Background
The diagnosis of twin-to-twin transfusion syndrome (TTTS) usually relies the presence of polyhydramnios in one sac with concomitant oligohydramnios in the other sac in a monochorionic diamniotic twin pregnancy. However, TTTS does not always show a linear progression and may present with cardiac compromise or critically abnormal Doppler velocimetry in either fetus before fluid measurements meet the typically used cutoff.
Objective
The aim of this study was to investigate the prevalence of atypical presentations of TTTS in a population undergoing laser fetoscopy.
Study Design
We performed a retrospective review of our database of TTTS laser fetoscopy from 2003 to the present. Our center is the regional referral center in the Pacific Northwest for minimally invasive treatment of complicated monochorionic twin pregnancies. Cases were labeled as “atypical” if fluid discordance did not meet formal TTTS criteria (oligohydramnios defined as maximum vertical pocket [MVP] <2 and polyhydramnios defined as MVP >8 before 20 weeks and >10 after 20 weeks). The rationale for consideration of laser fetoscopy was other evidence of severe TTTS such as significant cardiac compromise, evidence of twin anemia polycythemia sequence (TAPS), or persistent critically abnormal cord Dopplers.
Results
Three hundred seventy-nine cases of fetoscopic laser ablation for TTTS and its variants were available for review. Sixteen cases were excluded for a triplet pregnancy, 4 due to septostomy prior to referral to our center, 3 for monoamniotic pregnancy, and 11 for previous laser fetoscopy. Three hundred forty-five cases remained for evaluation. Among these, 25 cases were identified as “atypical,” equaling 7.24% of our population. Eleven of these were for stage 3 recipient disease, 3 were for stage 4 recipient disease, 4 were for stage 3 both in recipient and donor, 4 were for stage 3 donor disease, and 3 were for spontaneous TAPS.
Conclusion
In TTTS, severity of fetal compromise does not consistently correlate with fluid abnormalities meeting established criteria. This may be especially true in rapidly progressing cases. Attempts at rigid diagnostic amniotic fluid criteria may underestimate the severity and incidence of TTTS. This underscores the importance of careful surveillance, including arterial and venous Doppler velocimetry, of all monochorionic pregnancies.
Twin-twin transfusion syndrome (TTTS) is diagnosed in 10% to 15% of monochorionic twins and carries a high risk of morbidity and mortality.
The vast majority of monochorionic twin placentas have inter-twin vascular connections. Most commonly these involve a cotyledon of placenta supplied by one fetus with an artery, but draining via a vein to the other fetus also referred to as an AV anastomosis. Direct artery-to-artery (AA) or vein-to-vein (VV) connections exist, and, while likely causing less chronic transfer of blood, can contribute to the high risk of co twin demise in stage 5 disease.
TTTS is thought to be caused by a chronic net transfer of blood from one fetus to the other. The “donor” is thought to experience volume depletion, while the “recipient” is burdened with hypervolemia. Endocrine factors such as the activation of the renin-angiotensin-aldosterone system can also be transferred from one fetus to the other and may aggravate the cardiovascular compromise.
The diagnosis of TTTS is an ultrasound-based diagnosis. It traditionally requires the presence of polyhydramnios in one sac with concomitant oligohydramnios in the other sac in a monochorionic diamniotic twin pregnancy.
In 1999, a sonographic staging system was proposed by Quintero and has since been widely used.
The system includes 5 stages. Stage 1 is defined by concomitant oligohydramnios <2 cm in the donor and >8 cm in the recipient, based on the 5% and 95%, respectively. The presence of fluid discordance of stage 1 has been defined as a prerequisite for other stages.
Stage 2 is defined by a non-visualized bladder in the donor, stage 3 by critically abnormal Doppler velocimetry in either fetus, stage 4 by hydrops of either fetus, and stage 5 by demise of one or both fetuses.
The Eurofetus consortium modified these criteria by using >10 cm after 20 weeks. This was done to avoid cases that could have been disputed as having TTTS, as a maximum vertical pocket (MVP) of 8 to 10 is not uncommon after this gestational age.
The Quintero staging system suggests that development of TTTS always follows a linear progression. However, TTTS may develop rapidly and can present in advanced stages before traditional fluid criteria are met, especially in recipient disease.
The aim of the current study was to assess the prevalence of monochorionic twin pairs in a referral population that displayed signs of severe TTTS pathophysiology without meeting fluid criteria (referred to as “atypical TTTS”).
