Preimplantation genetic diagnosis
Assessment of the genetic status of a preimplantation embryo by biopsy and testing of a single cell is now an option for carriers of genetic anomalies, including single gene defects and chromosome rearrangements.0201 This technology, known as preimplantation genetic diagnosis (PGD), was developed in the early 1990s.
The aim of PGD is to reduce substantially the risk of an abnormal pregnancy, which can be 25% for autosomal recessive disorders such as cystic fibrosis and spinal muscular atrophy, or 50% for some chromosome rearrangements and autosomal dominant single gene defects such as Huntington disease.
Aneuploidy testing is rooted in the world of assisted conception,with the aim of improving the chances of pregnancy and live birth for couples undergoing IVF.
There are some chromosome aneuploidies, notably:-
- trisomy 21 (Down syndrome)
- trisomy 13 (Patau syndrome)
- trisomy 18 (Edwards syndrome)
These are compatible with survival to term, although the majority of such conceptuses are miscarried.
The congenital abnormalities associated with these syndromes may lead to neonatal death or lifelong physical and mental disability.
The removal of embryos carrying these aneuploidies from an IVF cohort would remove the risk of a pregnancy affected by them.
It also seems logical that the transfer of embryos with normal chromosomes should increase the chances of a successful pregnancy, which may be especially important if single embryo transfer becomes normal practice.
Aneuploidy testing was first reported in 1993.9301 It is an expensive and time-consuming test, for which couples are charged in addition to their IVF costs at those centres where it is offered.
In general, four groups of patients have been targeted for aneuploidy testing, although there has been a suggestion that this test should be part of routine IVF care.
The four groups generally targeted are:
older women, as they have an empirically
higher risk of chromosomally abnormal fetuses
-
women who have suffered repeated IVF failure, as
these failures may be the result of a high
prevalence of abnormal embryos in each cohort
-
women who have had recurrent miscarriages
(recurrent abortion), as
they may be caused by chromosome
aneuploidy
-
couples with severe male factor
infertility, as empirical data suggests that
embryos from such cycles have a high
prevalence of aneuploidy.0401
Aneuploidy
testing is now the most common reason for embryo
biopsy, with 1722 cycles submitted to the data
collection for the period January-December 2003.
Three reviews have summarised the studies on aneuploidy testing for raised maternal age
published prior to 2007.
The nonrandomised studies reported
increased pregnancy rates and reduced miscarriage
rates.
Mastenbroek et al.0701 have since published the results of a multicentre, randomised double-blind controlled trial on aneuploidy testing for raised maternal age. This trial found that the ongoing pregnancy and live birth rate was significantly lower in the women who had aneuploidy testing than in the control group. This study is the first to demonstrate that it results in lower success rates, in terms of both ongoing pregnancy and live birth.
Mastenbroek’s study provides additional weight to the arguments against the use of aneuploidy testing as a clinical service, although the design and execution of the Mastenbroek trial have been criticised by those with experience of aneuploidy testing as a clinical service, who suggest that these flaws were responsible for the adverse outcome reported.
Supporters of aneuploidy testing believe that in their hands it is of benefit to couples, not just in terms of pregnancy success rates but by allowing some unfortunate couples to learn that most of their embryos are found to be abnormal.
For women with recurrent miscarriage, there are data to indicate that their chances of successful deliveryare much higher when using natural conception than the published figure for success rates following IVF and aneuploidy testing. Subjecting these couple to IVF and preimplantation genetic testing with their associated financial and physical costs may not be justifiable.
The largest body of data for aneuploidy testing is for women of raised maternal age. Reports of non-randomised studies for this group have concluded, for instance, that:
There is an urgent need for further data on the efficacy of aneuploidy testing in the targeted groups.
- In vitro fertilization with preimplantation genetic screening.(2007-01)
- Comparison of the aneuploidy Frequency in embryos derived from testicular sperm extraction in obstructive and non-obstructive azoospermic men.(2004-01)
- Preimplantation genetic diagnosis. (2002-01)
- Diagnosis of major chromosome aneuploidies in human preimplantation embryos.(1993-01)
See Also::
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This is the personal website of David A Viniker MD FRCOG, Consultant Obstetrician and Gynaecologist at Whipps Cross University Hospital, London - Specialist Interests - Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.
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