Gynecol 1980 Jun;55(6):678-83. 129 Chittacharoen A, Leelapattana P, Phuapradit W. Umbilical Doppler velocimetry prediction of discordant twins. J Obstet Gynaecol Res 1999 Apr;25(2):95-8. 130 Grab D, Hutter W, Haller T, Sterzik K, Terinde R. Discordant growth in twin pregnancy-value of Doppler ultrasound. Geburtshilfe Frauenheilkd 1993 Jan;53(1):42-8. 131 Giles WB. Doppler ultrasound in multiple pregnancies. Baillieres Clin Obstet Gynaecol 1998 Mar;12(1):77-89. 132 Clode N, Casal E, Graca LM. Umbilical flowmetry in twin pregnancy. A method for identifying discordant fetal growth?. Acta Med Port 1992 Oct;5(9):483-4. 133 Behrens O, Wedeking-Schohl H, Mesrogli M, Degenhardt F, Schneider J. Doppler ultrasound in monitoring twin pregnancies with early discordant growth. Z Geburtshilfe Perinatol 1992 Sep-Oct;196(5):209-12. 134 Gerson AG, Wallace DM, Bridgens NK, Ashmead GG, Weiner S, Bolognese RJ. Duplex Doppler ultrasound in the evaluation of growth in twin pregnancies. Obstet Gynecol 1987 Sep;70(3):419-23. 135 Giles WB, Trudinger BJ, Cook CM. Fetal umbilical artery flow velocity-time waveforms in twin pregnancies. Br J Obstet Gynaecol 1985 May;92(5):490-7.

51

136 Oberg KC, Pestaner JP, Bielamowicz L, Hawkins EP. Renal tubular disgenesis in twin-twin transfusion syndrome. Pediatr Dev Pathol 1999 Jan-Feb;2(1):25-32. 137 Lazda EJ. Endocardial fibroelastosis in growth-discordant monozygotic twins. Pediatr Dev Pathol 1998 Nov-Dec;1(6):522-7. 138 Weiner CP, Ludomirski A. Diagnosis, pathophysiology, and treatment of chronic twin-to-twin transfusion syndrome. Fetal Diagn Ther 1994 Sep-Oct;9(5):283-90. 139 Salvolini E, Lucarini G, Cester N, Arduini D, Mazzanti L. Growth retardation and discordant twin pregnancy. An inmunomorphological and biochemical characterisation of the human umbilical cord. Biochem Mol Biol Int 1998 Nov;46(4):795-805. 140 D'Alton ME, Mercer BM. Antepartum management of twin gestation: ultrasound. Clin Obstet Gynecol 1990 Mar;33(1):42-51. 141 Bruner JP, Anderson TL, Rosemond RL. Placental pathophysiology of the twin oligohydramnios-polyhydramnios sequence and the twin-twin transfusion syndrome. Placenta.1998 Jan;19(1):81-86. 142 Blickstein I, Weissman A. Birth weight discordancy in male-first and female-first pairs of unlike-sexed twins. Am J Obstet Gynecol 1990 Mar;162(3):661-3. 143 Vetter K. Considerations on growth discordant twins. J Perinat Med 1993;21(4):267-72. 144 Blickstein I, Lancet M. The growth discordant twin. Obstet Gynecol Surv 1988 Sep;43(9):509-15. 145 Fakeye O. Twin birth weight discordancy in Nigeria. Int J Gynaecol Obstet 1986 Jun;24(3):235-8. 146 Bernasko J, Lynch L, Lapinsky R, Berkowitz RL. Twin pregnancies conceived by assisted reproductive techniques: maternal and neonatal outcomes. Obstet Gynecol 1997 Mar;89(3):368-72. 147 Johnson JM, Harman CR, Evans JA, MacDonald K, Manning FA. Maternal serum alpha-fetoprotein in twin preg-nancy. Am J Obstet Gynecol 1990 Apr;162(4):1020-5. 148 Samuels, P. Ultrasound in the management of the twin gestation. Clin Obstet Gynecol 1988 Mar;31(1):110-22. 149 Gaziano EP, Knox GE, Bendel RP, Calvin S, Brandt D. Is pulsed Doppler velocimetry useful in the management of multiple-gestations pregnancies?. Am J Obstet Gynecol 1991 Jun;164(6):1425-31. 150 Chittacharoen A, Leelapattana P, Phuapradit W. Umbilical Doppler velocimetry prediction of discordant twins. J Ob-stet Gynaecol Res 1999 Apr;25(2):95-8. 151 Schwarzler P, Ville Y, Moscosco G, Tennstedt C, Bollmann R, Chaoui R. Diagnosis of twin reversed arterial perfusion sequence in the first trimester by transvaginal color Doppler ultrasound. Ultrasound Obstet Gynecol 1999 Feb;13(2):143-6. 152 Donner C, Noel JC, Rypens F, van Kerkem J, Avni F, Rodesch F. Twin-twin transfusion syndrome--possible roles for Doppler ultrasound and amniocentesis. Prenat Diagn 1995 Jan;15(1):60-3. 153 Sohl S, David M. Doppler ultrasound study of a twin pregnancy with feto-fetal transfusion syndrome. Geburtshilfe Frauenheilkd 1994 Aug;54(8):475-7. 154 Ohno Y, Ando H, Tanamura A, Kurauchi O, Mizutani S, Tomoda Y. The value of Doppler ultrasound in the diagnosis and management of twin-to-twin transfusion syndrome. Arch Gynecol Obstet 1994;255(1):37-42. 155 Overton TG, Denbow ML, Duncan KR, Fisk NM First-trimester cord entanglement in monoamniotic twins. Ultra-sound Obstet Gynecol 1999 Feb;13(2):140-2. 156 Rodis JF, Egan JFX, Craffey A, et al. Calculated risk of chromosomal abnormalities in twin gestations. Obstet Gynecol 1990;76:1037-1041. 157 Appelman Z, Vinkler C, Caspi B. Chorionic villus sampling in multiple pregnancies. Eur J Obstet Gynecol Reprod Biol 1999 Jul;85(1):97-9. 158 Wapner RJ, Johnson A, Davis G, Urban A, Morgan P, Jackson L. Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling. Obstet Gynecol 1993 Jul;82(1):49-56. 159 Mielke G, Kiesel L, Backsch C, Erz W, Gonser M. Fetal sex determination by high resolution ultrasound in early pregnancy. Eur J Ultrasound 1998 Apr;7(2):109-14. 160 Costa T, Lambert M, Teshima I, Ray PN, Richer CL, Dallaire L. Monozygotic twins with 45,X/46,XY mosaicism discordant for phenotypic sex. Am J Med Genet 1998 Jan 6;75(1):40-4. 161 Kurosawa K, Kuromaru R, Imaizumi K, Nakamura Y, Ishikawa F, Ueda K, Kuroki Y. Monozygotic twins with discor-dant sex. Acta Genet Med Gemellol 1992;41(4):301-10. 162 Fujimoto A, Boelter WD, Sparkes RS, Lin MS, Battersby K. Monozygotic twins of discordant sex both with 45,X/46,X,idic(Y) mosaicism. Am J Med Genet 1991 Nov 1;41(2):239-45. 163 Gonsoulin W, Copeland KL, Carpenter RJ Jr, Hughes MR, Elder FF. Fetal blood sampling demonstrating chimerism in monozygotic twins discordant for sex and tissue karyotype (46,XY and 45,X). Prenat Diagn 1990 Jan;10(1):25-8. 164 Reindollar RH, Byrd JR, Hahn DH, Haseltine FP, McDonough PG. A cytogenetic and endocrinologic study of a set of monozygotic isokaryotic 45,X/46,XY twins discordant for phenotypic sex: mosaicism versus chimerism. 165 Schmidt R, Sobel EH, Nitowsky HM, Dar H, Allen FH Jr. Monozygotic twins discordant for sex. J Med Genet 1976 Feb;13(1):64-8. 166 Schinzel A. Karyotype-phenotype correlations in autosomal chromosomal aberrations. Prog Clin Biol Res 1993;384:19-31.

