- Email: [email protected]
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pregnancy rates were determined by fetal cardiac activity/number of embryos transferred or the number of retrievals. RESULTS: A total of 70 RPL couples produced 5 or fewer embryos that were suitable for biopsy. Of those, 47 decided to continue with the PGD procedure. The implantation and delivery rates were significantly higher in the group that received PGD (p⬍0.05; see Table 1). Although the spontaneous abortion rate was lower in the PGD group (4/22, 18.1% vs. 3/6, 50%), this difference was not statistically significant.
CONCLUSION: Even when 5 or fewer embryos were produced, the utilization of PGD was effective in increasing the delivery rate. PGD is therefore indicated for patients with idiopathic RPL irrespective of the number of embryos produced in the cycle. This finding may not be applicable to other poor responder patient groups; the effect of embryo number on other types of poor responders is under active investigation. Supported by: None.
Tuesday, October 24, 2006 4:45 pm O-139 PREIMPLANTATION GENETIC DIAGNOSIS (PGD) FOR ALL CYSTIC FIBROSIS (CF) CARRIER COUPLES: STRATEGY AND COST ANALYSIS. I. Tur-Kaspa, S. Rechitsky, G. Aljadeff, E. Grotjan, Y. Verlinsky. Reproductive Genetics Institute and Institute for Human Reproduction, Chicago, IL; Reproductive Genetics Institute, Chicago, IL; Serono, Inc., Rockland, MA; Pediatric Pulmonology, CF Center, Lutheran General Children’s Hospital, Park Ridge, IL. OBJECTIVE: CF is the most common lethal genetic disease in Caucasians in the US. Current guidelines recommend pre-conception and/or prenatal CF screening of parents. Although prenatal testing with possible elective termination is cost effective, many couples prefer to avoid the moral dilemma and psychological trauma of terminating a pregnancy. This may be a major reason contributing to the continuing birth of ⬎1,000 children affected with CF in the US each year. For most couples at risk for passing on genetic diseases to their offspring, PGD is a preferred strategy to prevent the birth of affected children compared to aborting an affected fetus or raising a sick child. We have performed a cost benefit analysis where the direct medical expense of using IVF-PDG by all carrier couples has been compared to the annual and lifetime medical costs of treating CF patients. DESIGN: Cost benefit analysis. MATERIALS AND METHODS: Direct cost of performing IVF-PGD was based on average costs in the Midwest. Success rates were projected from 2000-2005 data accumulated at RGI for IVF-PGD for CF carriers. Current life expectancy of CF patient is 37 years (CF Foundation - 4/21/06) and the estimated average annual direct cost of medical care for CF patient was $55,537 in 2000 (CF Foundation, unpublished data). Since CF is an autosomal recessive disorder, we calculated that for 1,000 babies born with CF each year it would require performing IVF-PGD on at least 4 times that number of couples. A decision making model was developed. A cost benefit analysis was then performed by comparing the annual cost of performing IVF-PGD for theoretical 4,000 couples to the annual direct medical costs saved by avoiding the need to treat 1,000 new CF patients each year. RESULTS: Take home healthy baby rate per IVF-PGD cycle (n⫽114) initiated to prevent CF with RGI was 31%. Treating 4,000 carrier couples for 1-6 cycles of IVF-PGD per year with a 31% take home baby rate would result in 3568 deliveries (89% deliveries in 4,000 hypothetical carrier couples) of healthy babies including the birth of 892 non affected children (25%) who theoretically would have been born otherwise with CF. The calculated total cost per patient for lifetime is $2 million (M), and for all 892 CF patients 1.8 billion dollars. The estimated direct cost for all IVF-PGD
FERTILITY & STERILITY威
cycles (n⫽11,511) was $235 M, and $263,000 would be spent to have one healthy baby instead of a sick child with CF. This would save $50 M annually that would have been expended in treating 892 new CF patients, or total lifetimes saving of $1.55 billion. The break-even point is expected after 4.7 years, and from this time on, hundreds of millions of dollars would be saved each year (i.e. $100 M, $244 M, $531 M, and ⬎$1 billion at the 7th, 10th, 16th and 26th years, respectively) after initiating IVF-PGD program for all CF carriers in the US. CONCLUSION: Offering IVF-PGD to all CF carrier couples who wish to conceive without facing the dilemma of possible pregnancy termination or raising a sick child is highly cost effective and will save hundreds of millions of direct health care dollars annually. The potential implications of implementing IVF-PGD for all CF carriers in the US are remarkable in the life of a family. Parents would not have to alter their reproductive plans and they may circumvent the psychological and financial burden of having an unhealthy child. Using this strategy, CF, as well as other genetic disorders, may become preventable diseases. Supported by: Reproductive Genetics Institute, Chicago, IL.
