Since the beginning of IVF technology, it has gone through the beginning of the first generation, the update of the second generation, and the change of the third generation. This reproductive technology is constantly maturing and improving with medical advances. The third generation IVF technology is an intergenerational advancement in human genetic medicine. Conventional IVF (first generation IVF) effectively solves infertility problems caused by female factors, such as tubal, endocrine, and uterine problems. The second generation of IVF (ICSI) solves the problem of infertility due to male factors. The third generation IVF technology (PGD) is a breakthrough innovation based on IVF and ICSI, known as pre-implantation genetic diagnosis, which greatly improves the fertility problems of people with chromosomal problems, prevents the transmission of genetic diseases, selects healthy blastocysts for transfer, and also greatly improves the transfer success rate.
What is PGD technology for third generation IVF?
PGD technology can test the embryos/blastocysts formed by cultivation, and the test material is usually taken from one cell of a 4-8 cell stage embryo or one cell of a blastocyst formed into more than 100 cells near the placenta for testing. The risk is much smaller. Therefore, it is best to choose an IVF clinic that has the capability to grow fertilized eggs to blastocyst before performing PGD screening.
PGD screening uses fluorescent in situ hybridization, where each chromosome has a unique region of DNA that is present on that particular chromosome only. When a small DNA probe comes in contact with that DNA region, it can be used to recognize these unique patterns and fluorescence or glow. Each probe can emit several different colors of light, allowing several chromosomes (or regions of chromosomes) to be tested simultaneously. This technique is known as FISH fluorescence in situ hybridization. As PGD technology continues to mature, the success of interphase nuclear single cell FISH technology and the development of a wide variety of FISH probes has expanded PGD to include the diagnosis of chromosomal disorders and can be very effective in identifying embryos/blastocysts carrying chromosomal and DNA genetic disorders.
Where can PGD be done for 3rd generation IVF
The experimental conditions for PGD technology are very demanding, and any small mistake in the operation can lead to serious clinical consequences. Some hospitals in China can perform PGD, but it is only limited to screening for some diseases, and all genetic diseases and chromosomal disorders are up to 125 types.
In terms of safety and health, PGD technology in the United States is the safest. Normally operated PGD does not lead to congenital defects or an increase in chromosomal variants. PGD is performed before the genetic material of the embryo is active, all cells inside the embryo are identical, and each cell is capable of developing into any part of the fetus, and extraction of the 1 cell used as the test does not have any effect. However, where the technology is not perfect, there is a high risk that the extraction of cells may be faulty, resulting in reduced activity or even death of the embryo/blastocyst. DR. Richard Buyalos, M.D., a leading fertility center in the U.S., suggests that even if PGD screening is done in the U.S., the technology is not available everywhere, but is limited to a few large laboratories in the U.S. that are qualified to perform it, and patients should not listen to the packaging rhetoric of some institutions.
Due to the current social trend, the number of people who marry late and have children late is increasing, and the number of older mothers remains high. Once an embryo carries a chromosomal disorder, it is likely to stop during development or give birth to a child with 18-3 or 21-3 somatic fetuses after a natural pregnancy. Based on the first and second generation, the third generation of IVF plays a very important role in eliminating diseased blastocysts and selecting healthy and high quality blastocysts for implantation, which can greatly improve the pregnancy success rate and at the same time guarantee that the child will be born as a healthy baby and achieve eugenic results.
Application groups.
Pre-implantation genetic diagnosis, chromosome identification, third generation IVF) can detect a variety of diseases, they include chromosomal abnormalities, single gene defects or sex-linked disorders. These include:
Chromosome 13: Chromosome 13 abnormalities occur in trisomy 13 (Patau syndrome) with a prevalence of about 1 in 5,000, due to the presence of an extra chromosome 13, which causes multiple malformations and most deaths within three years of birth. Polycystic kidney disease (large cysts in the kidneys), intestinal dysfunction.
