Monochorionic Twins and Twin Transfusion Syndrome Emanuel P

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Monochorionic Twins and Twin Transfusion Syndrome Emanuel P. Gaziano, M. D. Minnesotal Perinatal Physicians

Monochorionic Twins and Twin Transfusion Syndrome Emanuel P. Gaziano, M. D. Minnesotal Perinatal Physicians Abbott Northwestern Hospital, Minneapolis Professor, Department of Ob/Gyn University of Minnesota Emanuel Gaziano, MD Multiple Gestation Pregnancies

Multiple Gestations • Twins occurrence – 1/90 Natural – 1/45 ART • Ovulation induction

Multiple Gestations • Twins occurrence – 1/90 Natural – 1/45 ART • Ovulation induction increases: – Twins rate 4 X – Triplet or higher 72 X • MZ twins 3. 8 X Logerot-Lebrun. Contracept Fertil Sex: 1993; 21: 362 Luke B, Martin, JA. Clinical Obstetrics and Gynecology 47: 1, 2004

Multiple Gestations • Membranes • Placental symmetry • Blood vessels Type of placenta determines

Multiple Gestations • Membranes • Placental symmetry • Blood vessels Type of placenta determines frequency and severity of complications

What Type of Twining Event Has Occurred?

What Type of Twining Event Has Occurred?

Dizygotic or “Fraternal” Twin “arise from two fertilized ova” • ~ 2/3 of spontaneous

Dizygotic or “Fraternal” Twin “arise from two fertilized ova” • ~ 2/3 of spontaneous twin pregnancies are dizygotic Frequently affected by • Maternal ethnicity – Blacks highest in Africa > white intermediate in USA & Europe > Asians lowest in Japan & China – Maternal central gonadotropin levels – high FSH levels • Maternal Age – > 35 years old • Multi-parity • Maternal genetics – Previous / family history of dizygotic twins • Ovulation induction therapy

Dizygotic or “Fraternal” Twin “arise from two fertilized ova” • Dichorionic (2 placentas) &

Dizygotic or “Fraternal” Twin “arise from two fertilized ova” • Dichorionic (2 placentas) & Diamniotic • Membrane: 4 layers (2 chorion & 2 amnion)

Monozygotic or “Identical” Twin “arise from one fertilized ovum” • • • Constant rate

Monozygotic or “Identical” Twin “arise from one fertilized ovum” • • • Constant rate across population – 3 -5 / 1000 ~ 1/3 natural conception Can occur in ART Variable chorionicity Depends on when the Variable amnionicity zygote (fertilized ovum) divides Variable risk

Monozygotic or “Identical” Twin “arise from one fertilized ovum” • Monochorionic & Diamniotic •

Monozygotic or “Identical” Twin “arise from one fertilized ovum” • Monochorionic & Diamniotic • Dividing membrane: 2 layers of amnion with no interposing chorion

Placentation & Chorionicity

Placentation & Chorionicity

Placentation & Chorionicity Relative Risks Division of zygote Frequency Placentation Risk < 3 days

Placentation & Chorionicity Relative Risks Division of zygote Frequency Placentation Risk < 3 days 25% Di – Di 10% 75% Mono – Di 25% 2% Mono – Mono 50% Rare Conjoined 99% Mortality Rate after fertilization 4 – 8 days after fertilization 9 – 13 days after fertilization > 13 days after fertilization

Twin Gestations & Relative Risks Diamniotic-Dichorionic Diamniotic-Monochorionic • Age risk for aneuploidy higher than

Twin Gestations & Relative Risks Diamniotic-Dichorionic Diamniotic-Monochorionic • Age risk for aneuploidy higher than singleton rate • Age risk for aneuploidy same as singleton rate • Early loss greater than singleton • Early loss rate greater than Di-Di twins • Greater congenital anomaly rate compared to singleton • Greater congenital anomaly rate compared to Di-Di twins

