Postlaser persistent polyhydramnios after resolution of Twin to Twin Transfusion Syndrome

Abstract

Objective

Fluid abnormalities should resolve after fetoscopic laser surgery (FLS) for Twin to Twin Transfusion Syndrome (TTTS), but polyhydramnios occasionally persists. We sought to compare patients with persistent polyhydramnios (PP) to those with resolved polyhydramnios (RP) after FLS for TTTS.

Methods

Single‐center retrospective review of monochorionic twins who underwent FLS for TTTS from June 2014 to January 2024. Patients with RP had resolution of polyhydramnios ≤ 14 days after FLS. PP patients had a maximum vertical pocket (MVP) ≥ 8 cm in the former TTTS recipient > 14 days after FLS. Patients with septostomy, global membrane separation, membrane rupture within 2 weeks of laser, early recipient demise ≤ 14 days after FLS, TTTS recurrence, or undergoing repeat FLS were excluded. Pretreatment characteristics and birth outcomes were compared between PP and RP groups via Pearson or Fischer's exact chi‐squared and Mann–Whitney U test. We chose gestational age (GA) at delivery as our primary outcome.

Results

A total of 317 out of 336 (94.3%) patients had RP after FLS, and 19 (5.7%) patients had PP. PP recipients had higher pre‐FLS MVP (12.5 vs. 10.0 cm, p = 0.003), higher amnioreduction volumes (2000 vs. 1500 mL, p = 0.030), and higher postoperative day 1 MVPs (7.0 vs. 6.0 cm, p = 0.009). There was a trend toward a higher rate of preoperative recipient pyelectasis in patients with PP (p = 0.069). Average time to resolution of polyhydramnios was 2 days in RP group versus 28 days in the PP group (p < 0.001). Polyhydramnios resolved in 17/18 (94.4%) of PP cases with available outcomes. GAs at delivery, birth survival, and birthweight discordance were not different between groups.

Conclusion

PP occurred in 5.7% of patients after FLS for TTTS. Resolution of PP occurred in 94.4% of PP patients in a median of 28 days and was not associated with adverse obstetric outcomes. The trend of increased incidence of recipient pyelectasis suggests delayed resolution of recipient polyuria as a potential etiology of PP.

1. INTRODUCTION

Twin to Twin Transfusion Syndrome (TTTS) affects 10%–15% of monochorionic (MC) twin pregnancies and is characterized by disproportionate blood flow from a donor twin to a recipient twin across unidirectional arterio‐venous (AV) anastomoses [1, 2]. Donor hypovolemia leads to physiologic adaptations with decreased renal perfusion and subsequent oligohydramnios, defined as a maximum vertical pocket (MVP) less than 2 cm. Conversely, recipient hypervolemia results in polyuria and polyhydramnios (defined as MVP ≥ 8 cm) [3].

Fetoscopic laser surgery (FLS) is the primary management option for TTTS [2, 4, 5]. FLS aims to ablate all causative anastomosis and allows for the normalization of fetal blood volumes, seeking to eliminate hematologic imbalances between the twins. FLS using the Solomon technique offers the highest likelihood of achieving complete dichorionization of placental microanastomoses along the chorionic plate compared to traditional sequential or selective FLS methods [6] and is therefore associated with lower rates of TTTS recurrence [7, 8, 9]. FLS using the Solomon technique treats TTTS successfully in approximately 95% of cases [10] with recipient polyhydramnios typically resolving within 2 weeks of the procedure [1].

However, in some cases, polyhydramnios persists after successful FLS despite not meeting criteria for recurrent TTTS [10, 11]. In singleton pregnancies, polyhydramnios is associated with obstetric complications such as preterm labor, preterm premature rupture of membranes, and placental abruption [12, 13]. In MC twins, amniotic fluid abnormalities, including isolated polyhydramnios, may lead to earlier gestational age (GA) at delivery and increased risk of fetal death [14, 15]. Perinatal outcomes in patients with persistent polyhydramnios (PP) in the setting of resolved TTTS after FLS are unknown. We evaluated MC twins with TTTS treated by successful FLS not complicated by recurrent disease in a single‐center cohort for the resolution of polyhydramnios. We sought to compare pre‐, peri‐, and postoperative characteristics of patients with persistent recipient polyhydramnios to those whose polyhydramnios resolved within 2 weeks after FLS. Based on the known complications associated with singleton and twin polyhydramnios, we hypothesized that patients with PP would have earlier GA at delivery than patients with resolved polyhydramnios (RP).