52

167 Nieuwint A, Van Zalen-Sprock R, Hummel P, Pals G, Van Vugt J, Van Der Harten H, Heins Y, Madan K. ‘Identical’ twins with discordant karyotypes. Prenat Diagn 1999 Jan;19(1):72-6. 168 Carta G, Iovenitti P, D’Alfonso A, Mascaretti G, Moscarini M. Fetal malformations and chromosome abnormalities diagnosed at the Center of Prenatal Diagnosis of the University of Aquila in the 199-1998 triennium. Minerva Ginecol 1999 Oct;51(10):393-8. 169 Loevy HT, Miller M, Rosenthal IM. Discordant monozygotic twins with trisomy 13. Acta Genet Med Gemellol 1985;34(3-4):185-8. 170 Mielke G, Enders H, Goelz R, Klein-Vogler U, Ulmer R, Trautmann U. Prenatal detection of double aneuploidy trisomy 10/monosomy X in a liveborn twin with exclusively monosomy X in blood. Clin Genet 1997 Apr;51(4):275-7. 171 Pedersen IK, Philip J, Sele V, Starup J. Monozygotic twins with dissimilar phenotypes and chromosome complements. Acta Obstet Gynecol Scand 1980;59(5):459-62. 172 Cussen LJ, MacMahon RA. Germ cells and ova in dysgenetic gonads of a 46-XY female dizygotic twin. Am J Dis Child 1979 Apr;133(4):373-5. 173 Qureshi F, Jacques SM, Yaron Y, Kramer RL, Evans MI, Johnson MP. Prenatal diagnosis of cloacal dysgenesis se-quence: differential diagnosis from other forms of fetal obstructive uropathy. Fetal Diagn Ther 1998 Mar-Apr;13(2):69-74. 174 Peng Y, Shieh JL, Jung SM, Wan YL, Lih-Ma. Cyclopia in one of discordant twins: a case report. Chang Keng I Hsueh 1997 Sep;20(3):232-6. 175 Shih TY, Liu YJ, Lin YZ, Chen W, Wu KW, Ro GS. Amniotic band disruption complex: report of one case in twins. Chung Hua Min Kuo Hsiao Erh Ko I Hsueh Hui Tsa Chih 1991 Mar-Apr;32(2):115-21. 176 Nguyen Tan Lung R, Lalau P. Echographic diagnosis of cystic hygroma. Apropos of a case. J Gynecol Obstet Biol Reprod 1987;16(7):893-900. 177 Weill J, Boudailliez B, Piussan C, Ponte C. Cerebral and ocular abnormalities with anterior pituitary insufficiency of familial nature. J Genet Hum 1985 Jan;33(1):31-5. 178 Fried K, Micle S, Goldberg MD. Genetic microcephaly in a pair of monozygous twins. Teratology 1984 Apr;29(2):177-80. 179 Sagot P, David A, Talmant C, Pascal O, Winer N, Boog G. Russell-Silver syndrome: an explanation for discordant growth in monozygotic twins. Fetal Diagn Ther 1996 Jan-Feb;11(1):72-8. 180 Bailey W, Popovich B, Jones KL. Monozygotic twins discordant for the Russell-Silver syndrome. Am J Med Genet 1995 Aug 28;58(2):101-5. 181 Mahony BS, Filly RA, Callen PW. Amnionicity and chorionicity in twin pregnancies: prediction using ultrasound. Radiology 1985 Apr;155(1):205-9. 182 Mari G, Detti L, Levi-D'Ancona R, Kern L. "Pseudo" twin-to-twin transfusion syndrome and fetal outcome. J Perinatol 1998 Sep-Oct;18(5):399-403. 183 Nores J, Athanassiou A, Elkadry E, Malone FD, Craigo SD, D'Alton ME. Gender differences in twin-twin transfusion syndrome. Obstet Gynecol 1997 Oct;90(4):580-2. 184 Patten RM, Mack LA, Harvey D, Cyr DR, Pretorius DH. Disparity of amniotic fluid volume and fetal size: problem of the stuck twin-US studies. Radiology 1989 Jul;172(1):153-7. 185 Brown DL, Benson CB, Driscoll SG, Doubilet PM. Twin-twin transfusion syndrome:sonographic findings. Radiology 1989 Jan;170(1):61-3. 186 Weiner CP, Ludomirsky A. Diagnosis, pathophisiology and treatment of chronic twin-to-twin transfusion syndrome. Fetal Diagn Ther 1994 Sep-Oct;9(5):283-90. 187 Farmakides G, Schulman H, Saldona LR, Bracero LA, Fleischer A, Rochelson B. Surveillance of twin pregnancy with umbilical artery velocimetry. Am S Obstet Gynecol 1985 Dec 1;153(7):789-92. 188 Giles WB. Doppler ultrasound in multiple pregnancies. Baillieres Clin Obstet Gynaecol 1998 Mar;12(1):77-89. 189 Hecher K, Ville Y, Nicolaides KH. Color Doppler ultrasonography in the identification of communicating vessels in twin-twin transfusion syndrome and acardiac twins. J Ultrasound Med 1995 Jan;14(1):37-40. 190 Hecher K, Ville Y, Nicolaides KH. Fetal arterial Doppler studies in twin-twin transfusion syndrome. J Ultrasound Med 1995 Feb;14(2):101-8. 191 Hecher K, Ville Y, Snidjers R, Nicolaides KH. Doppler studies of the fetal circulation in twin-twin transfusion syn-drome. Ultrasound Obstet Gynecol 1995 May;5(5):318-24. 192 Sohl S, David M. Doppler ultrasound study of a twin pregnancy with feto-fetal transfusion syndrome. Geburtshilfe Frauenheilkd 1994 Aug;54(8):475-7. 193 Donner C, Noel JC, Rypens F, van Kerkem J, Avni F, Rodesch F. Twin-twin transfusion syndrome-possible roles for Doppler ultrasound and amniocentesis. Prenat Diagn 1995 Jan;15(1):60-3. 194 Weiner CP, Ludomirski A. Diagnosis, pathophysiology, and treatment of chronic twin-to-twin transfusion syndrome. Fetal Diagn Ther 1994 Sep-Oct;9(5):283-90. 195 Wittman BK, Baldwin VJ, Nichol B. Antenatal diagnosis of twin transfusion syndrome by ultrasound. Obstet Gynecol 1981;58:123-6. 196 Brennan JN, Diwan RV, Rosen MG, Bellon EM. Fetofetal transfusion syndrome: prenatal ultrasonographic diagnosis. Radiology 1982;143:535-6.

53

197 Ville Y. Management of Twin-Twin Transfusion Syndrome: An Open Multicentre Randomized Trial to Evaluate Serial Amniodrainage versus Endoscopic Placental Laser Surgery with Amniodrainage. Frontiers in Fetal Health;1999:1(6):2-5. 198 Berry SM, Puder KS, Bottoms SF, Uckele JE, Romero R, Cotton DB. Comparison of intrauterine hematologic and biochemical values between twin pairs with and without stuck twin syndrome. Am J Obstet Gynecol 1995 May;172(5):1403-10. 199 Arts H, van Eyck J, Arabin B. Fetal death of one twin in a monochorionic pregnancy with twin-twin transfusion syn-drome. J Reprod Med 1996 Oct;41(10):775-8. 200 Braat DD, Exalto N, Bernardus RE, Arts NF, Rajnherc JR. Twin pregnancy: case reports illustrating variations in transfusion syndrome. Eur J Obstet Gynecol Reprod Biol 1985 Jun;19(6):383-90. 201 Rumack CM, Wilson SR, Charboneau JW, eds. Diagnostic Ultrasound. St Louis; Mosby-Year Book;1991;745-758. 202 Dickinson JE. Severe twin-twin transfusion syndrome: current management concepts. Aust N Z Obstet Gynaecol 1995 Feb;35(1):16-21. 203 Van Gemert MJ, Sterenborg HJ. Haemodynamic model of twin-twin transfusion syndrome in monochorionic twin pregnancies. Placenta 1998 Mar-Apr;19(2-3):195-208. 204 Wax JR, Blakemore KJ, Blohm P, Callan NA. Stuck twin with cotwin noninmune hydrops: successful treatment by amniocentesis. Fetal Diagn Ther 1991;6(3-4):126-31. 205 Bajoria R. Abundant vascular anastomoses in monoamniotic versus diamniotic monochorionic placentas. Am J Obstet Gynecol 1998 Sep;179(3):788-93. 206 Hecher K, Ville Y, Nicolaides KH. Color Doppler ultrasonography in the identification of communicating vessels in twin-twin transfusion syndrome and acardiac twins. J Ultrasound Med. 1995;14:37-40. 207 Mielke G, Gonser M. Prenatal diagnosis and therapy of fetofetal transfusion syndrome. Z Geburtshilfe Neonatol 1998 Jul-Aug;202(4):141-8. 208 Urig MA, Clewell WH, Elliot JP. Twin-twin transfusion syndrome. Am J Obstet Gynecol 1990;163:1522-6. 209 Ries M, Beinder E, Gruner C, Zenker M. Rapid development of hydrops fetalis in the donor twin following death of the recipient twin in twin-twin transfusion syndrome. J Perinat Med 1999;27(1):68-73. 210 Mahony BS, Petty CN, Nyberg DA, Luthy DA, Hickok DE, Hirsch JH. The "stuck twin" phenomenon: ultrasono-graphic findings, pregnancy outcome, and management with serial amniocenteses. Am J Obstet Gynecol 1990 Nov;163(5):1513-22. 211 Bajoria R, Wigglesworth J, Fisk NM. Angioarchitecture of monochorionic placentas in relation to the twin-twin trans-fusion syndrome. Am J Obstet Gynecol 1995 Mar;172(3):856-63. 212 Brackley KJ, Kilby MD. Twin-twin transfusion syndrome. Hosp Med 1999 Jun;60(6):419-24. 213 Filkins KA, Beverly SE. Twin-twin transfusion syndrome: the challenge of etiology-based management decisions. Curr Opin Obstet Gynecol 1998 Dec;10(6):441-6. 214 Kilby MD, Howe DT, McHugo JM, Whittle MJ. Bladder visualization as a prognostic sign in oligohydramnios-polyhydramnios sequence in twin pregnancies treated using therapeutic amniocentesis.Br J Obstet Gynaecol 1997 Aug;104(8):939-42. 215 Elliot JP, Urig MA, Clewell WH. Aggressive therapeutic amniocentesis for treatment of twin-twin transfusion syn-drome. Obstet Gynecol 1991 Apr;77(4):537-40. 216 Golaszewski T, Plockinger B, Golaszewski S, Frigo P, Deutinger J, Bernaschek G. Prenatal management of fetofetal transfusion syndrome. Geburtshilfe Frauenheilkd 1995 Apr;55(4):218-22. 217 Pinette MG, Pan Y, Pinette SG, Stubblefield PG. Treatment of twin-twin transfusion syndrome. Obstet Gynecol 1993 Nov;82(5):841-6. 218 Dennis LG, et al. Twin-to-twin transfusion syndrome: aggressive therapeutic amniocentesis. Am J Obstet Gynecol. 1997 Aug;177(2):342-347. 219 Trespidi L, Boschetto C, Caravelli E, Villa L, Kustermann A, Nicolini U. Serial amniocenteses in the management of twin-twin transfusion syndrome: when is it valuable? Fetal Diagn Ther 1997 Jan;12(1):15-20. 220 Garry D, Lysikiewicz A, Mays J, Canterino J, Tejani N. Intra-amniotic pressure reduction in twin-twin transfusion syndrome. J Perinatol 1998 Jul-Aug;18(4):284-6. 221 Bajoria R. Chorionic plate vascular anatomy determines the efficacy of amnioreduction therapy for twin-twin transfu-sion syndrome. Hum Reprod 1998 Jun;13(6):1709-13. 222 Larroche JC, Droulle P, Delezoide AL, Narcy F, Nessmann C. Brain damage in monozygous twins. Biol Neonate 1990;57:261-78. 223 Saunders NJ, Snijders RJM, Nicolaides KH. Therapeutic amniocentesis in twin-twin transfusion syndrome appearing in the second trimester of pregnancy. Am J Obstet Gynecol 1992;166:820-4. 224 Pinette MG, Pan Y, Pinette SG, Stubblefield PG. Treatment of twin-twin transfusion syndrome. Obstet Gynecol 1993;82:841-6. 225 Trespidi L, Boschetto C, Caravelli E, Villa L, Kustermann A, Nicolini U. Serial amniocentesis in the management of twin-twin transfusion syndrome: When is it valuable? Fetal Diagn Ther 1997;12:15-20. 226 Mahony BS, Petty CN, Nyberg DA, Luthy DA, Hickok DE, Hirsch JH.. The stuck twin phenomenon: ultrasonographic findings, pregnancy outcome and management with serial amniocentesis. Am J Obstet Gynecol 1990;163:1513-22.