Chromosome 18: Trisomy 18 is a severe chromosomal abnormality with a prevalence of about 1 in 6,000 patients with trisomy 18 usually present with multiple organ defects and most die within the first year of life. It often causes Niemann-Pick disease (anemia, enlargement of liver, spleen, lymph nodes, dyspepsia and neurological defects, cancer of the pancreas and other diseases.
Chromosome 21: Down’s syndrome (Down’s syndrome)
Chromosome 22: Chronic myeloblastoma due to replacement of bone marrow by malignant white blood cells
Chromosome X: Duchenne muscular dystrophy (DMD), Turner’s syndrome, Fragile X syndrome
Y chromosome/acute myeloid leukemia
The normal female karyotype is XX and the male karyotype is XY. Sex chromosome abnormalities are more common, occurring in about 1 in 500 cases, and experts believe that about 25% of spontaneous abortions are due to sex chromosome abnormalities. The following are three common types of sex chromosome abnormalities.
Tul’ner syndrome (congenital absence of ovaries syndrome) has an incidence of 1 in 10,000 female infants and is the leading cause of chromosomal abnormalities that lead to the occurrence of miscarriage. The affected girl has no two X chromosomes and only one X chromosome: 45X. She grows up with short stature, abnormal neck, hypogonadism, abnormally small ovaries, and often heart and kidney disease. These symptoms are often not detected until pubertal development. The karyotype is 45,X.
Klinefeher syn-drome (congenital testicular hypoplasia) has an incidence of about 1 in 1000 male infants and is most notably characterized by a boy who reaches puberty with a very tall body and elongated limbs. The child has a redundant X chromosome with karyotype 47XXY, and often shows sexual hypoplasia, small testes, and inability to produce sperm, making him infertile. The pubic hair is female released, beard, axillary hair, pubic hair is sparse, no throat nodes, fine skin, some male patients have female breast.
Mixed gonadal dysgenesis (MGD), also known as XO/XY dyspareunia, is a combination, the most striking feature of which is the enlarged clitoris of the patient. The degree of sexual development affects the development of the internal and external genital organs.
XXX syndrome (Trisomy x syndrome) is the most common chromosomal abnormality in females. The chromosomal karyotype of XXX syndrome is 47,XXX; 48,XXXX, etc. The number of chromosomes is related to the severity of symptoms, the more X chromosomes, the more severe the symptoms.
Fragile X syndrome (Fragile x chromosome) is the most common cause of mental retardation in males, and is characterized by a protruding forehead, protruding jaw, large ears, large hands, and speech disorders, and a withdrawn personality. The karyotype is 46, Fra(x)Y.
Advantages.
(Pre-embryo transfer genetic diagnosis, chromosome identification, 3rd generation IVF) Is it safe?
Yes. Years of trials and statistics on babies born have shown that PGD does not result in an increase in congenital defects or chromosomal variants. PGD is performed before the embryo’s genetic material is ‘active’ because it is done so early that all cells inside the embryo are still identical and each cell is capable of developing into any part of the fetus. Removing cells from an early embryo does not alter the ability of the embryo to develop into a full normal pregnancy.
What is the accuracy of (pre-implantation genetic diagnosis, chromosome identification, third generation IVF)?
Although genetic testing is an important diagnostic tool, it is not without limitations. Single-cell genetic analysis is technically demanding and prone to a number of errors. Fluorescent in situ hybridization genetic testing (PGD-FISH) can only test for a limited number of chromosomes and cannot detect the rest of the abnormal chromosomes. Polymerase chain reaction gene testing (PGD-PCR) sometimes fails to detect individual gene defects. For chromosomal translocations, genetic testing cannot detect chromosomes other than the abnormal chromosome known to be involved in the translocation. The error rate of genetic testing for chromosomal abnormalities is approximately 10%. For chimeric chromosomes, the specific abnormal gene may be present in one cell of the embryo but not the other, which is often inadequate for genetic diagnosis. On the other hand, due to the limitations of genetic diagnosis, there may be diagnoses that show that all embryos are abnormal, but in fact one of them may be normal
What are the advantages of PGD (Pre-implantation Genetic Diagnosis, Chromosome Identification, Third Generation IVF)?
