Preimplantation genetic diagnosis
"[3][4] The term preimplantation genetic screening (PGS) refers to the set of techniques for testing whether embryos (obtained through IVF/ ICSI have an abnormal number of chromosomes (aneuploidy).
[20] A systematic review and meta-analysis of existing randomized controlled trials came to the result that there is no evidence of a beneficial effect of PGP as measured by live birth rate.
[citation needed] A woman carrying the gene for early-onset Alzheimer's disease used preimplantation genetic diagnosis (PGD) to ensure that her child would not inherit this condition.
Potential applications of preimplantation sex discernment include: In the case of families at risk for X-linked diseases, patients are provided with a single PGD assay of gender identification.
Such X-linked Mendelian diseases include Duchenne muscular dystrophy (DMD), and hemophilia A and B, which are rarely seen in females because the offspring is unlikely to inherit two copies of the recessive allele.
[citation needed] PGD has occasionally been used to select an embryo for the presence of a particular disease or disability, such as deafness, in order that the child would share that characteristic with the parents.
PGT-A, also called preimplantational genetic screening (PGS), improves pregnancy rates by allowing the discard of aneuploids and the selection of euploid embryos for transfer.
These errors lead to chromosomal abnormalities, such as aneuploidies (monosomies, trisomies, and polyploidies), which can impair embryo development and result in failed pregnancies or genetic disorders.
Currently, all PGD embryos are obtained by assisted reproductive technology, although the use of natural cycles and in vivo fertilization followed by uterine lavage was attempted in the past and is now largely abandoned.
COH is carried out either in an agonist protocol, using gonadotrophin-releasing hormone (GnRH) analogues for pituitary desensitisation, combined with human menopausal gonadotrophins (hMG) or recombinant follicle-stimulating hormone (FSH), or an antagonist protocol using recombinant FSH combined with a GnRH antagonist according to clinical assessment of the patient's profile (age, body mass index (BMI), endocrine parameters).
Theoretically, the biopsy can be performed at all preimplantation stages, but only three have been suggested: on unfertilised and fertilised oocytes (for polar bodies, PBs), on day three cleavage-stage embryos (for blastomeres) and on blastocysts (for trophectoderm cells).
There are different approaches to both steps, including mechanical, chemical, and physical (Tyrode's acidic solution) and laser technology for the breaching of the zona pellucida, extrusion or aspiration for the removal of PBs and blastomeres, and herniation of the trophectoderm cells.
Another drawback is the increased risk of diagnostic error, for instance due to the degradation of the genetic material or events of recombination that lead to heterozygous first polar bodies.
PZD uses a glass microneedle to cut the zona pellucida which makes it a mechanical dissection method that typically needs skilled hands to perform the procedure.
[39] In an attempt to overcome the difficulties related to single-cell techniques, it has been suggested to biopsy embryos at the blastocyst stage, providing a larger amount of starting material for diagnosis.
This figure is approximately four times higher than the average presented by the ESHRE PGD consortium data, where PB and cleavage-stage biopsy are the predominant reported methods.
On the other hand, delaying the biopsy to this late stage of development limits the time to perform the genetic diagnosis, making it difficult to redo a second round of PCR or to rehybridize FISH probes before the embryos should be transferred back to the patient.
Dual FISH was considered to be an efficient technique for determination of the sex of human preimplantation embryos and the additional ability to detect abnormal chromosome copy numbers, which is not possible via the polymerase chain reaction (PCR).
Several PCR-based assays have been developed for various diseases like the triplet repeat genes associated with myotonic dystrophy and fragile X in single human somatic cells, gametes and embryos.
The main advantage is that NGS can combine the detection of both aneuploidies and monogenic diseases with a single biopsy and has reduced affordable costs, making it more accessible.
Other centres argue that embryos diagnosed as monosomic could be transferred, because the false monosomy (i.e. loss of one FISH signal in a normal diploid cell) is the most frequently occurring misdiagnosis.
With the introduction in Europe of the single-embryo transfer policy, which aims at the reduction of the incidence of multiple pregnancies after ART, usually one embryo or early blastocyst is replaced in the uterus.
[66] Another study suggests that PGS with cleavage-stage biopsy results in a significantly lower live birth rate for women of advanced maternal age.
[71] The prospect of a "designer baby" is closely related to the PGD technique, creating a fear that increasing frequency of genetic screening will move toward a modern eugenics movement.
[78] The first type of argument is mainly made by a part of academia that believes that a disability or disorder likely implies a reduced quality of life for the unborn child.
Such de-selection or selective abortions are incompatible with ethics and human rights standards due to the discrimination perpetrated against intersex people on the basis of their sex characteristics.
[87]PGD combined with HLA (human leukocyte antigen) matching allows couples to select for embryos that are unaffected with a genetic disease in hopes of saving an existing, affected child.
[91] In contrast, the UK's use of PGD is regulated by the Human Fertilization and Embryology Act (HFEA), which requires clinics performing this technique to attain a license and follow strict criteria.
Firstly, in the attitudinal survey, women with a history of infertility, pregnancy termination, and repeated miscarriages reported having a more positive attitude towards preimplantation genetic diagnosis.
[112] The American Society for Reproductive Medicine (ASRM) states that "PGD should be regarded as an established technique with specific and expanding applications for standard clinical practice."
1♀︎ —Eggs are collected from a female by a thin needle passed either through vagina or through abdomen under ultrasound guidance [transvaginal or transabdominal ultrasound aspiration].
2a —The sperm and eggs are fertilized.
2b —The resulting embryos are kept safe and watched to see which will thrive.
3a —The embryos are allowed to develop; those that thrive are given identifiers.
3b —A genetic test is run on each embryo for a given trait and the results are matched with the embryos.
4 —The embryos without the desired trait are identified and discarded.
5 —The remaining embryos are allowed to grow to the point that they can be implanted.
6a —The embryos with the desired trait are implanted.
6b —The embryos result in a healthy pregnancy.
6c —Fraternal twins with the desired trait, not expressed in their mother, are born.