PREIMPLANTATION GENETIC SCREENING (PGS)
PGS refers to techniques where embryos from presumed chromosomally normal genetic parents are screened for aneuploidy. PGS enables the checking of all 23 sets of chromosomes including X and Y in each embryo so that only normal embryos are selected for transfer into the womb.
Example A : a pair of chromosome 21 (normal) or
three chromosomes of 21 (Down’s Syndrome)
Example B : abnormalities of chromosome 23 such as :
- XO (abnormal girl – Turner’s Syndrome),
- XXY (abnormal boy – Klinefelter’s) compared to
- XX (normal girl) or
- XY (normal boy)
Who should consider PGS?
You should consider PGS if:
- You are a woman over 35
- You have experienced recurrent pregnancy loss
- You have experienced several failed IVF cycles
- You have had a prior pregnancy with a chromosome abnormality
- Your partner has severe male factor infertility
- You want to improve your IVF pregnancy rate
Documented High Pregnancy Rates
In AFC, by applying PGS (24sure), only embryos with the correct copy number of chromosomes are transferred in IVF, hence improving pregnancy rates.
PREIMPLANTATION GENETIC DIAGNOSIS (PGD)
PGD refers specifically to when one or both genetic parents has a known genetic abnormality and testing is performed on an embryo to determine if it also carries a genetic abnormality. PGD is recommended when couples are at risk of transmitting a known genetic abnormality to their children. Only healthy and normal embryos are transferred into the womb, thus diminishing the risk of inheriting a genetic abnormality and late pregnancy termination.
Who should consider PGD?
You should consider PGD if:
- You and/ or your partner are carriers of single gene defects that may affect the health of a future child. The most common single gene disorder in China & Malaysia is α-Thalassaemia & β-Thalassaemia. Other single gene disorders include Breast Ca I (BRCA I), Breast Ca II (BRCA II), Huntington’s disease, Cystic fibrosis, Fragile-X syndrome, etc.
- You have a family history of X-linked disorders
- You and/ or your partner has a chromosome rearrangement (ie. translocations), which can cause implantation failure, recurrent pregnancy loss, or mental or physical problems in offspring
The following outlines our success rates in 3 categories – Blastocyst Transfer Program, IVF with and without MaCGH and Frozen-thawed Cycles.
Blastocyst Transfer Program
Fresh blastocyst transfer AFC yields high clinical pregnancy and implantation rates and avoids higher order of multiple pregnancies. The table below shows a review of AFC’s Blastocyst Transfer Program from July 2011 to June 2013 (23rd Congress of the Obstetrical & Gynaecological Society of Malaysia, 2014, Malaysia).
IVF with and without MaCGH
IVF failure is often due to unknowingly transferring embryos which are chromosomally abnormal. By applying MaCGH (24sure), only embryos with the correct number of chromosomes are transferred, hence improving pregnancy rates. The graph below shows the clinical pregnancy rates (CPR) for patients with and without MaCGH*.
Since July 2013, AFC had started using a new embryo freezing and thawing method (Cryotec Method, Japan) and it had led us to achieve a 100% post-thaw survival rate resulting in high clinical pregnancy rates. The table below shows the clinical outcome of AFC’s frozen-thawed cycles from July-February 2014 (23rd Congress of the Obstetrical & Gynaecological Society of Malaysia, 5-8 June 2014, Malaysia).
Donor Egg Program
Egg donation makes pregnancy possible for women who might not otherwise be able to get pregnant using their own eggs. AFC has one of the best egg donation programs in Malaysia. Regardless of fertility history, all recipients of all ages have almost an equal chance of success. The following table shows the clinical outcome in our Donor Egg Program in 2011 (Leong et al. Oocyte donation outcome at Alpha International Fertility Centre. BJOG 2012;119:Supplement 1 page137).
Alpha Fertility Centre is proud to announce the WORLD’s 1st successful pregnancy and live birth following Preimplantation Genetic Diagnosis MicroArray Comparative Genomic Hybridisation for Chromosome Inversion with fresh embryo transfer. This achievement was presented at the 11th International Conference on Preimplantation Genetic Diagnosis, Austria, May 2012.
Birth after Preimplantation Genetic Diagnosis (PGD) using Microarray Comparative Genomic Hybridisation (MaCGH) for chromosome inversion (1) (p35q42)
Colin S. S. Lee, S.Y. Low, W.Y. Leong
Introduction: A 37 year-old patient, whose husband has a balanced inversion of chromosome 1 (p35q42.1), had a history of 2 spontaneous miscarriages. Following PGD with MaCGH, 2 embryos with normal/ balanced chromosomes were transferred fresh in the same cycle, resulting in delivery of a live child.
Material & Methods: Twenty-two embryos were obtained following ICSI of which 12 had microarray copy number analysis PGD. Samples and reference DNAs were amplified and labelled according to manufacturer’s (BlueGnome) specifications. Labelled sample and reference DNAs were applied to microarrays (24Sure+) and co-hybridized overnight. Microarray slides were washed, dried, scanned and analysed using BlueFuse Software (BlueGnome), revealing whole and partial chromosome losses and gains, including unbalanced inversions.
Results: Results were obtained for 10 of 12 samples. Of the diagnosed samples, 5 were found to be affected with unbalanced pericentric inversion on chromosome 1, with or without other chromosome abnormalities. Three embryos with normal/ balanced chromosome 1 had other chromosome abnormalities. Only 2 embryos were found to have the complete chromosome complement, though a balanced inversion cannot be excluded. These 2 embryos were transferred on day 4 after oocyte pick-up. Both embryos implanted. One split into monozygotic twins which died at 17 weeks with associated twin-to-twin transfusion. The dead monozygotic twins were delivered at 25 weeks, while the live baby was delivered at 26 weeks and 2 days weighing 775 grams, requiring ventilation. As at the time of writing, the baby had been extubated and doing well. Preliminary karyotyping from placental tissue of the live child shows a normal chromosome complement with no inversion (46, XY). Karyotyping from placental tissue of the dead twins showed a normal chromosome complement with a balanced inversion of chromosome 1 i.e., 46, XX inv (1) (p35q42).
Conclusion: Clinical application of PGD microarray copy number analysis with fresh embryo transfer has been used successfully to detect unbalanced chromosome inversion, resulting in the live birth of a normal child.
C.S.S. Lee, S.Y. Low, W.Y. Leong. (May 2012). Birth after Preimplantation Genetic Diagnosis (PGD) using MicroAarray Comparative Genomic Hybridisation (MaCGH) for chromosome inversion (1) (p35q42). Reproductive BioMedicine Online, Vol.24 Suppl, S61, ISSN 1472-6483
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