Impact of Prolonged Embryo Storage on Reproductive and Neonatal Outcomes: a Systematic Review and Meta-analysis

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2024 Oct 19

PMID 39425814

Authors

Irene Zolfaroli

Monica Romeu Villarroya

Laura Beatriz Serralta Garcia

Jose Maria Rubio Rubio

Ana Monzo Miralles

Affiliations

Soon will be listed here.

Abstract

Purpose: To analyze the influence of embryo storage on reproductive and neonatal results in patients undergoing in vitro fertilization (IVF) treatment.

Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched from inception up to June 2024 for studies comparing reproductive and neonatal outcomes in patients undergoing frozen embryo transfer within 12 months from embryo storage versus more than 12 months after embryo storage. Data were pooled by meta-analysis using a random effects model.

Results: A total of 16 studies, involving 233,315 embryos were included. Patients undergoing frozen embryo within 12 months from embryo storage were associated with higher rates of live birth (OR 1.17, 95% CI 1.09-1.26, I = 78%) biochemical pregnancy (OR 1.26, 95% CI 1.08-1.47, I = 77.8%) clinical pregnancy (OR 1.24, 95% CI 1.12-1.38, I = 86.3%) and multiple pregnancy rate (OR 1.26, 95% CI 1.03-1.55, I = 69%). No significant differences between groups were shown in terms of survival rate (OR 1.52, 95% CI 0.65-3.58, I = 98.5%), miscarriage (OR 1.08, 95% CI 0.91-1.27, I = 77%), implantation rate (OR 1.17, 95% CI 0.90-1.52, I = 91.7%) and ectopic pregnancy (OR 0.98, 95% CI 0.80-1.20, I = 0%). In addition, prolonged embryo storage was not associated with higher rates of preterm delivery (OR 0.86, 95% CI 0.67-1.09, I = 8.3%), low weight at birth (OR 1.10, 95% CI 0.88-1.38, I = 24.3%) or congenital malformations (OR 0.90, 95% CI 0.65-1.25, I = 0.8%).

Conclusion: Prolonged embryo storage over 12 months is associated with lower rates of live birth, biochemical pregnancy, clinical pregnancy, and multiple pregnancy. However, important covariates such as reasons for delay of transfer, embryo quality, and improper handling of embryos could not be ruled out as causes of this reduction. Given these limitations, these conclusions should be viewed with caution.

Citing Articles

Embryonic and neonatal outcomes following double vitrification/thawing: a systematic review and meta-analysis.

Maleki-Hajiagha A, Shafie A, Rezayi S, Marvi M, Karimi R, Amidi F BMC Pregnancy Childbirth. 2025; 25(1):206.

PMID: 40012071 PMC: 11863950. DOI: 10.1186/s12884-025-07311-x.

References

Devroey P, Polyzos N, Blockeel C . An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011; 26(10):2593-7. DOI: 10.1093/humrep/der251. View

Bourdon M, Santulli P, Maignien C, Gayet V, Pocate-Cheriet K, Marcellin L . The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: A retrospective matched cohort study. PLoS One. 2018; 13(4):e0194800. PMC: 5890985. DOI: 10.1371/journal.pone.0194800. View

Weiss M, Luo C, Zhang Y, Chen Y, Kissin D, Satten G . Fresh vs. frozen embryo transfer: new approach to minimize the limitations of using national surveillance data for clinical research. Fertil Steril. 2022; 119(2):186-194. PMC: 11017290. DOI: 10.1016/j.fertnstert.2022.10.021. View

Lawrenz B, Coughlan C, Melado L, Fatemi H . The ART of frozen embryo transfer: back to nature!. Gynecol Endocrinol. 2020; 36(6):479-483. DOI: 10.1080/09513590.2020.1740918. View

Roelens C, Blockeel C . Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcomes: a review. Fertil Steril. 2022; 118(5):820-827. DOI: 10.1016/j.fertnstert.2022.09.003. View

Liberati A, Altman D, Tetzlaff J, Mulrow C, Gotzsche P, Ioannidis J . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009; 339:b2700. PMC: 2714672. DOI: 10.1136/bmj.b2700. View

Sterne J, Hernan M, Reeves B, Savovic J, Berkman N, Viswanathan M . ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355:i4919. PMC: 5062054. DOI: 10.1136/bmj.i4919. View

Borenstein M, Hedges L, Higgins J, Rothstein H . A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2015; 1(2):97-111. DOI: 10.1002/jrsm.12. View

Higgins J, Thompson S, Deeks J, Altman D . Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414):557-60. PMC: 192859. DOI: 10.1136/bmj.327.7414.557. View

10.

