Initially, PGT was based on polar body sampling and embryo biopsy at the cleavage stage, but the present standard shifted to blastocyst biopsy. The polar body approach is still, however, the only possibility for the ethnic groups where no embryos micromanipulation is allowed. The Preimplantation Genetic Diagnosis International Society (PGDIS) and the European Society of Human Reproduction and Embryology (ESHRE) Consortium have published an extensive set of best practice guidelines for PGT.26, 27 These recommendations cover PGT organization, genetic and treatment‐related counseling, psychologic evaluation, patient selection, all applicable technical issues, and quality control. The developments of preconception and PGT and the existing problems in the application of these early approaches to clinical practice are presented in this chapter, based on our 30 years' experience of over 22,000 PGT cycles, including 15,700 PGT‐A, 491 PGT‐HLA, and 6,778 PGT‐M, involving a spectrum of, approximately, 600 different monogenic conditions (Table 2.1).
Table 2.1 List of conditions for which preimplantation genetic testing (PGT) was performed and PGT‐M outcome: 30 years of original experience.
| Conditions | Gene | Type of inheritance | No. patients | No. cycles | No. embryo transfers | No. embryos transferred | Pregnancy % | No. deliveries |
|---|---|---|---|---|---|---|---|---|
| 3‐Hydroxyisobutyryl‐CoA hydrolase deficiency (HIBCHD) | HIBCH | AR | 1 | 1 | 1 | 2 | 0 | 0 |
| 3‐Methylglutaconic aciduria with deafness, encephalopathy, and Leigh‐like syndrome (MEGDEL) | SERAC1 | AR | 1 | 1 | 1 | 1 | 0 | 0 |
| Achondroplasia (ACH) | FGFR3 | AD | 8 | 17 | 11 | 14 | 7 | 6 |
| Achromatopsia 2 (ACHM2) | CNGA3 | AR | 1 | 1 | 1 | 1 | 1 | 1 |
| Achromatopsia 3 (ACHM3) | CNGB3 | AR | 3 | 4 | 4 | 5 | 2 | 2 |
| Acromesomelic dysplasia, Maroteaux type (AMDM) | NPR2 | AR | 1 | 1 | 2 | 2 | 1 | 1 |
| Acyl‐CoA dehydrogenase, medium‐chain, deficiency | ACADM | AR | 3 | 8 | 7 | 14 | 4 | 4 |
| Acyl‐CoA dehydrogenase, very long‐chain; (ACADVL) | ACADVL | AR | 5 | 6 | 6 | 11 | 2 | 2 |
| Adrenal hyperplasia, congenital, due to 21‐hydroxylase deficiency | CYP21A2 | AR | 23 | 34 | 26 | 42 | 17 | 17 |
| Adrenoleukodystrophy (ALD) | ABCD1 | XL | 17 | 33 | 20 | 29 | 11 | 11 |
| Agammaglobulinemia, X‐linked (XLA) | BTK | XL | 4 | 7 | 7 | 13 | 3 | 3 |
| Aicardi–Goutieres syndrome 5 (AGS5 + CF) | SAMHD1 | AR | 1 | 2 | 2 | 2 | 1 | 1 |
| Alagille syndrome 1 (ALGS1) | JAG1 | AD | 1 | 1 | 1 | 1 | 1 | 1 |
| Albinism, ocular, type i (OA1) | GPR143 | XL | 1 | 12 | 5 | 9 | 4 | 3 |
| Albinism, oculocutaneous, type ia (OCA1a) | TYR | AR | 4 | 7 | 6 | 9 | 3 | 3 |
| Albinism, oculocutaneous, type ii (OCA2) | OCA2 |