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biopsy after birth are described as “embryo biopsy syndrome”. In humans, embryo biopsy is associated with lower rates of live births and higher rates of miscarriage, perinatal death, placenta previa, and premature births with low birth weight. Additionally, children born after PGS showed higher likelihood of major abnormalities, more paramedical care, lower fluency and neurological optimality scores, more problem behavior, poorer cognitive and motor skills, lower levels in stress assessments, lower performance IQ, etc. Thus, PGS techniques (which including embryo biopsy, freezing and especially laser radiation) is not safe. The unsafe reason is also explained by Epicytohetics (the study of expression of cytoplasm).

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Keywords: preimplantation genetic screening; Preimplantation genetic test; aneuploidy; mosaicism; Hereditics; Epicytohetics; Safe.

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Embryo biopsy1 and preimplantation genetic diagnosis (PGD) is to prevent disable or life-threatening genetic diseases2-4. Just as hysterectomy is a major surgery on a woman, embryo biopsy is similarly a major surgery on a human embryo. The benefit from the embryo biopsy must outweigh its risks.

 

Since fluorescent in-situ hybridization (FISH) techniques were introduced to prevent X-linked hereditary diseases5, the presence of aneuploid cells in human embryos has been reported6 and preimplantation genetic screening (PGS) started. PGS was recently referred to preimplantation genetic testing for aneuploidy (PGT-A). If all embryos obtained by in vitro fertilization (IVF) were screened for aneuploidy before transfer, implantation and pregnancy rates would improve and miscarriage rates would decrease. The aim of PGS was for the “diagnosing and preventing inherited disease”7,8. The use of PGS was popularized in the USA in 2015 9. At the same time, the shortcomings of PGS were exposed. The embryos which were diagnosed as “mosaicism” or “aneuploidy” by PGS produced healthy babies with normal karyotyping10,11. It confirmed that PGS is not a hereditary test for “preventing inherited disease”12. Additionally, the techniques of embryo biopsy are universally used in the reproductive field, and are erroneously assumed to be very safe13,14. However, birth or number of the birth is not a scientific and statistical proof of its safety in human reproduction15-17. The following review showed that PGS is not safe.

 

Aneuploidy and laboratory factors in PGS

The following factors may damage microtubules and other cellular organelles, and can produce aneuploid cells in human embryos:

A. Environmental factors18: change in room and culture temperature, frequent removal of the embryos from the incubator, unsuitable culture medium, inadequate nutrition, poor air quality, etc.

B. Foreign forces and mechanical strength19: suction strength, denuding strength, biopsy pull and push strength, etc.

C. Physical factors: laser (electromagnetic radiation)20,21, freezing ice expansion, freezing and thawing osmolarity change, electrofusion, etc.

D. Chemical factors: cryoprotectant DMSO22, HCl acid, cytochalasin23, etc.

The use of these aneuploidy-producing techniques (most of them required for PGS) to prevent aneuploidy is not scientific.

 

Embryo biopsy is traumatic and unsafe

Embryo biopsy was based on the totipotent theory of early embryo cells24,25. Experiments provided potential for normal embryo development after blastomere removal26,27. In rabbits and mice, live births were reported after transferring the “2-cell” embryos (with only one of the blastomeres remaining intact)28,29. However, following embryo biopsy at the 2-cell stage, the rate of “half-embryo” development was significantly lower than the non-biopsied control15,16,30. Experiments of mouse and human embryos showed that biopsy had the least impact when performed at the 8-cell stage. It was significantly detrimental when performed at the 4-cell stage and was most detrimental when performed on morulae31,32. When trophectoderm cells were biopsied in the mouse, the results were also not safe. There was a significantly lower rate of fetal development33, a lower pregnancy rate34, and a lower number of embryos which reached the egg cylinder stage35. The loss of the ability of some blastocysts to re-expand might result in loss of the ability to hatch and implant36,37. Additionally, trophectoderm biopsy might reduce the number of cells to produce essential enzymes for implantation38.

