Meta-analysis of the embryo freezing transfer interval

Roberto Matorras, Jose Ignacio Pijoan, Irantzu Perez-Ruiz, Lucía Lainz, Iker Malaina, Sonia Borjaba, Roberto Matorras, Jose Ignacio Pijoan, Irantzu Perez-Ruiz, Lucía Lainz, Iker Malaina, Sonia Borjaba

Abstract

Background: The decision of whether frozen embryo transfer (FET) should be performed in the cycle immediately after OPU or at least one cycle later is controversial. FET could improve pregnancy rates in IVF; however, how much time is needed for the endometrium to return to optimal receptivity after ovarian stimulation is not known.

Methods: Electronic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies providing data on the influence of the interval between embryo freezing (or OPU) and FET in FET cycles published between January 1, 2007, and February 1, 2020.

Main findings: Data analyzed indicated that in the immediate FET cycles, there was a trend to an increased biochemical pregnancy rate (RR = 1.08; CI = 1.00-1.18), whereas the clinical pregnancy rate was somewhat higher, but without reaching statistical significance (RR = 1.07; CI = 0.99-1.15). The live birth rate was similar in the two groups (RR = 1.05; CI = 0.95-1.15), as was the implantation rate (RR = 0.98; CI = 0.83-1.16). Stratifying by embryo stage or FET type (freeze-all or FET after failed fresh transfer) showed no differences.

Conclusion: Systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a nonsignificant trend to better clinical pregnancy rate and it also avoids the psychological effects of prolonging the stress on prospective parents.

Keywords: IVF; delayed transfer; frozen embryo transfer; immediate transfer; pregnancy rates.

Conflict of interest statement

Conflict of interest: Roberto Matorras, José Ignacio Pijoan, Irantzu Perez‐Ruiz, Lucía Lainz, Iker Malaina, and Sonia Borjaba declare that they have no conflict of interest. Human/animal rights: This article does not contain any studies with human and animal subjects performed by the any of the authors.

© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart
FIGURE 2
FIGURE 2
Comparison of (A) maternal age, (B) oocytes retrieved, and (C) embryos transferred in the immediate and delayed FET. No significant differences were observed. REML, restricted maximum likelihood
FIGURE 3
FIGURE 3
(A) Meta‐analysis of studies reporting implantation rates by FET interval. Meta‐analysis of the data from 6 included series (5 publications) that reported implantation rate as an outcome showed that there were no significant differences between immediate and delayed FETs. (B) Meta‐analysis of studies reporting biochemical pregnancy rates by FET interval. Meta‐analysis of the data from 5 publications that reported biochemical pregnancy rate as an outcome showed a RR of 1.08 (CI 1.00‐1.18) in favor of immediate FET. REML, restricted maximum likelihood
FIGURE 4
FIGURE 4
(A) Meta‐analysis of studies reporting clinical pregnancy rates by FET interval. Meta‐analysis of the data from 11 series (10 publications) that reported clinical pregnancy rate as an outcome showed that the clinical pregnancy rate was significantly increased in the immediate FET. (B) Meta‐analysis of studies reporting live birth rates by FET interval. Meta‐analysis of the data from 11 series (10 publications) that reported live birth rate as an outcome showed that there were no significant differences between immediate and delayed FETs. REML, restricted maximum likelihood

