In Vitro Fertilization to In Virtual Fertilization Notes

In Vitro Fertilisation (IVF)

  • Overview of the IVF process:

    • Ovarian hyperstimulation.

    • Transvaginal oocyte retrieval.

    • Sperm preparation.

    • Sperm and egg incubation.

    • Embryo culture.

    • Embryo transfer.

    • Pregnancy.

    • Repeat step 6 if necessary.

Embryology Lab

  • Insemination Techniques:

    • ICSI (Intracytoplasmic Sperm Injection): The best sperm cell is selected by the embryologist and injected into the egg using a needle.

    • IVF: Sperm cells are added to the egg, and one sperm enters the egg on its own.

Embryo Development

  • Day 1: Fertilisation status is checked.

  • Days 2-5: The embryo grows and divides.

  • Day 4: The embryo compacts and contains 16-32 cells.

  • Day 5/6/7: Blastocyst stage.

    • Not every embryo reaches the blastocyst stage.

    • Aneuploidies can prevent growth (insufficient genetic information).

Preimplantation Genetic Testing and Trophectoderm Biopsy

Embryo Grading - The Gardner Grading

  • Performed at the blastocyst stage.

  • ICM (inner cell mass) and TE (trophectoderm) are graded based on size and compaction.

  • Grading scale:

    • 6AA being the best.

    • 1CC being poor.

    • Categories include: 6AA, 6AB, 6BB, 6BC, 6CC, 5AA, 5AB, 5BB, 5BC, 4AA, 4CC, 3AA, 2AA, 2AB, 2BB, 2BC, 2CC, 1AA, 1AB, 1BB, 1BC, 1CC

    • Embryos can be classified as good, best, poor or discard based on the grading.

'In Silico' Fertilisation and Embryo Grading

  • Can technology improve outcomes compared to humans?

    • Predict blastocyst formation.

    • Predict euploid embryos.

    • Predict implantation/live birth rate.

Time-Lapse Imaging

  • New annotation system tracks:

    • Cleavage pattern.

    • Number of cells after each division.

    • Blastocyst formation.

  • Examples of tracked events:

    • Fertilisation.

    • PB2 extrusion (2:40).

    • PN appearance (7:50).

    • 2PN (12:15).

    • 2PB Clear (12:15).

    • Syngamy (20:40).

    • 1st division (22:40).

    • 2 cell (27:30).

    • 2nd division (35:15).

    • 4 cell (38:05).

    • 3rd division (47:10).

    • 8 cell (62:40

Artificial Intelligence (AI) in IVF

  • Definitions:

    • AI: A program that can sense, reason, act, and adapt.

    • Machine Learning: Algorithms that improve performance with more data exposure.

    • Deep Learning: A subset of machine learning using multilayered neural networks.

Machine Learning

  • Training process:

    • Input raw data.

    • Algorithm processes data.

    • Model training occurs.

    • Output is generated by the trained model.

KID Score

  • Example of a traditional machine learning algorithm for embryo grading.

  • Based on:

    • Number of pronuclei.

    • tPNftPNf

    • t2t2

    • t3t3

    • t5t5

    • t8t8

  • Predicts implantation potential.

Deep Learning Models

  • CHLOE EQ as an example.

Data-Driven Approaches to IVF

  • Turning uncertainty into data-driven approaches.

  • Avenues: Integrating Digitalisation + AI at every step of the patient journey.

End-to-End Digitalisation

  • Components:

    • Pathology/Genetics labs, Electronic data capture (microscopy, witnessing, sperm/egg images).

    • Embryologist remote access, Clinical app, Patient app with payment & consent.

    • AI for oocyte & sperm assessment.

    • Fully integrated platform, Drugs dispensing, AI robotics, Cryostorage management.

    • Ultrasound machine (follicular scans, embryo transfer).

    • KPI (Key Performance Indicator) tracking.

AI-Driven Diagnostics

  • CASA sperm assessment.

  • 2D & 3D pelvic scan.

  • Hormone + genetic profiles.

  • Questionnaire + wearables.

Issues with AI-Based Embryo Selection Tools

Explainable AI (XAI)

  • Opening the 'black box' of AI to understand how decisions are made.

  • Provides annotations and explanations for AI outputs.

Sex Bias in Embryo Selection

  • Conflicting evidence regarding sex differences in developmental timings.

    • Some studies suggest XX embryos develop slower due to X chromosome inactivation.

    • Other studies find no differences.

    • References: Alfarawati et al., 2011, Serdarogullari et al., 2014, Carrasco et al., 2022

Methods for Investigating Sex Differences

  • N=1411 embryos with time-lapse and known sex information through PGT-A at blastocyst stage.

  • Three different embryo grading tools were used to compare outcomes between XX and XY embryos:

    1. Manual morphological grading of the blastocyst

    2. Traditional machine learning approaches (KID Score)

    3. Modern deep learning approaches (Chloe EQ)

Results of Sex Differences in Embryo Selection Algorithms

  • XY embryos received higher grades using manual grading and the KID score, but not using CHLOE EQ.

  • XY embryos (2.809 ± 0.628, N=669) received higher TE grades than XX embryos (2.656 ± 0.623, N=616) (U=179584, p<0.00001).

  • No difference observed in aneuploidy rates overall between XX (73/642) and XY (75/692) embryos (χ2\chi^2=0.0958, p=0.757).

  • KID Score differences in aneuploid XY vs XX.

Virtual Reality (VR) in Fertilisation

  • Immersion into a new virtual world using special headsets creating endless surroundings (Moon, island, virtual lecture auditorium, virtual lab).

Getting Started with VR

  1. Create your avatar.

  2. Access the virtual space through a device.

VR in Medicine and Surgery

  • Process:

    1. Image Acquisition (CT/MRI)

    2. Image Segmentation

    3. Importing the 3D model into the VR environment

Applications of VR in Medicine

  • Pre-op and post-op visualizations.

  • Double-Outlet Right Ventricle Repair.

  • Stent Implantation.

  • Siamese Twins Separation.

Hosting Events or Live Training in VR

Virtual Clinic

  • Patients can meet doctors/embryologists remotely in real-time.

  • Access patient records and embryology images in 3D.

  • Environment can replicate an actual IVF clinic.

Virtual Reality (VR) Software for ICSI & Embryo Biopsy

  • Technical training tool.

Mixed Reality (XR)

  • Physical reality and digital content are combined.

  • Digital 3D objects are superimposed on top of the ‘real’ reality.

Applications of Mixed Reality

  • Lab checklists.

  • Training and SOPs (Standard Operating Procedures).

  • Patient education.

The Virtual Hospital

  • Examples: AIMEDIS

Benefits of Virtualization

  • Virtual clinic.

  • Virtual patient interaction.

  • 24-h clinic.

  • Moving fertility care beyond clinic walls.

  • Saving costs.

  • Increasing patient satisfaction.