emanuel gaziano, md multiple gestation pregnancies monochorionic twins and twin transfusion syndrome...

Emanuel Gaziano, MDMultiple Gestation Pregnancies


Monochorionic Twins and Twin Transfusion SyndromeMonochorionic 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 P. Gaziano, M.D.

Minnesotal Perinatal Physicians

Abbott Northwestern Hospital, Minneapolis

Professor, Department of Ob/Gyn

University of Minnesota

Multiple GestationsMultiple Gestations

• Twins occurrence– 1/90 Natural – 1/45 ART

• Ovulation induction increases: – Twins rate 4X– Triplet or higher 72X

• MZ twins 3.8X

• Twins occurrence– 1/90 Natural – 1/45 ART

• Ovulation induction increases: – Twins rate 4X– Triplet or higher 72X

• MZ twins 3.8XLogerot-Lebrun. Contracept Fertil Sex:1993;21:362Luke B, Martin, JA. Clinical Obstetrics and Gynecology 47:1, 2004

Multiple GestationsMultiple Gestations

• Membranes

• Placental symmetry

• Blood vessels

• Membranes

• Placental symmetry

• Blood vessels

Type of placenta determines frequency and severity of complications

What Type of Twining Event Has Occurred?

Dizygotic or “Fraternal” Twin “arise from two fertilized ova”


• ~ 2/3 of spontaneous twin pregnancies are dizygoticFrequently 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

• ~ 2/3 of spontaneous twin pregnancies are dizygoticFrequently 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



• Dichorionic (2 placentas) & Diamniotic

• Membrane: 4 layers (2 chorion & 2 amnion)

• Dichorionic (2 placentas) & Diamniotic

• Membrane: 4 layers (2 chorion & 2 amnion)

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

• Variable amnionicity

• Variable risk

• Constant rate across population – 3-5 / 1000

• ~ 1/3 natural conception

• Can occur in ART

• Variable chorionicity

• Variable amnionicity

• Variable risk

Depends on when the zygote (fertilized ovum) divides



• Monochorionic & Diamniotic

• Dividing membrane: 2 layers of amnion with no interposing chorion

Placentation & Chorionicity

Placentation & Chorionicity Relative Risks

Placentation & Chorionicity Relative Risks

Division of zygote

Frequency Placentation RiskMortality Rate

< 3 daysafter fertilization

25% Di – Di 10%

4 – 8 daysafter fertilization

75% Mono – Di 25%

9 – 13 daysafter fertilization

2% Mono – Mono 50%

> 13 daysafter fertilization

Rare Conjoined 99%

Twin Gestations & Relative Risks

Twin Gestations & Relative Risks

Diamniotic-Dichorionic

• Age risk for aneuploidy higher than singleton rate

• Early loss greater than

singleton

• Greater congenital anomaly

rate compared to singleton

Diamniotic-Dichorionic

• Age risk for aneuploidy higher than singleton rate

• Early loss greater than

singleton


rate compared to singleton

Diamniotic-Monochorionic

• Age risk for aneuploidy same as singleton rate

• Early loss rate greater than

Di-Di twins


rate compared to Di-Di twins

Diamniotic-Monochorionic

• Age risk for aneuploidy same as singleton rate

• Early loss rate greater than

Di-Di twins


rate compared to Di-Di twins

Chorionicity & AmnionicityChorionicity & 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