Cimadomo D, Fabozzi G, Dovere L, Maggiulli R, Albricci L, Innocenti F . Clinical, obstetric and perinatal outcomes after vitrified-warmed euploid blastocyst transfer are independent of cryo-storage duration. Reprod Biomed Online. 2021; 44(2):221-227. DOI: 10.1016/j.rbmo.2021.09.027. View

11.

Ueno S, Uchiyama K, Kuroda T, Yabuuchi A, Ezoe K, Okimura T . Cryostorage duration does not affect pregnancy and neonatal outcomes: a retrospective single-centre cohort study of vitrified-warmed blastocysts. Reprod Biomed Online. 2018; 36(6):614-619. DOI: 10.1016/j.rbmo.2018.03.008. View

12.

Wirleitner B, Vanderzwalmen P, Bach M, Baramsai B, Neyer A, Schwerda D . The time aspect in storing vitrified blastocysts: its impact on survival rate, implantation potential and babies born. Hum Reprod. 2013; 28(11):2950-7. DOI: 10.1093/humrep/det361. View

13.

Zheng Q, Mo M, Zhang H, Xu S, Xu F, Wang S . Prolong cryopreservation duration negatively affects pregnancy outcomes of vitrified-warmed blastocyst transfers using an open-device system: A retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2022; 281:68-75. DOI: 10.1016/j.ejogrb.2022.12.012. View

14.

Li J, Yin M, Wang B, Lin J, Chen Q, Wang N . The effect of storage time after vitrification on pregnancy and neonatal outcomes among 24 698 patients following the first embryo transfer cycles. Hum Reprod. 2020; 35(7):1675-1684. DOI: 10.1093/humrep/deaa136. View

15.

Li W, Zhao W, Xue X, Zhang S, Zhang X, Shi J . Influence of storage time on vitrified human cleavage-stage embryos froze in open system. Gynecol Endocrinol. 2016; 33(2):96-99. DOI: 10.1080/09513590.2016.1207166. View

16.

Liang M, Lin M, Qin X, Yang R, Hu K, Li R . Long-term embryo vitrification is associated with reduced success rates in women undergoing frozen embryo transfer following a failed fresh cycle. Eur J Obstet Gynecol Reprod Biol. 2024; 296:244-249. DOI: 10.1016/j.ejogrb.2024.03.002. View

17.

Lin R, Zhou H, Wang C, Chen H, Shu J, Gan X . Does longer storage of blastocysts with equal grades in a cryopreserved state affect the perinatal outcomes?. Cryobiology. 2021; 103:87-91. DOI: 10.1016/j.cryobiol.2021.09.003. View

18.

Ma Y, Sun M, Wen T, Ding C, Liu L, Meng T . Storage time does not influence pregnancy and neonatal outcomes for first single vitrified high-quality blastocyst transfer cycle. Reprod Biomed Online. 2023; 47(4):103254. DOI: 10.1016/j.rbmo.2023.06.009. View

19.

Zhang J, Mao X, Wang Y, Chen Q, Lu X, Hong Q . Neonatal outcomes and congenital malformations in children born after human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles. Arch Gynecol Obstet. 2017; 296(6):1207-1217. DOI: 10.1007/s00404-017-4537-z. View

20.

Behl S, Joshi V, Larson N, Young M, Bilal M, Walker D . Vitrification versus slow freezing of human ovarian tissue: a systematic review and meta-analysis of histological outcomes. J Assist Reprod Genet. 2022; 40(3):455-464. PMC: 10033773. DOI: 10.1007/s10815-022-02692-w. View