54

227 Urig MA, Clewell WH, Elliott JP. Twin-twin transfusion syndrome. Am J Obstet Gynecol 1990;163:1522-6. 228 Elliott JP, Urig MA, Clewell WH. Aggressive therapeutic amniocentesis for treatment of twin-twin transfusion syn-drome. Obstet Gynecol 1991;77:537-40. 229 Reisner DP, Mahony BS, Petty CN et al. Stuck twin syndrome: outcome in thirty-seven consecutive cases. Am J Ob-stet Gynecol 1993;169:991-5. 230 Bruner JP, Rosemond RL. Twin-to-twin transfusion syndrome. A subset of the twin oligohydramnios-polyhydramnios sequence. Am J Obstet Gynecol 1993;169:925-30. 231 Dickinson JE. Severe twin-twin transfusion syndrome: current management concepts. Aust NZ J Obstet Gynecol 1995;35:16-21. 232 Bernirschke K, Kim CK. Multiple pregnancy. N Engl J Med 1973;288:1276-84. 233 Fusi L, Gordon H. Twin pregnancy complicated by single intrauterine death. Problems and outcome with conservative management. Br J Obstet Gynaecol 1990;97:511-6. 234 Liu S, Bernirschke K, Scioscia AL, Mannino FL. Intrauterine death in multiple gestation. Acta Genet Med Gemellol 1992;41:5-26. 235 Bejar R, Vigliocco G, Gramajo H et al. Antenatal origin of neurologic damage in newborn infants II. Multiple gesta-tions. Am J Obstet Gynecol 1990;162:1230-6. 236 Evrard et al.Underwater Nd:YAG laser coagulation of blood vessels in a rat model. Fetal Diagn Ther 1996 Nov;11(6):422-426. 237 Evrard VA, Deprest JA, Van Ballaer P, Lerut TE, Vandenberghe K, Brosens IA. Treatment of the twin-twin transfu-sion syndrome: initial experience using laser-induced interstitial thermotherapy. Fetal Diagn Ther 1996 Nov;11(6):390-397. 238 Ville Y, et al. Endoscopic laser coagulation in the management of severe twin-to-twin transfusion syndrome. Br J Obstet Gynaecol. 1998 Apr; 105(4): 446-453. 239 Deprest J, et al. Laser-induced thermotherapy for severe twin-twin transfusion syndrome. Fetal Diagn Ther. 1997 May; 12(3): 193-194. 240 Hecher K, et al. Umbilical cord coagulation by operative microendoscopy at 16 weeks' gestation in an acardiac twin. Ultrasound Obstet Gynecol. 1997 Aug; 10(2): 130-132 241 Lundvall L, Skibsted L, Graem. Limb necrosis associated with twin-twin transfusion syndrome treated with YAG-laser coagulation. Acta Obstet Gynecol Scand 1999 Apr;78(4):349-50. 242 Quintero RA, Morales WJ, Mendoza G, Allen M, Kalter CS, Giannina G, Angel JL. Selective photocoagulation of placental vessels in twin-twin transfusion syndrome: evolution of a surgical technique. Obstet Gynecol Surv 1998 Dec;53(12 Suppl):S97-103. 243 Rodeck C, Deans A, Jauniaux E. Thermocoagulation for the early treatment of pregnancy with an acardiac twin. N Engl J Med 1998 Oct 29;339(18):1293-5. 244Arabin B, Laurini RN, van Eyck J, Nicolaides KH. Treatment of twin-twin transfusion syndrome by laser and digoxin. Biophysical and angiographic evaluation. Fetal Diagn Ther 1998 May-Jun;13(3):141-6. 245 Stone CA, Quinn MW, Saxby PJ. Congenital skin loss following Nd:YAG placental photocoagulation. Burns 1998 May;24(3):275-7. 246 Deprest JA, Van Schoubroeck D, Van Ballaer PP, Flageole H, Van Assche FA, Vandenberghe K. Alternative tech-nique for Nd: YAG laser coagulation in twin-to-twin transfusion syndrome with anterior placenta. Ultrasound Obstet Gynecol 1998 May;11(5):347-52. 247 Sohn C, Wallwiener D, Kurek R, Hahn U, Schiesser M, Bastert G. Treatment of the twin-twin transfusion syndrome: initial experience using laser-induced interstitial thermotherapy. Fetal Diagn Ther 1996 Nov-Dec;11(6):390-7. 248 Ville Y, Hyett J, Hecher K, Nicolaides K. Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 1995 Jan 26;332(4);224-7. 249 De Lia JE, Kuhlmann RS, Lopez KP. Treating previable twin-twin transfusion syndrome with fetoscopic laser surgery: outcomes following the learning curve. J Perinat Med 1999;27(1):61-7. 250 De Lia JE, Kuhlmann RS, Harstad TW, Cruikshank DP. Fetoscopic laser ablation of placental vessels in severe pre-viable twin-twin transfusion syndrome. Am J Obstet Gynecol 1995 Apr;172(4):1202-8. 251 Hecher K, Plath H, Bregenzer T, Hansmann M, Hackeloer BJ. Endoscopic laser surgery versus serial amniocenteses in the treatment of severe twin-twin transfusion syndrome. Am J Obstet Gynecol 1999 Mar;180(3 Pt 1):717-24. 252 van Gemert MJ, Major AL, Scherjon SA. Placental anatomy, fetal demise and therapeutic intervention in monochori-onic twins and the transfusion syndrome: new hypotheses. Eur J Obstet Gynecol Reprod Biol 1998 May;78(1):53-62. 253 Saade GR, Belfort MA, Berry DL, Bui TH, Montgomery LD, Johnson A, O'Day M, Olson GL, Lindholm H, Garoff L, Moise KJ Jr. Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence. Fetal Diagn Ther 1998 Mar-Apr;13(2):86-93. 254 Suzuki S, Ishikawa G, Sawa R, Yoneyama Y, Otsubo Y, Araki T. Iatrogenic monoamniotic twin gestation with pro-gressive twin-twin transfusion syndrome. Fetal Diagn Ther 1999 Mar-Apr;14(2):98-101. 255 Quintero RA. Twin-to-twin transfusion syndrome. http://www.fetalmd.com 256 Lenery DJ, Vanlieferinghen P, Gasq M, Finkelstin F, Beaufrere AM, Beytout M. Featl umbilical cord ligation under ultrasound guidance. Ultrasound Obstet. Gynecol. 1994; 330: 469-71.

55

257 Jones JM, Sbarra AJ, Dilillo L, Cetrulo CL, D’Alton ME. Indomethacin in severe twin-to-twin transfusion syndrome. J Perinat, 1993; 10: 24-6. 258 DeLia JE, Emery MG, Sheafor SA, Jennison TA. Twin-twin transfusion syndrome: successful in-utero treatment with digoxin. Int. J. Gynecol. Obstet. 1985; 23: 197-201. 259 Bromley B, Benacerraf BR. Acute reversal of oligohydramnios-polyhydramnios sequence in monochorionic twins. Int J Gynaecol Obstet 1996 Dec;55(3):281-3.

260 Bruner JP, Rosemond RL. Twin-to-twin transfusion syndrome: a subset of the twin oligohydramnios-polyhydramnios sequence. Am J Obstet Gynecol 1993 Oct;169(4):925-30. 261 Shih JC, Shyu MK, Hsieh MH, Yang JH, Huang SF, Lin GJ, Hsieh FJ. Agenesis of the ductus venosus in a case of monochorionic twins which mimics twin-twin transfusion syndrome. Prenat Diagn 1996 Mar;16(3):243-6.

262 Machin GA. Re. Agenesis of the ductus venosus in a case of monochorionic twins which mimics twin-twin transfusion syndrome. Prenat Diagn 1996 Oct;16(10):971-2.

