Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup

Hardarson, Thorir; Bungum, Mona; Conaghan, J.; Meintjes, M.; Chantilis, S.J.; Molnar, Laszlo; Gunnarsson, Kristina; Wikland, Matts

doi:10.1016/j.fertnstert.2015.08.037

Cited by 70 publications

(45 citation statements)

References 39 publications

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“…In lower resource settings or in any setting addressing cost, a single medium could infer distinct economic advantages. Moreover, compatibility with time-lapse systems is undoubtedly a significant benefit and a key reason for the increasing popularity of continuous single medium protocols [20,35,40,60]. Of note, however, current evidence does not suggest a clear benefit of using time-lapse for embryo selection, and these systems generally increase the overall cost of the IVF procedure [62].…”

Section: Discussionmentioning

confidence: 99%

“…We further examined 23 studies for eligibility: -A total of three studies were excluded: Two studies used Fertilization and then Cleavage Medium and not a system for Cleavage and then Blastocyst [20,21], and one study was excluded because a different oxygen tension was used in the different groups [22]. -A total of 20 studies were included in this review: Ten studies that randomized oocytes/zygotes [23][24][25][26][27][28][29][30][31][32] and two studies that randomized women [33,34] were included in the forest plots; however, six studies that randomized oocytes/zygotes [35][36][37][38][39][40] and two studies that randomized women [41,42] were not included in the forest plots because it was not possible to extract data for the metaanalyses.…”

Section: Study Selectionmentioning

confidence: 99%

“…From the 20 studies included, only two were deemed to be at low risk of bias in every domain [34,35]. For nine studies, the information retrieved from the publications and from contacting the authors was insufficient for a complete assessment of the risk of bias; they were therefore deemed to be at unclear risk of bias [23, 25-28, 31, 38-40].…”

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

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Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials

Sfontouris

Martins

Nastri

et al. 2016

J Assist Reprod Genet

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Purpose The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. Methods We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. Results No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2 = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2 = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/ zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to Declaration of Authors' Roles Conception and design (CR, LR, WPM, IAS, and NR-F); search strategy (WPM, IAS); data extraction (WPM, PAN, IGRV, CON), analysis, and interpretation (all authors); writing the article (all authors). All authors had full access to all the data in the study and approved the final manuscript.Capsule In conclusion, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6 blastocyst stage. +0.12, ten studies including 7455 oocytes/zygotes, I 2 = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = −0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2 = 93 %). The overall quality of the evidence was very low for all these four outcomes. Electronic supplementary materialConclusions Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

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Section: Discussionmentioning

confidence: 99%

Section: Study Selectionmentioning

confidence: 99%

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

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Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials

Sfontouris

Martins

Nastri

et al. 2016

J Assist Reprod Genet

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“…Meanwhile, KSOM AA medium entered the Life Global marketplace as Global ® medium (LG; [48]), which was optimized as a single use medium that worked under the principle that embryos will select what they need at changing developmental stages. These diverging concepts continue today, although the increase acceptance of single-step media, especially in conjunction with time lapse imaging [49,50], has spurred more companies to develop additional single use media. Both Gardner and Lane [19,21,25], as well as Biggers and associates [34,48,51] provided us with sound science supporting their formulations and aimed to minimize embryo stress through consistency in amino acid and antioxidant supplementation, as well as using stable dipeptides of l-glutamine that minimized ammonium waste-product production [26,34,35,52].…”

Section: Discussionmentioning

confidence: 99%

Systematic Development, Validation and Optimization of a Human Embryo Culture System

