- Comparative Genomic Hybridization - aCGH
The Nilo Frantz Reproductive and Research Center provides a new exam technique for embryos which can double the chances of a successful artificial fertilization. It is called Comparative Genomic Hybridization (aCGH). The team in the Embriology Laboratory is working to develop a technique to analyze all 23 pairs of chromosomes in order to diagnose many genetic abnormalities which cannot currently be identified. The Center is a pioneer in the South of the country in terms of Preimplantation Genetic Diagnosis (PGD) with lasers, which can be used to genetically analyze embryos with the FISH (Fluorescence in situ hybridization) method before transferring it to the uterus. The PGD allows us to identify anomalies in some of the chromosomes, such as 13, 16, 18, 22, X, Y and 21, the last of which is responsible for Down's syndrome. The hybridization technique aims to increase the chances of pregnancy, especially in women over 35 years old, an age range in which the chances of getting pregnant decrease and the chances of genetic abnormalities, malformations and miscarriages increase.
This process will radically improve pregnancy rates in the near future. The new hybridization technique allows us to verify the 46 chromosomes in the pre-embryos from the 5th to 6th day after fertilization. Thus, we can transfer only the unaffected embryos to the uterus of the future mother. These cells are tested for different genetic illnesses - such as cystic fibrosis, Duchene muscular dystrophy and Huntington's disease. The analysis can only be done with couples who choose to have in vitro fertilization with preimplantation genetic diagnosis (PGD). With PGD the embryos are evaluated before they are transferred to the mother's uterus (before gestation).
Essentially, there are two laboratorial components in PGD. The first is related to collecting the material that will be analyzed, which is obtained through biopsy of an embryo. The second is the diagnostic test itself, which is usually done through two methodologies: polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH). As a general rule, FISH is used for chromosomal defects and PCR is used for genetic defects. PGD has been successfully applied to identify 30 monogenic diseases, as well as detect chromosomal imbalances in families with a history of chromosomal translocations. Learn more about the recommendations and main diseases that can be diagnosed with PGD.
- ICSI and high magnification ICSI
The chances that a couple will get pregnant depend on a series of factors, especially the quality of the embryo that is formed and whether it was a natural or in vitro fertilization cycle.
Infertility affects nearly 15% of couples in the reproductive age range. Estimates show that in 50% to 60% of cases there are varying degrees of problems with the male reproductive system. The quality of the embryo is directly related to the egg and the sperm that fertilize it. Normally, the sperm chosen for the intracytoplasmic sperm injection (ICSI) was evaluated in a common microscope, the same kind that is used in doctor's offices, which amplifies images up to 400 times.
A new procedure for treating infertility has emerged. It is called IMSI (Intracytoplasmatic Morfologically Select Sperm Injection), Super ICSI or high magnification ICSI. It consists of a series of high resolution lenses coupled with a computer that has the capacity to amplify the image up to 16,000 times, allowing the identification of small details of the head, neck and tail of the sperm. This technique is increasing pregnancy rates and decreasing the number of miscarriages.
See the stages
Choosing the best sperm
Sperm is selected using a microscope that can amplify an image up to 400 times.
In 2003, Israeli researchers developed a lens system that is capable of identifying small details on sperm.
Vacuoles in the heads of sperm, which are only visible with Super ICSI technology, are correlated with DNA abnormalities, and thus lower pregnancy rates.
A high resolution microscope than can magnify an image 8,500 to 16,000 times was recently developed. It allows us to evaluate the details of the sperm.
- IVM - In Vitro Maturation
Nilo Frantz Reproductive and Research Center is a pioneer in the country in developing a new fertilization technique called in vitro maturation (IVM), recommended for women who have the disease and cannot receive high doses of hormones. From the birth of the first baby in August 2008, to the first trimester of 2010, nine babies have been born with the help of this technology.
IVM is a safe option for infertility treatment in patients with polycystic ovary syndrome when there are signs of fertilization in either the male or female.
- PGD - Preimplantation Genetic Diagnosis
Preimplantation Genetic Diagnosis, more commonly known in Brazil as embryo biopsy or PGD, is a procedure in which a small biopsy is performed and embryos that carry genetic disorders are identified so only healthy embryos are transferred to the mother's uterus. This is beneficial for couples at high risk for certain diseases. Researchers from a number of different countries have attempted to perfect the technique in order to reduce the margin of error in the diagnosis of genetic diseases and increase success rates for in vitro fertilization.
