Automated oocyte retrieval, denudation, sperm preparation, and ICSI in the IVF laboratory: a proof-of-concept study and report of the first live births.

study questionCan multiple automated systems sequentially perform Day 0 IVF procedures: (i) sperm preparation, (ii) cumulus-oocyte complex (COC) retrieval and oocyte denudation, and (iii) ICSI? SUMMARY ANSWER: Automated sequential Day 0 procedures achieved fertilization in 64.3% of injected oocytes and 42.2% usable blastocyst formation in 11 cases, resulting in five healthy live births from nine patients with positive pregnancy tests. WHAT IS KNOWN ALREADY: The Day 0 procedures-sperm preparation, oocyte handling (e.g. finding and denudation), and ICSI-rely on embryologist skill. Automation in IVF laboratories has the potential to improve reproducibility, yet its implementation remains limited. Fully automated pipetting workflows replicating embryologist activities have not yet been achieved, though partial automation of key steps such as dish preparation and ICSI has been reported. STUDY DESIGN, SIZE, DURATION: Proof-of-concept pilot study with prospective allocation of sibling oocytes to automated or manual protocols. Here, we report on Day 0 automation in 11 cases using two or three automated systems (nicknamed 'pearls') in sequence. Single vitrified/warmed blastocyst transfers occurred between April and October 2024. This work was part of a larger research programme evaluating automation across multiple IVF laboratory procedures from gamete handling through blastocyst transfer and specifically demonstrates sequential automation across multiple Day 0 procedures within a single workflow. PARTICIPANTS/MATERIALS, SETTING,

methodsEleven consenting patients (three autologous, eight donor egg cycles) underwent IVF/ICSI following minimal or mild stimulation. The gametes were processed using either automated or manual protocols. The automated systems-Pearl 1 (sperm preparation), Pearl 2 (COC retrieval and oocyte denudation), and Pearl 3 (sperm selection, laser immobilization, and piezo-ICSI)-were used in various combinations. Multiple AIs were developed and deployed across these systems. This IRB-approved study was conducted at Hope IVF, Guadalajara, México. MAIN RESULTS AND THE ROLE OF CHANCE: The automated systems achieved 64.3% fertilization (45/70) and 42.2% usable blastocyst formation per zygote (19/45), compared to 81% (47/58) and 59.6% (28/47) with manual procedures. Transfers from the automated arm resulted in five live births, three biochemical pregnancies, and one early loss at 7 weeks. The live birth rate per transfer of a single warmed blastocyst in the automated arm was 5/12 (41.7%). LIMITATIONS, REASONS FOR CAUTION: The small sample size prevented statistical comparison between automated and manual procedures. Some steps required operator support via direct intervention or digital control. Autonomy (defined as automated execution without human intervention) was achieved only in sperm preparation and selected ICSI tasks. A larger study using an updated system is underway. WIDER IMPLICATIONS OF THE