 

The safety of embryo biopsy was systematically studied with mice models before the popularization of PGD in human39-41. “Embryo biopsy is safe” was a statement of relativity. The studies confirmed that embryo biopsy did not reduce the cell number in the offspring’s body, organs, and tissues; did not affect the birth weight; did not lead to deformed organs or tissues; and will not compromise functioning of major organs such as the heart, kidney, skeleton, etc. At the same time, absolute conditions for the safety of embryo biopsy were established. First, the 8-cell stage is the unique optimal time for embryo biopsy, rather than at 4-cell or blastocyst stage4. Second, the hatching rate (rather than blastocyst rate) after embryo biopsy should be >90% 42. Only such a high hatching rate will result in equivalent rates of implantation and foetal development for both biopsied and non-biopsied control groups. Third, only one cell (rather than two cells) should be biopsied from 8-cell embryos4,42. These conditions for safety of embryo biopsy (especially the 90% hatching rate after biopsy) require excellent micro-manipulation skills and are difficult for most laboratory staff to achieve1,3,43. Most studies that published the results of embryo biopsy with acid and laser did not have a 90% hatching rate comparable to the control group, nor did they have a 70% implantation rate, foetus rate, or normal birth rate43-45. Thus, embryo biopsy is unsafe for the incompetent laboratory staff to perform.

 

The safest biopsy technique

Human embryo biopsy includes acid3, laser46, and mechanical cutting techniques43,45,47 to open the human zona pellucida. The safest biopsy technique in human is day 3 biopsy with one point three-dimensional mechanical zona slitting (pierce at the 5 to 7 o’clock directions), which is similar to three-dimensional dissection45. However, one starting point leads to an advantage of the least disturbance of the non-biopsied embryonic cells, which is the key point for future babies’ health according to Epicytohetics. The opened zona appears like a blooming flower (from one point) towards the aimed cell (with a clear nucleus) for biopsy. A smooth beveled needle can be easily used to biopsy without pushing or pulling any neighboring cells. It is the most time-consuming but safest manipulation. If other unsafe biopsy techniques are used, the embryonic cells (that produce the baby or placenta) may be pushed, pulled, torn, lysed or deformed during embryo biopsy, which can break and dislocate microtubules in the cells. If some of the microtubules are severely damaged by biopsy, aneuploid cells will be produced with morphologic aberrations48.

 

Evaluation factors of safety after biopsy

A. Delay time. After embryo biopsy, the development of biopsied embryos will be delayed to allow the checkpoint and licensing system49,50 to restore their normal function. Then mitotic exit, i.e. cell cleavage continues51. When performing biopsy on day 3, the delay times for one point three-dimensional mechanical cutting, acid cutting, and laser cutting are about 2 hours, 3 hours, and 4 hours respectively according to our experiments. A shorter delay time is better. Our experiments showed: when performing blastocyst biopsy on day 5 with laser, the delay time may be between 2 to 24 hours. Laser may produce cell cycle mitotic exit time i.e. each cell cycle time to be longer forever.

B. Only in extremely poor embryo biopsy, the blastocyst rate will be lower than that in the control group44. The blastocyst rate is not a useful or sensitive indicator42.

C. The well-biopsied embryos will obtain a 90% hatching rate42.

D. The well-biopsied embryos will achieve the same 70% implantation rate and foetus rate as the non-biopsied ones, with a low miscarriage rate42,45.

E. If the microtubules and actin of the cells (which influence the normal differentiation of the foetal heart muscles, nervous system and endocrine system) are harmed, stillbirth will happen52. The well-biopsied embryos will achieve the same low premature birth rate, with the same live-birth rate and birth weight as the non-biopsied ones39 rather than worse53.

F. After birth, offspring should be healthy4,39. However, unhealthy offspring produced by poor embryo biopsy may show different symptoms and signs, which can be referred to as embryo biopsy syndrome (EB syndrome). Unhealthy offspring data in mice with EB syndrome after blastomere biopsy were reported by Zacchini et al.: increased or decreased body weight, impaired memory, impaired locomotor coordination, increased anxiety, altered response to stress, structural abnormalities in the corpora striatum and hippocampus, epigenetic and proteomic defects in the brain, impaired function of adrenal glands, and reduced fertility in 40-week-old female mice54. All studies quoted by Zacchini et al. mistakenly used unsafe 4-cell stage for biopsy rather than the safe 8-cell stage for biopsy. They also used a very toxic chemical - cytochalasin B - in the biopsy medium at an extremely high concentration55-60. Cytochalasin B is known as an important microtubule- and microfilament-disrupting drug23,61. When microtubules and microfilaments are disrupted, all kinds of abnormalities of organs and tissues will develop. Additionally, none of these studies showed that the manipulators had high hatching rates (90%) or high implantation and foetus rate (70%) after blastomere biopsy to ensure that their techniques were competent for embryo biopsy. In 2015, people popularized blastocyst biopsy with laser, and were prematurely confident in the safety of laser.