Chorionicity & Amnionicity • DC-DA – Thick membrane around each sac • MC-DA –

Chorionicity & Amnionicity • DC-DA – Thick membrane around each sac • MC-DA – Thick membrane around periphery, but thin membrane between sacs • MC-MA – Thick membrane around periphery and no visible membrane between sacs

Chorionicity & Amnionicity • DC-DA – Thick membrane around each sac • MC-DA –

Chorionicity & Amnionicity • DC-DA – Thick membrane around each sac • MC-DA – Thick membrane around periphery, but thin membrane between sacs • MC-MA – Thick membrane around periphery and no visible membrane between sacs

Chorionicity & Amnionicity • DC-DA – Thick membrane around each sac • MC-DA –

Chorionicity & Amnionicity • DC-DA – Thick membrane around each sac • MC-DA – Thick membrane around periphery, but thin membrane between sacs • MC-MA – Thick membrane around periphery and no visible membrane between sacs

Implications of Early Chorionicity Determination • The rate of miscarriage & perinatal death in

Implications of Early Chorionicity Determination • The rate of miscarriage & perinatal death in monochorionic twins > dichorionic twins • Death of a monochorionic fetus is associated with a high chance of sudden death or severe neurologic impairment in the co-twin • Genetic disorders & chromosomal abnormalities is dependent on chorionicity • Management of pregnancy

Complications

Complications

General Risks of Multiple Pregnancy Fetal Complications • Monozygotic twins – anomalies • Preterm

General Risks of Multiple Pregnancy Fetal Complications • Monozygotic twins – anomalies • Preterm births • Monochorionic twins • Growth restriction – TTTS • Early post-maturity – Acardiac twin • Fetal anomalies • Monoamniotic twins Maternal Complications – Cord entanglement • Preeclampsia – Conjoining • Placenta abruption – Death of a twin • Placenta previa • Pre & postpartum hemorrhage

Monozygotic Twins • Congenital anomalies – structural – Twins - 2 x singletons –

Monozygotic Twins • Congenital anomalies – structural – Twins - 2 x singletons – Monozygotic - 2 x dizygotic • 80 to 90 % of structural malformations are discordant

Monoamniotic Twins • Cord entanglement • Conjoining • Death of a twin

Monoamniotic Twins • Cord entanglement • Conjoining • Death of a twin

Monoamniotic Twins • The umbilical cords usually insert near one another • The placental

Monoamniotic Twins • The umbilical cords usually insert near one another • The placental vessels typically have large-caliber anastomoses between them – TTS is less common because imbalance in the two circulations could not be sustained for long period

Monoamniotic Twins • MC-MA twins have a further increased incidence of entangled cords

Monoamniotic Twins • MC-MA twins have a further increased incidence of entangled cords

Conjoined Twins • form when a single fertilized egg fails to divide completely to

Conjoined Twins • form when a single fertilized egg fails to divide completely to create two distinct individuals • 1 in 50, 000 to 1 in 200, 000

Twin Reversed Arterial Perfusion “Acardiac Twin” • 1% of MC Pregnancies • 1 in

Twin Reversed Arterial Perfusion “Acardiac Twin” • 1% of MC Pregnancies • 1 in 35, 000 Pregnancies • Acardiac twin perfused by deoxygenated blood from “pump” twin Flow in umbilical artery of abnormal twin is toward fetus

Twin Reversed Arterial Perfusion “Acardiac Twin” • Delayed cardiac function of one twin

Twin Reversed Arterial Perfusion “Acardiac Twin” • Delayed cardiac function of one twin

Twin Reversed Arterial Perfusion “Acardiac Twin” • Commonly edematous, cystic appearing mass (similar to

Twin Reversed Arterial Perfusion “Acardiac Twin” • Commonly edematous, cystic appearing mass (similar to cystic hygroma) • Absent cranium, cervical spine and upper extremities • No cardiac structures or activity • Lower half of body better developed

Twin Reversed Arterial Perfusion “Acardiac Twin”

Twin Reversed Arterial Perfusion “Acardiac Twin”