Tuesday, October 24, 2006 5:00 pm O-140 PREIMPLANTATION GENETIC DIAGNOSIS OF SINGLE GENE DISORDERS: CONCLUSIONS FROM THE APPLICATION OF NOVEL METHODOLOGIES TO MORE THAN 100 CASES. D. Wells, J. Sanchez, C. Gutierrez-Matteo, J. Fischer, S. Munne. Yale Univ, New Haven, CT; Reprogenetics, West Orange, NJ. OBJECTIVE: Preimplantation genetic diagnosis (PGD) represents an alternative to prenatal diagnosis for couples at risk of transmitting an inherited disorder to their children. This study focuses on data generated since our center expanded its diagnostic services to include PGD single gene disorders approximately two and a half years ago. We aimed to examine factors such as amplification efficiency, incidence and origin of DNA contaminants, diagnostic accuracy, outcome of IVF cycles, speed of diagnosis and level of demand. These statistics were also broken down by referring center and analyzed in order to establish the importance of variations in methods of blastomere biopsy and cell preparation. DESIGN: Retrospective analysis of clinical diagnostic data. MATERIALS AND METHODS: Most PGD cases (83/107) involved the analysis of blastomeres transported from independent IVF laboratories. A total of 41 different laboratories sent cells for analysis. Diagnostic protocols involved the application of novel multiplex-PCR methods. Where possible the strategies involved the amplification of the following fragments: 1. the mutation site(s); 2. polymorphism(s) linked to the mutation*; 3. DNA fingerprint marker(s)**. *Analysis of both mutation site and linked polymorphism provides two opportunities to detect mutant alleles. **Analysis of a fingerprint marker revealed the presence of DNA contaminants. RESULTS: Diseases diagnosed: 26 different disorders were diagnosed in a total of 107 PGD cycles referred by 41 different IVF centers. Cystic fibrosis was the most common reason for referral (37 cases). Protocols for several disorders not previously subject to preimplantation testing were designed and/or clinically applied. Diagnostic efficiency and accuracy: A diagnosis was obtained from 82% of embryos tested. No misdiagnoses were recorded in any cycles. DNA contamination: 1) No DNA contamination was detected in any negative controls set up at our center (0/107); 2) Negative controls sent by the referring laboratories had a contamination rate varying from 2.1% to 27% (mean 8.7%); 3) DNA fingerprint analysis detected the presence of non-embryonic DNA in 6.7% of blastomere samples. In 57% of cases the contaminant gave a fingerprint that does not match the mother, father, or any of our PGD staff. It is most likely that the origin of such contaminants is the IVF lab. Cycle data: Of the 99 cycles that had oocyte retrieval only 5% had no transfer. The pregnancy rate per transfer is currently 43%. Speed of diagnosis: Diagnostic results were available 9-30 hours from receipt of all samples. CONCLUSION: PGD was shown to be an effective alternative to prenatal diagnosis for patients with an ethical/religious objection to pregnancy termination and for infertile patients carrying a genetic disorder. Demand for this service more than doubled each year that it was offered. Pregnancy rate per transfer was 43%. No misdiagnoses were recorded. The fingerprinting marker was found to be extremely effective, detecting half of all DNA
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CONCLUSION: Even when 5 or fewer embryos were produced, the utilization of PGD was effective in increasing the delivery rate. PGD is therefore indicated for patients with idiopathic RPL irrespective of the number of embryos produced in the cycle. This finding may not be applicable to other poor responder patient groups; the effect of embryo number on other types of poor responders is under active investigation. Supported by: None.