2. MATERIALS AND METHODS

This is a retrospective analysis of prospectively collected data on MC twin gestations undergoing FLS for TTTS at a single fetal therapy center from June 2014 to January 2024. The protocol was approved by our institutional review board (IRB00249728). Our center routinely performs FLS utilizing the Solomon technique for equatorial dichorionization [16] followed by routine intraoperative amnioreduction with a goal recipient MVP of 4–6 cm at the end of the procedure. PP was defined as a maximum vertical pocket (MVP) ≥ 8 cm in the former TTTS recipient persisting longer than 14 days after FLS [3]. RP was defined as a former recipient MVP < 8 cm by 14 days after FLS [11]. Patients who met criteria for recurrent TTTS after FLS, defined as polyhydramnios (MVP ≥8 cm) oligohydramnios (MVP < 2 cm) either acutely worsening or persistent at 2 weeks after laser, and patients who underwent a repeat FLS for postlaser twin anemia‐polycythemia sequence (TAPS), were excluded from analysis [10]. Patients diagnosed with septostomy of the intertwin membrane, those with postoperative polyhydramnios that could not be confirmed to have persisted for 14 days after laser, patients with recipient demise or membrane rupture < 2 weeks after laser, with global membrane separation, and those without available data on the number of live births or GA at delivery, were excluded from analysis.

PP and RP groups were compared for pretreatment characteristics, FLS procedure details, and postoperative course. Data were obtained via chart review of electronic medical records for each patient and stored at a REDCap database prospectively managed at our institution. Our primary outcome was GA at delivery. We compared pre‐, intra‐, and postoperative characteristics, and evaluated time to polyhydramnios resolution, as secondary outcomes.

Pretreatment characteristics analyzed included GA at pretreatment timepoint, TTTS stage preceding FLS [17], presence of concurrent TAPS determined by middle cerebral artery (MCA) peak systolic velocity (PSV) discordance [18], or selective fetal growth restriction (sFGR) as determined by the Delphi criteria [19]; estimated fetal weight (EFW) of donor and recipient, and estimated fetal weight discordance (EFWD) ((larger fetus EFW − smaller fetus EFW)/ larger fetus EFW*100)). Recipient MVP was measured, and recipient cardiac function was assessed by recording left myocardial performance index (MPI) score, mitral or tricuspid E/A wave fusion, and the presence of mitral or tricuspid valve regurgitation. The frequency of recipient left MPI > 0.6 was collected as an indicator of cardiac dysfunction [20]. The frequency of donor or recipient MCA PSV > 1.5 multiples of the median (MoM) was collected as a marker of possible fetal anemia [21] and poor prognostic outcomes after laser [22]. The presence of recipient pyelectasis was recorded [23]. Data on cervical length and cervical interventions, either cerclage or pessary, was also collected.

Intraoperative data collected on each FLS procedure included GA, amnioinfusion volume, amnioreduction volume, and number of total anastomoses. The quality of vessel blanching, visualization, and if complete dichorionization was achieved were recorded by the surgical operator after the case and included for analysis. Vessel blanching is a subjective assessment of the quality of vessel closure based on visible whitening of the targeted region [24]. Visualization was used to describe fluid clarity, and dichorionization was considered complete if the laser line was felt to have traversed the vascular equator from end to end on the placenta. Evidence of septostomy or membrane separation were documented on postoperative ultrasounds [25].

Patients routinely underwent postoperative ultrasound monitoring to assess the normalization of amniotic fluid volumes and fetal condition. Ultrasounds were typically offered at our center on the first two postoperative days (POD). We subsequently recommend weekly ultrasounds for the first 4 weeks after laser, after which point we recommend routine monochorionic surveillance. Postdelivery outcome characteristics included intrauterine demise, resolution of polyhydramnios, time to polyhydramnios resolution in days, GA at delivery, fetal survival to birth, perinatal survival, recipient and donor birthweights (BWs), and birthweight discordance (calculated as (BW larger − BW smaller)/(BW larger)*100). Perinatal survival, where each fetus is considered an independent survivor, was calculated (number of fetuses surviving/ (number of pregnancies)*2).

Pretreatment, intraoperative, and postoperative characteristics were compared between PP and RP groups via Pearson or Fischer's exact chi‐squared and Mann–Whitney U tests. Statistical significance was defined as p < 0.05 and all analyses were performed using SPSS 29.0.2.0 (IBM).