Twin Transfusion • A syndrome occurring in MC pregnancies due to artery to vein

Twin Transfusion • A syndrome occurring in MC pregnancies due to artery to vein anastomoses in which the donor twin partially perfuses the recipient twin. • Also known as TTTS or TOPS (Twins oligohydramnios, polyhydramnios sequence. ) Emanuel Gaziano, MD Multiple Gestation Pregnancies

Twin-twin Transfusion Syndrome Outcome: • Without treatment, mortality is 90 -100% • Neurological morbidity:

Twin-twin Transfusion Syndrome Outcome: • Without treatment, mortality is 90 -100% • Neurological morbidity: 37% • If one fetus dies, there is a 25% risk of severe neurologic impairment probably due to hypotension, hypoxia or thromboembolism Adegbite AJOBG 190: 156, 2004 Turrentine et al. Am J Perinatol 13: 351, 1996 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Outcome • Less than 28 weeks survival 21% irrespective of method of management including

Outcome • Less than 28 weeks survival 21% irrespective of method of management including decompression amniocentesis or tocolytics. • Gondoulin W, et al. 1990, Obstet Gynecol 75: 214. Emanuel Gaziano, MD Multiple Gestation Pregnancies

Frequency • About 15% of monochorionic twins will show some evidence of twin to

Frequency • About 15% of monochorionic twins will show some evidence of twin to twin transfusion syndrome Emanuel Gaziano, MD Multiple Gestation Pregnancies

Frequency TTTS Twin Gestation Diamniotic Dichorionic (70 -80%) TTTS Rare Emanuel Gaziano, MD Multiple

Frequency TTTS Twin Gestation Diamniotic Dichorionic (70 -80%) TTTS Rare Emanuel Gaziano, MD Multiple Gestation Pregnancies Diamniotic monochorionic (20 -30%) MC-TTS MC-non TTS (6 -15%) (85 -94%)

Etiology • MC Twins • Vascular anastomoses • Unequal placental sharing • Abnormal size

Etiology • MC Twins • Vascular anastomoses • Unequal placental sharing • Abnormal size of umbilical cord • Velamentous insertion of cord Emanuel Gaziano, MD Multiple Gestation Pregnancies

Emanuel Gaziano, MD Multiple Gestation Pregnancies 4 to 7 Days after fertilization

Emanuel Gaziano, MD Multiple Gestation Pregnancies 4 to 7 Days after fertilization

Vascular arrangement TTTS Emanuel Gaziano, MD Multiple Gestation Pregnancies

Vascular arrangement TTTS Emanuel Gaziano, MD Multiple Gestation Pregnancies

Surface Vessels on Chorionic Plate • Artery to vein anastomoses primary defect • Actually

Surface Vessels on Chorionic Plate • Artery to vein anastomoses primary defect • Actually fewer balanced anastomoses • Nose to nose A-V connections Gaziano E, Harkness, U. Doppler Velocimetry and Multiple Gestation. In Doppler Ultrasound in Obstetrics and Gynecology, D. Maulik, ed. 2005 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Contrast Medium Demonstrating Vascular Anastomoses in MC Twins Emanuel Gaziano, MD Multiple Gestation Pregnancies

Contrast Medium Demonstrating Vascular Anastomoses in MC Twins Emanuel Gaziano, MD Multiple Gestation Pregnancies

Etiology: Hemoglobin Differences • Mean hemoglobin difference is 4. 8 gr/dl. • In cordocentesis

Etiology: Hemoglobin Differences • Mean hemoglobin difference is 4. 8 gr/dl. • In cordocentesis studies any range of hemoglobin differences have been observed even in the presence of hydrops in the recipient. • Neonatal criteria is more rigid for diagnosis requiring 5. 0 gr/dl difference Gaziano E, Harkness, U. Doppler Velocimetry and Multiple Gestation. In Doppler Ultrasound in Obstetrics and Gynecology, D. Maulik, ed. 2005 Emanuel Gaziano, MD Multiple Gestation Pregnancies

st Diagnosis: 1 Trimester • NT in Di. Mo twins • If NT abnormal

st Diagnosis: 1 Trimester • NT in Di. Mo twins • If NT abnormal measure DV • Abnormal NT + Abnormal DV predicts TTTS Sebire Human Reproduction, Vol. 15, No. 9, 2008 -2010, September 2000 Emanuel Gaziano, MD Multiple Gestation Pregnancies

