Preimplantation Genetic Testing for Aneuploidy (PGT-A)

The preimplantation genetic testing for aneuploidy (PGT-A) process comprises 7 steps and can take 6 to 8 weeks, depending on various factors like the IVF protocol used by your doctor, preparation required, and PGT-A process duration. Although the process is standardized, there is room for personalization and adjustments. The success rate of an IVF/ICSI + PGT-A considering the transfer of a euploid embryo is around a 50-55% clinical pregnancy rate. The indications for this technique most of the time include female age > 35 years old, recurrent miscarriage, implantation failure, and previous failed cycles among others. Embryo transfer occurs on a subsequent cycle after checking for chromosomal abnormalities. Below are the steps involved in the process:

​

1. Assessment to determine suitability for treatment.

• Blood tests such as AMH, FBC, TSH, and PRL are typically conducted alongside a transvaginal scan to assess the ovaries and uterus. The scan helps determine the ovaries' accessibility, and the number of antral follicles (antral follicular count or AFC), and ensures no cysts are present. The blood test helps determine the appropriate medication, dosage, and treatment prognosis in terms of the potential number of collected eggs. The scan also checks the uterus and its lining to ensure no fibroids or polyps are present. On the male side, it's essential to check semen analysis (SA) to know all the parameters and determine if IVF is the appropriate technique. If one or more parameters are altered, then intracytoplasmic sperm injection (ICSI) would be recommended. Some clinics request DNA fragmentation or hormonal profiles for the male partner too, as standard requirements.

 

2. Preparation for an in-vitro fertilization cycle

• Sometimes is recommended to take certain medications and supplements to optimize the quantity and quality of eggs retrieved and to improve sperm motility. These include Co-Q-10, a contraceptive pill, norethisterone, DHEA, and Testosterone gel. Preparation for females usually takes up to 3 weeks (21 days) whereas for males it can take up to 3 months. It is important to discuss with your doctor if preparation is recommended in your specific scenario.

 

3. Stimulation of ovaries using gonadotropins.

• During this stage, which lasts for about 10-12 days, the ovaries are stimulated with medications to induce follicle growth. Transvaginal ultrasounds are performed during this time to monitor the ovaries and count the number of follicles and their size. Blood tests are also taken to measure the estradiol level, which helps evaluate ovarian response. When follicles reach a size of 17-22 mm, a trigger shot is administered, and the patient is scheduled for an egg collection procedure typically 34-36 hours after the last injection.

 

4. Eggs are collected and then fertilised using IVF or ICSI.

• The egg collection procedure, commonly known as EC, is a 15-20 minute process carried out in a theatre. The method of performing the procedure varies based on the clinic and country policies and can be done under conscious sedation, local anaesthetics, or general anaesthesia. A transvaginal ultrasound probe is used to access the ovaries and extract as many eggs as possible. Once the procedure is completed, the follicular fluid and eggs are sent to the lab for assessment. This allows the embryologist to provide more feedback to the patients if required. The eggs are then either subjected to ICSI fertilisation or are combined with sperm for attempting IVF. The day after the EC the patients are informed about how many embryos were created and the next steps for instance the biopsy and elective freeze on day 5 and day 6.

 

5. Biopsy and genetic testing of the embryos.

• When the embryos have good morphological grading at the blastocyst stage, the embryologists perform a biopsy of the outer part of the embryo known as trophectoderm. The embryo is then frozen. Experts do the biopsy, and the risk of damaging the embryo is less than 2%. The biopsies are then sent to a PGT lab for analysis and to obtain the chromosomal genetic information. This helps determine the viability of the embryo for transfer. We typically only transfer euploid embryos, and in some cases, mosaic embryos are transferred after genetic counselling.

 

6. Preparation of the uterus & Embryo transfer procedure (ET)

• In preimplantation genetic testing for aneuploidy process, the embryo transfer procedure is often performed under a medicated cycle. This is also known as Medicated FET. The patient begins with estrogen (E2) medication on the first day of her menstrual period to prepare the lining of the uterus. Around two weeks after starting the preparation, a transvaginal scan is conducted to assess the thickness and pattern of the lining. If both parameters are good, the patient is given progesterone administration (P4) to open the implantation window. The patient is then scheduled for an ET after five full days of progesterone. The procedure is conducted in a theatre that is close to the lab. Most of the time, sedation is not required, and the entire process takes only 10-15 minutes. During ET, a vaginal procedure is performed where doctors insert a gynae speculum and an embryo transfer catheter. The embryo is then carefully placed inside the cavity of the uterus. To ensure accurate placement, the majority of clinics perform the procedure under abdominal ultrasound guidance.

 

7. Pregnancy test 

• The pregnancy test should be conducted normally after 10-14 days following the embryo transfer on the blastocyst stage (day 5). It is recommended to have a determination of B-HCG level in the blood rather than a urine test, as it is more precise. If the result is positive, instructions will be given to return after 4-6 weeks to perform a transvaginal scan to check the viability of the embryo. If the result is negative, the medication intake will stop and a conversation with your doctor will occur in most cases.