263 Kuller JA, Coulson CC, McCoy MC, Altman GC, Thorp JM Jr, Katz VL. Prenatal diagnosis of renal agenesis in a twin gestation. Prenat Diagn 1994 Nov;14(11):1090-2. 264 Wada H, Nunogami K, Wada T, Niida Y, Yachie A, Koizumi S. Diffuse brain damage caused by acute twin-twin transfusion during late pregnancy. Acta Paediatr Jpn 1998 Aug;40(4):370-3. 265 Zosmer N, Bajoria R, Weiner E, Rigby M, Vaughan J, Fisk NM. Clinical and echographic features of in utero cardiac dysfunction in the recipient twin in twin-twin transfusion syndrome. Br Heart J 1994 Jul;72(1):74-9. 266 Fesslova V, Villa L, Nava S, Mosca F, Nicolini U. Fetal and neonatal echocardiographic findings in twin-twin transfu-sion syndrome. Am J Obstet Gynecol 1998 Oct;179(4):1056-62. 267 Simpson LL, Marx GR, Elkadry EA, D'Alton ME. Cardiac dysfunction in twin-twin transfusion syndrome: a prospec-tive, longitudinal study. Obstet Gynecol 1998 Oct;92(4):557-62. 268 Watson WJ, Munson DP, Ohrt DW, Carlson G, Rhodes RB. Polyhydramnios -oligohydramnios in a twin pregnancy complicated by fetal glomerulocystic kidney disease. Am J Perinatol 1995 Nov;12(6):379-81. 269 Oberg KC, Pestaner JP, Bielamowicz L, Hawkins EP. Renal tubular dysgenesis in twin-twin transfusion syndrome. Pediatr Dev Pathol 1999 Jan-Feb;2(1):25-32. 270 Murphy KW. Intrauterine death in a twin: implications for the survivor. In Ward RH, Whittle M, eds. Multiple Pregnancy. London: RCOG Press, 1995: 218–30. 271 Saier F, Burden L, Cavanagh D. Fetus papyraceus: an unusual case with congenital anomaly of the surviving fetus. Obstet Gynecol 1975 Feb;45(2):217-20. 272 Wagner DS, Klein RL, Robinson HB, Novak RW. Placental emboli from a fetus papyraceous. J Pediatr Surg 1990 May;25(5):538-42. 273 Boente M del C, Frontini M del V, Acosta MI, Saleme C, Barrionuevo S, Asial R. Extensive symmetric truncal aplasia cutis congenita without fetus papyraceous or macroscopic evidence of placental abnormalities. Pediatr Dermatol 1995 Sep;12(3):228-30. 274 Visva-Lingam S, Jana A, Murray H, John E. Preterm premature rupture of membranes associated with aplasia cutis congenita and fetus papyraceous. Aust N Z J Obstet Gynaecol 1996 Feb;36(1):90-1. 275 Patten RM, Mack LA, Nyberg DA, Filly RA. Twin embolization syndrome: prenatal sonographic detection and sig-nificance. Radiology 1989 Dec;173(3):685-9 276 Dallay D, Soumireu-Mourat J. Problems posed by the death of one fetus in a twin pregnancy. Rev Fr Gynecol Obstet 1985 Dec;80(12):877-9 277 Schinzel AA, Smith DW, Miller JR. Monozygotic twinning and structural defects. J Pediatr 1979 Dec;95(6):921-30 278 Caballero P, Del Campo L, Ocon E. Cystic encephalomalacia in twin embolization syndrome. Radiology 1991 Mar;178(3):892-3 279 Fuentes A, Porter KB, Torres BA, Saadeh S, Duesenberg K, O'Brien WF. A twin gestation complicated by gastroschi-sis in both twins. J Clin Ultrasound 1996 Jan;24(1):48-50 280 Yancey MK, Brady K, Read JA. Sonographic evidence of fetal hydrothorax after in-utero death of monozygotic twin. J Clin Ultrasound 1991 Mar;19(3):162-166 281 Harrison SD, Cyr DR, Patten RM, Mack LA. Twin growth problems: causes and sonographic analysis. Semin Ultra-sound CT MR 1993 Feb;14(1):56-67 282 Elchalal U, Tanos V, Bar-Oz B, Nadjari M. Early second trimester twin embolization syndrome. J Ultrasound Med 1997 Jul;16(7):509-12 283 Sogaard K, Skibsted L, Brocks V. Acardiac twins: pathophisiology, diagnosis, outcome and treatment. Six cases and review of the literature. Fetal Diagn Ther 1999 Jan-Feb;14(1):53-9. 284 Zhioua F, Rezigua H, Khouja H, Merian S, Ferchiou M, Kammoun N, Gara F. Acardiac malformation: Ultrasono-graphic diagnosis. A case report. Rev Fr Gynecol Obstet 1993 Apr;88(4):267-72. 285 Landy HJ, Larsen JW Jr, Schoen M, Larsen ME, Kent SG, Weingold AB. Acardiac fetus in a triplet pregnancy. Tera-tology 1988 Jan;37(1):1-6.

56

286 Gibson JY, D´Cruz CA, Patel RB, Palmer SM. Acardiac anomaly: review of the subject with case report and emphasis on practical sonography. JCU J Clin Ultrasound 1986 Sep;14(7):541-5. 287 Cardwell MS. The acardiac twin. A case report. J Reprod Med 1988 Mar;33(3):320-2. 288 Hecher K, Ville Y, Nicolaides KH. Color Doppler ultrasonography in the identification of communicating vessels in twin-twin transfusion syndrome and acardiac twins. J Ultrasound Med 1995 Jan 14(1):37-40. 289 Schwarzler P, Ville Y, Moscosco G, Tennstedt C, Bollman R, Chaoui R. Diagnosis of twin reversed arterial perfusion sequence in the first trimester by transvaginal color Doppler ultrasound. Ultrasound Obstet Gynecol 1999 Feb;13(2):143-6. 290 Papa T, Dao A, Bruner JP. Pathognomonic sign of twin reversed arterial perfusion using Color Doppler sonography. J Ultrasound Med 1997 Jul;16(7):501-3. 291 Benson CB, Bieber FR, Genest DR, Doubilet PM. Doppler demonstration of reversed umbilical blood flow in an acar-diac twin. JCU J Clin Ultrasound 1989 May;17(4):291-5. 292 Sepulveda WH, Quiroz VH, Giuliano A, Henriquez R. Prenatal ultrasonographic diagnosis of acardiac twin. J Perinat Med 1993;21(3):241-6. 293 Shalev E, Zalel Y, Ben-Ami M, Weiner E. First trimester ultrasonic diagnosis of twin reversed arterial perfusion se-quence. Prenat diagn 1992 Mar;12(3):219-22. 294 Hanafy A, Peterson CM. Twin-reversed arterial perfusion (TRAP) sequence: case reports and review of literature. Aust N Z J Obstet Gynaecol 1997 May;37(2):187-91. 295 Benirschke K, des Roches Harper V. The acardiac anomaly. Teratology 1977 Jun;15(3):311-6. 296 Kaplan C, Benirschke K. The acardiac anomaly new case reports and current status. Acta Genet Med Gemellol 1979;28(1):51-9. 297 Moore CA, Buehler BA, McManus BM, Harmon JP, Mirkin LD, Goldstein DJ. Acephalus-acardia in twins with ane-uploidy. Am J Med Genet Suppl 1987;3:139-43. 298 Chaliha C, Schwarzler P, Booker M, Battash MA, Ville Y. Trisomy 2 in an acardiac twin in a triplet in vitro fertiliza-tion pregnancy. Hum Reprod 1999 May;14(5):1378-80. 299 Faguer C, Bonan J, Mulliez N, Migne G. Acardiac fetus. Presse Med 1996 Sep14;25(26):1191-4. 300 Blaicher W, Repa C, Schaller A. Acardiac twin pregnancy: associated with trisomy 2: Case report. Hum Reprod 2000 Feb;15(2):474-475. 301 Pavlova M, Fouron JC, Proulx F, Lessard M. Importance of intrauterine diagnosis of rudimentary autonomic circula-tion in an acardiac twin. Arch Mal Coeur Vaiss 1996 May;89(5):629-32. 302 Imai A, Hirose R, Kawabata I, Tamaya T. Acardiac acephalic monster extremely larger than its co twin. A case report. Gynecol Obstet Invest 1991;32(1):62-4. 303 Pezzati M, Cianciulli D, Danesi G. Acardiac twins. Two case reports. J Perinat Med 1997;25(1):119-24. 304 Sanjaghsaz H, Bayram MO, Qureshi F. Twin reversed arterial perfusion sequence in conjoined, acardiac, acephalic twins associated with a normal triplet. A case report. J Reprod Med 1998 Dec;43(12):1046-50. 305 Cox M, Murphy K, Ryan G, Kingdom J, Whittle M, McNay M. Spontaneous cesation of umbilical blood flow in the acardius fetus of a twin pregnancy. Prenat diagn 1992 Aug;12(8):689-93. 306 Chang DY, Chang RY, Chen RJ, Chen CK, Cheng WF, Huang SC. Triplet pregnancy complicated by intrauterine fetal death of conjoined twins from an umbilical cord accident of an acardius. A case report. J Reprod Med 1996 Jun;41(6):459-62. 307 Willcourt RJ, Naughton MJ, Knutzen VK, Fitzpatrick C. Laparoscopic ligation of the umbilical cord of an acardiac fetus. J Am Assoc Gynecol Laparosc 1995 May;2(3):319-21. 308 Quintero R, Munoz H, Hasbun J, Pommer R, Gutierrez J, Sanchez J, Hidalgo G, Caerstens E, Munoz L, Ramirez R. Fetal endoscopic surgery in a case of twin pregnancy complicated by reversed arterial perfusion sequence. Rev Chil Ob-stet Ginecol 1995;60(2):112-6. 309 Sepulveda W, Bower S, Hassan J, Fisk NM. Ablation of acardiac twin by alcohol injection into the intraabdominal umbilical artery. Obstet Gynecol 1995 Oct;86(4):680-1. 310 Hecher K, Reinhold U, Gbur K, Hackeloer BJ. Interruption of umbilical blood flow in an acardiac twin by endoscopic laser coagulation. Geburtshilfe Frauenheilkd 1996 Feb;56(2):97-100. 311 Hecher K, Hackeloer BJ, Ville Y. Umbilical cord coagulation by operative microendoscopy at 16 weeks´ gestation in an acardiac twin. Ultrasound Obstet Gynecol 1997 Aug;10(2):130-2. 312 Sanchioni L, Presti C, Morotti R, Zuliani G, Kustermann A, Buscaglia M, Gandini S. Twin pregnancy with acephalic acardiac fetus. Anatomo-clinical description cases. Ann Ostet Ginecol Med Perinat 1990 May-Jun;111(3):174-80. 313 Ko TM, Tzeng SJ, Hsieh FJ, Chu JS. Acardius anceps: report of 3 cases. Asia Oceania J Obstet Gynaecol 1991 Mar;17(1):49-56. 314 Natho W, Kirsch M, Abet L, Bollmann R, Prenzlau P, Grauel EL, Bartho S. Perinatal imaging diagnosis in twin preg-nancies with humanus amorphus. Zentralbl Gynakol 1990;112(11):679-88. 315 Wigglesworth JS, Singer DB, eds. Textbook of Fetal and Perinatal Pathology. Cambridge, MA: Blackwell Scientific Publications;1991;221-262 316 Chan DP. Thoracoomphalopagus diagnosed before delivery. Med J Aust 1976 Apr 3;1(14):480,482-3