PGD (Pre-implantation Genetic Diagnosis, Chromosomal Identification, Third Generation IVF) is a test that screens for normal embryos in the areas above the embryo that are most susceptible to chromosomal variation. The PGD (Pre-implantation Genetic Diagnosis, Chromosome Identification, Third Generation IVF) screening technique gives embryos a greater chance of being born in utero, less natural mortality, and also reduces the risk of having offspring with abnormal chromosomes (e.g. Down syndrome). PGD technology allows embryologists to diagnose whether an embryo has a gene for a genetic disorder before the embryo is implanted during the IVF procedure. Screening for genetically abnormal embryos through PGD can increase the rate of healthy embryo implantation and reduce the incidence of spontaneous miscarriage and triploid chromosomal abnormalities
PGD (pre-implantation genetic diagnosis, chromosome identification, third generation IVF) sex screening/sex selection?
Every pregnancy has a 50% chance of being male and a 50% chance of being female, but some families have more children of the same sex. The use of PGD can help these couples to obtain children of the less populated sex in their families can harmonize and balance the sex of the family population.
Pre-implantation Genetic Diagnosis
1. What is pre-implantation genetic diagnosis/screening (PGD/PGS)? Pre-implantation genetic diagnosis/screening is the testing of embryos that have reached day 3 or 5 of development for abnormalities in chromosome number and structure. The test data will help the doctor to select embryos with normal chromosome number and structure for transfer into the mother. Currently, a more advanced test is the use of gene chip technology to screen all 46 chromosomes of the embryo to select embryos with normal chromosome number and structure for transfer. The use of this test can improve the clinical pregnancy rate of patients, reduce the risk of early miscarriage and reduce birth defects.
2. What are aneuploidy and what are the common related diseases? Aneuploidy refers to cells with one or several additional complete chromosomes and partial chromosome fragments missing or added to the chromosome set, and is used to describe chromosomal abnormalities. There are 23 pairs of chromosomes (22 autosomes and 1 sex chromosome) in a healthy human body, for a total of 46 chromosomes. In fact, more than 50% of the early miscarried embryos in IVF treatment are caused by aneuploidy. In addition, aneuploidy can cause stillbirths, birth defects, etc. Common aneuploidy-related disorders include trisomy 21 (congenital stupidity, also known as Down’s syndrome), trisomy 18, and trisomy 13. Down syndrome manifests as mental retardation, malformation of the five senses, and an average life expectancy of 35 to 50 years. embryos with trisomy 18 and trisomy 13 have abnormal development in the brain, bones, heart, reproductive organs, and other tissues, and will have a high rate of miscarriage, and newborns will die shortly after birth.
3. Why does aneuploidy increase with the age of a woman? Every woman has a fixed number of follicles preserved in her ovaries from birth. This number decreases with age. A healthy woman expels one mature egg every month. However, as she ages, these preserved follicles age. During the process of differentiation of these aging follicles into mature eggs, the number of chromosomes may be lost or increased and structural abnormalities may occur, resulting in aneuploid eggs. The relationship between the rate of aneuploidy production and age is detailed in the following table: Woman’s age Aneuploidy risk rate Embryos Neonates 34 years and younger 21-66% <5% 35-37 years 44-70% 0.5-1% 38 years and older 55-80% 1-20%
4. How does pre-implantation genetic diagnosis/screening (PGD/PGS) help patients? Pre-implantation genetic screening involves testing each individual embryo for the number and structure of the 46 chromosomes and selecting embryos with normal chromosome number and structure for implantation into the mother. The transfer of embryos with normal chromosome number will greatly increase the clinical pregnancy rate, reduce the risk of early miscarriage, and reduce the birth rate of children with aneuploidy-related disorders.