 

PGT is not safe

A. Laser harms embryos

Laser is the only effective tool for trophectoderm biopsy. Laser is a kind of electromagnetic radiation. The major laser systems used in PGS are: “Saturn”, “OCTAX” and “LYKOS” or “ZILOS” systems with infrared “class 1” laser (1480 or 1460 nm wavelength). “Class 1” (according to international IEC 60825) is: “the light is contained in an enclosure, which will not directly radiate to our eyes”. However, the laser was mistakenly designed to point toward the human embryos. While facing laser, both our retinas and human embryos are vulnerable. The microtubules, actin, and other cell organelles in our human embryo cells and retina cells are harmed21,62. The damage by laser in embryos is latent, which usually cannot be detected within 24 hours48,63. This kind of damage (such as the harm to microtubules) cannot be repaired, and will be inherited by future generations12,64. Many studies confirmed the safety of laser biopsy, and showed better results comparing with acid biopsy44,46,65. However, laser biopsy did cause visible and detrimental effects on embryonic and fetal development21,48.

 

In the air, laser light moves straight in long distance (refractive index: air: 1.00). However, during embryo biopsy, the laser light does not move straight. It first arrives at the mirror. It reflects and passes through the magnifying glass of the objective lens, the heating glass plate, the plastic dish, the medium and embryo zona. All of these objects contain different refractive index (water: 1.33; glass: 1.52; polystyrene dish: 1.6, etc.) and will produce high laser diffusion. After laser biopsy, people cannot directly observe any harm to the embryonic microtubules, or centrosome, or DNA under general microscope44, but the burnt and broken microtubules are obviously observed under electron tomography21. Laser diffusion can be severe during biopsy. A simple example: The heating glass on the microscope is composed of tin dioxide which contains high refractive index. More than 20% laser light will be refracted by countless tiny tin dioxide “mirrors” to any direction, to all cells of the embryos and the manipulators’ eyes. In assisted hatching, fragmentation observed in the embryos was random and did not specifically originate from the blastomere adjacent to the site of laser63. It showed that the laser is an invisible microtubule and centrosome cutting scattergun in embryo biopsy21.

 

In insects and animals, lasers have shown very harmful effects. In a Drosophila experiment, embryos were radiated by laser and, while the doses did not eliminate nuclei or cells, up to 50% of adults from those embryos had defects in the thorax66. In a zebrafish experiment, lasers produced centrosome disruption, which inhibited peripheral neural axon outgrowth. Some neurons had either no peripheral axon or short axons. Some of the cells also displayed ectopic protrusions of the axons from the cell body67. It confirmed that laser radiation can harm neuron differentiation, which can ultimately affect brain function. In mice, laser use was associated with increased DNA damage in embryos20. In other studies, many laser-exposed embryos exhibited morphologic aberrations such as isolated blastomere arrest and embryo growth delay; a significant decrease in fetal development48; and significantly fewer cell numbers in completely hatched blastocysts compared to the control group20,68. When biopsy with laser, one group of mice pups were born with heavier hearts and another group with lighter kidneys. The laser radiation is harmful to the organ differentiation and pup health69.

 

In humans, embryo biopsy using laser also shows safety concerns: Laser-biopsied human embryos reached subsequent embryonic stages at significantly later time-points, which hindered the hatching70. There was also a significantly lower mean number of nuclei in the laser-biopsied embryos on day 6 compared with the control group44. Experiments performed in our laboratory and Vitrolife Company showed scary results: After blastocyst biopsy with laser cutting, freezing and thawing, sometimes all of the thawed blastocyst cells in some blastocysts were scattered singly on the culture dish without any cell to cell connection. This finding confirmed that laser harmed every cell (including the inner cell mass) in the blastocysts despite no observed signs of damage during biopsy or before freezing.

 

B. Negative consequences in pregnancy and children

In the following available published studies, half of the embryos underwent acid biopsy and half underwent laser biopsy. After 2015, almost all blastocyst biopsy was performed by laser biopsy.

 

In Denmark, “compared with spontaneously obtained pregnancies, the risk of placenta previa after PGD was only significant in pregnancies obtained after embryo biopsy with laser but not acid”71. It suggests that the delay recovery time after laser radiation may influence timely implantation.

