Preimplantation Genetic Diagnosis of Monogenic Diseases (PGD-M)

Preimplantation Genetic Diagnosis of Monogenic Diseases (PGD-M)

Preimplantation genetic diagnosis of monogenic diseases (PGD-M) is a state-of-the-art technique that enables couples who wish to have children to detect hereditary monogenic diseases before the embryos are implanted in the uterus. This technique is particularly important for couples who are known to be carriers of hereditary diseases or have a high risk of transmitting them. The steps involved in PGD-M are generally as follows:

1. Counseling and Preparation

• Patients go to the genetics laboratory and have a blood sample taken.

• Couples receive genetic counseling and discuss the risks and details of the procedure.

• Appropriate genetic tests are carried out and the couple’s carrier status is determined.

This phase can take between a few weeks and a few months. Couples must be present in Istanbul for at least two days during this phase. It is not necessary to wait for the test results.

2. IVF Procedure (In Vitro Fertilization)

• This phase requires presence in Istanbul for about 15 days.

• Ovarian stimulation: The woman’s ovaries are stimulated by hormone therapy to produce multiple eggs.

• Egg retrieval.

• Fertilization: The retrieved eggs are fertilized in the laboratory with the male partner’s sperm, creating an embryo.

3. Development of the Embryo

• The embryos develop in the laboratory over several days and usually reach the blastocyst stage on the fifth day.

4. Biopsy and Genetic Testing

• This stage lasts a few weeks.

• Biopsy: A few cells are carefully removed from the blastocyst embryo without damaging it.

• Genetic testing (PGD-M): A genetic test is carried out on the removed cells to identify certain genetic diseases. This test is used to determine whether the disease is present or not.

5. Embryo Selection

• Healthy, disease-free embryos are selected based on the results of the genetic tests. The aim of this step is to maximize the probability that the child will not carry the genetic disease.

6. Embryo Transfer

• The woman must stay in Istanbul for 3 to 4 days for this step.
• The selected embryo or embryos are transferred to the partner’s uterus. After the transfer, a certain period of time must be waited to determine whether the pregnancy has been successful.

7. Pregnancy Test

• A pregnancy test is carried out approximately two weeks after the embryo transfer.

PGD-M is an advanced technology that can prevent the transmission of genetic diseases from one generation to the next. This procedure offers couples the opportunity to have genetically healthy children, but also raises ethical and moral considerations. It is important that couples are informed and supported at every stage of the process.

The process of preparing genetic tests (gene configuration) in the laboratory is crucial, especially for complex procedures such as preimplantation genetic diagnosis (PGD). This process involves several steps, from identifying the specific genetic markers used to detect carriers of genetic diseases or conditions to verifying the applicability of the test. Below is a step-by-step description of the process for preparing genetic tests in the laboratory:

Disease and Mutation Identification

• The first step is to clearly identify the specific genetic disease for PGD and the mutation(s) causing that disease. This step usually begins with the information the couple receives during genetic counseling.

Selection of Genetic Markers

• Once the specific mutations of the gene(s) responsible for the disease are identified, genetic markers capable of detecting these mutations are selected. These markers allow precise detection of the genetic variations associated with the disease.

Preparation of Reference DNA

• To assess the accuracy and sensitivity of the genetic test, reference DNA samples with (positive control) and without (negative control) mutations are usually prepared. In this way, the specificity and sensitivity of the test can be measured.

Optimization of the PCR (Polymerase Chain Reaction)

• PCR is a technique for amplifying a specific part of DNA. The optimization of PCR conditions is necessary for the amplification of specific genetic markers to be used for PGD. This guarantees the sensitivity and specificity of the test.

Design and Optimization of Probes

• In some cases, specially designed probes are used to detect specific genetic mutations. These probes bind specifically to the target DNA sequence and are labeled to detect the presence or absence of the mutation.

Experimental Validation

• To verify the accuracy of the prepared genetic test, experiments are carried out on samples with and without previously known mutations. This validation process guarantees the reliability of the test and its suitability for clinical use.

Quality Control

• Quality control procedures are carried out before and after each test application. They guarantee the consistency and reliability of the test results.

Reporting and Interpretation

• The test results are reported in detail for use in genetic counseling. These reports help couples and doctors to understand the genetic situation and possible risks.

This preparation process is fundamental to the success of genetic testing and PGD in particular. Each step must be carefully planned and executed to maximize the accuracy, reliability, and applicability of the test in the clinical context.