• 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

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

• 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

General Risks of Multiple PregnancyGeneral Risks of Multiple Pregnancy

Fetal Complications

• Preterm births

• Growth restriction

• Early post-maturity

• Fetal anomalies

Maternal Complications

• Preeclampsia

• Placenta abruption

• Placenta previa

• Pre & postpartum hemorrhage

Fetal Complications

• Preterm births

• Growth restriction

• Early post-maturity

• Fetal anomalies

Maternal Complications

• Preeclampsia

• Placenta abruption

• Placenta previa

• Pre & postpartum hemorrhage

• Monozygotic twins anomalies

• Monochorionic twins– TTTS

– Acardiac twin

• Monoamniotic twins– Cord entanglement

– Conjoining

– Death of a twin

• Monozygotic twins anomalies

• Monochorionic twins– TTTS

– Acardiac twin

• Monoamniotic twins– Cord entanglement

– Conjoining

– Death of a twin

Monozygotic TwinsMonozygotic Twins

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

• 80 to 90 % of structural malformations are discordant

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

• 80 to 90 % of structural malformations are discordant

Monoamniotic TwinsMonoamniotic Twins

• Cord entanglement

• Conjoining

• Death of a twin

• Cord entanglement

• Conjoining

• Death of a twin


• 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

• 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


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

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

Conjoined TwinsConjoined 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

• 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 35,000 Pregnancies

• Acardiac twin perfused by deoxygenated blood from “pump” 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

Flow in umbilical artery of abnormal twin is toward fetus



• Delayed cardiac function of one twin• Delayed cardiac function of one 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

• 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 Twin Transfusion Twin 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.)

• 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.)



Twin-twin Transfusion SyndromeTwin-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

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, 2004Turrentine et al. Am J Perinatol 13:351,1996



Outcome 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.

• 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.



FrequencyFrequency

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

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



Frequency TTTSFrequency TTTS

Twin GestationTwin Gestation

Diamniotic DichorionicDiamniotic Dichorionic(70-80%)(70-80%)

TTTS RareTTTS Rare

Diamniotic monochorionicDiamniotic monochorionic(20-30%)(20-30%)

MC-TTSMC-TTS(6-15%)(6-15%)

MC-non TTSMC-non TTS(85-94%)(85-94%)



EtiologyEtiology

• MC Twins • Vascular anastomoses• Unequal placental

sharing• Abnormal size of

umbilical cord• Velamentous insertion

of cord

• MC Twins • Vascular anastomoses• Unequal placental

sharing• Abnormal size of

umbilical cord• Velamentous insertion

of cord



4 to 7 Days after fertilization



Vascular arrangementTTTS

Vascular arrangementTTTS



Surface Vessels on Chorionic PlateSurface Vessels on Chorionic Plate

• Artery to vein anastomoses primary defect

• Actually fewer balanced anastomoses

• Nose to nose A-V connections

• 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



Contrast Medium Demonstrating Vascular Anastomoses in MC Twins

Contrast Medium Demonstrating Vascular Anastomoses in MC Twins



Etiology: Hemoglobin DifferencesEtiology: 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


• 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




Diagnosis: 1st TrimesterDiagnosis: 1st Trimester

• NT in DiMo twins• If NT abnormal measure

DV• Abnormal NT +

Abnormal DV predicts TTTS

Sebire Human Reproduction, Vol.15, No. 9, 2008-2010, September 2000

• NT in DiMo twins• If NT abnormal measure

DV• Abnormal NT +

Abnormal DV predicts TTTS

Sebire Human Reproduction, Vol.15, No. 9, 2008-2010, September 2000



20 week scan20 week scan

TWIN A: HC=23 1/7ths Wks TWIN B: HC=20 6/7ths Wks

TWIN A: AC=23 4/7ths Wks TWIN B: HC=19 5/7ths Wks



20 week scan 20 week scan



20 week scan20 week scan

TWIN B: Cord Insertion TWIN B Umbilical Artery Doppler



Ultrasound of TTTSUltrasound of TTTS

• Features of MC Features of MC PlacentaPlacenta

• Fused placentaFused placenta• Thin dividing Thin dividing

membranemembrane• Dissimilar AF volumesDissimilar AF volumes

• Features of MC Features of MC PlacentaPlacenta

• Fused placentaFused placenta• Thin dividing Thin dividing

membranemembrane• Dissimilar AF volumesDissimilar AF volumes



Sonographic Signs TTTSSonographic Signs TTTS

• Oligohydramnios– Donor sac <2 cm

• Hydramnios– Recipient sac >8cm

• Growth discordance• Thin dividing

membrane• Same gender pair

• Oligohydramnios– Donor sac <2 cm

• Hydramnios– Recipient sac >8cm

• Growth discordance• Thin dividing

membrane• Same gender pair

Blickstein I. Obstet Gynecol 1990;76:714-22Blickstein I. Obstet Gynecol 1990;76:714-22