 

In Spain, 1,512 women showed that PGS was associated with lower rates of ongoing pregnancies and live births72.

 

In the Netherlands between 1995 and 2014, 439 pregnancies in 381 women after PGD/PGS resulted in 364 live born children by 311 deliveries. Miscarriage and perinatal death rate = 29.2% (439 – 311)/439, which was extremely high. It resulted in 2.5% children with major malformations, 1.4% with minor malformations, 1.1% with chromosomal abnormality, 20% premature births, and <15% with low birth weight73. PGS was associated with a significantly lower rate of ongoing pregnancies and live births in women of advanced maternal age53. Children born after PGS have a 2.5% chance of major abnormalities74 and they received more paramedical care (for speech, physical, or occupational therapy) than controls75. From a cognitive standpoint, PGS children have been shown to have lower neurologic optimality scores and lower fluency scores compared to controls76,77. Regarding socio-emotional development, teachers’ scores revealed more externalizing (p = 0.011) and total problem (p = 0.019) behavior in PGD children than in IVF/ICSI children78.

 

In the UK, PGD/PGS children were more likely to have lower birth weight, at <2500 g (24.5%), compared with naturally conceived controls (1.5%; p < 0.0001), and earlier birth than controls (p < 0.0001) 79. Our experiments suggest that four factors may be related to the lower birth weight: First: Laser may produce cell cycle mitotic exit time i.e. each cell cycle time to be longer forever. Thus the fetuses derived from laser biopsied embryos may contain lesser cell cleavage cycles than the control group at the birth time; Second, blastocyst biopsy may harm normal development of the placenta due to lesser trophectoderm cells to be remained; Third, the manipulation of embryo biopsy may harm cytoskeleton of the cells which influence the remained cells to contain inferior functions; Fourth, early birth.

 

In Belgium, in 102 two-year old children, two PGD/PGS children had major malformations at birth. About 2/3 cases underwent a two-blastomere biopsy and these children’s body weights were lower than the controls (p = 0.021) 80. In 581 PGD/PGS cases, the pregnancy rate was extremely low [484 / (1443+1310)] = 17.6%. Moreover, the perinatal death rate was significantly higher than that in the control (ICSI) group81.

 

In Greece, PGD children had increased frequency of poor cognitive and motor skills. PGD parents reported lower levels of stress assessments in their children compared to naturally conceived children (p < 0.01). And the occurrence of defensive response significantly differed between the groups evaluated82.

 

In Israel, a study showed: 40.7% PGD children demonstrated mixed hand-eye dominance, while this was found in just 20% of general population, which may reflect how PGD affects individuals’ cognitive functioning. In another study, 44% PGD children had a significant difference between their verbal IQ and performance IQ (PIQ) scores due to obviously low PIQ scores (compared to 27% in the general population). This finding suggests that subjects may have mixed lateralized cerebral hemisphere dysfunction. Furthermore, PGD children showed significantly lower intensity (p < 0.001) and a significantly higher threshold of response in activity (p = 0.007). They were significantly less moody (negative mood) (p < 0.001) and significantly less active (p < 0.001) 83. These phenotypes of EB syndrome show that the invasive biopsy procedure may have affected the developing fetus and children on both medical and neuropsychological levels.

 

In the USA, using national data between the 2005 and 2013 donor oocyte – recipient cycles, it was reported that live birth rates for PGS cycles were reduced by 35% (p < .001) 84. According to data from the Centers for Disease Control and Prevention (CDC), premature birth rate (34-36 weeks of gestation) in the U.S.A. was significantly increasing between 2015 and 2018 annually (2014: 6.82%; 2015: 6.87%; 2016: 7.09%; 2017: 7.17%; 2018: 7.28%; p < 0.05) 85,86. In Obstetrics, a higher premature birth rate means that more babies may develop mental retardation. This USA data suggests that a great scale of PGS since 2015 has been associated with significantly harmful effects on those children’ mental functions.

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(Note: In Australia, birth defect after PGT was reported as 11.0% (17 / 155 = 11.0%), while natural birth defects in Australia population is 1.7% each year. Embryo biopsy in PGT increased 5.5 times of birth defects. It is a horrible result of embryo biopsy. When DNA in the nuclei of cells are intact, the sharp increase of birth defect is closely related to any damage or deformation of the cytoplasm during embryo biopsy. Data reported by Lewis et al., RBMO 2021, 42: 609-619).