Material and Methods
We performed a retrospective review of monochorionic twins treated with fetoscopic laser ablation of communicating placenta vessels at The Fetal Therapy Program at Evergreen Health from 2003 to 2015.
The Fetal Therapy Program at Evergreen Health is the regional referral center in the Pacific Northwest for fetal therapy including minimally invasive treatment of complicated monochorionic twin pregnancies.
The protocol was approved by the Western Institutional Review Board, and all patients signed informed consent for inclusion in the database at the time of preoperative evaluation.
All patients were seen for preoperative evaluation by one of two physicians (BP or MW). Evaluation included a detailed anatomic evaluation of both fetuses, Doppler velocimetry of the umbilical and middle cerebra arteries, the umbilical vein, and the ductus venosus. Cardiac evaluation included a targeted fetal echocardiogram. The myocardial performance index (TEI) was assessed starting in 2009 to formalize assessment of cardiac function.
All studies were performed with GE Voluson E8 (Fairfield, Connecticut) or Philips IU 22 (Bothell, Washington).
Cases were labeled as typical if the fluid discordance met formal TTTS criteria defined as oligohydramnios with an MVP <2 and polyhydramnios with an MVP >8 before 20 weeks and >10 after 20 weeks, the latter based on stricter Eurofetus criteria. Otherwise, staging criteria of the Quintero staging system were applied.
Cases were labeled as “atypical” if fluid discordance was present but did not meet criteria, in addition to other signs of severe disease in the spectrum of TTTS (critically abnormal Doppler velocimetry consistent with at least Quintero stage 3 or evidence of recipient cardiomyopathy based on abnormal TEI index).
The rationale for consideration of laser fetoscopy was other evidence of severe TTTS such as significant cardiac compromise based on absent or reversed a wave in the ductus venosus, evidence of recipient cardiomyopathy due to abnormal TEI index, evidence of severe twin anemia polycythemia sequence (TAPS), or critically abnormal cord Dopplers (persistent absent or reversed end-diastolic flow) in addition to amniotic fluid discordance.
All procedures were performed by one or both (if available) of the investigators (BP and MW) under spinal anesthesia. Preoperative ultrasound mapping of the cord insertions on the placenta, the anticipated vascular equator, and the operative trocar insertion site into the recipient twin sac was performed in the operating room.
Lidocaine (10 mL of 1%) was infiltrated into the subcutaneous tissues under ultrasound guidance. A 10F Cook cannula with a check flow valve and a pyramidal trocar was then introduced into the recipient sac under ultrasound guidance, and 40 mL of fluid was aspirated and sent for culture and karyotype/microarray if desired by the parents.
A straight or curved introducer with a laser channel housing a 2.2-mm fiberoptic Stortz fetoscope (Tuttlingen, Germany) was then introduced into the recipient sac and the vascular equator was identified. All anastomosing vessels were ablated with the use of a Diode laser at 30 to 35 Watts. Starting in 2013, the technique was modified to include “solomonization” of the placenta. In this technique, a thin line is lasered across the placenta connecting all anastomosing vessels to avoid missing minute connections.
An amnio-reduction was then carried out with the aim of leaving the fluid in the high normal-mild polyhydramnios range (MVP of 7–9 cm) while limiting the amnio-reduction volume to 3000 mL.
Patients were admitted for observation until the next day and evaluated with an ultrasound examination the following day prior to discharge.
Follow-up information was obtained from the referring provider after delivery.
Statistical analysis was carried out with a Student t -test.
Results
Three hundred seventy-nine cases of fetoscopic laser ablation for TTTS and its variants were available for review. A total of 34 cases were excluded due to conditions compromising ability to assess fluid pockets: 16 cases due to triplet pregnancy, 4 cases due to septostomy prior to referral to our center, 3 for monoamniotic pregnancy, and 11 for previous laser fetoscopy.
Three hundred forty-five cases remained for evaluation. Among these, 25 cases were identified as “atypical,” equaling 7.24% of our population.
Of the 25 cases, the majority (76%) included recipient disease manifesting with abnormal DV Doppler/UV pulsations and/or abnormal TEI index.