References

    1. Xie X, Zou L, Shen Y, Xiong F, Chen J. Vitrification technology in whole embryo freezing. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010;35:673‐678.
    1. De Geyter C, Calhaz‐Jorge C, Kupka MS, et al. European IVF‐monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020:hoz038.
    1. Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Freeze‐all policy: fresh vs. frozen‐thawed embryo transfer. Fertil Steril. 2015;103:1190‐1193.
    1. Zhu Q, Chen Q, Wang L, et al. Live birth rates in the first complete IVF cycle among 20 687 women using a freeze‐all strategy. Hum Reprod. 2018;33:924‐929.
    1. McArthur SJ, Leigh D, Marshall JT, de Boer KA, Jansen RP. Pregnancies and live births after trophectoderm biopsy and preimplantation genetic testing of human blastocysts. Fertil Steril. 2005;84:1628‐1636.
    1. Griesinger G, Schultz L, Bauer T, Broessner A, Frambach T, Kissler S. Ovarian hyperstimulation syndrome prevention by gonadotropin‐releasing hormone agonist triggering of final oocyte maturation in a gonadotropin‐releasing hormone antagonist protocol in combination with a “freeze‐all” strategy: a prospective multicentric study. Fertil Steril. 2011;95:2029‐2033.
    1. Ortega‐Hrepich C, Stoop D, Guzmán L, et al. A "freeze‐all" embryo strategy after in vitro maturation: a novel approach in women with polycystic ovary syndrome? Fertil Steril. 2013;100:1002‐1007.
    1. Chen ZJ, Shi Y, Sun Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. New Engl J Med. 2016;375:523‐533.
    1. Horowitz E, Mizrachi Y, Farhi J, Shalev A, Raziel A, Weissman A. Modified natural‐cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle? Reprod Biomed Online. 2019;39:439‐445.
    1. Lass A, Williams G, Abusheikha N, Brinsden P. The effect of endometrial polyps on outcomes of in vitro fertilization (IVF) cycles. J Assist Reprod Genet. 1999;16:410‐415.
    1. Liu KE, Hartman M, Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019;39:49‐62.
    1. Santos‐Ribeiro S, Siffain J, Polyzos NP, et al. To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt? Fertil Steril. 2016;105(5):1202‐1207.
    1. Simón C, Cano F, Valbuena D, Remohí J, Pellicer A. Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Hum Reprod. 1995;10:2432‐2437.
    1. Aurrekoetxea I, Ruiz‐Sanz JI, del Agua AR, et al. Serum oxidizability and antioxidant status in patients undergoing in vitro fertilization. Fertil Steril. 2010;94:1279‐1286.
    1. Junovich G, Mayer Y, Azpiroz A, et al. Ovarian stimulation affects the levels of regulatory endometrial NK cells and angiogenic cytokine VEGF. Am J Reprod Immunol. 2011;65:146‐153.
    1. Haouzi D, Dechaud H, Assou S, De Vos J, Hamamah S. Insights into human endometrial receptivity from transcriptomic and proteomic data. Reprod Biomed Online. 2012;24:23‐34.
    1. Weissman A.IVF worldwide survey results: frozen‐thawed embryo transfer; 2017. . Accessed on 24 April 2020.
    1. Higgins C, Healey M, Jatkar S, et al. Interval between IVF stimulation cycle and frozen embryo transfer: Is there a benefit to a delay between cycles? Aust N Z J Obstet Gynaecol. 2018;58:217‐221.
    1. Huang J, Lu X, Xie Q, Lin J, Cai R, Kuang Y. Timing of frozen‐thawed embryo transfer after controlled ovarian stimulation in a non‐elective freeze‐all policy. Ann Transl Med. 2019;7:752.
    1. Lattes K, Checa MA, Vassena R, Brassesco M, Vernaeve V. There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze‐all strategy. Hum Reprod. 2017;32:368‐374.
    1. Maas KH, Baker VL, Westphal LM, Lathi RB. Optimal timing of frozen embryo transfer after failed IVF attempt. Fertil Steril. 2008;90:S285.
    1. Volodarsky‐Perel A, Eldar‐Geva T, Holzer HEG, Schonberger O, Reichman O, Gal M. Cryopreserved embryo transfer: adjacent or non‐adjacent to failed fresh long GnRH‐agonist protocol IVF cycle. Reprod BioMed Online. 2017;34:267‐273.
