April 2 for the patients of the clinic Lada was signed the first contract in Odessa for the procedure of genetic research of embryos. Today these patients have all the data on the genetic status of their future children. The path to this has been a long one for the Clinic, and we are glad that our client-oriented approach can provide patients with the most advanced technologies.
After many attempts, failures and wasted time we can finally make it a thing of the past thanks to the use of new technologies. A new trend in reproductive medicine, preimplantation genetic screening, makes it possible to transfer only those embryos that do not have chromosomal abnormalities and are likely to become healthy children later. And with the help of the preimplantation genetic diagnosis (PGD) service, we can help couples in which one of the spouses has a genetic disease to give birth to a child without the carriage of pathogenic mutations. Plus, we have committed to transporting biological material. In their dewars, our embryologists personally deliver the valuable cargo.
“It will soon be considered a crime for parents to have a child carrying a heavy burden of genetic disease” – so believed Robert Edwards, Nobel laureate and founder of in vitro fertilization (IVF). We have the same point of view. Sign up for a consultation with our reproductive specialist and find out if you have any indications for the procedure!
We also invite you to read the article of our clinical embryologist – Alexander Petrenko.
Preimplantation genetic diagnosis and its role in assisted reproductive technologies
Preimplantation genetic diagnosis (PGD) emerged almost simultaneously with the emergence of clinical embryology in the modern sense, developing in parallel. Robert Edwards, who developed the method of in vitro fertilization and later received the Nobel Prize, in 1967 for the first time performed a biopsy of the embryo of a laboratory animal in order to determine the sex. The first successful childbirth after PGD began in 1990, the diagnosis was carried out due to the risk of inheriting an X-linked disease, adrenoleukodystrophy.
Today, PGD uses methods such as polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), next generation sequencing (NGS).
Two terms should be distinguished: preimplantation genetic diagnosis and preimplantation genetic screening (PGS). In the first case, a search is made for markers of a known genetic disease of the parents in the resulting embryos. When conducting PGS, genetics determine the presence of aneuploidy in the embryos under study, when it is not known about any genetic diseases of the parents, but the parents are at risk for aneuploidy.
According to the Order of the Ministry of Health No. 787 dated 09.09.2013, prenatal genetic diagnosis can be carried out at the patients’ own request after filling out an application according to the approved form.
Candidates for PGD are:
- Couples with a family history of X-linked disorders;
- Couples with chromosome translocations that cause impaired implantation, repeated abortion, mental or physical disabilities in children;
- Carriers of autosomal recessive disease;
- Risk of autosomal dominant disease;
In addition, PGD can be applied in the case of:
- HLA typing needs;
- Needs to get Rh-.
Thus, three groups of patients who are advised to consult about the need for PGD:
- Patients with gender-related diseases (haemophilia, fragile X-chromosome syndrome, vitamin D-resistant rickets, most muscular dystrophies, etc.);
- Patients with diseases caused by mutations in one gene (cystic fibrosis, Tay-Sachs disease, Huntington’s chorea, sickle cell anaemia, etc.);
- Patients with chromosomal abnormalities (abnormalities in the number or structure of chromosomes).
Candidates for ASG are:
- Advanced maternal age of the patient;
- Couples with recurrent abortion;
- Couples with repeated failed IVF cycles;
- A partner with multiple male factors of infertility.
The first group of patients is characterized by a high frequency of obtaining aneuploid embryos. So, in patients aged 35-39 years, the incidence of aneuploidy is more than 20%, while at the age of more than 40 years, this indicator is 40% or more. Often, aneuploidy causes spontaneous abortion.
The group with repeated abortion, according to international recommendations, should include patients with two or more spontaneous abortions at a gestational age of up to 20 weeks. According to the literature, in such situations, 50-80% of abortions have chromosomal abnormalities, and patients with recurrent abortion have a higher incidence of aneuploid embryos than other couples.
The third group includes patients with 3 or more unsuccessful IVF attempts, when it was possible to obtain and transfer high quality embryos. Although the reasons for this may be various disorders (immunological factor, female factors, etc.), studies indicate that this sample of patients has a higher frequency of chromosomal abnormalities in embryos.
The fourth group includes patients in whom the frequency of aneuploidy is explained by the presence of multiple male factors of infertility. According to the literature, even in relatively healthy patients with normozoospermia, up to 3-8% of spermatozoa contain chromosomal aberrations. This indicator increases significantly when infertility factors are added (for example, low sperm count, morphological abnormalities, poor motility), up to 27-74% of the total sperm count. Conducting PGS of embryos of this group of patients reduces the risk of aneuploid embryo transfer.
There are several options for collecting material for PGD / PGS. Among them are distinguished:
- Polar body biopsy;
- Embryo biopsy with blastomere removal on day 3;
- Biopsy of the trophectoderm on the 5th day.
Each of these methods has certain advantages and disadvantages. So, for example, when biopsy of the field body of an oocyte, the paternal DNA is not taken into account, it is possible to study only the maternal part of the genome of the future embryo. This imposes a number of restrictions, which, for example, can be significant in the diagnosis of a sex-linked disease.
With a biopsy of the embryo on the 3rd day and removal of the blastomere, this problem does not arise, since the embryo already contains both the maternal and paternal genomes. However, the results may be inaccurate, and mosaicism is often found in such embryos. Even if the embryo contains blastomeres with an aneuploid set, they may be eliminated by the 5th day, which makes the embryo diploid and suitable for transfer. In addition, according to the literature, with a biopsy on day 3, embryo survival may decrease.
A biopsy on the 5th day solves a number of problems: the problem of the amount of material (a biopsy of the trophectoderm takes place and, during it, a sufficient number of cells are taken), the problem of the frequency of mosaicism (with a high probability, the embryo, if it was mosaic, eliminated in the course of its development aneuploid elements), the effect on the embryo in this situation is minimal. For this reason, the Lada clinic uses the study of this particular material.
- PGD / PGS are routine tests in reproductive medicine;
- For some categories of patients, PGD / PGS is shown; by law, patients have the right to request these studies to be carried out without indications, if desired;
- When there is a risk of transmission of a sex-linked genetic disease, it is necessary to resort to selection of embryos by sex;
- According to the literature, the safest biopsy method is a biopsy of the trophectoderm on the 5th day.
Used materials from the Medscape base