One of the most important discoveries came out of a simple change: waiting two more days to perform the genetic biopsy on the embryo. Before, analysis was only possible on the third day after fertilization. It was found that performing analyses on the fifth day, when the embryo becomes a blastula, increases pregnancy rates. The main goal is to obtain a healthy embryo, a successful pregnancy and especially the birth of a perfect baby.
Preimplantation Genetic Diagnosis (PGD) is recommended for the following cases:
- Determining and preventing diseases linked to the X chromosome, such as hemophilia, Duchenne muscular dystrophy and mental retardation.
- Identifying aneuploidies (defects in the number of chromosomes) which frequently occur when mothers are older, because the cellular division process is less efficient. Down's syndrome is one of the most common issues related to aneuploidies.
- Genetic diseases such as cystic fibrosis (defect in chromosome 7) can also be prevented through the opsy of embryos.
- Tay-Sachs disease (predominant in Jewish families), sickle-cell disease and hundreds of other illnesses.
- Women more than 35 years old where there is a proportionally greater number of abnormal eggs.
- Couples in which the female is more than 37 years old and is unable to get pregnant after two cycles of in vitro fertilization.
- Men and women with structural chromosomal abnormalities.
- Multiple miscarriages.
- Previous pregnancy with chromosomal abnormality.
- Men with severely altered semen.
- Carriers of recessive or autosomal dominant diseases linked to sex.
- Failed attempts at in vitro fertilization procedures.
- Men and women with genetic diseases linked to the X or Y chromosome.
- Hereditary diseases such as cystic fibrosis, hemophilia, etc.
- It has also been studied as a way to reduce the transmission of genetic predisposition mutations, such as hereditary cancer, HLA typing and genetic diagnosis for hematology diseases.
- Chromosomal, numeric or structural abnormalities.
- The presence of a chromosomal reorganization (Robertsonian translocations, translocations and reciprocal inversions) can lead to difficulties getting pregnant, miscarriages and congenital malformations. PGD is extremely useful in these cases.
- It is also recommended in the case of numeric, pure or mosaic chromosomal abnormalities.
- In the case of monogenic diseases and those linked to chromosomal reorganization, an informative genetic study must be performed before the PGD cycle, in order to confirm that the diagnosis is reliable and to adjust the technique for each individual case.
- Certain gene mutations can indicate certain diseases that can appear at different stages of life, such as neurofibromatosis, familial adenomatous polyposis or genetic breast cancer (BRCA1, BRCA2).
List of the main diseases that can be diagnosed through PGD linked with PCR-R, FISH and CGH-array:
- Fanconi anemia
- Glutaric acidemia type 1
- Alpha 1-antitrypsin deficiency
- Spinocerebellar ataxia 1, 2 and 3
- Spinal muscular atrophy
- Sickle-cell disease
- Congenital disorder of glycosylation type 1a
- Myotonic dystrophy
- Huntington's disease
- Menkes Disease
- Spondyloepiphyseal dysplasia (Schmidt)
- Tay-Sachs disease
- Duchenne and Becker muscular dystrophy
- Torsion dystonia 1
- Facioscapulohumeral muscular dystrophy
- Familial dysautonomia
- Amyotrophic lateral sclerosis
- Tuberous sclerosis
- Spinal and bulbar muscular atrophy
- Multiple exostosis
- Emery-Dreifuss muscular dystrophy
- Cystic Fibrosis
- Hyperinsulinemic hypoglycemia
- Hemophilia A and B
- Pigmentary incontinence
- Metachromatic leukodystrophy
- Hemophagocytic lymphohistiocytosis
- Multiple endocrine neoplasia (MEN2)
- Neurofibromatosis type I and II
- Norrie disease
- Osteogenesis imperfecta (brittle bone disease)
- Familial adenomatous polyposis
- Familial amyloid polyneuropathy
- Hypokalaemic periodic paralysis
- Hereditary spastic paraplegia
- Autosomal dominant polycystic kidney disease
- Autosomal recessive polycystic kidney disease
- Smith-Lemli-Opitz syndrome
- Crouzon syndrome
- Alport syndrome
- Pompe syndrome
- Lynch syndrome
- Marfan syndrome
- Holt–Oram syndrome
- Hunter syndrome, (Mucopolysaccharidosis Type II)
- Nonsyndromic sensorineural deafness
- Alpha thalassemia
- Beta thalassemia
- Treacher Collins syndrome
- Von Hippel–Lindau
- Fragile X syndrome