Ultrasound of TTTSUltrasound of TTTS



TTTSTTTS



Ultrasound TTSUltrasound TTS

• Assess cord insertion site for each twin

• Assess cord insertion site for each twin



Ultrasound TTTSUltrasound TTTS

• Assess for velamentous insertion

• Assess for velamentous insertion



Ultrasound TTTSUltrasound TTTS

• Assess Placental Mass• Assess Placental Mass



Other sonographic signs TTTSOther sonographic signs TTTS

• Echogenic bowel• Cardiac: enlargement,

tricuspid regurgitation,

ROF obstruction• Pulmonary artery

calcification

• Echogenic bowel• Cardiac: enlargement,

tricuspid regurgitation,

ROF obstruction• Pulmonary artery

calcification



Doppler In TTTSDoppler 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

• 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



Abnormal Doppler also predicts poor outcome in TTTS

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

anastomosesTaylor et al, 2000 Am J Obstet Gynecol

183:1023

• 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

anastomosesTaylor et al, 2000 Am J Obstet Gynecol

183:1023



Extreme Cases of TTTSExtreme Cases of TTTS

When cord Hb differences are >5 Doppler values in Donor and Recipient

may be similar



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.

• 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.

J Perinatol 19:550-555





• 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

• 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



Twin-twin Transfusion SyndromeTwin-twin Transfusion Syndrome



Options for TreatmentOptions for Treatment

• Septostomy

• Amnioreduction

• Laser separation of the circulations

• Feticide

• Septostomy

• Amnioreduction

• Laser separation of the circulations

• Feticide



Options for TreatmentOptions for Treatment

Septostomy• Separates the dividing

membrane• Equalizes fluid pressure• Usually small holes

punctured in the dividing membrane

• Risk for cord entanglement

Septostomy• Separates the dividing

membrane• Equalizes fluid pressure• Usually small holes

punctured in the dividing membrane

• Risk for cord entanglement

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

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.Technique similar to genetic amnio: larger

needle and vacuum bottle.



Prospective randomized trial comparing amnioreduction to septostomy

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.

• 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.



DeLia 1995 N=26 Severe TTTS by LaserDeLia 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).

• DeLia 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.

• 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).

• DeLia 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.



Laser vs AmnioreductionLaser 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.

• 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.



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

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

Laser versus Amnioreduction for Severe TTTS

0

20

40

60

80

100

Survival IUFD Abn HeadUS

GA atBirth

Laser

Amnio



Long-term neurodevelopmental outcome of children born after laser for severe TTTS

Long-term neurodevelopmental outcome of children born after laser for severe TTTS

N=167 follow up to 3 years and 2months

• 145 (86.8%) showed normal development,

• 12 infants (7.2%) showed minor neurologic abnormalities,

• 10 infants (6.0%) major neurologic abnormalities.

N=167 follow up to 3 years and 2months

• 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.



Long-term neurodevelopmental outcome of children born after Laser for severe TTTS

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.

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.



Perinatal death rate higher when laser used for treatment of TTTS in Stage I and II (p=.02)

Perinatal death rate higher when laser used for treatment of TTTS in Stage I and II (p=.02)

Quintero et al, Am J Obstet Gynecol 2003;188:1333



Perinatal death rate lower when laser used for treatment of TTTS in Stage III and IV (p=.02)Perinatal death rate lower when laser used for treatment of TTTS in Stage III and IV (p=.02)

Quintero et al, Am J Obstet Gynecol 2003;188:1333



Two prospective randomized clinical trials

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.

• The Eurofetus trial in Europe

• The National-Institutes-of-Health-sponsored trial in the United States

• Compare aggressive serial amnioreduction to fetoscopic laser photocoagulation.

2011 NIH Trial2011 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.

• 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.



Cochrane ReviewCochrane 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

• 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





Treatment SummaryTreatment 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)

• 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)



Discordant Growth (AEDF)Discordant Growth (AEDF)



Thank you!

emanuel gaziano, md multiple gestation pregnancies monochorionic twins and twin transfusion syndrome...

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