1. What is third generation IVF? How does it differ from the first and second generation?
Classic first generation IVF uses a puncture needle to remove the eggs and combine them with sperm outside the body and transfer the fertilized embryos to the uterine cavity, avoiding the process of combining sperm and eggs in the fallopian tubes under physiological conditions, so it is mainly used in cases of blocked fallopian tubes; second generation IVF is for men with low, weak or teratogenic spermatozoa, these patients have poor sperm quality and often find it difficult to drill into the eggs by themselves to complete the fertilization process. The third generation of IVF is a new technology derived from the first and second generation, its academic name is pre-implantation diagnosis (PGD), as the name suggests, it adds a diagnostic step to IVF. As the name suggests, it adds a diagnostic step to IVF, the general process is that the doctor creates multiple embryos at once through ovulation promotion and in vitro fertilization, and before transferring these embryos to the mother’s uterus, a small number of cells are taken from each embryo for testing, that is, the chromosomes or genes of the embryos are screened, and only qualified embryos are transferred, while unqualified embryos will be eliminated. With this process, the birth of defective offspring is eliminated, and for families at risk for chromosomal abnormalities or other hereditary diseases, this technology provides a guarantee for the safety of offspring.
2. What hereditary diseases can be screened by IVF III?
Broadly speaking, hereditary diseases include monogenic genetic disorders, polygenic genetic disorders and chromosomal disorders.
(1) Monogenic genetic diseases are genetic diseases caused by a single disease-causing gene, such as thalassemia, hemophilia, myotonic dystrophy, etc.
(2) Polygenic genetic diseases require multiple genes acting in concert with certain environmental factors to develop, e.g. hypertension, tumors, diabetes, etc.
(3) Chromosomal disorders are a large group of disorders caused by structural or numerical alterations of chromosomes. The numerical alterations usually have obvious phenotypic abnormalities, such as low intelligence, peculiar facial features, growth retardation, etc., whereas whether the structural alterations have phenotypic abnormalities depends on whether there is an increase or decrease in the number of genes. On the contrary, if the structural changes are accompanied by an increase in the number of genes, it is called a balanced structural rearrangement, and the patient does not have any physical or intellectual abnormalities, but it can affect fertility.
Due to the large number of genes and the environmental factors involved in the development of polygenic genetic disorders, it is not yet possible to determine the susceptibility of offspring through PGD. In theory, PGD can be used to screen offspring for monogenic genetic disorders as long as the causative gene is clear, but due to the high technical difficulty and cost, PGD is currently only available for a limited number of monogenic disorders in clinical practice. The vast majority of chromosomal disorders can be screened for offspring by PGD.
3.Who needs third generation IVF?
(1) Balanced translocation and inversion carriers
(2) Infertile couples with a history of 3 or more previous spontaneous abortions
(3) Couples with infertility caused by male factor
(4) Couples with 2 or more failed IVF implantations in the past and are ready to undergo IVF again
(5) Patients with some monogenic genetic diseases.
4.Why are the third generation IVF fees more expensive than the first and second generation?
The first step is embryo biopsy, i.e. a small number of cells are removed from the embryo for testing, which requires a special laser punch, a special culture dish and specific reagents; the second step is diagnosis, i.e. testing of the removed cells, which is commonly used in fluorescence in situ hybridization and gene chip technology, both of which require imported reagents and consumables. Both techniques require imported reagents and consumables, which are expensive, and in addition require the configuration of fluorescence microscopes, hybridizers, scanners and other equipment. Therefore, the cost of third-generation IVF reagents and equipment is much higher than that of ordinary IVF. In addition, unlike ordinary clinical diagnosis or testing, the material available for diagnosis in the third generation of IVF is extremely small, usually only 5-10 cells, which is quite difficult and time-consuming to operate, so its labor cost is also much higher than that of the first or second generation.
5. What is the difference between third generation IVF and traditional prenatal diagnosis?
Traditional prenatal diagnosis includes chorionic villus biopsy, amniocentesis, ultrasonography, etc. The chorionic villus biopsy is relatively early, usually at 10-12 weeks of gestation, amniocentesis after 16 weeks of gestation, and ultrasound malformation screening until 22-24 weeks of gestation, all three methods require pregnancy before diagnosis can be made. The third generation IVF does the opposite, diagnosing first and then getting pregnant, bringing the diagnosis forward to before the embryo implantation into the mother’s uterus, which has a great effect on reducing the physical and mental pain of pregnant women.
6. Is third generation IVF safe for future generations?
The third generation of IVF requires the removal of a small number of cells from the embryo, and whether this process affects the normal development of the embryo has been a concern for scientists from various countries. Studies have shown that when the embryo is first formed, there is no clear division of labor between the cells that perform the specific tasks, and each cell has the potential to differentiate into various organs, and the early embryo has a strong compensatory capacity. It is not that third generation IVF is absolutely safe, as with other new medical technologies, the birth of any new technology is a double-edged sword, and its real effect may take decades or even centuries to make an accurate judgment, so although China allows it to be carried out, it must be strictly approved by the health administration department to avoid abuse of the technology, and to strictly ensure that the operation process is standardized and orderly.
7. What is the success rate of third generation IVF?
The age of the pregnant woman and the number of embryos obtained are the key factors affecting the success rate. Third-generation IVF is often performed on patients with genetic diseases, recurrent spontaneous miscarriages, balanced translocation and oligozoospermia, etc. They are usually older and have fewer embryos obtained, and after PGD screening, the number of embryos available for transfer is even smaller. However, clinical pregnancy does not mean that a healthy offspring can be born, while third-generation IVF, due to embryo screening, has a lower miscarriage rate and a significantly lower birth defect rate than regular IVF once a pregnancy occurs.
8. Can third generation IVF be misdiagnosed?
As with any diagnostic technology, PGD cannot be 100% accurate. The European PGD Collaborative Group reported that the misdiagnosis rate of PGD for monogenic diseases is only 0.47%, while the accuracy rate of PGD for chromosomal diseases is generally reported to be around 95%.
9. Does having a third generation test mean that the fetus is 100% normal?
No. PGD can only screen for a known genetic factor, for example, for carriers of balanced translocation of chromosomes 2 and 5, we can only screen the embryo for chromosomes 2 and 5, but not for other chromosomes; similarly, for carriers of myotonic dystrophy, we can only screen for the causative gene, but it is unknown whether the embryo carries other causative genes and whether the embryo has normal chromosomes. For this reason, after PGD, a successful pregnancy must be followed by a routine prenatal examination and, if necessary, some special tests.