57

317 Monteagudo A, Timor-Tritsch I.E. Ultrasound and Multifetal Pregnancy. 1st ed. The Parthenon Publishing Group Inc.;1998;87-112 318 Hernandez-Valencia M, Baruch Pavon Rojas A, Ferrer Ponce LA, Alvarez Muñoz M. Janiceps cephalo-thoraco-abdominopagus pregnancy. Ginecol Obstet Mex 1998 Dec;66:499-502 319 Quiroz VH, Sepulveda WH, Mercado M, Bermudez R, Fernandez R, Varela J. Prenatal ultrasonographic diagnosis of thoracopagus conjoined twins. J Perinat Med 1989;17(4):297-303. 320 Grutter F, Marguerat P, Maillard-Brignon C, De Grandi P, Pescia G. Thoracopagus fetus. Ultrasonic diagnosis at 16 weeks. J Gynecol Obstet Biol Reprod 1989;18(3):355-9. 321 Spencer R. Conjoined twins: theoretical embryologic basis. Teratology 1992 Jun;45(6):591-602 322 Divon MY, Weiner Z. Ultrasound in twin pregnancy. Semin Perinatol 1995 Oct;19(5):404-12 323 Koontz Wl, Herbert WN, Seeds JW, Cefalo RC. Ultrasonography in the antepartum diagnosis of conjoined twins. A report of two cases. J Reprod Med 1983 Sep;28(9):627-30 324 Weston PJ, Ives EJ, Honore RLH, Lees GM, Sinclair DB, Schiff D. Monochorionic diamniotic minimally conjoined twins: a case report. Am J Med Genet 1990 Dec;37(4):558-61 325 Boulot P, Deschamps F, Hedon B, Laffargue F, Viala JL. Conjoined twins associated with a normal singleton: very early diagnosis and successful selective termination. J Perinat Med 1992;20(2):135-7 326 Demidov VN, Stygar AM, Voevodin SM, Iantovskii IuR. Ultrasonic diagnosis of malformations during the 1st trimes-ter of pregnancy. Sov Med 1991;(12):25-8 327 Lam YH, Sin SY, Lam C, Lee CP, Tang MH, Tse HY. Prenatal sonographic diagnosis of conjoined twins in the first trimester: two case reports. Ultrasound Obstet Gynecol 1998 Apr;11(4):289-91 328 Bonilla-Musoles F, Raga F, Bonilla F Jr, Blanes J, Osborne NG. Early diagnosis of conjoined twins using two-dimensional color Doppler and three-dimensional ultrasound. J Natl Med Assoc 1998 Sep;90(9):552-6 329 Maymon R, Halperin R, Weinraub Z, Herman A, Schneider D. Three-dimensional transvaginal sonography of con-joined twins at 10 weeks: a case report. Ultrasound Obstet Gynecol 1998 Apr;11(4):292-4 330 Hubinont C, Kollman P, Malvaux V, Donnez J, Bernard P. First-trimester diagnosis of conjoined twins. Fetal Diagn Ther 1997 May-Jun;12(3):185-7 331 Cazeneuve C, Nihoul-Fekete C, Adafer M, Yassine B, Boury R, Wahhabi M, Lajarrige C, Dumez Y, Aubry MC, Moriette G. Conjoined omphalopagus twins separated at fifteen days of age. Arch Pediatr 1995 May;2(5):452-5 332 Yang CC, Wu RC, Kuo PL, Yang HB, Chou NH. Prenatal diagnosis of dicephalic conjoined twins:report of a case. J Formos Med Assoc 1994 Jul;93(7):626-8 333 Barth RA, Filly RA, Goldberg JD, Moore P, Silverman NH. Conjoined twins: prenatal diagnosis and assessment of associated malformations. Radiology 1990 Oct;177(1):201-7 334 Monni G, Useli C, Ibba RM, Lai R, Olla G, Cao A. Early antenatal sonographic diagnosis of conjoined syncephalus-craniothoraco-omphalopagus twins. Case report. J Perinat Med 1991;19(6):489-92. 335 Conjoined twins-an epidemiological study based on 312 cases. The International Clearinghouse for Birth Defects Monitoring Systems. Acta Genet Med Gemellol 1991;40(3-4):325-35 336 Abossolo T, Dancoisne P, Tuaillin J, Orvain E, Sommer JC, Riviere JP. Early prenatal diagnosis of asymmetric cepha-lothoracopagus twins. J Gynecol Obstet Biol Reprod 1994;23(1):79-84 337 Furuya A, Okawa I, Matsukawa T, Kumazawa T. Anesthetic management of cesarean section for conjoined twins. Masui 1999 Feb;48(2):195-7 338 Van der Brand SF, Nijhuis JG, van Dongen PW. Prenatal ultrasound diagnosis of conjoined twins. Obstet Gynecol Surv 1994 Sep;49(9):656-62 339 Hilfiker ML, Hart M, Holmes R, Cooper M, Kriett J, Collins D, Allshouse M. Expansion and division of conjoined twins. J Pediatr Surg 1998 May;33(5):768-70 340 Karsdorp VH, van der Linden JC, Sobotka-Plojhar MA, Prins H, van der Harten JJ, van Vugt JM. Ultrasonographic prenatal diagnosis of conjoined thoracopagus twins: a case report. Eur J Obstet Gynecol Reprod Biol 1991 Apr 16;39(2):157-61 341 Vaughn TC, Powell LC. The obstetrical management of conjoined twins. Obstet Gynecol 1979 Mar;53(3 Suppl):67S-72S 342 Stoll-Simona U, Ingold W, Tanner H. A rare increase in the incidence of Siamese twin deliveries. Geburtshilfe Frauen-heilkd 1979 Feb;39(2):147-51 343 Al Muti Zaitoun A, Chang J, Booker M. Diprosopus (partially duplicated head) associated with anencephaly: a case report. Pathol Res Pract 1999;195(1):45-50 344 Amr SS, Hammouri MF.Craniofacial duplication (diprosopus): report of a case with a review of the literature. Eur J Obstet Gynecol Reprod Biol 1995 Jan;58(1):77-80. 345 La torre R, Fusaro P, Anceschi MM, Montanino-Oliva M, Modesto S, Cosmi EV.Unusual case of caudal duplication (dipygus). J Clin Ultrasound 1998 Mar-Apr;26(3):163-5 346 Mir E, Sencan A, Karaca I, Gunsar C, Etensel B. Truncal duplication: a case report. Pediatr Surg Int 1998 Dec;14(3):227-8 347 Spencer R, Robichaux WH. Prosopo-thoracopagus conjoined twins and other cephalopagus-thoracopagus intermedi-ates: case report and review of literature. Pediatr Dev Pathol 1998 Mar-Apr;1(2):164-71

58

348 Chen CP, Lee CC, Liu FF, Jan SW, Lin MH, Chen BF. Prenatal diagnosis of cephalothoracopagus janiceps mono-symmetros. Prenat Diagn 1997 Apr;17(4):384-8 349 Ramadani HM, Johnshrud N, al Nasser M, Rayes O. The antenatal diagnosis of cephalothoracopagus Janiceps con-joined twins. Aust N Z J Obstet Gynaecol 1994 Feb;34(1):113-5 350 Koltuksuz U, Eskicioglu S, Mehmetoglu F. Minimally conjoined omphalopagus twinning: a case report. Eur J Pediatr Surg 1998 Dec;8(6):368-70 351 Jain PK, Budhwani KS, Gambhir A, Ghritlaharey R. Omphalopagus parasite: a rare congenital anomaly. J Pediatr Surg 1998 Jun;33(6):946-7 352 Sathekge MM, Venkannagari RR, Clauss RP. Scintigraphic evaluation of craniopagus twins. Br J Radiol 1998 Oct;71(850):1096-9 353 Nicolini U, Dell'Agnola CA, Ferrazzi E et al: Ultrasonic prenatal diagnosis of fetus in fetu. JCU 11:321-2, 1983 354 Bomsel F, Stroh-Marcy A, Thabaut S, et al: Fœtus in fœtu: un cas dépisté par échographie anténatale. JEMU 6:163-8,1985 355 Heifetz SA, Alrabeeah A, Brown BS et al: Fetus in fetu: a fetiform teratoma. Pediatr Pathol 8: 215-26, 1988. 356 Chitrit Y, Zorn B, Scart G et al: Foetus in foetu surrenalien: un cas evoque par l'echographie prenatale. Revue de la litterature. J Gynecol Obstet Biol Reprod (Paris) 19: 1019-22, 1990. 357 Martinez Urrutia MJ, Lopez Pereira P et al: Abdominal mass: “fetus in fetu”. Acta Pædiatr Scand 79: 121-2, 1990. 358 Sada I, Shiratori H, Nakamura Y: Antenatal diagnosis of fetus in fetu. Asia Oceania J Obstet Gynaecol 12: 353-6, 1986. 359 Grant P, Pearn JH: Fœtus in fœtu. Med J Aust 1: 1016-9, 1969. 360 Krafka J: Teratoma: an explanation of its cause based on the organizer theory of embryology. Arch Pathol 21:756, 1936. 361 Carles D, Alberti EM, Serville F, et al: Fœtus in fetu et monstre acardiaque: un mécanisme morphogénique commun explique-t-il les similitudes de ces deux malformations? Arch Anat Cytol Pathol 39: 77-82, 1991. 362 Chateil JF, Diard F, Bondonny JM, et al: Foetus in foetu testiculaire intraperitoneal. Pediatrie 45: 255-7, 1990. 363 Alpers CE, Harrison MR: Fetus in fetu associated with an undescended testis. Pediatr Pathol 437-46, 1985. 364 Corona Reyes D, Navarro Cruz RA, Toxtle Tlamani R, et al: Fetus in fetu originado en un testiculo criptorquidico. Bol Med Hosp Infant Mex 39: 680-4, 1982. 365 Potter EL: Pathology of the fetus and newborn (2nd Ed.) Chicago, Year Book Med Pub 1962: p.183-7. 366 Willis RA: The structure of teratoma. J Pathol Bacteriol 40:1-36, 1935. 367 Young GW: Case of a fœtus found in the abdomen of a boy. Med Chir Trans 1:234, 1809. 368 Highmore N: Case of a fœtus found in the abdomen of a young man, at Sherborne, in Dorsetshire. Royal Collegue of Surgeons, London, 1815 30pp 2pl. 369 Phillips E: Account of a case in which parts of a fœtus were found in a tumour situated in the abdomen of a girl two and a half year old. Medico-chirugical Transactions, 6:124-7, 1815, 370 Taylor S: Case of included ovum. Transactions of the Pathological Society of London. 38:440-4, 1887. 371 McNutt WF: Case Report. Pacific Med J 37:118, 1894. 372 von Haberer H: Operativ entferater Fötus in Föto. Zentralbl Chir 66:840, 1939. 373 Eng HL, Chuang JH, Lee TY, Chen WJ: Fetus in fetu: a case report and review of the literature. J Pediatr Surg 24: 296-9, 1989. 374 Kimmel DL, Moyer EK, Peale AR, et al: A cerebral tumor containing five human fetuses. A case of fetus in fetu. Anat Rec 106:141-65, 1950. 375 Povysilova V: Encranius s mnohotnymi rudimentarnimi fetus in fetu u nedonoseneho chlapce. [Encranius with multi-ple rudimentary fetus in fetu in a premature boy]. Cesk Patol 19: 49-54, 1983. 376 Brines RJ: A large teratoma containing rudimentary arm bones and a hand. JAMA 103:338, 1934. 377 Gale CW, Willis RA: A retroperitoneal digit-containing teratoma. J Pathol Bacteriol 56:403-9, 1944. 378 Wollin E, Ozonoff MB: Serial development of teeth in an ovarian teratoma. N Engl J Med 265:897-8, 1961. 379 Oberman B: Intracranial teratoma replacing brain: report of a case. Arch Neurol 11:423-6, 1964. 380 Afshar F, King TT, Berry CL: Intraventricular fetus in fetu. Case report. J Neurosurg 56:845-9, 1982. 381 Bernal Sprekelsen JC, Bernal Cascales M: Fetus in Fetu: Ein Fallbericht einer extrem seltenen Ursache von Bauchtu-moren beim Sling. Z Kinderchir 45: 317-8, 1990. 382 Bomsel F, Stroh-Marcy A, Thabaut S et al: Fœtus in fœtu: un cas dépisté par échographie anténatale. JEMU 6:163-8,1985. 383 Boyce MJ, Lockyer JW, Wood CBS: Fœtus in fœtu: serological assessment of monozygotic origin by automated analysis. J Clin Pathol 25:793-8, 1972. 384 Broghammer BJ, Wolf RS, Geppert CH: The included twin or fetus in fetu–a case report. Radiology 80:844-6, 1963. 385 Burtner CD, Conn AG: Fetus in fetu: case report. W V Med J 84: 123-5, 1988. 386 Chi JG, Yoon SL, Park YS et al: Fetus in fetu: report of a case. Am J Clin Pathol 82:115-9, 1984. 387 Du Plessis JPG, Winship WS, Kirstein JDL: Fetus in fetu and teratoma: a case report and review. S Afr Med J 48:2119-12, 1974. 388 Farris JM, Bishop RC: Surgical aspects of included twins. Surg 28:443-8, 1950.

