Clinical Outcomes Following Preimplantation Genetic Diagnosis

Data on the clinical outcomes were reported from 1416 PGD embryo transfer cycles performed in our centre [1] and from 1670 PGD transfer cycles collected from 25 different centres by ESHRE PGD Consortium [2]. These transfers resulted in 338 (23.9%) and 309 (18.5%) clinical pregnancies, respectively, and birth of 539 unaffected children, overall (260 and 269, respectively), with multiple pregnancies observed in approximately one third of the cases. The overall congenital malformation rate was 5.4% and 6.6%, respectively, which is not different from population prevalence, of which only 2.25% and 3.9%, respectively, were attributable to the major abnormalities.

Overall, approximately 7000 PGD cycles have presently been performed, with further wider application not only in the United States and Western Europe, but also in the Eastern Mediterranean and Asian countries. Also, an increasing number of PGD cases are being performed for conditions that have never been practiced in traditional prenatal diagnosis, such as preimpantation gender determination for social reasons, performed in India [3] and Jordan [4]. However, the majority of PGD cycles are still performed for chromosomal disorders, with the ratio of PGD cycles for chromosomal and single-gene disorders ofapproximately 3:1, the latter including late-onset disorders with genetic predisposition, the proportion of which is gradually increasing. Approximately 2000 PGD cycles have currently been performed for singlegene disorders, with outcome data available for hundreds of clinical pregnancies and babies, sug-gestingthe acceptable accuracy ofPGD, which may be further improved by the above-mentioned new developments in DNA analysis of single cells (see Chapter 2). As presented in Chapter 3, a relatively high pregnancy rate (approximately 39%) was observed in PGD for single-gene disorders, despite transfer of only 2.2 embryos per cycle on the average. This maybe explained by the fact that these are fertile couples of younger reproductive age (under 35 years) compared with the poor-prognosis IVF patients referred for aneuploidy testing.

In PGD for chromosomal disorders, the indications are also expanding, with further obvious interest in PGD for translocations, because of a strong impact of PGD on reducing the spontaneous abortion rate in carriers ofbalanced translocations. The majority of these cycles have been performed in two centres, including Reprogenet-ics and ours [5-7], with an increasing number of other centres, which performed a few dozen PGD cycles for translocations, such as the Brussels [8], SISMER [9], London [10], and Seoul [11] centres. The available experience demonstrates a clear advantage of PGD for translocations over traditional prenatal diagnosis, as shown above, attributable to a poor meiotic outcome, particularly in reciprocal translocations (see Section 5.2). As mentioned, the accuracy ofPGD for translocation has recently been improved by the introduction of increasing numbers of subtelomeric probes and the technique of blastomere nucleus conversion to metaphase, which will allow a reliable testing for any complex chromosomal rearrangement. The experience of more than 500 cycles accumulated at the present time further confirms the previous

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