Clinical Management of In Vitro Fertilization With Preimplantation Genetic Diagnosis

Ilan Tur-Kaspa, M.D.


Semin Reprod Med. 2012;30(4):309-322. 

In This Article

The Future of PGD

PGD may now be offered to patients with all known single-gene disorders, chromosomal rearrangement, for HLA-matched siblings, cancer predisposition genes, and for late-onset disorders with or without disclosure.[4,23,121,122,129,133,140,141]

PGS for advanced maternal age, repeated pregnancy loss, repeated IVF failures, and severe male infertility was on the rise until 2007.[25,45,119,122,142–147] So far RCTs have failed to demonstrate the suggested benefit of PGS for advanced maternal age in routine IVF/ICSI treatments when one to two blastomeres were biopsied on day 3 and were analyzed by fluorescent in situ hybridization.[23] New studies analyzing either polar bodies or blastocysts for 24 chromosomes are ongoing in Europe and the United States, and they may shed new light on the use of PGS.[24,26–28] Two leading U.S. ART groups recently achieved outstanding results with PGS. Scott et al[28] conducted the first RCT on 24-chromosome PGS by quantitative polymerase chain reaction and fresh ET on day 5 and 6 in a small group of patients age <43 years. They achieved 92% clinical pregnancy rates in the PGS group compared with 60% in the control. Schoolcraft et al[27] performed PGS by single-nucleotide polymorphism-based microarray after trophectoderm biopsy, cryopreservation by vitrification, and later FETs (mean patient age was 38 years). They achieved a 56% LBR per oocyte retrieval and 71% per ET. The possibility to test for monogenic disorders or translocations together with aneuploidy makes PGD methods even more attractive.[4,136,148,149]

In 2006 Tur-Kaspa et al[150] and Offit et al[140] were the first to suggest that PGD should be viewed as a modern modality of preventive medicine.[5] Taking into account medical and psychological consideration as well as cost-benefit analysis, health-care professionals can contribute to the translation of ART and PGD into the practice of preventive medicine. This can be done by introducing PGD into routine care for families affected by childhood-onset genetic disorders, late-onset diseases, and hereditary cancer, and for children who are in need of HSCT.[4,5,140] Every couple of reproductive age who carry a genetic disorder may clinically benefit from PGD and should be counseled on it.

PGD should be an option not only for the few couples that can afford it.[4,5] IVF-PGD should be offered to all carrier couples that wish to conceive a healthy infant instead of one affected with a genetic disorder. Recently, two independent cost-benefit analyses, by Tur-Kaspa et al[5] and Davis et al,[151] demonstrated that offering IVF with PGD to all carrier couples of cystic fibrosis (CF), as an example, is highly cost effective and can save billions of dollars in direct medical costs. The implications of implementing a national IVF-PGD program for all carriers who wish for this procedure are remarkable not only from an economic perspective but also from a moral and personal perspective for families that carry a genetic disorder. Delivering a healthy infant instead of one affected with a debilitating and life-shortening disease means avoiding not only the direct medical treatment expenses and the significant loss of productivity for the patients and their caregivers over a lifetime but also gaining a normal quality of life. Therefore, Tur-Kaspa et al[5] have suggested that a large-scale national IVF-PGD program as a novel preventive medical strategy for diseases like CF may have a profound potential in modern health-care systems. PGD should be encouraged to become an integral part of any health-care system and should be covered by medical insurances. Once given the option, the final decision is of course for the couple to make. When a cure is found to a specific disease, this rationale should be reevaluated.

Biopsy for PGD may affect implantation potential, but in general seems to be safe, except when two cells are removed on day 3. Children born after PGD have similar outcomes to regular IVF/ICSI infants. Optimization and individualization of ovarian stimulation and collaborations with experienced centers should allow PGD to continue with any number of oocytes/embryos available. SET may be offered to young patients after PGD or PGS for 24 chromosomes[152] with good quality blastocysts to avoid a multiple pregnancy. Better clinical management of IVF-PGD treatments will improve its outcome.


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