59

389 Fujikura T, Hunter WC: Retroperitoneal fetus in fetu. Obstet Gynecol 13:547-54, 1959. 390 Galatius-Jensen F, Rah DH, Uhm IK, el al: Fetus in fetu. Br J Radiol 38:305-8, 1965. 391 George V, Khanna M, Dutta T: Fetus in fetu. J Pediatr Surg. 18: 288-9, 1983. 392 Griscom T: The roentgenology of abdominal masses. AJR 93:447-63, 1965. 393 Grosfeld JL, Stepita DS, Nance WE et al: Fetus in fetu: an unusual cause for abdominal mass in infancy. Ann Surg 180:80-84, 1974. 394 Gross RE, Clatworthy HW: Twin fetuses in fetu. J Pediatr 38:502-8, 1951. 395 Gürses N, Gürses N, Bernay F: Twin fetuses in fetu and a review of the literature. Z Kinderchir. 45: 319-22, 1990. 396 Janovski NA: Fetus in fetu. J Pediatr 61:100-4, 1962. 397 Kakizoe T, Tahara M: Fetus in fetu located in the scrotal sac of a newborn infant: a case report. J Urol 107:506-8, 1972. 398 Karasimbarao KL, Mitra SK, Pathak IC: Sacrococcygeal fetus in fetu. Indian Pediatr 21:820-2, 1984. 399 Knox AJS, Webb AJ: The clinical features and treatment of a fetus in fetu: two cases reports and a review of the litera-ture. J Pediatr Surg 7: 434, 1972. 400 Lal M: A fœtus in the abdomen of a young boy. Med J Malaya 25:307-310, 1971. 401 Lamabadusarya SP, Atukrale AW Soysa PE et al: A case of fetus in fetu. Arch Dis Child 47:305-7, 1972. 402 Lee EYC: Fœtus in fœtu. Arch Dis Child 40:689-93, 1965. 403 Lewis PH: Fœtus in fœtu and the retroperitoneal teratoma. Arch Dis Child 36:220-6, 1961. 404 Lord JM: Intra-abdominal fœtus in fœtu. J Pathol Bacteriol 72:627-41, 1956. 405 Maxwell RW: Endocyme fœtus in a Fiji infant. Br Med J 732-3, 1947. 406 Montupet P, Sinico M, Soulier YA et al: Fœtus in fœtu: rapport de 2 cas et analyse de la littérature. Chir Pediatr 25:37-42, 1984. 407 Nadimpalli VR, Reyes H, Manaligold JR: Retroperitoneal teratoma with fetuses. Teratology 39:233-6, 1989 408 Nocera RM, Davis M, Hayden CK Jr et al: Fetus-in-fetu. AJR 138: 762-4, 1982. 409 Numanoglu I, Yavuz Gödemir A et al.: Fetus in fetu. J Pediatr Surg 5:472-3, 1970. 410 Ouimet A, Russo P: Fetus in fetu or not? J Pediatr Surg. 24: 926-7, 1989. 411 Prasad KR, Rai VK, Chowdhary DK: Fetus in fetu. J Indian Med Assoc 77:134-6, 1981. 412 Rastogi V, Singhal PK, Taneja SB: Fetus in fetu. Indian Pediatr. 25: 584-6, 1988. 413 Sangvichien S, Sutthiwan P: Fetus in fetu and teratoma: their genesis and the formation of vertebral column. J Med Assoc Thai.65:505-10,1982. 414 Sutthiwan P, Sutthiwan I, Tree-trakan T: Fetus in fetu. J Pediatr Surg. 18: 290-2, 1983. 415 Wiel MA, Tortollo G, Butti et al: Teratoma fetiforme breve nota su di un caso. Chir Pat Sper 178-81, 1970. 416 Yasuda Y, Mitomori T, Matsuura A et al: Fetus-in-fetu: report of a case. Teratology. 31: 337-44, 1985. 417 Hing A, Corteville J, Foglia RP, Bliss DP Jr, Donis-Keller H, Dowton SB. Fetus in fetu: molecular analysis of a feti-form mass. Am J Med Genet 1993 Sep 1;47(3):333-41. 418 Willis RA: Pathology of tumors. St Louis, Mo, CV Mosby, p 941, 1948. 419 Brunkow CW: Pediatric gynecology. Schauffler Chicago p220-6, 1942. 420 Sadler TW: Langman's Medical embryology. 5th Ed. Baltimore. Williams & Wilkins p171, 1985. 421 Hawkins EP: Fetus in fetu or not. J Pediatr Surg. 25: 583-4, 1990. 422 Nochomovitz LE, Rosai J: Current concepts on the histogenesis, pathology and immunochemistry of germ cells tumors of the testis. Pathol Ann 13:327-62, 1978. 423 Wakai S: On the origin of intracranial teratomas. No To Shinkei. 41: 947-53, 1989. 424 Wang PH, Chao HT, Taeng JY, Yang TS, Chang SP, Yuan CC, Ng HT. Laparoscopic surgery for heterotopic pregnan-cies: a case report and a brief review. Eur J Obstet Gynecol Reprod Biol 1998 Oct;80(2):267-71. 425 Giacomello F, Larciprete G, Valensise H, Romanini C. Spontaneous heterotopic pregnancy with live embryos: an insidious echographic problem in the first trimester. Therapeutic problems. A clinical case and review of the literature. Minerva Ginecol 1998 Apr;50(4):151-5. 426 Kably Ambe A, Werner von der Meden, Alarcon J, Garcia Leon JF, Reyes Cuervo H. Early diagnosis of heterotopic pregnancy with viability of the intrauterine fetus. Report of two cases and review of the literature. Ginecol Obstet Mex 1995 Aug;63:346-8. 427 Bassil S, Pouly JL, Canis M, Janny L, Vye P, Chapron C, Bruhat MA. Advanced heterotopic pregnancy after in vitro fertilization and embryo transfer, with survival of both the babies and the mother. Hum Reprod 1991 Aug;6(7):1008-10. 428 Jerrard D, Tso E, Salik R, Barish RA.Unsuspected heterotopic pregnancy in a woman without risk factors.: Am J Emerg Med 1992 Jan;10(1):58-60. 429 Tummon IS, Whitmore NA, Daniel SA, Nisker JA, Yuzpe AA. Transferring more embryos increases risk of het-erotopic pregnancy. Fertil Steril 1994 Jun;61(6):1065-7. 430 Svare JA, Norup PA, Thomsen SG, Hornnes PJ, Maigaard S, Helm P, Petersen K, Andersen AN. Heterotopic preg-nancy after in vitro fertilization. Ugeskr Laeger 1994 Apr 11;156(15):2230-3. 431 Barron Vallejo J, Ortega Diaz R, Kably Ambe A. Heterotopic pregnancy with intrauterine dizygotic twins following embryo transfer in the blastocyst phase. Ginecol Obstet Mex 1999 Apr;67:169-72.