20 week scan TWIN A: HC=23 1/7 ths Wks TWIN A: AC=23 4/7 ths

20 week scan TWIN A: HC=23 1/7 ths Wks TWIN A: AC=23 4/7 ths Wks Emanuel Gaziano, MD Multiple Gestation Pregnancies TWIN B: HC=20 6/7 ths Wks TWIN B: HC=19 5/7 ths Wks

 20 week scan Emanuel Gaziano, MD Multiple Gestation Pregnancies

20 week scan Emanuel Gaziano, MD Multiple Gestation Pregnancies

20 week scan TWIN B: Cord Insertion Emanuel Gaziano, MD Multiple Gestation Pregnancies TWIN

20 week scan TWIN B: Cord Insertion Emanuel Gaziano, MD Multiple Gestation Pregnancies TWIN B Umbilical Artery Doppler

Ultrasound of TTTS • • Features of MC Placenta Fused placenta Thin dividing membrane

Ultrasound of TTTS • • Features of MC Placenta Fused placenta Thin dividing membrane Dissimilar AF volumes Emanuel Gaziano, MD Multiple Gestation Pregnancies

Sonographic Signs TTTS • Oligohydramnios – Donor sac <2 cm • Hydramnios – Recipient

Sonographic Signs TTTS • Oligohydramnios – Donor sac <2 cm • Hydramnios – Recipient sac >8 cm • Growth discordance • Thin dividing membrane • Same gender pair Blickstein I. Obstet Gynecol 1990; 76: 714 -22 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound of TTTS Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound of TTTS Emanuel Gaziano, MD Multiple Gestation Pregnancies

TTTS Emanuel Gaziano, MD Multiple Gestation Pregnancies

TTTS Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound TTS • Assess cord insertion site for each twin Emanuel Gaziano, MD Multiple

Ultrasound TTS • Assess cord insertion site for each twin Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound TTTS • Assess for velamentous insertion Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound TTTS • Assess for velamentous insertion Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound TTTS • Assess Placental Mass Emanuel Gaziano, MD Multiple Gestation Pregnancies

Ultrasound TTTS • Assess Placental Mass Emanuel Gaziano, MD Multiple Gestation Pregnancies

Other sonographic signs TTTS • Echogenic bowel • Cardiac: enlargement, tricuspid regurgitation, ROF obstruction

Other sonographic signs TTTS • Echogenic bowel • Cardiac: enlargement, tricuspid regurgitation, ROF obstruction • Pulmonary artery calcification Emanuel Gaziano, MD Multiple Gestation Pregnancies

Doppler In TTTS • Initial studies: CW no difference in Doppler values (Trudinger) •

Doppler In TTTS • Initial studies: CW no difference in Doppler values (Trudinger) • Abnormal UA Doppler values may be seen in either donor or recipient but more common in Donor. • Abnormal Doppler values predict adverse outcomes. • Role for Doppler in Staging of TTTS • Abnormal venous values seen in TTTS Gaziano E, Harkness, U. Doppler Velocimetry and Multiple Gestation. In Doppler Ultrasound in Obstetrics and Gynecology, D. Maulik, ed. 2005 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Abnormal Doppler also predicts poor outcome in TTTS • Umbilical artery PI Doppler difference

Abnormal Doppler also predicts poor outcome in TTTS • Umbilical artery PI Doppler difference is greater in MC twins who are destined to develop hydrops. • Poor prognostic factors in TTTS: zero or REDF in umbilical artery Doppler Abnormal venous Doppler Absence of artery to artery anastomoses Taylor et al, 2000 Am J Obstet Gynecol 183: 1023 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Extreme Cases of TTTS When cord Hb differences are >5 Doppler values in Donor