3. RESULTS

A total of 453 MC twins meeting the inclusion criteria underwent FLS for TTTS during the study period. Twelve patients were excluded due to having a repeat FLS; 5 for postlaser TAPS and 7 for recurrent TTTS. Four patients were excluded due to recurrent TTTS managed expectantly or with amnioreduction, and 9 additional patients were excluded for other postlaser surgery such as intrauterine transfusion or selective fetal reduction. Patients with septostomy (41 (9.1%), membrane rupture (16 (3.5%)) or recipient demise (14 (3.1%)) ≤14 days after laser, global membrane separation (3 (0.6%)), and those who were lost to follow up (17 (3.8%)) were excluded. Of 336 eligible patients, 317 (9.3%) had RP and 19 (5.7%) had PP (Figure 1).

FIGURE 1.

Study population description. Patients included underwent fetoscopic laser surgery (FLS) for Twin to Twin Transfusion Syndrome (TTTS) and were excluded for recurrent TTTS, repeat fetoscopic laser surgery (FLS), septostomy, or lost to follow‐up.

GA at pretreatment, distribution of TTTS stage, and the presence of concurrent TAPS or sFGR were not different between PP and RP groups. Pretreatment estimated fetal weight (EFW) for both donors and recipients, EFW discordance, cervical length, and cerclage or pessary were also similar between groups. PP recipients had a higher pre‐FLS MVP (median 12.5 [interquartile range (IQR) 9.8–15.9] vs. 10.0 [IQR 8.9–11.7] cm, p = 0.003). There were no differences in MCA PSV MoM discordance or incidence of MCA PSV > 1.5 MoM in either the recipient or the donor. There were no differences in most markers of recipient cardiac dysfunction: mitral or tricuspid regurgitation, fused mitral E/A wave, or left myocardial performance index (MPI) > 0.6. Recipients in the RP group were more likely to have a fused tricuspid E/A wave prelaser (23.1 vs. 0%, p = 0.018). There was a trend toward an increased incidence of prelaser recipient pyelectasis in PP recipients (10.5 vs. 1.9%, p = 0.069) (Table 1).

TABLE 1.

Pretreatment characteristics for persistent polyhydramnios after laser for TTTS.

	Persistent polyhydramnios N = 24	Resolved polyhydramnios N = 355	p value
GA at pretreatment (weeks)	20.1 [18.9–22.0]	19.3 [17.9–21.9]	0.362
TTTS Stage
I	2 (10.5)	73 (20.6)
II	7 (36.8)	118 (33.3)
III	7 (36.8)	141 (39.7)
IV	3 (15.8)	23 (6.5)	0.172
TAPS	2 (10.5)	37 (11.7)	1.000
sFGR	3 (15.8)	104 (32.8)	0.137
Recipient EFW (g)	362 [250–452]	291 [218–456]	0.292
Donor EFW (g)	301 [205–417]	225 [163–364]	0.200
EFW discordance	20.5 [11.4–26.9]	20.1 [11.3–29.2]	0.565
Recipient MVP (cm)	12.5 [9.8–15.9]	10.0 [8.9–11.7]	0.003
MCA discordance	0.18 [0.07–0.33]	0.20 [0.09–0.36]	0.761
MCA > 1.5 MoM recipient	1 (5.3)	16 (5.1)	1.000
MCA > 1.5 MoM donor	1 (5.3)	1 (4.8)	0.706
Recipient cardiac dysfunction
Mitral regurgitation	4 (21.1)	51 (16.2)	0.532
Tricuspid regurgitation	9 (47.4)	176 (56.2)	0.483
Fused mitral E/A	0 (0)	28 (9.0)	0.388
Fused tricuspid E/A	0 (0)	72 (23.1)	0.018
Left MPI > 0.6	7 (41.2)	135 (44.0)	1.0000
Recipient pyelectasis	2 (10.5)	6 (1.9)	0.069
Cervical length (mm)	36.8 [32.0–42.9]	38.0 [32.4–44.0]	0.388
Cervical intervention
Cerclage	1 (5.3)	25 (7.9)	1.000
Pessary	0 (0)	27 (8.5)	0.383

Note: Data are presented as number (percent) or median [interquartile range].

Abbreviations: GA, gestational age; EFW, estimated fetal weight; MoM, multiples of median; MVP, maximum vertical pocket; MPI, myocardial performance index; POD, postoperative day; sFGR, selective fetal growth restriction; TAPS, twin anemia polycythemia sequence; TTTS, Twin to Twin Transfusion Syndrome.