60

432 Pistofidis GA, Mastrominas MJ, Dimitropoulos K. Laparoscopic management of heterotopic pregnancies. J Am Assoc Gynecol Laparosc 1995 Aug;2(4):42-3. 433 Loret de Mola JR, Austin CM, Judge NE, Assel BG, Peskin B, Goldfarb JM. Cornual heterotopic pregnancy and cor-nual resection after in vitro fertilization/embryo transfer. A report of two cases. J Reprod Med 1995 Aug;40(8):606-10. 434 Hanf V, Dietl J, Gagsteiger F, Pfeiffer KH. Bilateral tubal pregnancy with intra-uterine gestation after IVF-ET: therapy by bilateral laparoscopic salpingectomy; a case report. Eur J Obstet Gynecol Reprod Biol 1990 Oct;37(1):87-90. 435 Rondeau JA, Hibbert ML, Nelson KM. Combined tubal and cornual pregnancy in a patient without risk factors. A case report. J Reprod Med 1997 Oct;42(10):675-7. 436 Ginsburg ES, Frates MC, Rein MS, Fox JH, Hornstein MD, Friedman AJ. Early diagnosis and treatment of cervical pregnancy in an in vitro fertilization program. Fertil Steril 1994 May;61(5):966-9. 437 Andersen BB. Succesful intrauterine term pregnancy after resection of corneal pregnancy. Eur J Obstet Gynecol Re-prod Biol 1999 May;84(1):99-100. 438 Beck P, Silverman M, Oehninger S, Muasher SJ, Acosta AA, Rosenwaks Z. Survival of the cornual pregnancy in a heterotopic gestation after in vitro fertilization and embryo transfer. Fertil Steril 1990 Apr;53(4):732-4. 439 Chen SU, Yang YS, Ho HN, Ko TM, Hsieh FJ, Lee TY. Combined cornual pregnancy and intrauterine twin pregnancy after in vitro fertilization and embryo transfer: report of a case. J Formos Med Assoc 1992 Oct;91(10):1002-5. 440 Leach RE, Ney JA, Ory SJ. Selective embryo reduction of an interstitial heterotopic gestation. Fetal Diagn Ther 1992;7(1):41-5. 441 Scheiber MD, Cedars MI. Successful non-surgical management of a heterotopic abdominal pregnancy following em-bryo transfer with cryopreserved-thawed embryos. Hum Reprod 1999 May;14(5):1375-7. 442 Pisarska MD, Casson PR, Moise KJ Jr, DiMaio DJ, Buster JE, Carson SA. Heterotopic abdominal pregnancy treated at laparoscopy. Fertil Steril 1998 Jul;70(1):159-60. 443 Fernandez H, De Ziegler D, Imbert MC, Cambet B, Frydman R, Papiernick E. Advanced combined intra-uterine and ovarian gestations: case report. Eur J Obstet Gynecol Reprod Biol 1990 Dec;37(3):293-6. 444 Ogunniyi SO, Faleyimu BL, Odesanmi WO, Fasubaa OB. Ovarian pregnancy causing obstructed labor at term in a heterotopic gestation. Int J Gynaecol Obstet 1990 Mar;31(3):283-5. 445 De Muylder X, De Loecker P, Campo R. Heterotopic ovarian pregnancy after clomiphene ovulation induction. Eur J Obstet Gynecol Reprod Biol 1994 Jan;53(1):65-6. 446 Svare J, Norup P, Grove Thomsen S, Hornnes P, Malgaard S, Helm P, Petersen K, Nyboe Andersen A. Heterotopic pregnancies after in-vitro fertilization and embryo transfer- a Danish survey. Hum Reprod 1993 Jan;8(1):116-8. 447 Rizk B, Tan SL, Morcos S, Riddle A, Brinsden P, Mason BA, Edwards RG. Heterotopic pregnancies after in vitro fertilization and embryo transfer. Am J Obstet Gynecol 1991 Jan;164(1):161-4. 448 Wu MY, Chen HF. Chen SU, Chao KH, Yang YS, Huang SC, Lee TY, Ho HN. Heterotopic pregnancies after con-trolled ovarian hyperstimulation and assisted reproductive techniques. J Formos Med Assoc 1995 Oct;94(10):600-4. 449 Botta G, Fortunato N, Merlino G. Heterotopic pregnancy following administration of human menopausal gonadotropin and following in vitro fertilization and embryo transfer: two case reports and review of the literature. Eur J Obstet Gyne-col Reprod Biol 1995 Apr;59(2):211-5. 450 Li HP, Balmaceda JP, Zouves C, Cittadini E, Casas PF, Johnston I, Asch RH. Heterotopic pregnancy associated with gamete intra-fallopian transfer. Hum Reprod 1992 Jan;7(1):131-5. 451 Goldman JA, Dicker D, Dekel A, Feldberg D, Ashkenazi J. Successful management and outcome of heterotopic triplet in vitro fertilization (IVF) gestation: twin tubal and surviving intrauterine pregnancy. J In Vitro Fert Embryo Transf 1991 Oct;8(5):300-2. 452 Prapas Y, Prapas N, Chatziparasidou A, Konstantinou P, Viassis G. Ovarian hyperstimulation syndrome and het-erotopic pregnancy after IVF. Acta Eur Fertil 1994 Nov-Dec;25(6):331-3. 453 Mascarenhas L, Elliot B. Severe ovarian hyperstimulation syndrome, embryo reduction and heteropic pregnancy. Hum Reprod 1993Aug;8(8):1329-31. 454 Su WH, Wang PH, Chang SP. Unusual presentation of heterotopic pregnancy: a case report. Chung Hua I Hsueh Tsa Chih 1998 Oct;61(10):608-12. 455 Johnson N, McComb P, Gudex G. Heterotopic pregnancy complicating in vitro fertilization. Aust N Z J Obstet Gynae-col 1998 May;38(2):151-5. 456 Mantzavinos T, Kanakas N, Zourlas PA. Heterotopic pregnancies in an in-vitro fertilization program. Clin Exp Obstet Gynecol 1996;23(4):205-8. 457 Fishman DA, Padilla LA, Keh P, Cohen L, Frederiksen M, Lurain JR. Management of twin pregnancies consisting of a complete hydatidiform mole and normal fetus. Obstet Gynecol 1998 Apr;91(4):546-50. 458 Choi-Hong SR, Genest DR, Crum CP, Berkowitz R, Goldstein DP, Schofield DE. Twin pregnancies with complete hydatidiform mole and coexisting fetus: use of fluorescent in situ hybridization to evaluate placental X- and Y-chromosomal content. Hum Pathol 1995 Nov;26(11):1175-80. 459 Steller MA, Genest DR, Bernstein MR, Lage JM, Goldstein DP, Berkowitz RS. Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus. Obstet Gynecol 1994 Jan;83(1):35-42.

61

460 Miller D, Jackson R, Ehlen T, McMurtrie E.Complete hydatidiform mole coexistent with a twin live fetus: clinical course of four cases with complete cytogenetic analysis.Gynecol Oncol 1993 Jul;50(1):119-23. 461 Jeanty P, Rodesch F, Struyven J: The vanishing twin. Ultrasonics 2:25?31, 1981 462 Landy HJ, Keith L, Keith D. The vanishing twin. Acta Genet Med Gemellol 1982;31(3-4):179-94. 463 Landy HJ, Weiner S, Corson SL, Batzer FR, Bolognese RJ. The “vanishing twin”: ultrasonographic assessment of fetal disappearance in the first trimester. Am J Obstet Gynecol 1986 Jul;155(1):14-9. 464 Sulak LE, Dodson MG. The vanishing twin: pathologic confirmation of an ultrasonographic phenomenon. Obstet Gynecol 1986 Dec;68(6):811-5. 465 Saidi MH. First trimester bleeding and the vanishing twin. A report of three cases. J Reprod Med 1988 Oct;33(10):831-4. 466 Jauniaux E, Elkazen N, Leroy F, Wilkin P, Rodesch F, Hustin J. Clinical and morphologic aspects of the vanishing twin phenomenon. Obstet Gynecol 1988 Oct;72(4):577-81. 467 Janet Tomko, RDMS, Oksana Baltarowich, MD Synechial band (or amniotic fold) as a differential diagnosis for van-ishing twin. www.TheFetus.net 468 Benirschke K. Intrauterine death of a twin: mechanisms, implications for surviving twin, and placental pathology. Semin Diagn Pathol 1993 Aug;10(3):222-31. 469 Wagner DS, Klein RL, Robinson HB, Novek RW. Placental emboli from a fetus papyraceous. J Pediatr Surg 1990 May;25(5):538-42. 470 Csecsei K, Toth Z, Szeifert GT, Papp Z. Pathological consequences of the vanishing twin. Acta Chir Hung 1988;29(2):173-82. 471 Bergh C, Moller A, Nilsson L, Wikland M. Obstetric outcome and psychological follow-up of pregnancies after em-bryo reduction. Hum Reprod 1999 Aug;14(8):2170-5. 472 De Catte L, Camus M, Bonduelle M, Liebaers I, Foulon W. Prenatal diagnosis by chorionic villus sampling in multiple pregnancies prior to fetal reduction. Am J Perinatol 1998 May;15(5):339-43. 473 Fasouliotis SJ, Schenker JG.Multifetal pregnancy reduction: a review of the world results for the period 1993-1996..Eur J Obstet Gynecol Reprod Biol 1997 Dec;75(2):183-90 474 Evans MI, Dommergues M, Wapner RJ, Goldberg JD, Lynch L, Zador IE, Carpenter RJ Jr, Timor-Tritsch I, Brambati B, Nicolaides KH, Dumez Y, Monteagudo A, Johnson MP, Golbus MS, Tului L, Polak SM, Berkowitz RL.International, collaborative experience of 1789 patients having multifetal pregnancy reduction: a plateauing of risks and outcomes.J Soc Gynecol Investig 1996 Jan-Feb;3(1):23-6. 475 Ormont MA, Shapiro PA. Multifetal pregnancy reduction. A review of an evolving technology and its psychosocial implications. Psychosomatics 1995 Nov-Dec;36(6):522-30. 476 Stone J, Berkowitz RL. Multifetal pregnancy reduction and selective termination. Semin Perinatol 1995 Oct;19(5):363-74 477 Fang Q, Zhuang G, Zhou C. Clinical use of selective reduction in multifetal pregnancies. Chung Hua I Hsueh Tsa Chih 1995 Aug;75(8):459-62, 509. 478 Brambati B, Tului L. First trimester fetal reduction: its role in the management of twin and higher order multiple preg-nancies. Hum Reprod Update 1995 Jul;1(4):397-408. 479 Brambati B, Tului L, Baldi M, Guercilena S. Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome. Hum Reprod 1995 Apr;10(4):818-25. 480 Stone J, Lynch L. Multifetal pregnancy: risks and methods of reduction. Mt Sinai J Med 1994 Oct;61(5):404-8. 481 Chen SC, Lee FK, Chang SP, Too LL, Shu LP, Ng HT. Selective embryo reduction in multiple pregnancies resulting from assisted conception. Chung Hua I Hsueh Tsa Chih (Taipei) 1994 Jan;53(1):37-41. 482 Check JH, Nowroozi K, Vetter B, Rankin A, Dietterich C, Schubert B.The effects of multiple gestation and selective reduction on fetal outcome.J Perinat Med 1993;21(4):299-302. 483 Sebire NJ, D'Ercole C, Sepulveda W, Hughes K, Nicolaides KH.Effects of embryo reduction from trichorionic triplets to twins.Br J Obstet Gynaecol 1997 Oct;104(10):1201-3. 484 Maymon R, Herman A, Shulman A, Halperin R, Arieli S, Bukovsky I, Weinraub Z.First trimester embryo reduction: a medical solution to an iatrogenic problem.Hum Reprod 1995 Mar;10(3):668-73. 485 Papiernik E, Grange G, Zeitlin J. Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?. J Perinat Med 1998;26(5):365-70. 486 Evans MI, Littman L, Richter R, Richter K, Hume RF Jr.Selective reduction for multifetal pregnancy. Early opinions revisited. J Reprod Med 1997 Dec;42(12):771-7. 487 Haning RV Jr, Seifer DB, Wheeler CA, Frishman GN, Silver H, Pierce DJ. Effects of fetal number and multifetal reduction on length of in vitro fertilization pregnancies. Obstet Gynecol 1996 Jun;87(6):964-8. 488 Berkowitz RL, Lynch L, Stone J, Alvarez M.The current status of multifetal pregnancy reduction.Am J Obstet Gynecol 1996 Apr;174(4):1265-72. 489 Dommergues M, Aknin J, Boulot P, Nisand I, Lewin F, Oury JF, Herlicoviez M, Dumez Y, Evans MI. Embryo reduc-tion in multiple pregnancies. A French multicenter study. J Gynecol Obstet Biol Reprod (Paris) 1994;23(4):415-8.

