P-145 Impacts of double biopsy and double vitrification on the clinical outcomes following euploid blastocyst transfer: a systematic review and meta-analysis
Authors: Chapple V , Bickendorf K , Qi F , Peirce K , Wang R , Natalwala J , Liu Y 
Published: July 2024

Abstract

Study question
Do “double biopsy + double vitrification” and “single biopsy + double vitrification” compromise subsequent clinical outcomes following euploidy blastocyst transfer?

Summary answer
Both “double biopsy + double vitrification” and “single biopsy + double vitrification” led to reduced ongoing and clinical pregnancy rates and elevated miscarriage rates

What is known already
It is not uncommon to have inconclusive results following blastocyst biopsy and preimplantation genetic testing for aneuploidy (PGT-A). One option for these blastocysts is a second biopsy for re-test after warm, followed by a second vitrification. Furthermore, for better workflow, laboratories may choose to routinely vitrify all blastocysts formed followed by a subsequent biopsy post warm at a preferred timing, after which a second vitrification would be required. However, there is currently a lack of systematic evaluation in the literature regarding potential clinical risks associated with the above-mentioned applications in reference to the conventional “single biopsy + single vitrification” approach.

Study design, size, duration
A systematic review and meta-analysis were performed, with a protocol registered with PROSPERO (CRD42023469143). A search of PUBMED, EMBASE, and the Cochrane Library for relevant studies was carried out on 30 August 2023, using the keywords ‘biopsy’ and ‘vitrification’ and associated variations respectively. Only studies involving frozen transfers of euploid blastocysts tested via PGT-A were included, with those tested via PGT-M or PGT-SR excluded.

Participants/materials, setting, methods
Study groups included blastocysts having undergone “double biopsy + double vitrification” or “single biopsy + double vitrification”, with “single biopsy + single vitrification” used as control. The primary outcome was live birth rate while secondary outcomes included ongoing pregnancy, clinical pregnancy, miscarriage, and post warm survival rates. Random effects meta-analysis was performed with risk ratios (RR) and 95% confidence interval (CI) used to present outcome comparisons.

Main results and the role of chance
Following duplicate removal, a total of 607 records were identified after the initial search. After screening of titles and abstracts, 37 records were included for further eligibility assessment. For meta-analysis, 9 studies (5 full articles and 4 abstracts) were eventually included. Compared to “single biopsy + single vitrification”, “double biopsy + double vitrification” was associated with significantly reduced live birth rates (5 studies, n = 10,068; RR = 0.57, 95% CI = 0.35–0.94; I2=82%), ongoing pregnancy rates (2 studies, n = 4,659; RR = 0.69, 95% CI = 0.51–0.94; I2=2%), clinical pregnancy rates (5 studies, n = 17,673; RR = 0.79, 95% CI = 0.71–0.89; I2=0%), and elevated miscarriage rates (7 studies, n = 22,332; RR = 1.64, 95% CI = 1.02–2.64; I2=53%). However, no significant changes were found in post warm survival rates (p &gt; 0.05, respectively). Furthermore, “single biopsy + double vitrification” was also linked with significantly decreased ongoing pregnancy (3 studies, n = 5,980; RR = 0.84, 95% CI = 0.70–1.00; I2=61%), clinical pregnancy rates (5 studies, n = 12,136; RR = 0.84, 95% CI = 0.72–0.99; I2=71%), and increased miscarriage (5 studies, n = 17,781; RR = 1.25, 95% CI = 1.02–1.53; I2=3%) rates. But live birth rate and post warm survival rate were not affected (p &gt; 0.05, respectively).

Limitations, reasons for caution
All studies included in this meta-analysis were retrospective with varying levels of heterogeneity for different outcomes. Not all studies have accounted for potential confounding factors, therefore only unadjusted data could be used in the main meta-analysis. Only one study reported neonatal outcomes, making it impossible to perform meta-analysis.

Wider implications of the findings
Our data clearly indicated adverse impacts by “double biopsy + double vitrification” and “single biopsy + double vitrification” on clinical outcomes following euploid blastocyst transfers. If possible, such approaches should be avoided in routine practice, and patients should be carefully consulted about the risks when offered with such approaches.

Trial registration number
CRD42023469143