Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
First Clinical Pregnancies with an ICSI Robot
26 Pages Posted: 6 Sep 2022More...
Background: Intracytoplasmic sperm injection (ICSI) is a laboratory procedure that has been conducted in most IVF centers by highly experienced embryologists manually. Since it involves micromanipulation and is technically demanding, its successful rates may vary significantly depending on the experience of each operator. Here, we developed an automated ICSI (ICSIA) robot that requires minimal manual intervention with the aim to standardize the consistency of technique and clinical results and carried out a translational project to evaluate its performance.
Methods: The ICSIA robot was developed to have supervised automated control on critical steps of the sperm injection procedure, including injection pipette advancement, zona pellucida and oolemma penetration with piezo pulses, and pipette removal after sperm release. Manual intervention is only required for immobilization and capture of spermatozoa with a joystick gamepad and to release the sperm in the ooplasm, without the need for micromanipulation skills. The robot was first tested in animal models, including mouse, hamster and rabbit oocytes, and subsequently using discarded human oocytes that were injected with latex microbeads. Finally, the translational project included a first small clinical pilot trial with donor oocytes to study the feasibility of the robot in a clinical setting. In the different models tested, the ICSIA robot was controlled by engineers with no micromanipulation experience and results compared to those obtained with manual ICSI performed by experienced embryologists.
Findings: The developed ICSIA robot demonstrated a high degree of consistency and operator skill independence in the different animal models tested as well as in the pre-clinical validations performed in discarded human oocytes, where results were equivalent to those obtained in manual controls carried out in parallel. In the clinical validation, 32 metaphase II oocytes were obtained from 3 donors, which were randomly assigned to be injected either with the ICSIA robot or manually by conventional ICSI. In total, from the 14 oocytes injected with ICSIA, 13 (93%) fertilized correctly and 8 (61.5%) developed into good quality blastocysts, which were biopsied for preimplantation genetic testing of aneuploidies (PGT-A). Out of the 8 blastocysts tested, 4 (50%) were diagnosed as chromosomally normal. In the manual control, 16 (88.8%) oocytes out of the 18 injected fertilized correctly and 12 (75%) reached the blastocyst stage and were biopsied, resulting in 10 (83%) that were diagnosed as euploid. Three euploid blastocysts from the ICSIA robot group have been transferred into two recipients, which resulted in two ongoing pregnancies.
Interpretation: The ICSIA robot showed high proficiency in injecting animal and human oocytes when operated by inexperienced personnel. The preliminary results obtained in this first clinical pilot trial are within the key performance indicators that have been established for the manual conventional ICSI technique. To our knowledge, this is the first time that human pregnancies are obtained from embryos produced using an automated ICSI robot. Next steps will involve improving engineering processes to speed up the whole sperm injection process and automate some other steps of the ICSI procedure, e.g., sperm capture and immobilization.
Funding Information: This study was privately funded.
Declaration of Interests: SM is a shareholder and officer of Overture Life. NC-B and GC are shareholders of Embryotools. JZ is shareholder of New Hope Fertility Center. All other authors have no conflict of interests.
Ethics Approval Statement: Animal care and procedures were conducted according to protocols approved by the Ethics Committee on Animal Research of the Science Park of Barcelona (PCB), Spain. All animals were purchased from Janvier Labs. The first IRB was approved to conduct a pre-clinical validation using discarded human oocytes from ICSI cycles, as these are immature at the time of denudation (IRB: Comité de Ética de la Investigación con medicamentos del Parc de Salut Mar, Barcelona, Spain; Protocol # 2021/9933/I). The second IRB was obtained to conduct a clinical pilot study to evaluate the feasibility of the developed robot in a few oocyte-donation cycles (WCG IRB, USA, study # 1318771). Specific consent was obtained from donors and patients participating in the two phases of the project.
Suggested Citation: Suggested Citation