Success after Preimplantation Genetic Testing for Aneuploidies (PGT-A)
PGT-A was offered for
Previous IUI failures
Previous IVF/ICSI failures
Previous history of repeated spontaneous miscarriages
Balanced Translocations and inversions
Advanced maternal age
Poor quality oocytes/embryos
We started offering the FISH technique for PGT-A in 2001 for five common chromosomal aneuploidies (13, 18,21, and sex chromosomes). Our clinical pregnancy rate was 28.1% per cycle and 35.9% per couple. Our clinical pregnancy rate with PGT-A/PGS for all 24 chromosomes is 42% per cycle and 51% per couple.
PGT-A by FISH for a Robertsonian Translocation (The first case from India, 2010):
A young couple married for four years with a history of 2 missed abortions after natural conception visited us with a request for PGT. The wife was found to be the carrier of a balanced Robertsonian translocation t(13;14). After IVF-ICSI, a single blastomere was biopsied from each of the embryos and FISH was set up in 2 rounds to check for aneuploidy of chromosomes 13 and 14. One normal embryo was obtained in that cycle and transferred at the blastocyst stage resulting in a successful pregnancy followed by full-term live birth—the first case from India for PGT-A for Robertsonian translocation.
PGT-SR by FISH for a Reciprocal Translocation (The first case from India, 2014):
A couple with a history of five early miscarriages due to a balanced reciprocal translocation t(6;19) in the wife was referred for preimplantation genetic testing for structural abnormality (PGT-SR) by fluorescence in situ hybridization (FISH). A Day 3 embryo biopsy was performed. FISH using centromere and subtelomere probes for chromosomes 6 and 19 was carried out. The embryos with unbalanced translocations were not transferred. The embryos which showed either balanced translocation or absence of translocation were transferred. Pregnancy was achieved in the same cycle itself and resulted in the birth of a healthy baby. This is the first baby after PGD for a reciprocal translocation in India.
We have offered PGT-SR using the FISH technique for various translocations where aCGH/NGS technique fails to detect the abnormality.
PGT-SR by FISH for inversion and cryptic translocation (The first report from India, 2016):
A couple with a history of recurrent miscarriages and implantation failures had karyotyping done in three laboratories which showed that the husband had an insertion or inversion of chromosome 12. On pre-PGT workup for inversion 12 by FISH, an additional anomaly of a cryptic translocation between terminal regions of one copy of chromosomes 9 and 12 each were detected in the husband. After PGT-SR on blastomeres, the normal and balanced embryos transferred at the blastocyst stage resulted in the birth of healthy twins conceived in the first cycle itself. First report from India for successful live births after PGT-SR for inversion and cryptic translocation.
PGT-SR by FISH for a complex chromosomal rearrangement involving a cryptic translocation (The first report from India, 2018):
A non-consanguinous Indian couple had a son with an unbalanced translocation t (16;17) detected after microarray. Prenatal diagnosis during the second pregnancy showed a similarly affected fetus. The husband was a carrier of a balanced translocation. We then recommended IVF-ICSI with PGT-SR by FISH as the terminal portions of the chromosomes were involved, whereas PGT-SR by aCGH was impossible. During pre-PGT workup with FISH probes, we found the involvement of 3rd partner chromosome 9 in the translocation, which was not picked up in the previous pregnancies or husband’s analysis by aCGH. After IVF-ICSI, trophectoderm biopsy at the blastocyst stage was carried out, and FISH was performed in 3 different rounds. The lady conceived after a frozen embryo transfer in the next cycle—the first report from India for PGT-SR by FISH for cryptic three-way translocation.
PGT-A by aCGH/NGS:
We offer PGT-A for all 24 chromosomes using aCGH/NGS technology. Our clinical pregnancy rate is 42% per cycle and 51% per couple. Our implantation rate is 53%.
PGT-M for Beta thalassemia
Beta thalassemia is one of the significant genetic disorders affecting the Indian population. Mutations in the beta-globin gene cause this disorder. When both parents are carriers of a mutation in the beta-globin gene, there are higher chances of having an affected child (autosomal recessive inheritance). We have several pregnancies following PGT-M for this disorder.
PGT-M for Beta thalassemia with HLA matched savior sib
A couple came to us with a daughter who was a beta thalassemia major and on blood transfusion for survival. The couple was carrier for beta thalassemia mutations and were interested to get a HLA matched savior sibling to cure their daughter’s disease through bone marrow stem cell transplant using PGT technology. The couple underwent 3 IVF-ICSI-PGT cycles to get one euploid beta thalassemia unaffected and HLA matched embryo. The mother conceived using this embryo delivered a normal healthy boy, the savior sib whose cord blood and bone marrow stem cells will be used in future to transplant to his beta thalassemia major sister.
PGT-M for Neurofibromatosis
A couple came to us where the male partner had symptoms of Neurofibromatosis Type 1. This was an autosomal dominant condition. This meant that a single altered copy of the gene was sufficient to cause the disease in the future baby. With multiple IVF cycles, sufficient embryos were collected, and PGT-M was used to select an unaffected embryo for successive transfer. The lady delivered a male child free of Neurofibromatosis.
PGT-M for Hereditary predisposition for BRCA1 mutation:
A couple came to our clinic with a history of 3 recurrent miscarriages through IUI and IVF treatment. The maternal side of the female partner had a strong history of ovarian and breast cancer. Her grandmother and 2 of her maternal aunts had breast cancer, her mother had ovarian cancer, and her maternal uncle had prostate cancer. She was found to be heterozygous for the BRCA1 mutation. As this was an autosomal dominant condition, there was a high risk of having cancer in future progeny. Hence we counselled the couple and offered PGD for BRCA1 mutation through the ICSI/PGT-M procedure. After the transfer of mutation-free embryos, the woman carried a twin pregnancy and gave birth to two normal male children at full term. Since then, we have had several live births for this disorder.
PGT-M for Tay-Sachs disease
Tay–Sachs disease is a genetic disorder that destroys nerve cells in the brain and spinal cord. Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15. It is inherited from a person’s parents in an autosomal recessive manner. A non-consanguineously married couple came to our clinic for PGT. Their child died due to Tay- Sachs disease. Pre-PGT workup was carried out, and the couple was found to be mutation carriers. Within 3 IVF cycles, sufficient embryos were collected, and PGT-M with PGT-A was carried out to select cytogenetically normal and unaffected embryos for successive transfer. The woman delivered a normal healthy child free of disorder.
PGT-M for Propionic Acidemia
Propionic Academia is an autosomal recessive disorder where the parents are carriers of the mutation. A consanguinously married couple came to our clinic whose previous child passed away due to a homozygous mutation in the PCCA gene. Pre-PGD workup was carried out to confirm the mutation. Two IVF cycles created sufficient embryos for PGT-M with PGT-A. Euploid unaffected embryo transfer resulted in ongoing pregnancy. The woman delivered a normal healthy child free of disorder.
PGT-M for Duchenne Muscular Dystrophy (DMD)
A couple came to our clinic with a history of DMD in the family. It is an X-linked disorder where 50% of females can be carriers, and 50% of males will be affected. Her brother passed away due to DMD, and she was found to be a carrier of DMD mutation. A sufficient number of embryos were obtained through multiple cycles, and PGT-A followed PGT-M for DMD. We have had several pregnancies after PGT-M for this condition.