Of the 19 cases of recipient disease, 11 were for stage 3 recipient disease, 3 were for stage 4 recipient disease, and 5 were for stage 3 both in recipient and donor. One case was for stage 3 recipient disease coexisting with preclinical TAPS. This case presented with cardiac dysfunction the recipient and notable discordance in peak middle cerebral artery (MCA) velocity, though not meeting criteria for TAPS (peak MCA >1.5 in the donor).
Three were for isolated severe stage 3 donor disease, though a notable fluid discordance suggested an element of TTTS, even though formal fluid criteria were not met. Two cases were isolated spontaneous TAPS.
Distribution of atypical TTTS cases between donor and recipient is summarized in Table 1 .
| n | Recipient | Donor |
|---|---|---|
| 11 | Stage 3 | |
| 3 | Stage 4 | |
| 5 | Stage 3 | Stage 3 |
| 3 | Stage 3 | |
| 1 | Stage 3/TAPS | Preclinical TAPS |
| 2 | TAPS | TAPS |
The ultrasound characteristics of all atypical TTTS cases are detailed in Table 2 .
| Case | GA at diagnosis | Stage | Donor MVP | Recipient MVP | Rec Doppler abnormality | Donor Doppler abnormality | Rec. EFW % | Donor EFW % |
|---|---|---|---|---|---|---|---|---|
| 1 | 21.6 | 3D/3R | 1.9 | 8.1 | UV pulsation, abnl TEI | UA REDF | 95 | 5 |
| 2 | 23 | 3D | 2 | 9.9 | UA AEDF/ interm. REDF | 72 | 4 | |
| 3 | 23.1 | 3D/3R | 2.7 | 17 | abnl DV | UA REDF | 74 | 1 |
| 4 | 21.1 | 3R | 2.3 | 14 | abnl DV, UV puls | 71 | 3 | |
| 5 | 19.9 | 3D | 2 | 9.8 | AEDF | 16 | 1 | |
| 6 | 16.9 | 3R | 2.6 | 8.6 | abnl DV | 49 | 39 | |
| 7 | 20.6 | 3R/3D | 1 | 9.8 | abnl DV, UV puls | UA AEDF | 1 | 1 |
| 8 | 24.4 | 3R | 2.2 | 14.2 | abnl TEI | 37 | 4 | |
| 9 | 24.1 | 4R | 4.2 | 15.8 | hydrops, abnl DV UA TEI | 53 | 52 | |
| 10 | 20.6 | 4R | 4.3 | 10.1 | hydrops, abnl DV UA TEI | 47 | 30 | |
| 11 | 22.6 | TAPS | 5.9 | 6.4 | Peak MCA Mom 0.43 | Peak MCA MoM 2.59 | 1 | 15 |
| 12 | 17 | 3R | 2.7 | 11 | abnl DV | 42 | 50 | |
| 13 | 23.4 | 3D/3R | 3 | 11 | abnl DV, UV puls | UA AEDF | 52 | 13 |
| 14 | 23.9 | TAPS | 5.9 | 7.2 | peak MCA MoM 0.65 | peak MCA MoM 1.6 | 53 | 1 |
| 15 | 20.6 | 4R | 7 | 9.9 | hydrops, abnl DV/TEI | 49 | 3 | |
| 16 | 24.7 | 4R | 3.4 | 9.7 | hydrops, abnl TEI | 3 | 1 | |
| 17 | 23.3 | 3R | 6.5 | 13.4 | UV pulsation | 33 | 3 | |
| 18 | 16.6 | 3D/3R | 1.2 | 7 | UV pulsation | UA AEDF | 67 | 3 |
| 19 | 20.1 | 3R/TAPS | 5.2 | 13.1 | abnl TEI, peak MCA MoM 0.65 | peak MCA MoM 1.3 | 94 | 88 |
| 20 | 19.2 | 3R | 3.2 | 10.5 | abnl DV/TEI | 16 | 2 | |
| 21 | 22.1 | 3R | 4.1 | 14.2 | UV pulsation | 27 | 26 | |
| 22 | 16.7 | 3R | 0 | 7.4 | abnl DV, UV puls | 25 | 8 | |
| 23 | 19.7 | 3D | 4.2 | 10.2 | UA REDF | >90 | <10 | |
| 24 | 18.7 | 3D | 4.2 | 9.5 | UA AEDF, interm. REDF | >90 | <10 | |
| 25 | 21.9 | 3R | 3.2 | 14 | abnl TEI | 77 | 71 |
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