Indications for PGD

- Recurrent Miscarriage 
- Unsuccessful IVF Cycles (>2)
- Unexplained Infertility 
- Advanced Maternal Age
- Male Factor Infertility 
- History of Chromosomally Abnormal Child or Pregnancy
- Family history of structural chromosomal condition
- Family history of X-linked disease
- Inherited genetic disorders

Currently, there are mainly two groups of patients for which PGD is indicated.

• The first group consists of couples with a high risk of transmitting an inherited condition. This can be a monogenic disorder (autosomal recessive, autosomal dominant or X-linked disorders) or a chromosomal structural aberration (such as a balanced translocation). Generally, these couples oppose to prenatal diagnosis followed by selective termination of pregnancy, either for moral or religious reasons or because they have undergone already several abortions. In addition, there are infertile couples that carry an inherited condition, which opt for PGD as it can be easily combined with their IVF treatment.

• The second group consists of couples that undergo IVF treatment and whose embryos are screened for chromosome aneuploidies (PGS) to increase the chances of an ongoing pregnancy. The main indications for PGS are an advanced maternal age, a history of recurrent miscarriages or repeated unsuccessful implantation. It has also been proposed for patients with obstructive and non-obstructive azoospermia. 


Nowadays, PGD is available for a large number of monogenic disorders. The most frequently diagnosed autosomal recessive disorders are cystic fibrosis, Beta-thalassemia, sickle cell disease and spinal muscular atrophy type 1. The commonest dominant diseases are myotonic dystrophy,Huntington's disease and Charcot-Marie-Tooth disease type 1A; and in the case of the X-linked diseases, most of the cycles are performed for fragile X syndrome, haemophilia A and Duchenne muscular dystrophy. Though it is quite infrequent, some centers report PGD for mitochondrial disorders or two indications simultaneously.

In the case of chromosomal abnormalities, PGD is mainly carried out for reciprocal and Robertsonian translocations, and few cases for other abnormalities such as chromosomal inversions or deletions.

Aneuploidy screening is probably the most frequent indication for PGD, mainly suggested to couples undergoing IVF with an advanced maternal age and for patients with repetitive IVF failure. The principle behind it is that, since it is known that numerical chromosomal abnormalities explain most of the cases of pregnancy loss, and a large proportion of the human embryos are aneuploid, the selective replacement of euploid embryos should increase the chances of a successful IVF treatment. Different studies provide indications that PGS increases the implantation rate (Gianaroli et al., 1999; Munne et al., 1999; Munne et al., 2002; Rubio et al., 2003) and lowers the spontaneous abortion rate (Munne et al., 2005), though other studies indicate that there are no significant differences for patients with an advanced maternal age (Kahraman et al., 2000; Staessen et al., 2004), with a poor implantation rate (Kahraman et al., 2000) or with recurrent idiopathic miscarriages (Platteau et al., 2005). It is thus clear that large randomised-controlled studies are still necessary to measure the real impact of this technique for the different indications. A recent systematic review on PGS can be found in the Cochrane database (Twisk et al., 2006)

A fourth group of indications can be defined that includes all the ethically difficult cases. These include situations such as HLA typing of the embryo, so that the child born out of this treatment could be a cord-blood stem cell donor for a sick sibling. Verlinsky and collaborators described the first case in 2001. HLA typing has meanwhile become an important PGD indication in five countries, USA (Verlinsky 2001), Italy (Fiorentino et al., 2004, 2005), Turkey (Kharaman 2004), Belgium (Van de Velde 2004), Australia (Marshall 2004). The HLA matching can be combined with the diagnosis for monogenic diseases such as Fanconi anaemia or Beta-thalassemia in those cases where the ill sibling is affected with this disease, or be performed on its own for cases such as children with leukaemia. The main ethical argument against is the possible instrumentalization of the child, although some authors maintain that the Kantian imperative is not breached since the future donor child will not only be a donor but also become a loved individual within the family.

Another difficult case is the non-disclosure PGD for Huntington's disease. It is applied in those cases in which the patients do not wish to know their carrier status but want to have offspring free of the disease. This procedure can bring practitioners in difficult situations, e.g. when no embryos are available for transfer and a mock transfer has to be carried out to avoid the patient to suspect that he/she is a carrier and the lack of embryos is due to the fact that they are all affected. The ESHRE ethics task force currently recommends using exclusion testing instead. Exclusion testing is based on a linkage analysis with polymorphic markers, in which the parental and grandparental origin of the chromosomes can be established. This way, only embryos are replaced that do not contain the chromosome derived from the affected grandparent, avoiding the need to detect the mutation itself.

A more recent application of PGD is to diagnose late-onset diseases and (cancer) predisposition syndromes. It can be argued that PGD for late-onset diseases is unethical since the individuals remain healthy until the onset of the disease, usually in the fourth decade of life. On the other hand, the high probability or certainty of developing some disorders, and their incurable nature, can lead to a stressful life, waiting for the first symptoms to occur and to an early death. In the case of predisposition syndromes, such as BRCA1 mutations predisposing to breast cancer, it can be argued that there is no certainty of getting the disease and that the disease can usually be treated. It is a fact that although PGD is often regarded as an early form of prenatal diagnosis, the nature of the requests for PGD often differs from the prenatal diagnosis requests. Some of the widely accepted indications for PGD, such as the previously mentioned, would not be acceptable for prenatal diagnosis.