Pgd/pgs – Pre-implantation Genetic Diagnosis

Recent scientific progresses allowed the identification of inheritable genetic diseases and/or chromosomal abnormalities already in the early phases of embryo development, before a pregnancy is established. The procedure is known as Pre-implantation Genetic Diagnosis and is performed during a cycle of in-vitro fertilization.


Preimplantation Genetic Diagnosis can be performed for two different purposes:


    • PGD, namely the diagnosis of monogenic diseases in the embryo in presence of a specific mutation in the parental genome which predisposes to an increased risk of transmitting a genetic disease to the offspring (e.g., cystic fibrosis, beta-thalassemia, etc.).


  • PGD-A or PGS (Preimplantation Genetic Diagnosis for Aneuploidies), which is applied to identify de novo chromosomal abnormalities and that represents the broadest indication to preimplantation genetics at present. In the case of PGD-A, the method used for the chromosomal analysis is identical for all the patients. The main aim of PGD-A is to improve the efficiency of IVF by minimizing the risks associated with reproduction in infertile couples and especially with advanced maternal age.

Couples who undergo an IVF cycle may require to be informed about the state of health of the embryos produced (Article 14, Italian Law No. 40/2004). In these cases, and depending on each specific indication, they can proceed with PGD. The diagnosis is performed starting from a small cellular biopsy from the embryo(s) obtained during the cycle.


In the most experienced and technologically-advanced centers, the material on which the genetic testing is performed consists of multiple cells taken at day 5/6/7 of embryo in-vitro development from a portion of the blastocyst known as trophectoderm. This stage of embryo development ensures a greater reliability of the genetic analysis, as well as the absence of any impact upon embryo reproductive potential following the biopsy, which implies that the embryo is not harmed at all by this procedure. The cells are collected through a micromanipulator to be then put into PCR test tubes and sent to a genetic center where the analysis will be carried out (the figure below is a sequence representing the biopsy procedure). In the GENERA centers trophectoderm biopsy has been performed since 2011 according to the method represented hereafter, which has been published in 2014 in the prestigious journal Human Reproduction (Capalbo et al., Human Reproduction 2014).


Nowadays, PGD-A is definitely the main application of genetics technologies in the preimplantation era. Its aim is the improvement of the efficiency of an IVF cycle by providing a safer IVF treatment, especially in terms of lower miscarriage and multiple pregnancy rates, as well as no risk for chromosomally abnormal pregnancies.

It is well known that as a woman’s reproductive age increases, there is also an exponential increase of the chromosomal abnormalities in the embryos she produces, as shown in the figure hereafter adapted from an important study based on the analysis of more than 15,000 blastocyst biopsies (Frasiniak et al., Fertility and Sterility 2014).



The aims of PGD-A are:

  • To decrease the miscarriage rate (on average in 39 years old patients the miscarriage rate is about 40%, but through PGD-A this rate drops down to 7-8%);
  • To minimize the incidence of pregnancies of fetuses affected by chromosomal abnormalities such as Down Syndrome, trisomy 13 and 18, …;
  • To avoid unnecessary time spent by waiting for a negative pregnancy test (on average a patient of 39 years produces 60% of aneuploid blastocysts and 35% of IVF cycles undertaken at this age do not have any chromosomally normal embryo);
  • To increase the full-term delivery rate of a healthy baby per embryo transfer (which increases on average up to 50% regardless of a woman’s age, provided that at least one normal embryo is identified by PGD-A);
  • To minimize the occurrence of twin and multiple pregnancies (after being defined through aneuploidy testing, normal embryos show a very high implantation potential, therefore single embryo transfer could be performed with high confidence. Double or multiple embryo transfer can be avoided, and the incidence multiple pregnancies can be minimized. This in turn prevents all the obstetrical and neonatal risks related with them);
  • To reduce the precious time that a couple needs to invest to achieve a healthy full term pregnancy.


PGD is mainly performed through three different molecular techniques:

  • PCR (Polymerase Chain Reaction), which is mainly used for the diagnosis of monogenic diseases;
  • SNP (Single Nucleotide Polymorphism) microarray, which is mainly adopted to carry out comprehensive chromosome testing (at our center it is mainly used for couples who are carriers of reciprocal translocations or other structural abnormalities);
  • qPCR (quantitative Polymerase Chain Reaction), which can detect whole chromosome aneuploidies for all the 24 chromosomes in our genome. This method, which is exclusively provided by our center in Europe, ensures the highest diagnostic accuracy in reporting these chromosomal abnormalities in PGD.

The molecular analysis method adopted for PGD at GENERA centers is qPCR, a platform for the screening of all 24 chromosomes, that ensures maximum reliability and diagnostic accuracy as demonstrated in several scientific publications (Treff et al., Fertility and Sterility 2012; Capalbo et al., European Journal of Human Genetics 2014). An example of the results obtained after the analysis of 24 chromosomes via qPCR is shown in the following figure.


For the summary of the results obtained at our center during PGS cycles, go to Success Rate

All diagnostic tests are carried out by the GENETYX laboratory