et al. 2020

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Objective: To develop and validate a reliable in vitro culture system for human embryos. Design: Retrospective analyses of a series of four studies were conducted between 2006 and 2010 to assess the effect of incubator type (CO 2 box versus Tri-gas minibox), media type, oil type, and hyaluronate supplementation. Optimization of in vitro blastocyst development was verified by assessing our National CDC/ART Surveillance reports between 2010 and 2016. Material and Methods: All patients experienced controlled ovarian hyperstimulation, followed by egg retrieval 35 h post-hCG. Cumulus-oocyte complexes were temporarily cultured in P1 or LG Fert medium plus HSA. Eggs were moved to a more complex media (G-medium or Global ® -LG medium) containing a synthetic protein and embryo adhesion supplement (SPS and EAS, respectively; mLG) post-ICSI insemination. Zygotes were assigned to group culture in 25 µl droplets under oil (light mineral oil or paraffin oil; 37 • C) and embryo development was evaluated on Days 3, 5, and 6 and transferred on Day 3 to 5 depending on the number/quality of embryos available and the IVF history of the patient. Transfers were performed under ultrasound guidance, primarily using a Sureview-Wallace catheter, and enriched ET medium containing 500 µg/mL EAS. Results: Pilot study results (Expt. 1) showed that a mLG single-step medium could be effectively used in combination with Sanyo MCO-5 tri-gas (TG) incubators. Once adapted to SCIRS Lab in 2007 (Expt. 2), the latter culture system yielded improved blastocyst production and pregnancy outcomes compared to CO 2 in air sequential incubation in P1/Multi-blast medium. In Expt. 3, the mLG/TG system yielded high levels of ≥2BB quality blastocysts (51 to 66%) across all age groups, and greater (p < 0.05) pregnancy success/live birth rates using fewer embryos transferred on Day 5 versus Day 3. After validating its clinical effectiveness, mLG was then prospectively compared to a new generation G-media (1.5 & 2.5; Expt. 4) and determined that the crossover treatment using paraffin oil (Ovoil™) allowed the mLG system to be optimized. Subsequently, a compilation of our Annual CDC/ART reported data over six years verified the overall viability of in vitro cultured and vitrified blastocysts produced in the mLG/TG system. Conclusion: By systematically evaluating and implementing various components of an embryo culture system we were able to optimize blastocyst development over the last decade. Our mLG/TG culture system modified an exceptionally well designed KSOM AA LG medium using endotoxin-free EAS and SPS additives to support cellular membrane wellness under stressful in vitro conditions (e.g., culture, cell biopsy, vitrification). Our use of the mLG/TG culture system has proven to be effective, creating reliably high blastocyst production, implantation, and healthy live births.

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“…Eleven morphokinetic parameters were evaluated, and only four parameters (t7, t8, t3c4c-time between the irst observation of 3 and 4 completely separated blastomeres, and t5c7c-time between the irst observation of 5 and 7 completely separated blastomeres) difer signiicantly between embryos cultured in altered media. The authors concluded that single-step culture medium is as nutrient as sequential media for blastocyst development [35]. Costa-Borges et al compared embryo morphokinetics in single culture media with and without medium renewal on Day 3 of culture.…”

Section: Efect Of the Type Of Culture Media On Embryo Morphokineticsmentioning

confidence: 99%

Embryo Morphokinetics Based on Time-Lapse Observation

Tabibnejad¹

2017

Embryo Cleavage

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Embryo incubation and evaluation are critical steps in assisted reproductive technology (ART). Conventionally, embryo assessment has been done by embryologists through removing embryos from a conventional incubator during the culture period. Over recent years, time-lapse systems (TLS) have been established which can take digital images of embryos at key points and time intervals. This technique allows embryologists to assess the embryo quality in the steady culture environment. According to TLS studies and prepared algorithm models, it seems that TLS alone or in combination with conventional morphology can be considered as a useful diagnostic tool to determine high-quality embryos and improve embryonic implantation and pregnancy rates. In addition, there were remarkable diferences between embryo developmental time points and intervals regarding embryo gender, embryo fragmentation, and type of ovarian stimulation protocol. For conident conclusion, time-lapse imaging should be evaluated in further studies, and the system should be evaluated for cost/beneit ratio efectiveness in individual laboratory.Keywords: embryo cleavage, embryo morphokinetics, embryoscope, time-lapse imaging IntroductionAssisted reproductive technology (ART) may help infertile couples to realize their dream to have a child in their family, but pregnancy and live birth rates following in vitro fertilization (IVF) still remain low. It is ideal to identify viable embryos with the highest implantation potential to raise IVF success rates. In the traditional IVF practice, embryo assessments are mainly based on the morphologic observation and grade of embryologists at each stage of oocyte and embryonic development. Some features including oocyte and embryo quality, blastomere numbers and regularity, the percentage of fragmentation, and cytoplasmic granularity have been deined as prognostic indicators of successful pregnancy. This traditional embryo assessment method may have some detrimental efects on embryo growth because frequently opening and closing of incubators often cause to the change of embryo culture environmental steadiness. In order to reduce the inter-and intra-observer diference change, the time-lapse imaging (TLI) has been introduced into in vitro fertilization (IVF) laboratory. The application of time-lapse technology to the clinical IVF laboratory has supported more detailed observations on the embryo development researches quickly.The aim of this chapter is to determine whether TLI is useful for selection of "top quality" embryos for transfer to improve ART outcome rather than conventional morphological evaluation. The possible correlation between embryos' sex, embryo fragmentation, treatment protocols, diferent culture media, and embryo morphokinetics will be examined based on some new researches of TLI facilities. Furthermore, various algorithms and predictive models designed in ART cycles with TLI will be discussed.

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Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup

Abstract: NCT01939626.

Cited by 70 publications

References 39 publications

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials

Systematic Development, Validation and Optimization of a Human Embryo Culture System

Embryo Morphokinetics Based on Time-Lapse Observation

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