Automation of Gamete Preparation, Intracytoplasmic Sperm Injection (ICSI), Embryo Culture, and Vitrification

Study Overview
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Brief Summary
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Patients suffering from infertility may seek assisted conception treatment. In a full treatment cycle, the sperm and eggs (gametes) from the intended parents will be looked after by skilled laboratory staff (embryologists) who will rely on manual laboratory processes to achieve fertilization. The most commonly employed method to achieve fertilization is intracytoplasmic sperm injection (ICSI), a treatment that involves the injection of a single sperm cell directly inside an egg. The embryos so obtained are then be maintained in an appropriate environment (incubator) for several days before deciding whether they can be immediately used to attempt to establish a pregnancy (embryo transfer), or should be frozen in preparation for a future treatment (cryopreservation). The laboratory steps required to complete a full assisted conception treatment (from sperm and egg retrieval, to fertilization, and then to embryo transfer and/or cryopreservation) are often manual and time-consuming, and thus the success of the treatment is highly dependent on the skill of individual staff and outcomes can be affected by fatigue, stress, and workload. The combination of robotics and artificial intelligence (AI) has the potential to provide improvements to, and standardize, the fertility laboratory, but such integration has not been achieved routinely. Other medical fields, such as regenerative medicine, have long benefited from the implementation of robotic solutions; however, modern automation has yet to find its way into the fertility laboratory. The goal for Conceivable Life Sciences (the study sponsor) is the delivery of a suite of solutions that, collectively, will allow a fully autonomous ICSI cycle to take place (from sperm/egg preparation, to sperm injection, to embryo culture and cryopreservation) in an effort to reduce costs, assist laboratory staff, and possibly, improve outcomes. The purpose of this study is to deliver a core aspect of this project: the digital control and individual automation of all key steps of a complete laboratory workflow. The data generated in this study will help the future development of these automated systems. Patients undergoing an ICSI treatment may be recruited in this study. Their gametes (sperm and/or eggs) may be distributed across two groups (test and control) and undergo one or more elements of an automated full assisted conception workflow (for the test group) or a standard assisted conception workflow (for the control group). Robotic automation may include any of the following steps: robotic sperm preparation, robotic oocyte selection and denudation, robotic sperm injection, automated embryo culture, and automated cryopreservation. The resulting embryos may be employed for embryo transfer. The main hypothesis of this study is that the use of robotic assistants as part of a full assisted conception cycle may improve laboratory workflows without reducing the treatment success rates.

Official Title
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Automation of Gamete Preparation, Intracytoplasmic Sperm Injection (ICSI), Embryo Culture, and Vitrification: A Proof of Concept Study

Conditions
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Infertility

Intervention / Treatment
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* Device: Gamete preparation, ICSI, embryo culture and vitrification robot assistant
* Other: Routine Manual ICSI Workflow


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medical indication to perform ICSI. Informed consent signed by the patients before treatment. Medical indication for the use of autologous or donor oocytes. Medical indication for the use of autologous or donor sperm. Motile sperm. Exclusion Criteria: Recurrent pregnancy loss. Previous history of total fertilization failure. Surgical sperm retrieval. Severe male factor infertility. Known semen liquefaction problems. Any other case abnormalities that could potentially reduce success rates according to the criteria of the senior embryologist in charge.

Ages Eligible for Study
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Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group (Robot-assisted gamete preparation, ICSI, embryo culture and vitrification)<br> | Device: Gamete preparation, ICSI, embryo culture and vitrification robot assistant<br>* Patients undergoing an assisted conception treatment with medical indication to perform ICSI may be recruited in this study. The study will follow a sibling-oocyte and/or sibling embryo study design where oocytes and/or embryos obtained from a specific patient or couple will be randomly distributed across two groups (test and control) and undergo one or more elements of an automated assisted conception laboratory workflow (for the test group) or a standard assisted conception laboratory workflow (for the control group). Before distributing the samples, an embryologist will slightly blur the vision of the samples so that their morphology can no longer be clearly assessed. Robotic automation may include any of the following steps: robotic sperm preparation, robotic oocyte selection and denudation, robotic sperm injection, automated embryo culture, and automated cryopreservation. The resulting embryos may be employed for embryo transfer.<br>|
| Active Comparator: Control group (routine manual ICSI workflow)<br> | Other: Routine Manual ICSI Workflow<br>* Routine Manual Icsi Workflow<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timing | Time to complete each automated procedure | 6 weeks from enrolment | 
| Efficiency | proportion of automated procedures achieving their goal | 6 weeks from enrolment | 
| Autonomy | proportion of completed procedure not requiring human intervention | 6 weeks from enrolment | 
| Walk-away time | time savings realized by an embryologist who is able to attend other duties while the robotic assistant is at work | 6 weeks from enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sperm survival and quality (seminogram) |  | 6 weeks from enrolment | 
| Proportion of oocytes fertilized |  | 6 weeks from enrolment | 
| Embryos survival and quality (by morphology assessment) |  | 6 weeks from enrolment | 
| Clinical pregnancy rates following embryo transfer |  | 8 weeks from enrolment |