62

490 Evans MI, Hume RF Jr, Yaron Y, Kramer RL, Johnson MP.Multifetal pregnancy reduction. Baillieres Clin Obstet Gynaecol 1998 Mar;12(1):147-59. 491 Chitkara U, Berkowitz RL, Wilkins IA, Lynch L, Mehalek KE, Alvarez M. Selective second-trimester termination of the anomalous fetus in twin pregnancies.Obstet Gynecol 1989 May;73(5 Pt 1):690-4. 492 Benson CB, Doubilet PM, Acker D, Heffner LJ.Multifetal pregnancy reduction of both fetuses of a monochorionic pair by intrathoracic potassium chloride injection of one fetus. J Ultrasound Med 1998 Jul;17(7):447-9. 493 Yaron Y, Johnson KD, Bryant-Greenwood PK, Kramer RL, Johnson MP, Evans MI. Selective termination and elective reduction in twin pregnancies: 10 years experience at a single centre. Hum Reprod 1998 Aug;13(8):2301-4. 494 Berkowitz RL.Ethical issues involving multifetal pregnancies.Mt Sinai J Med 1998 May;65(3):185-90; discussion 215-23. 495 Berkowitz RL, Stone JL, Eddleman KA. One hundred consecutive cases of selective termination of an abnormal fetus in a multifetal gestation. Obstet Gynecol 1997 Oct;90(4 Pt 1):606-10. 496 Lipitz S, Peltz R, Achiron R, Barkai G, Mashiach S, Schiff E. Selective second-trimester termination of an abnormal fetus in twin pregnancies.J Perinatol 1997 Jul-Aug;17(4):301-4. 497 Stewart KS, Johnson MP, Quintero RA, Evans MI.Congenital abnormalities in twins: selective termination. Curr Opin Obstet Gynecol 1997 Apr;9(2):136-9. 498 Sebire NJ, Sepulveda W, Hughes KS, Noble P, Nicolaides KH. Management of twin pregnancies discordant for anen-cephaly. Br J Obstet Gynaecol 1997 Feb;104(2):216-9. 499 Lipitz S, Shalev E, Meizner I, Yagel S, Weinraub Z, Jaffa A, Shalev J, Achiron R, Schiff E.Late selective termination of fetal abnormalities in twin pregnancies: a multicentre report.Br J Obstet Gynaecol 1996 Dec;103(12):1212-6. 500 Yaron Y, Bryant-Greenwood PK, Dave N, Moldenhauer JS, Kramer RL, Johnson MP, Evans MI. Multifetal pregnancy reductions of triplets to twins: comparison with nonreduced triplets and twins. Am J Obstet Gynecol 1999 May;180(5):1268-71. 501 Smith-Levitin M, Kowalik A, Birnholz J, Skupski DW, Hutson JM, Chervenak FA, Rosenwaks Z.Selective reduction of multifetal pregnancies to twins improves outcome over nonreduced triplet gestations.Am J Obstet Gynecol 1996 Oct;175(4 Pt 1):878-82. 502 Bollen N, Camus M, Tournaye H, Wisanto A, Van Steirteghem AC, Devroey P. Embryo reduction in triplet pregnan-cies after assisted procreation: a comparative study. Fertil Steril 1993 Sep;60(3):504-9. 503 Vauthier-Brouzes D, Lefebvre G. Selective reduction in multifetal pregnancies: technical and psychological aspects. Fertil Steril 1992 May;57(5):1012-6 504 Evans MI, Goldberg JD, Horenstein J, Wapner RJ, Ayoub MA, Stone J, Lipitz S,Achiron R, Holzgreve W, Brambati B, Johnson A, Johnson MP, Shalhoub A, Berkowitz RL. Selective termination for structural, chromosomal, and mende-lian anomalies: international experience. Am J Obstet Gynecol 1999 Oct;181(4):893-7. 505 Coffler MS, Kol S, Drugan A, Itskovitz-Eldor J.Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.Hum Reprod 1999 Jul;14(7):1875-8. 506 Wapner RJ. Genetic diagnosis in multiple pregnancies. Semin Perinatol 1995 Oct;19(5):351-62. 507 Anderson RL, Goldberg JD, Golbus MS. Prenatal diagnosis in multiple gestations: 20 years´ experience with amnio centesis. Prenat Diagn 1991 Apr;11(4):263-70. 508 Ghidini A, Lynch L, Hicks C, Alvarez M, Lockwood CJ.The risk of second-trimester amniocentesis in twin gestations: a case-control study.Am J Obstet Gynecol 1993 Oct;169(4):1013-6. 509 Kidd SA, Lancaster PA, Anderson JC, Boogert A, Fisher CC, Robertson R, Wass DM. Fetal death after exposure to methylene blue dye during mid-trimester amniocentesis in twin pregnancy. Prenat Diagn 1996 Jan;16(1):39-47. 510 Gluer S. Intestinal atresia following intraamniotic use of dyes. Eur J Pediatr Surg 1995 Aug;5(4):240-2. 511 Van der Pol JG, Wolf H, Boer K, Treffers PE, Leschot NJ, Hey HA, Vos A. Jejunal atresia related to the use of me-thylene blue in genetic amniocentesis in twins. Br J Obstet Gynaecol 1992 Feb;99(2):141-3. 512 Jeanty P, Shah D, Roussis P. Single-needle insertion in twin amniocentesis. J Ultrasound Med 1990 Sep;9(9):511-7. 513 Buscaglia M, Ghisoni L, Bellotti M, Marconi AM; Zamperini P, Stripparo L, Molinari A, Grimoldi MG, Rossella F. Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal insertion of the needle. Prenat Diagn 1995 Jan;15(1):17-9. 514 Van Vugt JM, Nieuwint A, van Geijn HP. Single-needle insertion: an alternative technique for early second-trimester genetic twin amniocentesis. Fetal Diagn Ther 1995 May-Jun;10(3):178-81. 515 Sebire NJ, Noble PL, Odibo A, Malligiannis P, Nicolaides KH. Single uterine entry for genetic amniocentesis in twin pregnancies. Ultrasound Obstet Gynecol 1996 Jan;7(1):26-31. 516 Benifla JL, Goffinet F, Dorai E, Proust A, De Crepy A, Madelenat P. Emergency cervical cerclage after 20 weeks´ gestation: a retrospective study of 6 years´ practice in 34 cases. Fetal Diagn Ther 1997 Sep-Oct;12(5):274-8. 517 Lewis R, Mercer BM. Selected issues in premature rupture of the membranes: herpes, cerclage, twins, tocolysis and hospitalization. Semin Perinatol 1996 Oct;20(5):451-61. 518 Maly Z, Deutinger J. Decrease in cerclage incidence in multiple pregnancies by vaginal ultrasound monitoring. Z Geburtshilfe Perinatol 1993 Jul-Aug;197(4):162-4. 519 Michaels WH, Schreiber FR, Padgett RJ, Ager J, Pieper D. Ultrasound surveillance of the cervix in twin gestations: management of cervical incompetency. Obstet Gynecol 1991 Nov;78(5):739-44.

63

520 Jones JM, Sbaua AJ, Cetrulo CL. Antepartum management of twin gestation. Clin Obstet Gynecol 1990 Mar;33(1):32-41. 521 Newton ER. Antepartum care in multiple gestation. Semin Perinatol 1986 Jan;10(1):19-29.