Extreme Cases of TTTS When cord Hb differences are >5 Doppler values in Donor and Recipient may be similar Emanuel Gaziano, MD Multiple Gestation Pregnancies

Quintero Staging of twin-twin transfusion syndrome • Stage I – Amniotic fluid differences •

Quintero Staging of twin-twin transfusion syndrome • Stage I – Amniotic fluid differences • Stage II – Absence of bladder • Stage III – Critically abnormal Dopplers • Stage IV – Presence of ascites or frank hydrops • Stage V – Demise of either fetus. Emanuel Gaziano, MD Multiple Gestation Pregnancies J Perinatol 19: 550 -555

Quintero Staging of twin-twin transfusion syndrome • Stage II – Diastolic flow in UA

Quintero Staging of twin-twin transfusion syndrome • Stage II – Diastolic flow in UA and forward flow in the DV • Stage III – Zero or AED flow in UA and reverse flow in DV J Perinatol 19: 550 -555 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Twin-twin Transfusion Syndrome Emanuel Gaziano, MD Multiple Gestation Pregnancies

Twin-twin Transfusion Syndrome Emanuel Gaziano, MD Multiple Gestation Pregnancies

Options for Treatment • • Septostomy Amnioreduction Laser separation of the circulations Feticide Emanuel

Options for Treatment • • Septostomy Amnioreduction Laser separation of the circulations Feticide Emanuel Gaziano, MD Multiple Gestation Pregnancies

Options for Treatment Septostomy • Separates the dividing membrane • Equalizes fluid pressure •

Options for Treatment Septostomy • Separates the dividing membrane • Equalizes fluid pressure • Usually small holes punctured in the dividing membrane • Risk for cord entanglement Emanuel Gaziano, MD Multiple Gestation Pregnancies Amnioreduction • Reduce amniotic fluid volume in the recipient sac. • Usually for Stage I or II • Decompress when DVP >11 • Decompress to normal range <DVP of 8 • Risk: infection

Technique similar to genetic amnio: larger needle and vacuum bottle. Emanuel Gaziano, MD Multiple

Technique similar to genetic amnio: larger needle and vacuum bottle. Emanuel Gaziano, MD Multiple Gestation Pregnancies

Prospective randomized trial comparing amnioreduction to septostomy • Survival in each group was 65%

Prospective randomized trial comparing amnioreduction to septostomy • Survival in each group was 65% • No data on neurologic outcome Saade GR, Moise K, Dormar KA et al: Randomized trial of septostomy verses amnioreduction in the treatment of twin oligohydramnios polyhydramnios sequence (TOPS). American Journal of Obstetrics and Gynecology (abstr) 187: 3, 2003. Emanuel Gaziano, MD Multiple Gestation Pregnancies

De. Lia 1995 N=26 Severe TTTS by Laser • Surviving fetuses were delivered for

De. Lia 1995 N=26 Severe TTTS by Laser • Surviving fetuses were delivered for obstetric reasons at a mean of 32. 2 weeks (range, 26 to 37 weeks). • Fifty-three percent (28 of 53) of fetuses survived • 96% (27 of 28) showed normal development at a mean of 35. 8 months of follow-up (range, 1 to 68 months). • De. Lia JE, et al: Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome. American Journal of Obstetrics and Gynecology 172: 1202, 1995. Emanuel Gaziano, MD Multiple Gestation Pregnancies

Laser vs Amnioreduction • N=73 women were treated between 1995 and 1997 in one

Laser vs Amnioreduction • N=73 women were treated between 1995 and 1997 in one center by fetoscopic laser photocoagulation • N=43 patients were treated at another center between 1992 and 1996 by serial amnioreduction. • Hecher K, et al: Endoscopic laser surgery versus serial amniocentesis in the treatment of severe twin-twin transfusion syndrome. American Journal of Obstetrics and Gynecology 180: 717, 1999. Emanuel Gaziano, MD Multiple Gestation Pregnancies

