The effect of storage time after vitrification on pregnancy and neonatal outcomes among 24 698 patients following the first embryo transfer cycles

Abstract

STUDY QUESTION To evaluate the impact of storage time after vitrification on embryo viability, pregnancy outcomes and neonatal outcomes. SUMMARY ANSWER The prolonged storage time of vitrified embryos negatively affected pregnancy outcomes, including biochemical pregnancy rate, clinical pregnancy and live birth rate; but did not influence neonatal outcomes. WHAT IS KNOWN ALREADY Although vitrification has been the fundamental tool of ART treatments in recent years, few studies have explored the influence of storage period after vitrification on embryonic and clinical outcomes. STUDY DESIGN, SIZE, DURATION A retrospective study was performed among 24 698 patients with the first vitrified embryo transfer following a freeze-all strategy during the period from January 2011 to December 2017. PARTICIPANTS/MATERIAL, SETTING, METHODS A total of 24 698 patients met the inclusion criteria and were grouped according to the storage time (11 330 patients in Group 1 with storage time <3 months, 9614 patients in Group 2 with storage time between 3 and 6 months, 3188 patients in Group 3 with storage time between 6 and 12 months and 566 in Group 4 with storage time between 12 and 24 months). The pregnancy outcomes and neonatal outcomes were compared between different storage time groups. Multivariate logistic regression and linear regression were performed to evaluate the independent effect of storage time on clinical outcomes, adjusting for important confounders. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for potential confounding factors, the chance of biochemical pregnancy (Group 1 as reference; Group 2: adjusted odds ratio (aOR) = 0.92, 95% CI 0.87–0.97; Group 3: aOR = 0.83, 95% CI 0.76–0.90; Group 4: aOR = 0.68, 95% CI 0.56–0.81), clinical pregnancy (Group 2: aOR = 0.91, 95% CI 0.86–0.96; Group 3: aOR = 0.80, 95% CI 0.73–0.87; Group 4: aOR = 0.65, 95% CI 0.54–0.79) and live birth (Group 2: aOR = 0.89, 95% CI 0.85–0.95; Group 3: aOR = 0.83, 95% CI 0.76–0.91; Group 4: aOR = 0.59, 95% CI 0.48–0.72) significantly decreased with the increasing storage time, whereas the relationship between miscarriage, ectopic pregnancy and storage time did not reach statistical significance. In addition, there was no evidence of differences in adverse neonatal outcomes (preterm birth, low birthweight, high birthweight, macrosomia or birth defects) between groups. LIMITATION, REASONS FOR CAUTION Our study was limited by the retrospective design from a single center, the conclusion from our study needs to be verified in further studies. WIDER IMPLICATIONS OF THE FINDINGS This study provides new findings about the relationship between prolonged storage time of vitrified embryos and clinical outcomes and offers evidence for the safety of using long-stored embryos after vitrification. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (grant nos. 81903324, 81771533, 81571397, 81701523), National Key Research and Development Program of China (grant no. SQ2018YFC100163). None of the authors have any conflicts of interest to declare.

Storage Time of Cryopreserved Embryos and Pregnancy Outcomes: A Dose-Response Meta-Analysis

“…However, using multivariable logistic regression analysis, Ueno et al found that only the time from insemination to vitrification correlated with survival rates but not the duration of cryostorage [4]. In contrast, a recently published study, which investigated the effect of the storage time of embryos on pregnancy outcomes in 24 698 patients following the first embryo transfer cycles, found the rates of implantation, clinical pregnancy, multiple pregnancy, and live births decreased with prolonged storage time, although no significant difference in survival rates was found between the different groups [24]. Although the sample Test for overall effect: Z = 1.10 (p = 0.27)…”

The Morphology of Inner Cell Mass Is the Strongest Predictor of Live Birth After a Frozen-Thawed Single Embryo Transfer

“…A clinical pregnancy was defined as a positive serum β-hCG 14 days after transfer, and a gestational sac can be documented by ultrasound 28–35 days after transfer. The miscarriage rate was defined as the number of clinical pregnancy losses divided by the number of clinical pregnancies ( 23 ). There were 27 patients of vanishing twin syndrome (VTS) in this study.…”

Effect of Day 3 and Day 5/6 Embryo Quality on the Reproductive Outcomes in the Single Vitrified Embryo Transfer Cycles

“…The same vitrification method was employed throughout the whole study period. There were 4 vitrification operators involved in the study, all of whom have been well trained to perform vitrification technically as described in our previous study ( 18 ).…”