EAST 501 Lecture 12: 563 Lec 12 - Feb 5
21 Jun 2018
School
Department
Course
Professor
Feb 5th – Lec 12 Robaire
Presentation: Male infertility - ICSI
OUTLINE:
1. What is ICSI, and how often is it used?
2. Are there risks associated with using ICSI?
3. Two alternative to ICSI: IMSI and ROSI
4. How can ICSI be improved?
WHAT IS ICSI
-Form of assisted reproductive techniques (ART)
-Intracytoplasmic sperm injection
-Single sperm injected into oocyte
-Bypasses steps in fertilization
-First successful birth – January 14, 1992
oprocedure was discovered a few years before this
-PZD: spermatozoa injected interior to zona pellucida (use until 1988)
-SUZI: spermatozoa are injected into Perivitelline Space (used until 1989)
odoesn’t go as deep into the oocyte
ICSI: A BRIEF HISTORY
-lab in Belgium
-technician made a mistake left the mistake in the incubator
oallowed it to continue to grow – this was a decision made by the lab
-injection directly into the oolema, surpassing the zona layer
-resulted in fertilization of oocyte
-never approved by ethics board as it was a mistake not the intention of the technician
-no literature published about the discovery
GLOBAL USE OF ICSI
-infertility is not limited to developed countries
-data from developing countries is lacking all data presented is from developed countries
-ICSI use higher than proposed male-factor-infertility rates
-all this data is from developed countries
-in developing countries some of the data may be less reliable due to the stigma associated with infertility
GRADUAL INCREASE IN THE USE OF ICSI IN CANADA
-ICSI has become a front-line treatment often included in the very first cycles of IVF
-2005: 60% of IVF cycles with ICSI
-2006: 64% of IVF cycles with ICSI
-2007: 68% of IVF cycles with ICSI
-2008: 71% of IVF cycles with ICSI
-use of ICSI in Canada has increased 11% in 4 years percentage takes into account the increase in the number of
clinics
ICIS USE BASED ON INFERTILITY DIAGNOSIS
Year Diagnosis % of all IVF cycles % of all ICSI cycles
2004 Male factor 8.8 54.5
1
find more resources at oneclass.com
find more resources at oneclass.com
Feb 5th – Lec 12 Robaire
Presentation: Male infertility - ICSI
Tubal factor 37.7 21.1
2008 Male factor 31.9 95
Tubal factor 10.4 30
-now use ICSI >95% of the time in the IVF protocol (male factor)
-Tubal factor = female factor of infertility
othis is the reason that IVF was pushed to be developed
o~18% increase from 2004-2008 in ICSI
OVER-USE OF ICSI IN NON-MALE FACTOR INFERTILITY
-RCT in the UK 415 couples at 4 UK centers (awaiting conventional IVF) – 435 treatment cycles
-randomly assigned IVF or ICSI (IVF 224; ICSI 211)
-The implantation rate was higher in the IVF group than in the ICSI groups (30% vs. 22%)
-mean associated laboratory time: significantly increased more of the couple’s time that they are putting into
the treatment (when using the ICSI)
oIVF: 22.9 minutes
oICSI: 74 minutes
-No advantage with use of ICSI for clinical outcome in cases of non-male-factor infertility
US NATIONAL TRENDS FOR USE OF ICSI
-all cycles: 36.4% in 1996 to 76.2% in 2012
oall cycles experienced an increase
-male factor infertility: 76.3% to 93.3%
-non-male factor infertility: 15.4% to 66.9%
othis is the most significant increase
oif it not an useful in female infertility,
why is this the largest increase?
REASONS FOR THE INCREASED USE OF ICSI
-Medically related factors:
odecline in semen quality
ohigher proportion of subfertility
oincreased parental age
orate of testis cancer
-Non-medically related factors:
ostates with insurance coverage had a higher ratio of ICSI after diagnosis of male-factor infertility
oprivatization of ART clinics in both the US and CANADA (becoming privatized in CAN)
ore-coup costs of establishing the technique in their labs, and incorporate it in the clinical management
if you do have the ability of providing ICSI you have the machinery and the technicians $$
THE GUARNTEE OF FERTILIZATION USING ICSI
-EXP: prospective cohort study done in Austria small sample size
oGroup A: 22 patient – unexplained infertility
No significant different in the fertilization rate/oocyte
5/22 failure of fertilization with IVF
0/22 failed to achieve fertilization with ICSI
oGroup B: 24 patients – borderline semen
2
find more resources at oneclass.com
find more resources at oneclass.com
Feb 5th – Lec 12 Robaire
Presentation: Male infertility - ICSI
significant difference in fertilization rate/oocyte
11/24 failure of fertilization with IVF
0/24 failed to achieve fertilization with ICSI
oConclusion: 22.7% of unexplained infertility and 45.8% of patients with borderline semen would have
experienced total failure of fertilization
without the ICSI protocol many of the patients would not been able to have their own baby
FINANCIAL IMPLICATIONS: ICSI COMPARED TO STANDARD IVF
-IVF: $7,750-12,250CAD ($250 for semen analysis, $2500-7000 for medication and $5000 for the IVF)
-IVF/ICSI: $10,000-17,000 ($200 for orientation, $5000 IVF, medication $2,000-7,000, $750 freezing embryos)
-ICSI itself costs ~$1500
THE ICSI INJECTION IS DAMAGING TO THE GAMETES
-ICSI = gross manipulation of cells compared to IVF much more of a physical manipulation
-ICSI bypasses the natural physiological interactions between the sperm and the egg = effects on the sperm and
egg
-this damages the egg by:
ointroducing foreign matter into the cell, such as ROS or culture medium
ocausing physical trauma by piercing the cell with the needle damaging the meiotic spindles
oinjecting allows foreign/exogenous material to get into the cell (can be culture medium or ROS)
ROS usually contained inside the cell
oegg cells usually have cumulus cells around them that are protective to egg
in ICSI the cumulus cells are not there and therefore any of the ROS damage is unable to be
rescued
othe sperm are also damaged by the injection process
lack of physical interaction with oocyte
ligands aren’t binding to receptors and cell signaling
pathways are happening
this results in abnormal sperm head decondensation
ICSI RISK ASSOCIATED WITH SELECTION OF GAMETES
-in normal cases you must have competent sperm in order for fertilization to occur you cannot have damaged
sperm interacting with an egg (usually)
-in ICSI: going around the natural fertilization subfertile sperm can be used in ICSI
-DNA damaged sperm
ogenetic anomalies or structural defects, such as fragmented DNA
otypically subfertile due to DNA damage
otelomere damage when the sperm is frozen due to lack of cryoprotection especially due to lack of
histones
-Sperm mitochondrial DNA
-Fertilization of anomalous female gametes
opoor eggs can also be selected
ICSI CAN BE DAMAGING IN ANIMAL MODELS
-DNA damaged sperm can result in (IN MICE):
oearly embryo death
3
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
First successful birth january 14, 1992: procedure was discovered a few years before this. Pzd: spermatozoa injected interior to zona pellucida (use until 1988) Suzi: spermatozoa are injected into perivitelline space (used until 1989: doesn"t go as deep into the oocyte. Global use of icsi infertility is not limited to developed countries data from developing countries is lacking all data presented is from developed countries. Icsi use higher than proposed male-factor-infertility rates all this data is from developed countries in developing countries some of the data may be less reliable due to the stigma associated with infertility. Gradual increase in the use of icsi in canada. Icsi has become a front-line treatment often included in the very first cycles of ivf. 2008: 71% of ivf cycles with icsi use of icsi in canada has increased 11% in 4 years percentage takes into account the increase in the number of clinics.