There were no intraoperative differences between groups except for the amnioreduction volume. PP patients underwent a higher volume amnioreduction than RP patients (median 2000 [IQR 1500–2570] vs. 1500 [IQR 1100–2000] mL, p = 0.030). GA at laser, amnioinfusion volume, number of anastomoses and surgeon impression of completeness of vessel blanching, clear visualization, and completeness of the dichorionization were not different between groups (Table 2).

TABLE 2.

Fetoscopic laser characteristics for persistent polyhydramnios after laser for TTTS.

	Persistent polyhydramnios N = 24	Resolved polyhydramnios N = 355	p value
GA at laser (weeks)	20.3 [19.1–22.1]	19.6 [18.1–22.0]	0.423
Amnioinfusion volume	225 [0–450]	500 [50–1000]	0.092
Amnioreduction volume	2000 [1500–2570]	1500 [1100–2000]	0.030
Total anastomoses	15 [10–26]	16 [11–21]	0.974
Complete vessel blanching	18 (94.7)	293 (92.4)	1.000
Clear visualization	18 (94.7)	261 (82.3)	0.217
Complete dichorionization	19 (100)	291 (91.8)	0.381

Note: Data are presented as number (percent) or median [interquartile range].

Abbreviation: GA, gestational age.

Postoperatively, there was no difference in the rate of fetal demise for recipients or donors, MCA discordance on POD1, or incidence if MCA > 1.5 MoM in the recipient or donor on POD1. PP patients had higher recipient MVP on postoperative day 1 (median 7.0 [IQR 5.5–8.3] vs. 6.0 [IQR 5.1–7.1] cm, p = 0.009). PP resolved before delivery in 17 of 18 patients with available data, but median time to resolution was 28 days (IQR 22–61) compared to 2 days (IQR 2–2) in RP patients (Table 3, Figure 2). GA at delivery was not different between PP and RP patients (median 33.5 [IQR 31.0–35.4] vs. 32.6 [IQR 29.0–34.3] weeks, p = 0.159). Similarly, there was no difference in live births, birthweight of the recipient or donor, or BW discordance (Table 3).

TABLE 3.

Postoperative course of persistent polyhydramnios after laser for TTTS.

	Persistent polyhydramnios N = 24	Resolved polyhydramnios N = 355	p value
Recipient POD1 MVP	7.0 [5.1–8.3]	6.0 [5.1–7.1]	0.009
MCA discordance POD1	0.26 [0.12–0.35]	0.37 [0.18–0.68]	0.464
MCA > 1.5 MoM POD1 recipient	5 (33.3)	69 (25.7)	0.699
MCA > 1.5 MoM POD1 donor	1 (7.7)	39 (15.7)	0.548
Fetal demise
Recipient	0 (0)	4 (1.3)	1.000
Donor	2 (10.5)	38 (12.0)	1.000
Polyhydramnios resolved	17/18 (94.4)	—	—
Time to polyhydramnios resolution (days)	28 [22–61]	2 [2–2]	<0.001
GA at delivery	33.5 [31.0–35.4]	32.6 [29.2–34.3]	0.159
Live births
0	0 (0)	16 (5.0)
1	2 (10.5)	36 (11.4)
2	17 (89.5)	265 (83.6)	0.593
Perinatal survival	36/38 (94.7)	566/634 (89.3)	—
Recipient birthweight (g)	2040 [1510–2566]	1871 [1362–2266]	0.086
Donor birthweight (g)	1895 [1640–2200]	1606 [1017–1988]	0.280
Birthweight discordance	7.1 [4.4–13.7]	10.2 [4.7–21.9]	0.280

Note: Data are presented as number (percent) or median [interquartile range]. Fraction denominator indicates number of patients with available data.

Abbreviations: GA, gestational age; MoM, multiples of median; MVP, maximum vertical pocket; POD, postoperative day.

FIGURE 2.

Progression of polyhydramnios after laser for Twin to Twin Transfusion Syndrome (TTTS). Time to resolution of polyhydramnios. Postoperative maximum vertical pockets (MVPs) of the former recipient, in cm, are plotted at each recorded day postoperatively. Resolved polyhydramnios (RP) are plotted as blue dots and persistent polyhydramnios (PP) are plotted as orange. The horizontal line on the y‐axis demarcates 8 cm, the definition of polyhydramnios.

