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IMSI - Stephen Harbottle imsi workshop presentation march 2011 - IMSI takes ICSI to the next level. ICSI involves injecting sperm directly into your egg, before we transfer it into your womb. During IMSI a very high power microscope to magnify the sperm around 7000 times. This allows us to see in great detail how the sperm looks and to select the best sperm for the ICSI procedure. IMSI is a very new development and is showing promise for a specific group of patients. Once the best sperm has been selected the IMSI procedure is carried out in exactly the same way as ICSI.
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Cambridge IVFCreating your future
MRMC 2011
IMSI Workshop; use of the RI System
Stephen J. HarbottleLead Clinical Embryologist
Cambridge IVFCreating your future
MRMC 2011
Introduction
• ICSI is a well established technique– First pregnancy reported in 1992
• IMSI is a natural extension to ICSI– MSOME to actively select sperm for injection– Use of high power microscopy and digital imaging
• Optimise procedure to minimise environmental stress• Identify appropriate IMSI patient group
– Maximise success rate
Cambridge IVFCreating your future
MRMC 2011
MSOME
• Motile Sperm Organelle Morphology Examination (MSOME) is aimed to define the state of 6 sub cellular organelles;– Acrosome, Post Acrosomal lamina, Neck, Mitochondria, Tail, nucleus
Cambridge IVFCreating your future
MRMC 2011
Defining the ‘Normal Sperm’
• Criteria for Morphologically Normal Nucleus– Smooth, symmetric, and oval configuration
• Shape– Average length 4.75 ± 0.28 μm– Long > 5.31 μm | Short<4.19 μm– Average width 3.28 ±0.20 μm– Narrow < 2.88 μm | Wide >3.68 μm
• Content– No extrusion or invagination of the nuclear chromatin mass– No vacuoles with diameter greater than 0.78 ±0.18 μm
Cambridge IVFCreating your future
MRMC 2011
Significance of Nuclear Normalcy
• Normalcy of the sperm NUCLEUS was found to be a significant factor in pregnancy occurrence by ICSI procedure
Bartoov , B et al. Fertility and Sterility. 2003 Dec;80(6)
IMSI ICSI
Pregnancy Rate (%) 50% 25%
Abortion Rate (%) 13% 33%
Cambridge IVFCreating your future
MRMC 2011
Examples of Vacuolation
Cambridge IVFCreating your future
MRMC 2011Grade Description
I No Vacuolation
II <2 Small Vacuoles
III>2 small or >=1 large
Vaculoes
IVLarge Vacuole and
other head abnormalities
Vanderzwalmen et al, 17(5): 617-627, 2008
Cambridge IVFCreating your future
MRMC 2011
IMSI - Technical Development
• Intracytoplasmic Morphologically Selected Sperm Injection (IMSI)
• Clinical use first reported in 20011
– Oil Immersion x150 Lens1, DIC Illumination1
– Optimum magnification for IMSI; x6000 - x70001,2,3
• Use of oil and DIC microscope not optimal for clinical practice– Alternative oil free digital system developed to improve IMSI
efficiency without compromising performance & results 1 Souza Setti, A et al. Reprod Biomed Online. 2010 Oct;21(4):450-5
2 Nadalini, M et al. Reprod Biomed Online. 2009;19 Suppl 3:45-55
3 Ai, L et al. Zhonghua Nan Ke Xue. 2010 Sep;16(9):826-9
Cambridge IVFCreating your future
MRMC 2011
IMSI – The RI System Hardware
IMSI Workstation Digital Camera Objective
Cambridge IVFCreating your future
MRMC 2011
Cambridge IVFCreating your future
MRMC 2011
IMSI UK Update – Study #1
• Patient Group– ICSI Failure (>3 cycles)– Repeated miscarriage– Teratozoospermia (<4% Normal Forms)– Poor blastocyst development
• RI IMSI system– Magnification x6300 (x60 air objective with digital zoom)
• Methodology– All sperm selected and collected before oocyte injection
commenced
Cambridge IVFCreating your future
MRMC 2011
Results
Chau et al, Fertility 2011
Cambridge IVFCreating your future
MRMC 2011
IMSI UK Update – Study #2
• Patient Group– Patients with more than 6 eggs had ICSI & IMSI
• Sperm graded prior to injection;
• RI IMSI system– Magnification x6300 (x60 air objective with digital zoom)
Grading Category Description
Grade I No Vacuolation
Grade II <2 Small Vacuoles
Grade III >2 small or >=1 large Vaculoes
Grade IV Large Vacuole and other head abnormalitiesVanderzwalmen et al, 2008
Cambridge IVFCreating your future
MRMC 2011
Results
Best et al, Fertility 2011
(n=114) (n=108)
Grade Description
I No Vacuolation
II <2 Small Vacuoles
III>2 small or >=1 large
Vaculoes
IVLarge Vacuole and other
head abnormalities
Cambridge IVFCreating your future
MRMC 2011
IMSI – Our Plans
• Clinical IMSI to roll out in June 2011• Partnership with Research Instruments
– RI system has been demonstrated to be the most user friendly, cost and time effective system for clinical use
– Randomised prospective treatment study to contribute to UK IMSI dataset
– Prospective clinical study to assess the effect of sperm preparation technique
– Further work on sperm quality (grade) and its correlation to rates of fertilisation, cleavage, embryo development & implantation
Cambridge IVFCreating your future
MRMC 2011
Optimising the IMSI procedure
• Use PVP to slow sperm and aid analysis and capture
PVP MSOME Selection (5µl)
PVP Injection (5µl)
Oocyte Injection (5µl)
• Use of Micropipette to trap a single good prognosis sperm for detailed analysis prior to selection
• Collect and store good prognosis sperm prior to loading oocytes into the injection dish
Cambridge IVFCreating your future
MRMC 2011
The Isolator ConceptThe Isolator Concept
• Isolator units linked together with ‘pass through’ incubators linking units together
• Workspace heated, gassed and humidified to user specification
• Built in HEPA and carbon filtration system‒ Effective against particulates and VOC’s
• Gametes and embryos are never exposed to suboptimal conditions
• Significant increase in clinical treatment results
Cambridge IVFCreating your future
MRMC 2011
Summary
• MSOME is a valuable clinical tool in the assessment of male factor infertility
• IMSI is an effective treatment option for patients following failed ICSI treatment
• IMSI may confer some protection against miscarriage when compared to ICSI
• IMSI may improve success in cases of unexplained infertility
• Optimise IMSI technique to reduce gamete stress• Develop systems to maintain biological conditions
Cambridge IVFCreating your future
Thank you for your Attention
Terima Kasih