Introduction
Twin-Twin Transfusion Syndrome (TTTS) is a condition that can affect twin gestations that share 1 placenta. This disorder highlights the importance of determining the chorionicity (number of placentas) and amnionic (number of amniotic sacs) for all twin gestations, influencing management. Twin gestations can be dichorionic diamniotic (2 placentas, and 2 amniotic sacs), monochorionic diamniotic (MCDA, 1 placenta, and 2 amniotic sacs), or monochorionic monoamniotic (MCMA, 1 placenta, and 1 amniotic sac).
In the most accepted model of monozygotic twinning, the number of placentas and amniotic sacs depends upon when the splitting of the zygote occurs; dichorionic diamniotic twins result when splitting occurs between days 1 to 3, MCDA twins result when splitting occurs between days 3 to 8, MCMA twins result when splitting occurs between days 8 to 13, and conjoined twins result when splitting occurs on or after day 13. Ultrasound findings that help distinguish dichorionic and monochorionic twin gestations include a “lambda sign” in DC and a “T sign” in MC twin gestations. The “T sign” is created by the thin dividing membrane between 2 amniotic sacs when there is only 1 placenta supporting both gestations (monochorionic). This requires an absence of the “lambda” or “twin peak” sign, which is seen when each gestation is supported by its placenta (dichorionic). The greatest risk of developing TTTS is in monochorionicity, which is more common in MCDA twins than MCMA twin gestations.
To diagnose TTTS prenatally, an ultrasound must show a single placenta, 1 twin with oligohydramnios and the other with polyhydramnios. Oligohydramnios is typically defined as a maximal vertical pocket of 2 cm. In comparison, polyhydramnios is typically defined as a maximal vertical pocket of > 8 cm. Growth discordance and intrauterine growth restriction can occur but are not required to diagnose TTTS. In monoamniotic twin gestations, findings consist of polyhydramnios and fetal bladder differences.
Etiology
The principal etiology of TTTS is an increased number of arteriovenous anastomoses deep in the placenta; these are capillary connections that occur in the cotyledon portion of the placenta. Unidirectional flow can occur in these AV anastomoses and result in the shunting of blood towards 1 twin and away from the other when the AV anastomoses are unbalanced. Arterioarterial anastomoses and venovenous anastomoses can have bidirectional flow and are found more superficially on the placenta. AA anastomoses are considered protective against TTTS and are decreased in twin gestations with TTTS. MCMA twins are thought to have more AA anastomoses, which is a theoretical reason why rates are lower in these twins than in MCDA twins.
The hypovolemia experienced by 1 twin causes renal hypoperfusion, which stimulates the renin-angiotensin-aldosterone system in that twin. This leads to oliguria and oligohydramnios. The hypervolemia experienced by the other twin causes cardiac stretch, which increases atrial natriuretic peptide and brain natriuretic peptide release in that twin. This inhibits the renin-angiotensin-aldosterone system and leads to polyuria and polyhydramnios. Atrioventricular valve insufficiency, diastolic dysfunction, and pulmonary stenosis or atresia can be seen in the recipient. In contrast, vascular changes due to increased collagen synthesis and hypertrophy of the vascular media and smooth muscle layers can be seen in the donor.
Epidemiology
It is estimated that twin births account for about 2% to 4% of births worldwide. Based upon data from the National Vital Statistics System of the National Center for Health Statistics of the Centers for Disease Control and Prevention, the prevalence of twin births in the United States in 2018 was about 33 per 1000 live births or about 3% of live births. This is an increase in twinning rate from about 1.8% in the U.S. in 1980. Of twin gestations, an estimated 67% are dizygotic, and 33% are monozygotic. Among monozygotic twins, approximately 75% are MCDA. TTTS occurs at a rate of about 8-10% of MCDA twin gestations, about 6% of MCMA twin gestations, and it is estimated that 1 to 3 per 10,000 births are affected by TTTS. As there is a possibility of monozygotic twinning with in vitro fertilization, TTTS can also occur in such pregnancies. There is little data regarding the prevalence of each stage of TTTS. Based upon data from referral centers, the Society for Maternal-Fetal Medicine (SMFM) estimates a prevalence of Stage I: 11% to 15%, Stage II: 20% to 40%, Stage III: 38% to 60%, Stage IV: 6% to 7%, and Stage V: 2%.
History and Physical
The physical findings of the fetuses expected of this disease depend upon the stage of TS. Still, at the very least, they must include oligohydramnios in 1 amniotic sac and polyhydramnios in the other. As mentioned above, in monoamniotic gestations, polyhydramnios are seen in the amniotic sac and differences in the fetal bladders. In cases of significant oligohydramnios, the amnion surrounding the donor twin can appear “stuck” to the twin on ultrasound.
Mothers may experience no symptoms, symptoms before TTTS is diagnosed, and/or symptoms after TTTS is diagnosed. In a survey of women who had a pregnancy complicated by TTTS, symptoms were experienced by almost half of these women before their diagnosis. Rapid weight gain, a feeling of swelling, and pain were the most common symptoms experienced by these women, followed by contractions and “other.”
