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STUDY QUESTION Is there a cumulative toxicity of disposables used in IVF procedures? SUMMARY ANSWER A toxicity may be detected when consumables are used cumulatively, while no toxicity is detected when the same consumables are used and tested individually. WHAT IS KNOWN ALREADY Many components of items used in IVF laboratories may impair human embryonic development. Consequently, it is necessary to screen all reagents and materials which could be in contact with gametes and embryos. Toxicity tests, such as the mouse embryo assay and the human sperm motility assay (HSMA), are used by manufacturers as quality control tools to demonstrate the safety of their products. This evaluation is currently individually performed for each single consumable. However, during an IVF cycle, several devices are used sequentially, potentially creating a cumulative exposure to chemical contaminants, which could not be detected for individually tested consumables. STUDY DESIGN, SIZE, DURATION The objective of this observational study conducted from March 2021 to October 2022 was to evaluate with the HSMA methodology if there was a cumulative toxicity when several disposables are sequentially used. Fourteen categories of consumables currently used in routine IVF procedures were studied, which included devices used for sperm and oocyte collection (cups, condoms, and oocyte aspiration needles), manipulation (flasks, tubes, tips, pipettes, embryo transfer catheters, syringes, and gloves), culture (dishes), and storage (straws). PARTICIPANTS/MATERIALS, SETTING, METHODS After obtaining patient consent, the surplus semen assessed as having normal parameters according to the World Health Organization 2010 criteria were used to perform the HSMAs. First, each consumable was tested individually. Then, associations of three, four, and five consumables, previously validated as non-toxic when tested individually, were analyzed. HSMAs were conducted three times to ensure reproducibility, with a defined toxicity threshold of a sperm motility index (SMI) below 0.85 in at least two of three tests. MAIN RESULTS AND THE ROLE OF CHANCE Thirty-six references of disposables were first individually tested across 53 lots. Forty-nine (92%) demonstrated compliance. However, four (8%) devices revealed toxicity: one lot of 1 ml syringes, two lots of sperm cups, and one lot of 25 cm2 flasks. These four references were excluded from the IVF routine procedures. A total of 48 combinations of consumables were assessed, involving 41 lots from 32 references that were previously individually tested. Among the evaluated combinations, 17 out of 48 (35%) associations exhibited toxicity with a SMI below 0.85 for two of the three tests (n = 8) or all the three tests (n = 9). Notably, three out of 17 (18%) of the three-consumable associations, five out of 16 (31%) of the four-consumable associations, and nine out of 15 (60%) of the five-consumable associations were found not compliant. The toxicity did not originate from a single consumable, because only consumables that were individually pre-validated as non-toxic were included in the combinations, but the toxicity had a cumulative origin. The risk of cumulative toxicity increased with the number of consumables included in the association (Cochran–Mantel–Haenszel statistic, P  = 0.013). LIMITATIONS, REASONS FOR CAUTION The high proportion of non-compliant combinations of disposables can be attributed directly to the extreme rigorous extraction conditions employed during the tests, which could deviate from the conditions encountered in routine clinical use. Also, the methodology employed in the HSMAs (e.g. toxicity extraction duration, sperm concentrations, and protein supplementation of the medium) can influence the sensitivity of the tests. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the significance of performing toxicity testing on devices before introducing them into clinical practice. Disposables should be tested individually to detect immediate toxicities and also in combination. Our results advocate rationalizing the number of consumables used in each IVF procedure and re-evaluating the use of glass consumables. STUDY FUNDING/COMPETING INTEREST(S) This study received fundings from GCS Ramsay Santé pour l'Enseignement et la Recherche (Paris, France) and the Centre de Biologie Médicale BIOGROUP (Le Chesnay-Rocquencourt, France). The authors declare that they have no conflict of interest that could be perceived as prejudicing the impartiality of the reported research. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]