 

C. Blastocyst biopsy and freezing are unsafe

During blastocyst biopsy, about five cells are removed from the trophectoderm by laser cutting. Most of the other trophectoderm cells are pulled and deformed, which harm microtubules severely. When the laser beam breaks through the trophectoderm, the blastocyst cavity will collapse and shrink fast. The inner cell mass will usually be rapidly pulled towards the laser biopsy location, thus making it susceptible to direct and strong laser radiation. Some of the remaining trophectoderm cells, which will become part of the placenta, will be directly radiated or killed by the laser beam during the laser cutting. In this manner, blastocyst biopsy will not only lead to inconsistent or even wrong genetic results due to the broken biopsied cells and the fractured, contaminated chromosomes, but also lead to unhealthy development of the placenta and fetus.

 

Cryopreservation itself is also not safe. In a mice experiment, the fluorescence intensity of both vitrified and slow frozen embryos was significantly lower for tubulin, actin, and nucleus compared to that in non-cryopreserved embryos (p <0.001) 87. Vitrification had a higher incidence of damaged blastomeres compared with fresh embryos. And the proportion of abnormal spindles was significantly higher in vitrified/warmed embryos (p<0.05) 88. “The level of abnormally shaped spindles, often associated with chromosome lagging, or congression failure, was significantly higher in the vitrified group compared with the fresh group (p<0.05)” 89. Cryopreservation also increases aneuploid cells in the embryos. “Significantly (p<0.05) higher proportion of chaotic embryos in the study (24.1%) compared to the control group (6.3%) was observed”90.

 

Cryopreservation immediately following embryo biopsy is also unsafe. Any surgeon understands that if two major surgeries are performed in succession on the same patient on the same day, most bodies cannot handle the stress. This is similar for embryos because embryos also need time to recuperate51 between embryo biopsy and freezing. Current cryopreservation procedures are less successful when biopsied human embryos are cryopreserved91. The implantation rate in the biopsied vitrified-warmed transferred embryos was significantly lower than that in biopsy-fresh transferred embryos (p <0.05) 13,92.

 

D. Horrible “Eugenics”

PGS has led to the discarding of a large number of human embryos that are diagnosed as “aneuploidy” or “mosaicism”. If 60% of human embryos were diagnosed as aneuploidy or mosaicism, in which there were identical repeated results in 24.5% (13/53) 93, the misdiagnosed and discarded embryos would be 60% X (1 - 24.5%) = 45.3%. The Society for Assisted Reproductive Technology data of all age groups in 2016 showed 120,160 IVF cycles94. If the average number of embryos for PGS per cycle was five and only half of these patients underwent PGS, the total number of discarded embryos would be 5 X ½ X 120,160 X 45.3% = 136,081. If 30% of these embryos could have developed into babies and the 2017 to 2019 IVF data was the same as that in 2016, the total number of embryos “discarded” that could have developed into healthy foetuses (from 2016 to 2019) would be 136,081 X 30% X 4 = 163,297. Thus, the large-scale use of PGS results in a holocaust of “Eugenics”. This is an unsafe, inhumane, and unethical practice.

 

Embryo biopsy syndrome explained by Epicytohetics

In March 2019, U.S. Congress issued “Personhood” concerns about PGS. These legitimate concerns included: First, wrong concepts of “aneuploidy” and “mosaicism” in human embryos. Second, PGS causing misdiagnoses in heredity. Third, many healthy human embryos to be discarded. Fourth, safety problems of embryo biopsy in PGS. The third and fourth concerns are discussed in detail in the above sections.

 

Why will improper embryo biopsy produce unhealthy babies with embryo biopsy syndrome? This is because the biopsy may deform and harm the cytoplasm of the remaining embryonic cells, which results in poor differentiation of cytoplalsm. Epicytohetics, the study of expression of cytoplasm, explains how cytoplasm damage can lead to abnormal, unhealthy phenotypes in offspring with normal genome (DNA)12.