Evaluation
Based upon the SMFM Guideline on TTTS, an ultrasound at 10 to 13 weeks evaluating viability, chorionicity, crown-rump length, and nuchal translucency is recommended for women with twin gestation. Future development of TTTS is associated with the crown-rump length and nuchal translucency abnormalities. Additional ultrasound findings that are associated with TTTS include velamentous umbilical cord insertion and intertwin membrane folding. Once MCDA twin gestation is established, it is recommended that women return for ultrasound scanning every 2 to 4 weeks to monitor for the development of TTTS, which typically develops in the second trimester and is usually seen between 16 and 26 weeks.
At 16 weeks, it is recommended to begin performing an ultrasound to assess the maximal vertical pocket in each amniotic sac as well as fetal bladders with repeat scans every 2 weeks until delivery. This scanning frequency is recommended due to the variability in progression to TTTS. Delivery timing differs depending upon individual characteristics of each pregnancy complicated by TTTS, including stage and intervention effects; thus, considering these characteristics, SMFM recommends delivery timing around 34 to 37 weeks if possible. To promote fetal lung maturation, SMFM also recommends considering steroids between gestational ages of 24 to 34 weeks, especially due to the higher risk of preterm birth in this population.
Limited data demonstrate the benefit of utilizing Doppler studies of the umbilical artery as a screening tool for TTTS. Still, the SMFM states it can be used when a size and/or fluid discrepancy is noted. Doppler studies of the umbilical artery, umbilical vein, and ductus venosus in each twin help establish staging once TTTS is diagnosed. SMFM also recommends fetal echocardiography in MCDA twin gestations due to the increased risk of congenital heart disease in this population, especially in gestations with TTTS, which negatively affects the recipient twin’s heart. Due to the increased risk of preterm labor and miscarriage in both twin gestations and TTTS, in addition to shortened cervix occurring in about 6% to 7% of pregnancies complicated by TTTS, evaluating the cervix length has also been recommended. Counseling for the mother and her partner is recommended.:
Treatment / Management
There are multiple management options available once TTTS is diagnosed. These include expectant management, amnioreduction, intentional septostomy (not commonly performed currently), fetoscopic laser photocoagulation, selective reduction, and voluntary pregnancy termination. Amnioreduction is typically performed to correct the polyhydramnios to 8 cm, can be performed at any point > 14 weeks, and can be performed once or serially. Selective reduction is not considered unless the TTTS has reached stage III or IV.
Fetoscopic laser photocoagulation is performed under ultrasound guidance, typically between 15 to 26 weeks of gestation, to create “2 chorions,” each supplying 1 twin. The procedure can be completed outside of this timeframe, but there are different disadvantages in these timeframes; at under 16 weeks, there is a greater risk of PPROM, and at over 25 weeks, there is greater difficulty in coagulation due to the increased size of vessels. It has been recommended that AV, AA, and VV anastomoses be selectively coagulated rather than nonselectively coagulated. However, there is concern that some anastomoses could be missed, resulting in a greater risk of recurrence of TTTS and twin anemia polycythemia sequence (TAPS).
The Solomon technique was then developed, consisting of coagulating in a thin line from 1 end of the placenta to the other after finding and coagulating the anastomoses. This technique does result in fewer TTTS recurrences, decreased development of TAPS, and increased perinatal survival, but there is a greater risk of placental abruption. Based upon the available data, the authors of the 2019 Update on TTTS in Best Practice and Research Clinical Obstetrics and Gynaecology recommend a partial Solomon technique in which anastomoses are coagulated as well as a small area along the division of the placenta to optimize sufficient anastomoses coagulation and salvaging of a healthy placenta. Management recommendations differ based on the stage of TTTS and gestational age and are outlined below:
Stage I: Expectant management is recommended due to outcomes similar to amnioreduction and fetoscopic laser photocoagulation. Weekly ultrasound checks can be considered. Additionally, only about 25% of Stage I TTTS progresses in stage, and with expectant management, the survival of at least 1 twin occurs in most pregnancies.
Stage II, III, IV: Fetoscopic laser photocoagulation is recommended at these stages at gestational age 26 weeks. A multicenter RCT conducted by Senat et al demonstrated better outcomes after fetoscopic laser coagulation than serial amnioreductions, including increased survival rates of 1 or both twins, delivery at greater gestational ages, and superior neurological outcomes.] It should be noted that this study did not include TTTS at Stage I and, thus, should not be applied to the management of that stage.
Stage V: No interventions have been evaluated at this stage.
Differential Diagnosis
Preterm premature rupture of membranes (PPROM) and premature rupture of membranes, amniotic fluid discrepancy caused by an anomaly in 1 twin, selective fetal growth restriction, and TAPS are in the differential diagnosis for TTTS. Before diagnosing TTTS, it is important to determine whether the mother has experienced a rupture of membranes by asking about any fluid leakage with or without contractions. sIUGR is defined by 1 twin displaying an estimated weight of 10% based upon gestational age. Growth differences can occur as part of TTTS or separately from it. TAPS can occur spontaneously in MCDA twins (1% to 5%) or as a complication of fetoscopic laser photocoagulation (16%). Ultrasound findings prenatally include Doppler abnormalities in the MCA flow of both the donor and recipient twin, which indicate anemia in the donor and polycythemia in the recipient.