How Successful Is Preimplantation Genetic Diagnosis? What Can Be Done To Make It

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How Successful Is Preimplantation Genetic Diagnosis? What Can Be Done

To Make It More Successful?

http://www.medicalnewstoday.com/medicalnews.php?newsid=32263

Researchers at the conjoint meeting of the American Society for

Reproductive Medicine and the Canadian Fertility and Andrology

Society will present data on the extent of the use of Preimplantation

Genetic Diagnosis (PGD) and its effectiveness as treatment accessory

to IVF.

PGD, first performed on human embryos in the late 1980's, requires

that one or two cells, or blastomeres, be removed from an embryo and

analyzed for genetic or chromosomal defects. PGD is recommended for

patients who have a history of heritable genetic disease, unexplained

recurrent pregnancy loss or several failed IVF cycles, and for women

of advanced maternal age.

Dr Jacques Cohen of Reprogenetics in West Orange, New Jersey will

present data from 100 United States IVF centers that referred PGD

testing to one reference laboratory. From 1995 to February 2005, a

total of 4079 cases testing for aneuploidy (chromosomal

abnormalities) were performed by the lab on a total of 33, 572

embryos. The average age of the female patients was 37.5 and 32% of

the embryos analyzed were normal. In 3331 of the cases, the patients

had embryos transferred; on average, two normal embryos were

transferred. For patients in 2540 of these cycles, information was

obtained on pregnancy results: there were 931 pregnancies, with 1218

fetal heartbeats observed, 640 deliveries, 341 on-going pregnancies

and 164 miscarriages. The researchers observed that the pregnancy

rate varied greatly depending on the IVF center and the diagnosis for

the patients' infertility.

Jill Fisher of Reprogenetics will report on 539 PGD cases referred to

the laboratory from 100 US IVF clinics for testing for

translocations. During the period from 1995 to February 2005, the lab

analyzed 4,597 embryos to determine if a segment of a chromosome had

relocated on that chromosome or moved to another chromosome. The

patients' average age was 34 and 19% of the embryos tested normal.

However, in 422 cycles patients were able to have an embryo

transferred with an average of 1.3 normal embryos per transfer.

Pregnancy information was available for 462 cycles; of these, there

were 138 pregnancies and 176 fetal heartbeats. There have so far been

113 deliveries among this group, with 40 on-going pregnancies and 15

miscarriages. Previously, these patients had miscarried 88% of their

pregnancies; after PGD, the miscarriage rate was down to 9%.

From the Reproductive Genetics Institute in Chicago, IL, Dr. Yury

Verlinsky reports on 3631 PGD cycles. Of these, 756 analyzed embryos

for single gene disorders and/or preimplantation HLA matching (human

lymphocyte antigen) for couples at high risk of having a child with a

genetically transmitted disease or who already had a child needing

matched stem-cell transplantation from a sibling. This screening

resulted in the transfer of 1292 embryos resulting in 244 clinical

pregnancies, the birth of 210 babies, and 35 on-going pregnancies.

Aneuploidy detection was the goal of 2646 test cycles for poor-

prognosis IVF patients with an average age of 38.5. Their testing led

to 2110 transfers of 4486 normal embryos, 554 clinical pregnancies,

the birth of 411 infants and 91 on-going pregnancies. Couples who

were carriers of balanced translocations underwent 232 cycles of PGD

with 162 transfers of 275 normal embryos resulting in 57 clinical

pregnancies and the birth of 42 healthy children. Overall the

accuracy rate for PGD at the Institute was 99.5%; 80% of cases had

normal or HLA-matched embryos available for transfer.

Scientists at the Reproductive Genetics Institute also investigated

the value of additional testing for aneuploidy for embryos undergoing

PGD for Mendelian disorders (genetic diseases) and HLA typing. Two

thousand and seventy-four blastomeres were tested for copy numbers of

a variety of different chromosomes and the results indicated that

without testing the copy number of the chromosome on which the

disease causing gene is found, misdiagnosis in PGD for single gene

disorders cannot be ruled out. They especially recommend aneuploidy

testing for patients seeking PGD for HLA matching because many of

those patients are of advanced reproductive age.

Researchers at New York University investigated the connection

between embryo aneuploidy and morphology. Reviewing all of their

cases of IVF with PGD for aneuploidy done over a three and a half

year period, they found that, in 58 cases, 412 of 524 biopsied

embryos were aneuploid. Normal embryos were average in appearance and

their morphology scores were not significantly different from

abnormal embryos. Blastomere asymmetry (difference in the size and

shape of blastomeres within one embryo) was seen in 72 embryos, of

which 86% tested abnormal. For part of the study, investigators were

blinded to all PGD and embryo transfer records and used Day-3 embryo

selection criteria (a visual standard) to recommend the likely

candidate embryos for transfer. In this exercise, 6 cycles with

embryos evaluated solely on looks would have had only aneuploid

embryos transferred.

" We need to work to increase the availability of preimplantation

genetic diagnosis and its use for patients for whom it is indicated.

Strategic use of PGD techniques can ultimately result in fewer

pregnancies lost to miscarriage and a reduction in the number of

multiple pregnancies when we can be sure we are transferring just one

or two normal embryos, " said Gibbons, MD, President-Elect of

SART.

O-116 Cohen et al, Results of PGD for Chromosome Abnormality in 4079

Cycles

O-236 Fischer et al, Results of PGD for Translocations in 539 Cycles

O-237 Verlinsky, et al, Accuracy and Outcomes of 3631 Preimplantation

Genetic Diagnosis Cycles Performed at One Center

O-136 Rechitsky et al, Potential Impact of PCR-Based Aneuploidy

Testing on Accuracy and Outcomes of Pre-Implantation Genetic

Diagnosis (PGD) for Mendelian Disorders and HLA Typing

O-238 Fino et al, How Good is Embryo Morphology at Predicting

Chromosomal Integrity? When is Aneuploidy PGD Useful?

The American Society for Reproductive Medicine, founded in 1944, is

an organization of close to 8,500 physicians, researchers, nurses,

technicians, and other professionals dedicated to advancing knowledge

and expertise in reproductive biology. Affiliated societies include

the Society for Assisted Reproductive Technology, The Society for

Male Reproduction and Urology, the Society for Reproductive

Endocrinology and Infertility, and the Society of Reproductive

Surgeons.

The CFAS includes more than 400 obstetricians and gynaecologists,

urologists, reproductive endocrinologists, research scientists, and

other health care professionals from every province as well as

several members from other countries. The Mission of the society is

to promote the study of, education about and research on fertility,

sterility and andrology, respond to social needs in regard to the

complexities of human reproduction, provide expertise in the

accreditation of clinical and laboratory therapeutics in new

reproductive technologies, and establish valid processes for the

measurement of outcomes of therapy.

Highlights From The Conjoint Meeting Of The American Society For

Reproductive Medicine And The Canadian Fertility And Andrology Society

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