    1. Kaye L, Marsidi A, Rai P, et al. Frozen blastocyst transfer outcomes in immediate versus delayed subsequent cycles following GnRH agonist or hCG triggers. J Assist Reprod Genet. 2018;35:669‐675.
    1. He Y, Zheng H, Du H, et al. Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing. Reprod Biol Endocrinol. 2020;18(1):PMC6953147.
    1. Ozgur K, Bulut H, Berkkanoglu M, Humaidan P, Coetzee K. Frozen embryo transfer can be performed in the cycle immediately following the freeze‐all cycle. J Assist Reprod Genet. 2018;35:135‐142.
    1. Santos‐Ribeiro S, Polyzos NP, Lan VTN, et al. The effect of an immediate frozen embryo transfer following a freeze‐all protocol: a retrospective analysis from two centres. Hum Reprod. 2016;31:2541‐2548.
    1. Song J, Xiang S, Sun Z. Frozen embryo transfer at the cleavage stage can be performed within the first menstrual cycle following the freeze‐all strategy without adversely affecting the live birth rate: A STROBE‐compliant retrospective study. Medicine. 2019;98:e17329.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
    1. Wells G, Shea B, O’Connell D, et al.The Newcastle‐Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta‐analysis; 2011. . Accessed on 24 April 2020.
    1. Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod. 2006;21:2845‐2849.
    1. Reichman DE, Chung P, Meyer L, Greenwood E, Davis O, Rosenwaks Z. Consecutive gonadotropin‐releasing hormone‐antagonist in vitro fertilization cycles: does the elapsed time interval between successive treatments affect outcomes? Fertil Steril. 2013;99:1277‐1282.
    1. Bayoglu Tekin Y, Ceyhan ST, Kilic S, Korkmaz C. The impact of the time interval on in‐vitro fertilisation success after failure of the first attempt. J Obstet Gynaecol. 2015;35:403‐406.
    1. Nouri K, Tempfer CB, Walch K, Promberger R, Dag S, Ott J. Predictive value of the time interval between embryo loading and transfer for IVF/ICSI success: a prospective cohort study. Reprod Biol Endocrinol. 2015;29(13):51.
    1. Li H, Li L, Lu X, Sun X, Ng EHY. Comparison of the effect of immediate versus delayed transfer following a stimulated IVF cycle on the ongoing pregnancy rate of frozen‐thawed embryo transfer cycles: a study protocol for a randomised controlled trial. BMJ Open. 2018;17(8):e020507.
    1. Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S. Fresh versus frozen embryotransfers in assisted reproduction. Cochrane Database Syst Rev. 2017;3:CD011184.
    1. Coates A, Kung A, Mounts E, et al. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial. Fertil Steril. 2017;107:723‐730.
    1. Somigliana E, Busnelli A, Paffoni A, et al. Cost‐effectiveness of preimplantation genetic testing for aneuploidies. Fertil Steril. 2019;111:1169‐1176.
    1. Devroey P, Polyzos NP, Blockeel C. An OHSS‐Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011;26:2593‐2597.
    1. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen thawed embryo transfer in normal responders. Fertil Steril. 2011;96:344‐348.
    1. Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta‐analysis of reproductive outcomes. Hum Reprod Update. 2019;25:2‐14.
    1. Simón C, Velasco JJG, Valbuena D, et al. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle‐stimulating hormone step‐down regimen. Fertil Steril. 1998;70:234‐239.
    1. Nikas G, Develioglu OH, Toner JP, Jones HW Jr. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod. 1999;14:787‐792.
    1. Richter KS, Shipley SK, McVearry I, Tucker MJ, Widra EA. Cryopreserved embryo transfers suggest that endometrial receptivity may contribute to reduced success rates of later developing embryos. Fertil Steril. 2006;86:862‐866.