4. DISCUSSION

Of 336 MC twin patients who underwent successful FLS for TTTS, 19 (5.7%) of former recipients had PP 14 days after Solomon laser. Ultimately, PP was not associated with earlier GA at delivery or decreased survival and resolved in 94.4% of patients with available data prior to delivery at a median time of 28 days after FLS. Patients with PP had higher recipient MVPs pretreatment, underwent higher amnioreduction volumes intraoperatively, and despite these higher amnioreduction volumes, had higher postoperative MVPs on POD1 after FLS. Preoperative recipient pyelectasis was more common in patients with PP, though this association did not reach statistical significance.

Few authors have published a detailed description of the resolution of recipient polyhydramnios after laser. Assaf et al. describe 174 consecutive patients who underwent selective laser via the sequential technique, when feasible, which may have a different resolution pattern compared to Solomon laser utilized in our cohort [11, 26]. They did not exclude patients with TTTS recurrence or repeat laser and describe that 95% of recipient MVPs normalized by week 8 after FLS [11]. Our rate of resolution is similar but time to resolution was shorter at 28 days (∼4 weeks), possibly because we excluded patients with recurrent TTTS from our cohort, and possibly also due to differences in laser technique.

Although we hypothesized that patients with PP would have more obstetric complications related to polyhydramnios, our data did not support this theory. We chose GA at delivery as our primary outcome as a proxy for long‐term complications in MC twins [27, 28], and also could not identify differences in survival outcomes between groups. Although these findings could be impacted by closer surveillance in twins with PP, as we recommend weekly follow‐up after FLS in patients with ongoing discordances, it is reassuring that with proper surveillance, PP was not associated with poorer outcomes compared to patients with resolution of their polyhydramnios after laser.

In terms of the potential etiology of PP, our data suggest that PP is not a function of inadequate fluid removal during intraoperative amnioreduction, but appears to be associated with higher amniotic fluid production both pre‐ and postoperatively, evidenced by higher pre‐ and postlaser MVPs along with higher amnioreduction volumes intraoperatively. This hypothesis is further supported by the increased prevalence of preoperative recipient pyelectasis in the PP group. The severity of recipient polyhydramnios has been linearly correlated with increased recipient production of atrial natriuretic protein [29]. Alterations in renin and angiotensin in TTTS donors and recipients [30, 31] may further impact fetal urine production. Although differences in fetal renal function pre‐FLS tend to normalize by the time of delivery [32], resolution is not immediate, as extremely premature infants delivering shortly after laser continue to demonstrate alterations in biomarkers of renal function [33]. Ultimately, renal remodeling due to TTTS pathophysiology [34] likely plays a role in ongoing abnormalities in fetal urine production even after successful laser. Thus, isolated PP after FLS for TTTS does not appear to be related to ongoing anastomoses, but to residual, more slowly resolving polyurea in the former recipient. Additionally, although not statistically significant, it is clinically notable that the PP group had a 15.8% rate of Stage IV TTTS, which may warrant further consideration.

This study is limited by its retrospective nature, numerically few patients with PP, and by the absence of long‐term follow‐up. As a referral center, we also do not have access to all outside ultrasounds, which precluded our ability to assess if ongoing pyelectasis ultimately resolved or continued postnatally. Finally, there were inconsistencies with the number of follow‐up scans performed at our referral center. Some patients were lost to follow up, whereas others returned to the center more frequently for ongoing complications, skewing our longitudinal data toward more at‐risk patients.

Despite these limitations, our data offer additional insights on the etiology and risk of PP after laser surgery for TTTS. Study strengths include an overall large population of patients undergoing laser surgery, and single center data with a high degree of accuracy.

5. CONCLUSION

In conclusion, PP occurred in 5.7% of MC twin pregnancies after curative FLS for TTTS. PP typically resolved before delivery and was not associated with adverse obstetric outcomes. Further research into the pathophysiology of PP is indicated and may lead to improved understanding of recipient polyhydramnios in the setting of TTTS.

AUTHOR CONTRIBUTIONS

Mackenzie Simon‐Collins, Rachana Tanksali, Julie Alan, and Maryn Day: Reviewed data; drafted the manuscript and produced figures. Camille Shantz: Conducted data review; statistics; generation of the data tables and manuscript review. Mara Rosner, Sarah Millard, Michelle Kush, Jena Miller, and Ahmet Baschat: Conceptualized the project; provided patient data and reviewed the manuscript.

CONFLICT OF INTEREST STATEMENT

The authors report no conflict of interest.

ETHICS STATEMENT

This study protocol was reviewed and approved by the Johns Hopkins Institutional Review Board, IRB00249728.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.