findingsThis study demonstrates the feasibility of automating Day 0 IVF procedures, with the potential to improve standardization and reduce protocol drift, fatigue, and operator variability. Our findings support a phased integration of automation to meet growing ART demands. STUDY FUNDING/COMPETING INTEREST(S): The study was sponsored by Conceivable Life Sciences. A.C.-B. is an employee, shareholder, and company officer at Conceivable Life Sciences and also holds shares in IVF 2.0. G.M.-R. is a stock option holder at Conceivable Life Sciences and has received consulting fees from both Conceivable Life Sciences and IVF 2.0. A.F.-S.F. is an employee and stock option holder at Conceivable Life Sciences. N.C.-B. is a stock option holder at Conceivable Life Sciences and has received consulting fees from the company, and he is also an employee, shareholder, and company officer at Embryotools. A.M. is a shareholder and company officer at Conceivable Life Sciences and holds shares in TMRW Life Sciences. M.A. is a stock option holder at Conceivable Life Sciences and has received consulting fees and travel support from the company; she has also received consulting fees from TMRW Life Sciences. G.S. is an employee and stock option holder at Conceivable Life Sciences and has received consulting fees from IVF 2.0. C.M. is an employee and stock option holder at Conceivable Life Sciences. E.H.-M. is an employee and stock option holder at Conceivable Life Sciences. R.V.-M. is an employee and stock option holder at Conceivable Life Sciences and has received consulting fees from IVF 2.0. V.M. is an employee and stock option holder at Conceivable Life Sciences. E.M. is an employee of Embryotools. A.V.A. has no conflicts of interest to declare. V.O.-H. is an employee and stock option holder at Conceivable Life Sciences and has received consulting fees from IVF 2.0. F.A.-G. is an employee and stock option holder at Conceivable Life Sciences. A.Á.L. is an employee and stock option holder at Conceivable Life Sciences. M.A. is an employee of Embryotools. Q.M.-A. is an employee of Embryotools. J.G.E.F. is an employee and stock option holder at Conceivable Life Sciences. L.M.C.O. has no conflicts of interest to declare. C.P.B. is an employee and stock option holder at Conceivable Life Sciences. D.J.S.-G. has no conflicts of interest to declare. J.C. is an employee, shareholder, stock option holder, and company officer at Conceivable Life Sciences and holds shares in IVF 2.0, Althea Science, TMRW Life Sciences, Kindbody, and Reproductive Healthcare. Furthermore, A.C.-B., G.M.-R., A.F.-S.F., A.M., A.Á.L., and J.C. declare inventorship on US patent 12,349,940 B2 protecting automated oocyte denudation. A.C.-B., G.M.-R., A.F.-S.F., C.M., R.V.-M., V.O.-H., E.H.-M., V.M., A.M., and J.C. declare inventorship on US patent 12,245,793 B2 protecting robotic handling systems for IVF laboratories. A.C.-B., G.M.-R., A.F.-S.F., C.M., G.S., V.M., J.C., and A.M. declare inventorship on US patent 12,178,475 B1 protecting automated sperm preparation. A.C.-B., G.M.-R., A.M., and J.C. declare inventorship on US patent 12,180,441 B1 protecting laboratory workflow automation. A.C.-B., G.M.-R., A.F.-S.F., A.M., C.M., R.V.-M., V.O.-H., N.C.-B., A.Á.L., and J.C. declare inventorship on US patent 12,268,418 B2 protecting automated oocyte preparation. A.C.-B., G.M.-R., R.V.-M., V.O.-H., N.C.-B., E.H.-M., A.M., J.C., and A.F.-S.F. declare inventorship on US patent 12,310,625 B2 protecting automated ICSI. A.C.-B., G.M.-R., A.F.-S.F., C.M., V.O.-H., and A.M. declare inventorship on US patent 12,253,516 B2 protecting optical systems for IVF automation. A.C.-B., G.M.-R., A.M., J.C., A.F.-S.F., C.M., R.V.-M., V.O.-H., G.S., N.C.-B., and J.G.E.F. declare inventorship on US patent 12,226,125 B2 protecting automated vitrification. A.C.-B., G.M.-R., C.M., R.V.-M., V.O.-H., N.C.-B., V.M., and J.C. declare inventorship on US patent US 12,478,405 B2 protecting automated dish-based sperm preparation. A.C.-B., G.M.-R., C.M., N.C.-B., M.A., A.M., and J.C. declare inventorship on a pending patent application protecting automated dish preparation technology. A.C.-B., G.M.-R., N.C.-B., and J.C. declare inventorship on a pending patent application protecting automated oocyte denudation. N.C.-B., J.C., A.M., E.H.-M., and A.C.-B. declare inventorship on a pending patent application protecting automated vitrification systems. A.C.-B., G.M.-R., V.O.-H., and J.C. declare inventorship on a pending patent application protecting COC detection technology. TRIAL REGISTRATION NUMBER: NCT06074835 (ClinicalTrials.gov, 4 October 2023).