Pre-natal (birth) NIPT

---

Non-invasive prenatal testing (NIPT) is a method used to determine the risk for the fetus

being born with certain chromosomal abnormalities. The test normally only involves

blood drawing from pregnant women, therefore, is noninvasive. 

The chromosomal abnormalities include the most common aneuploidies, such as Trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome), as well as the additional items, such as sex chromosome aneuploidies, rare autosomal aneuploidies, 22q11.2 microdeletion (DiGeorge syndrome), other microdeletions, and microduplications. The NIPT can also report fetal sex and fetal fraction (if requested by parents).

The NIPT analyzes small DNA fragments (<200 bp) in the maternal blood called cell- free fetal DNA (cffDNA) that present in the blood of pregnant women. The fetal DNA molecules are free floating outside of cells and represent a median of 10.2% of total cell-free DNA between 10 and 11 weeks of pregnancy. The discovery of cffDNA has opened possibilities to analyze fetal genetic materials in a noninvasive manner without posing any risk to the fetus.

For physicians, it is important to recommend this test for pregnancies where:

• A high risk for abnormality is found serum screening.
• Certain abnormalities on ultrasound are identified.
• There is a family history of chromosomal conditions or birth defects.
• Couples have had a child with a chromosomal disorder.
• A couple has a history of infertility or pregnancy loss (miscarriages or stillbirths).

All pregnant women who need insight into their baby’s development can benefit from

the test, regardless of their age. NIPT is recommended for all types of pregnancies. Medical societies today support the use of NIPT as the first line of screening for all pregnancies, irrespective of the risk.

Numerous novel techniques have been developed to utilize the cfDNA for NIPT; We apply the NGS technology which has high accuracy (99,9%). 

We offer testing using Illumina technology Sequencing of the full fetal genome which provides a comprehensive view of the chromosomes. 

This method offers an enhanced counting technique along with cutting edge algorithms to determine the risk of aneuploidies based on a ratio between chromosomes of interest to multiple reference chromosome.

• Helps identify fetuses at risk of serious chromosomal abnormality
• Gives reassurance to expecting parents
• Leads to better management of a child’s genetic health by providing early information.
• Prepares for birth and early intervention wherever possible

The inability to achieve and maintain a pregnancy and is considered a major disease of the reproductive system. 

Infertility affects approximately 1 in 6 couples worldwide. In couples experiencing pregnancy delay, male infertility accounts for about 35% and female infertility for about 45% of the cases. The remaining cases are caused by a combination of male and female factor.

Infertility can be caused by many reasons, including genetic changes. 10-15% of men and women have genetic changes associated with infertility.

In males, in 65% of infertility cases, diagnosis of infertility is achieved by biochemical and instrumental testing, such as hormone checks, ultrasounds and semen analysis.

Biologically, formation of sperms (spermatogenesis) is genetically complex and requires an orchestrated expression of over 4000 genes. It is currently estimated that known genetic factors such as chromosomal abnormalities, aneuploidies, Y chromosome microdeletions, and single-gene defects are responsible for at least 15%–30% of male infertility. 

Several studies have identified additional genetic factors that include single-gene and multiple-gene defects that are associated with male infertility in the past two decades. 

However, despite of the genetic screening, the etiology remains obscure in most infertile men (~40%),

Genetic abnormalities leading to infertility in females comprise:

• large chromosome abnormalities such as Turner syndrome (monosomy X),
• submicroscopic chromosome deletion and duplications, and
• DNA sequence variations in the genes that control numerous reproduction biological processes such as oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs.

Primary ovarian insufficiency (POI) is one of major conditions associated with female infertility. This condition can be related to abnormal chromosome segregation, deficiency in DNA repair, insufficient hormonal synthesis or signaling, defects in pathways that affect folliculogenesis, oocyte maturation and/or ovulation.

In women with POI, genetic testing provides early identification which is invaluable as

egg harvesting and cryopreservation at a young age can be performed to preserve fertility.

Also called Pre-implantation Genetic screening: is a test that examines chromosomal material of an in vitro fertilized (IVF) embryos before implantation. It involves removing one or more cells from an IVF embryo to test genetic defects.

• PGT-A: Detects Numerical chromosomal abnormalities (aneuploidy).
• PGT-SR: Detects chromosomal Structural rearrangements (Translocations) abnormalities
• PGT-M: Detects Single gene analysis, for families with risk of articular genetic disease.

PGT is done after fertilization when the embryo is 3 to 5 days old. At this stage, there are enough cells from which the DNA can be isolated, thus ensuring test success. 

We apply the NGS technology for PGT. NGS compared to other methods:

• Rapid and convenient
• Screening of all 23 pairs of chromosomes for abnormalities in one test
• Able to detect greater than 10 Mb gains and losses in chromosomes
• Higher resolution – 1Mb areas are analysed to provide data with high confidence
• High sensitivity in detecting Aneuploidy (100 % sensitivity)
• High specificity and accuracy (99.98% specificity)
• Lower chances of test failure with NGS

PGT-A screening method facilitates the selective implantation of embryos that have a

normal number of chromosomes (Euploid Embryos).

• One in two human preimplantation-IVF embryos are chromosomally abnormal.
• Up to 40% of morphologically normal embryos harbor aneuploidies.

Most common conditions that are detectable by PGT-A are:

• Turner Syndrome
• Klinefelter Syndrome
• Down Syndrome
• Edwards Syndrome
• Patau Syndrome
• Other trisomies and monosomies that increase the risk of implantation failure and miscarriage
• Segmental Gain and Losses (>10Mb) in chromosomes which can lead to abnormalities in the embryo

Structural rearrangements in chromosomes can include events like translocations. These rearrangements can sometimes lead to infertility, miscarriage, or genetic disorders in offspring.

PGT-SR helps identify embryos that carry these structural abnormalities before implantation, allowing individuals and couples to select embryos with a normal chromosomal structure, thereby increasing the chances of a successful pregnancy and healthy baby.

Genetically inherited diseases may pass on to the children. PGT-M test would help to select a healthy embryo from parents known to be carriers of X-linked or single gene disorders or have a child affected with an inheritable disorder.

• PGT-M can test for most single gene disorders
• PGT-M allows the clinician to select embryos that do not carry the single gene disorder being tested for the implantation
• By using PGT-M the single gene disorder can be prevented from being passed on from one generation to the next

PGT is recommended for:

• Couples undergoing IVF
• Advanced maternal age
• Patients with repeated implantation failure or recurrent pregnancy loss while undergoing IVF
• Women over 35 years old undergoing IVF
• Couples with recurrent miscarriages
• Positive history of chromosomal abnormalities in the family
• Diagnosed carriers of chromosomal aberrations

• Reduces the number of IVF cycles required to achieve a successful pregnancy. 73% pregnancy rate with PGT-A vs 36% without using PGT-A
• Increases success rate for single embryo transfer
• Reduces the likelihood of miscarriage due to Aneuploidies
• Increases reproductive success rates in women above 35 years
• By using PGT-M the single gene disorder can be prevented from being passed on from one generation to the next