 

Two animal and one human model showed results of altered phenotype in offspring when the cytoplasm (or cytoskeletons) was changed. In the first case, in freshwater animal Hydra, the axis direction of actin (i.e. the polarity) in excised pieces determined whether the regenerating offspring would be normal (single body axis) or abnormal (multiple body axes). When the excised polarity was abnormal, about two-thirds of offspring showed abnormal body axes or multiple axes. When the excised axis direction was correct, only about 10% of offspring showed abnormal body axes or multiple axes64. This study confirmed that damage of the cytoskeleton (rather than DNA) and its direction can produce abnormal expression in offspring. In the second case, cloning a Polo horse of the same genotype (i.e. the same genome or DNA) produced many different cytotypes (or phenotypes) in the cloned offspring because they were cloned with the different cytoplasm of the recipient oocytes. The different recipient cytoplasm contains different cytoplasmic spatial structures, polarity and cytoskeleton configuration after their nuclei are removed. This causes many different phenotypes to be produced, from different defects to different abilities in the cloned Polo horses95. This shows that phenotype is determined not only by gene (genotype) but also by cytoplasm (cytotype). In human, improper change of cytoplasmic condition will lead to unhealthy phenotype (such as neuropathy and immune problems) in offspring and heredity96. The reason is:

 

The cytoplasm (such as cytoskeleton and microtubules) is closely related to differentiation. When microtubules are abnormal, they will lead to increased neuronal branching, shortened neurites, axons that do not connect to postsynaptic cells, and impaired synapse functioning67,97-101. These abnormal microtubules do not return to their normal length, numbers, or spatial positions in the embryonic cells, and such abnormalities can be inherited to the further differentiated cells. Thus, the abnormal microtubules can produce abnormal neuron or mental function76,82,83,102.

 

Normal functioning of neutrophils, macrophages and lymphocytes in the immune system also depend on intact cytoskeletal and cytoplasm structures103,104. Altered cytoskeletal structure will influence normal development of both neural and immune systems simultaneously105-107. Thus, immune problems are another consequence of abnormal cytoplasm, which cannot be diagnosed by any DNA or genetic tests due to the normal DNA and genes96.

 

In muscles, cytoskeleton actin filaments slide past myosin filaments toward the middle of the muscle unit sarcomere to produce muscle contraction108. The heart is the most heavily worked muscle in the body. Even subtle changes in these cardiac-specific contractile proteins – changes that would not cause any noticeable consequences in other tissues – can cause serious heart disease. It can also result in early heart failure103. Thus disturbance of the cytoskeleton will likely produce severe muscle and heart problems. Stillbirth and perinatal mortality can result from this52,72,73,81.

 

In brief, cells are the basic unit of the organs in the human body. Changes or deformation in the cellular cytoskeletons will produce inferior cellular structures and inferior differentiation of all kinds of cells. These cells appear morphologically normal under the microscope, but their microtubules (i.e. the future nerve fibers after cell differentiation) were obviously observed with cut and broken points by laser with nanotechnique - electron tomography21. These harmed and inferior cells produce inferior organs and systems (such as inferior placenta) with inferior functionality71, ultimately producing complications such as premature births, babies with low birth weight, children with low body weights73,79,80,85,86, and different types of neuropathy83. Although these less healthy babies contain normal DNA and genes (i.e. they have normal genetics), they have abnormal cytoskeletons in Epicytohetics.

 

Conclusion

PGS (PGT-A) is a large-scale practice that does not adhere to the indication of major medical surgery on human embryos for prevention of severe hereditary diseases. The designers of PGS assumed that embryo biopsy, especially blastocyst biopsy, is safe enough to practice on the general population. They also assumed that all of the babies born after embryo biopsy would be healthy and the number of births is high enough to suggest that those babies would be normal. The hypothesis of PGS is to screen out the “aneuploid” or “mosaicism” embryos, and the “euploid” embryos would lead to healthier babies. PGS is subjective and lacks scientific basis in embryo differentiation. It is based on the wrong theory that DNA is the only hereditary material in human beings and only Epigenetics is related to the health of babies. PGS neglects the hereditary function and differentiation function of cytoplasm in the nervous system, immune system and muscle system in Epicytohetics. PGS breaks down the normal internal and external environment of human embryos by laser radiation, blastocyst biopsy and freezing. The traumatic embryo biopsy techniques will be harmful to future babies with embryo biopsy syndrome. The embryo biopsy syndrome in these babies will be inherited to future generations. The embryo biopsy syndrome showed that the manipulators were lack of knowledge, method, skill and evaluating ability to safely perform embryo biopsy. Thus, PGS and laser biopsy should be discontinued in clinical practice as producing a healthy baby is the first consideration for parents and society.

 

 

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