5.What are the suitable groups for pre-implantation genetic diagnosis/screening (PGD/PGS)? The suitable groups for pre-implantation genetic screening are as follows: (1) Patients older than 35 years of age; (2) Patients with ≥3 spontaneous miscarriages, excluding uterine or endocrine factors; (3) Couples who have given birth to children with chromosomal abnormalities; (4) Patients who have not conceived after more than 3 transplants (including fresh and frozen transplants); (5) Couples with chromosomal number and structure abnormalities, such as Roche’s translocation, partial Creutzfeldt-Jakob syndrome, etc.
6. Why is it necessary to screen for 46 chromosomes? Aneuploidy is not present on one or a few fixed chromosomes alone, but can occur on any of the chromosomes in the entire chromosome set. Traditional testing methods will only detect a few common abnormal chromosomes, and will miss those that are not detected. Only after screening for all chromosomes can a normal embryo be selected for implantation into the mother, thus greatly reducing the risk of miscarriage and birth defects.
7. Will preimplantation heritage diagnosis/screening (PGD/PGS) have any effect on the embryos? No. Pre-implantation genetic screening is performed on embryos that have reached day 3 or 5 of development for single cell (oogenesis) or 3-4 cell (blastocyst) testing. The cells in embryos at this period have not yet differentiated into different types of cells and are all totipotent, and testing one cell from these cells will not affect the development and growth of the whole embryo. Pre-implantation genetic diagnosis/screening (PGD/PGS) has been widely used in clinical practice overseas.
8.What are the advantages of PGD/PGS technology in our hospital? The genetic department of our hospital was established in 1979, and is one of the core departments of the prenatal diagnosis center and newborn disease screening center in Shaanxi Province. In 2001, the Department of Health approved the registration of “Shaanxi Prenatal Diagnostic Center” and “Shaanxi Newborn Screening Center”. At present, the genetic room is equipped with molecular biology equipment such as Agilent scanner, mass spectrometer and gene sequencer, and the results are analyzed by a doctor in molecular biology. Relying on the strong technical platform of our genetic laboratory, our fertility center adopts the most advanced gene chip technology for pre-implantation genetic diagnosis/screening, which can effectively improve the clinical pregnancy rate of assisted conception patients and reduce the rate of miscarriage and birth defects.
9. How is IVF-PGS performed? For PGS, the beginning part of the IVF cycle is the same and all include the following three main steps: ・ Super ovulation treatment ・ Egg retrieval ・ Egg and sperm fertilization to obtain embryos The most common method nowadays is to biopsy the embryos on the third day after egg fertilization. The embryologist will remove one cell from each multicellular (6-8 cells) embryo separately. They will prepare the biopsy cells in a special way, which contains representative chromosomes of the embryo; they will then send them to the genetic laboratory. In the future, for the frozen embryo process, most biopsies will be performed on day 5 (blastocyst trophoblast ectoderm biopsy) at the same time as embryo freezing and transfer. If the biopsy is done on day 3, embryos without chromosomal abnormalities can be transferred into the female patient’s uterus on day 5. Other normal embryos, which are largely mature by day 5 or 6, can be frozen (cryopreserved) for future use. A more novel technique called “trophoblast biopsy” allows for a few cells to be obtained from day 5 embryo sacs and is therefore more accurate. Using this technique to transfer a single embryo with normal chromosomal embryos has a very high chance of a healthy and safe birth, while the likelihood of twins is very low.
10. What is the alternative to IVF-PGS? The alternative to IVF-PGS is for a couple to conceive naturally or through conventional fertility treatments, or prenatally using similar molecular diagnostic techniques through chorionic villus sampling (CVS) or amniocentesis. Using these methods requires more samples to be taken during pregnancy and the reporting of test results is more time consuming. There is still a possibility of misdiagnosis with this, but it is less likely than PGS. At this point, however, the only options for the couple are either to have a child with the defect or to terminate the pregnancy.