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Randomized controlled trial of twin-twin transfusion syndrome laser surgery: the sequential trial - 05/07/24

Doi : 10.1016/j.ajog.2024.06.009 
Ramen H. Chmait, MD a, , Lisa M. Korst, MD, PhD b, Arlyn S. Llanes, RN a, Kristine R. Rallo, RN a, Andrew H. Chon, MD c, Martha A. Monson, MD d, e, Moshe Fridman, PhD f, Rubén A. Quintero, MD g, h
a Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 
b Childbirth Research Associates, LLC, North Hollywood, CA 
c Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 
d Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Intermountain Health, Salt Lake City, UT 
e Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, UT 
f AMF Consulting, Los Angeles, CA 
g The USFETUS Research Consortium, Miami, FL 
h The Fetal Institute, Miami, FL 

Corresponding author: Ramen H. Chmait, MD.
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Abstract

Background

Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome can vary by surgical technique and has been proposed to explain differences in donor twin survival.

Objective

This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor, and the selective technique, in which the occlusion of the vascular communications is performed in no particular order.

Study Design

A single-center, open-label, randomized controlled trial was conducted in which twin-twin transfusion syndrome patients were randomized to sequential vs selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) vs last. The primary outcome measure was donor twin survival at birth.

Results

A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (274 of 320 [85.6%] vs 271 of 322 [84.2%]; odds ratio, 1.12 [95% confidence interval, 0.73–1.73]; P=.605). Superficial anastomoses occurred in 177 of 642 cases (27.6%). Donor survival was lower in the superficial anastomosis group vs those with only arteriovenous communications (125 of 177 [70.6%] vs 420 of 465 [90.3%]; adjusted odds ratio, 0.33 [95% confidence interval, 0.20–0.54]; P<.001). In cases with superficial anastomoses, donor survival was independent of the timing of ablation or surgical technique. The postoperative mean middle cerebral artery peak systolic velocity was lower in the sequential vs selective group (1.00±0.30 vs 1.06±0.30 multiples of the median; P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence or absence of donor twin preoperative critical abnormal Doppler parameters and the presence or absence of arterioarterial anastomoses. Depending on these factors, 4 categories of patients resulted: (1) Category 1 (347 of 642 [54%]), no donor twin critical abnormal Doppler + no arterioarterial anastomoses: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (143 of 642 [22%]), critical abnormal Doppler present + no arterioarterial anastomoses: donor survival was 89.9% vs 75.7%; (3) Category 3 (73 of 642 [11%]), no critical abnormal Doppler + arterioarterial anastomoses present: donor survival was 94.7% vs 74.3%; and (4) Category 4 (79 of 642 [12%]), critical abnormal Doppler present + arterioarterial anastomoses present: donor survival was 47.6% vs 64.9%.

Conclusion

Donor twin survival did not differ between the sequential vs selective laser techniques and did not differ if superficial anastomoses were ablated first vs last. The donor twin’s postoperative middle cerebral artery peak systolic velocity was improved with the sequential vs the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to determine whether using these categories to guide the choice of surgical technique will improve outcomes.

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Key words : arterioarterial anastomosis, critical abnormal Dopplers, donor twin, fetal demise, fetal surgery, feto-fetal transfusion syndrome, fetoscopic surgery, laser ablation, laser photocoagulation of communicating vessels, monochorionic twins, multifetal gestation, recipient twin, TTTS, vascular communications


Plan


 L.M.K. and M.F. are independent contractors assisting with research studies. The remaining authors have nothing to disclose.
 Presented orally at the 44th annual meeting of the Society for Maternal-Fetal Medicine, National Harbor, MD, Feb. 12, 2024.
 This study is registered on Clinicaltrials.gov (Identification number NCT02122328; NCT02122328). The date of registration was on April 14, 2014. The date of initial participant enrollment was on June 9, 2010.
 No external funding was provided for this study.
 Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures), will be shared. In addition, data on the study protocol will be available. Data will be available beginning 12 months and ending 36 months following article publication for investigators whose proposed use of the data has been approved by an independent review committee (“learned intermediary”) identified for this purpose. Data will be available for individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication. After 36 months, the data will be available in our university’s data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found by contacting the lead author.
 Cite this article as: Chmait RH, Korst LM, Llanes AS, et al. Randomized controlled trial of twin-twin transfusion syndrome laser surgery: the sequential trial. Am J Obstet Gynecol 2024;XXX:XX–XX.


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