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Pre-implantation Genetic Screening:A four-year experience
Mehdi Totonchi, PhDGenetics Department, Royan Institute
Outlines
• IVF
• Embryo Biopsy
•PGD/PGS
•Array-CGH technology
•Our Results in PGS lab (2015-2019)
• The major goal of ART is to produce healthy and viable offspring.
• The birth of the first ‘test-tube baby’ Louise Brown, in 1978 was a landmark advance for reproductive medicine, setting the stage for a new area of medicine.
Infertility Treatment: Forty years of ART
1. Polar Body Biopsy
2. Cleavage-stage Biopsy
3. Trophectoderm Biopsy
Embryo Biopsy
Disadvantages:1. Won’t detect aneuploidies from paternal
contribution2. Won’t detect mitotic errors3. Requires two samples tested per cycle
1. Polar Body Biopsy
Advantages:1. Doesn’t remove any material from embryo2. Only legal option in some countries3. Sufficient time for analysis before transfer
Gresham et. al. 2008, Nat Rev Genet
Advantage:
1. Practiced most widely
2. Test both maternal and paternal contribution
3. Sufficient time for analysis before transfer
4. Applicable for most patients
Disadvantages:1. Mosaicism is most common at this stage2. Viability of embryo may be affected3. ADO
2. Cleavage-stage Biopsy
Gresham et. al. 2008, Nat Rev Genet
Advantages:
1. Less mosaicism than day-3
2. Reducing ADO and improving sensitivity
3. Test both paternal and maternal contribution
4. Little impact on viability of embryo
Disadvantages:1. More time pressured in context of fresh transfer2. No appropriate for patient with few blastocysts
Gresham et. al. 2008, Nat Rev Genet
3. Trophectoderm Biopsy
1) PGD: Preimplantation Genetic Diagnosis, 1990
Techniques may be used to enable people with specific inherited conditions in their family to avoid passing them onto their children.
• Known single gene disorders
• Known chromosomal abnormalities
• Sex selection for X-linked disorders
2) PGS: Preimplantation Genetic Screening,Embryos from IVF patients can be screened for chromosomal abnormalities before being transferred to the uterus as a method of embryo selection.
• Couples undergoing IVF at risk for aneuploidy • Maternal age > 35-year old• Prior trisomic conception• With recurrent pregnancy losses• Prior failed IVF cycles (>3 prior embryo transfers with high quality, morphologically normal embryos)
Embryo testing can be conducted in two ways
17
19
17
19
FISH:100-500 kb probesNeeds a prior information
Array-CGH:~50 KbGlobal survey of genome
Cytogenetic tools: FISH vs. aCGH
Normal male embryo
Normal female embryo
Abnormal case
Patients to be subjected of PGS by array-CGH
Total Embryos: 875Normal Embryos: 221 (25.2%)
2015- 2019
(51/147) (51/213)
34.93%
23.94%
Clinical Pregnancy Rate in ART failure & RM
40% 40%
29.03%
13.33%
Clinical Pregnancy Rate: One- vs. Two-Embryo Transfer
(19/90) (28/52)
21.11%
53.85%
Clinical Pregnancy Rate: Fresh vs. Frozen
(14/82) (14/58) (33/131) (33/88)
17.07%
24.13%25.19%
37.5%
Blastomere vs. TE biopsy
Embryo quality on the day of biopsy vs. pregnancy
Embryo quality on the day of transfer vs. pregnancy
Poor = before compactionGood = Compaction and MorulaExcellent = Early-, mid-, and expanded- blastocystN.D. = Not Determined
Detected chromosomal abnormality in ART failures
Origin of non-disjunction in human autosomal trisomies
Adapted from Nicolaidis & Petersen (1998)
64% of abnormal embryos are not detected by FISH
463
165
aCGH FISH
(Chr. 13
18
21
22
X/Y
Sensitivity of FISH vs. aCGH
Conclusion
• Age in ART failures and RM.• Fresh vs. Frozen embryo transfer.• One- vs. Two-embryo transfer.• Day-3 versus Day-5 biopsy.• Chromosomes 1, 16 and 19 as major abnormality in ART failure & RM.• Sensitivity of FISH vs. aCGH.
Acknowledgments:
Genetic Group:Hamid Gourabi, PhD
Navid Almadani, MD
Babak Baba Abbasi,
Morteza Kimiaei,
Embryology Group:Mojtaba Rezazadeh, PhD
Popak Eftekhari, PhD
Gynecology Group:Dr. Madani, MD
Dr. Ashrafi, MD
Don Leigh, PhD
Australia
Andrology Group:Dr. Sedighi Gilani, MD
There is a Life BehindEvery PGT
Thanks for your attention