    1. Papanikolaou E, Chartomatsidou T, Timotheou E, et al. In Freeze‐All Strategy, Cumulative Live Birth Rate (CLBR) Is Increasing According to the Number of Blastocysts Formed in Women <40 Undergoing Intracytoplasmic Sperm Injection (ICSI). Front Endocrinol (Lausanne). 2019;10:427.
    1. Montoya‐Botero P, Polyzos NP. The endometrium during and after ovarian hyperstimulation and the role of segmentation of infertility treatment. Best Pract Res Clin Endocrinol Metab. 2019;33:61‐75.
    1. Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014;102:10‐18.
    1. Bringhenti F, Martinelli F, Ardenti R, La Sala G. Psychological adjustment of infertile women entering IVF treatment: differentiating aspect and influencing factors. Acta Obstet Gynecol Scand. 1997;76:431‐443.
    1. Matthiesen SM, Frederiksen Y, Ingerslev HJ, Zachariae R. Stress, distress and outcome of assisted reproductive technology (ART): a meta‐analysis. Hum Reprod. 2011;26:2763‐2776.
    1. Miller N, Herzberger EH, Pasternak Y, et al. Does stress affect IVF outcomes? A prospective study of physiological and psychological stress in women undergoing IVF. Reprod Biomed Online. 2019;39:93‐101.
    1. Bui BN, Torrance HL, Janssen C, et al. Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? Study protocol of the SCRaTCH‐OFO trial: a randomized controlled trial. BMC Pregnancy Childbirth. 2018;18:511.
    1. Ferrick L, Lee YSL, Gardner DK. Reducing time to pregnancy and facilitating the birth of healthy children through functional analysis of embryo physiology. Biol Reprod. 2019;101:1124‐1139.
    1. Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen‐thawed embryo transfer. Cochrane Database Syst Rev. 2017;7:CD003414.
    1. Lawrenz B, Coughlan C, Melado L, Fatemi HM. The ART of frozen embryo transfer: back to nature!. Gynecol Endocrinol. 2020;18:1‐5.
    1. Xi Q, Tao Y, Qiu M, Wang Y, Kuang Y. Comparison Between PPOS and GnRHa‐Long Protocol in Clinical Outcome with the First IVF/ICSI Cycle: A Randomized Clinical Trial. Clin Epidemiol. 2020;12:261‐272.
    1. Montoya‐Botero P, Martinez F, Rodríguez‐Purata J, Rodríguez I, Coroleu B, Polyzos NP. The effect of type of oral contraceptive pill and duration of use on fresh and cumulative live birth rates in IVF/ICSI cycles. Hum Reprod. 2020;35(4):826‐836.
    1. Mizrachi Y, Horowitz E, Farhi J, Raziel A, Weissman A. Ovarian stimulation for freeze‐all IVF cycles: a systematic review. Hum Reprod Update. 2020;26:118‐135.
    1. Harrison KL, Breen TM, Hennessey JF, et al. Patient age and success in a human IVF programme. Aust N Z J Obstet Gynaecol. 1989;29:326‐328.
    1. Templeton A, Morris JK, Parslow W. Factors that affect outcome of in‐vitro fertilisation treatment. Lancet. 1996;348:1402‐1406.
    1. Connell MT, Richter KS, Devine K, et al. Larger oocyte cohorts maximize fresh IVF cycle birth rates and availability of surplus high‐quality blastocysts for cryopreservation. Reprod Biomed Online. 2019;38:711‐723.
    1. Matorras R, Matorras F, Mendoza R, et al. The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates. Hum Reprod. 2005;20:2923‐2931.
    1. Matorras R, Otero B, Mendoza R, et al. Quality of additional embryos transferred on pregnancy outcomes in IVF: predictions using a mathematical approach. Reprod Biomed Online. 2014;29:200‐208.
    1. Igarashi M. Rebound phenomenon of the human ovarian function and its therapeutic application in female sterility; preliminary report. Fertil Steril. 1957;8:362‐372.
    1. Buckler HM, Evans CA, Mamtora H, Burger HG, Anderson DC. Gonadotropin, steroid, and inhibin levels in women with incipient ovarian failure during anovulatory and ovulatory rebound cycles. J Clin Endocrinol Metab. 1991;72:116‐124.
    1. Talaulikar VS, Belli A, Manyonda I. GnRH agonists: do they have a place in the modern management of fibroid disease? J Obstet Gynecol India. 2012;62:506‐510.

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