 Hecher K, et al: Endoscopic laser surgery versus serial amniocentesis in the treatment

Hecher K, et al: Endoscopic laser surgery versus serial amniocentesis in the treatment of severe twin-twin transfusion syndrome. American Journal of Obstetrics and Gynecology 180: 717, 1999 Emanuel Gaziano, MD Multiple Gestation Pregnancies

Long-term neurodevelopmental outcome of children born after laser for severe TTTS N=167 follow up

Long-term neurodevelopmental outcome of children born after laser for severe TTTS N=167 follow up to 3 years and 2 months • 145 (86. 8%) showed normal development, • 12 infants (7. 2%) showed minor neurologic abnormalities, • 10 infants (6. 0%) major neurologic abnormalities. Graef C. Am J Obstet Gynecol. 2006 Feb; 194(2): 303 -8. Emanuel Gaziano, MD Multiple Gestation Pregnancies

Long-term neurodevelopmental outcome of children born after Laser for severe TTTS No difference in

Long-term neurodevelopmental outcome of children born after Laser for severe TTTS No difference in outcome for the former donors/recipients (P =. 349) CONCLUSION: intrauterine laser coagulation seems to be the best treatment option for severe twin-twin transfusion syndrome. Graef C. Am J Obstet Gynecol. 2006 Feb; 194(2): 303 -8. Emanuel Gaziano, MD Multiple Gestation Pregnancies

Perinatal death rate higher when laser used for treatment of TTTS in Stage I

Perinatal death rate higher when laser used for treatment of TTTS in Stage I and II (p=. 02) Emanuel Gaziano, MD Multiple Gestation Pregnancies Quintero et al, Am J Obstet Gynecol 2003; 188: 1333

Perinatal death rate lower when laser used for treatment of TTTS in Stage III

Perinatal death rate lower when laser used for treatment of TTTS in Stage III and IV (p=. 02) Emanuel Gaziano, MD Multiple Gestation Pregnancies Quintero et al, Am J Obstet Gynecol 2003; 188: 1333

Two prospective randomized clinical trials • The Eurofetus trial in Europe • The National-Institutes-of-Health-sponsored

Two prospective randomized clinical trials • The Eurofetus trial in Europe • The National-Institutes-of-Health-sponsored trial in the United States • Compare aggressive serial amnioreduction to fetoscopic laser photocoagulation. Emanuel Gaziano, MD Multiple Gestation Pregnancies

2011 NIH Trial • The trial had uncovered higher mortality among recipient twins who

2011 NIH Trial • The trial had uncovered higher mortality among recipient twins who received laser treatment. But overall, survival of one or both twins of the same pregnancy was no different between the two treatments. In addition, there was no difference between survival rates of donor twins and recipient twins. Emanuel Gaziano, MD Multiple Gestation Pregnancies

Cochrane Review • Laser coagulation resulted in less overall death (48% vs. 59%) when

Cochrane Review • Laser coagulation resulted in less overall death (48% vs. 59%) when compared with amnioreduction. • The results suggest that endoscopic laser coagulation of anastomotic vessels should be considered in the treatment of all stages of TTTS to improve perinatal and neonatal outcome Emanuel Gaziano, MD Multiple Gestation Pregnancies

Treatment Summary • Most studies show outcomes for laser separation superior to amnioreduction. •

Treatment Summary • Most studies show outcomes for laser separation superior to amnioreduction. • Always exceptions due to the small placental mass and complications due to velamentous insertions in some MC pregnancies. • Spontaneous improvement occurs in some cases (anastomoses change) Emanuel Gaziano, MD Multiple Gestation Pregnancies

Discordant Growth (AEDF) Emanuel Gaziano, MD Multiple Gestation Pregnancies

Discordant Growth (AEDF) Emanuel Gaziano, MD Multiple Gestation Pregnancies

Thank you! Emanuel Gaziano, MD Multiple Gestation Pregnancies

Thank you! Emanuel Gaziano, MD Multiple Gestation Pregnancies