Tuesday, October 24, 2006 4:45 pm O-139 PREIMPLANTATION GENETIC DIAGNOSIS (PGD) FOR ALL CYSTIC FIBROSIS (CF) CARRIER COUPLES: STRATEGY AND COST ANALYSIS. I. Tur-Kaspa, S. Rechitsky, G. Aljadeff, E. Grotjan, Y. Verlinsky. Reproductive Genetics Institute and Institute for Human Reproduction, Chicago, IL; Reproductive Genetics Institute, Chicago, IL; Serono, Inc., Rockland, MA; Pediatric Pulmonology, CF Center, Lutheran General Children’s Hospital, Park Ridge, IL. OBJECTIVE: CF is the most common lethal genetic disease in Caucasians in the US. Current guidelines recommend pre-conception and/or prenatal CF screening of parents. Although prenatal testing with possible elective termination is cost effective, many couples prefer to avoid the moral dilemma and psychological trauma of terminating a pregnancy. This may be a major reason contributing to the continuing birth of ⬎1,000 children affected with CF in the US each year. For most couples at risk for passing on genetic diseases to their offspring, PGD is a preferred strategy to prevent the birth of affected children compared to aborting an affected fetus or raising a sick child. We have performed a cost benefit analysis where the direct medical expense of using IVF-PDG by all carrier couples has been compared to the annual and lifetime medical costs of treating CF patients. DESIGN: Cost benefit analysis. MATERIALS AND METHODS: Direct cost of performing IVF-PGD was based on average costs in the Midwest. Success rates were projected from 2000-2005 data accumulated at RGI for IVF-PGD for CF carriers. Current life expectancy of CF patient is 37 years (CF Foundation - 4/21/06) and the estimated average annual direct cost of medical care for CF patient was $55,537 in 2000 (CF Foundation, unpublished data). Since CF is an autosomal recessive disorder, we calculated that for 1,000 babies born with CF each year it would require performing IVF-PGD on at least 4 times that number of couples. A decision making model was developed. A cost benefit analysis was then performed by comparing the annual cost of performing IVF-PGD for theoretical 4,000 couples to the annual direct medical costs saved by avoiding the need to treat 1,000 new CF patients each year. RESULTS: Take home healthy baby rate per IVF-PGD cycle (n⫽114) initiated to prevent CF with RGI was 31%. Treating 4,000 carrier couples for 1-6 cycles of IVF-PGD per year with a 31% take home baby rate would result in 3568 deliveries (89% deliveries in 4,000 hypothetical carrier couples) of healthy babies including the birth of 892 non affected children (25%) who theoretically would have been born otherwise with CF. The calculated total cost per patient for lifetime is $2 million (M), and for all 892 CF patients 1.8 billion dollars. The estimated direct cost for all IVF-PGD
FERTILITY & STERILITY威
cycles (n⫽11,511) was $235 M, and $263,000 would be spent to have one healthy baby instead of a sick child with CF. This would save $50 M annually that would have been expended in treating 892 new CF patients, or total lifetimes saving of $1.55 billion. The break-even point is expected after 4.7 years, and from this time on, hundreds of millions of dollars would be saved each year (i.e. $100 M, $244 M, $531 M, and ⬎$1 billion at the 7th, 10th, 16th and 26th years, respectively) after initiating IVF-PGD program for all CF carriers in the US. CONCLUSION: Offering IVF-PGD to all CF carrier couples who wish to conceive without facing the dilemma of possible pregnancy termination or raising a sick child is highly cost effective and will save hundreds of millions of direct health care dollars annually. The potential implications of implementing IVF-PGD for all CF carriers in the US are remarkable in the life of a family. Parents would not have to alter their reproductive plans and they may circumvent the psychological and financial burden of having an unhealthy child. Using this strategy, CF, as well as other genetic disorders, may become preventable diseases. Supported by: Reproductive Genetics Institute, Chicago, IL.
Tuesday, October 24, 2006 5:00 pm O-140 PREIMPLANTATION GENETIC DIAGNOSIS OF SINGLE GENE DISORDERS: CONCLUSIONS FROM THE APPLICATION OF NOVEL METHODOLOGIES TO MORE THAN 100 CASES. D. Wells, J. Sanchez, C. Gutierrez-Matteo, J. Fischer, S. Munne. Yale Univ, New Haven, CT; Reprogenetics, West Orange, NJ. OBJECTIVE: Preimplantation genetic diagnosis (PGD) represents an alternative to prenatal diagnosis for couples at risk of transmitting an inherited disorder to their children. This study focuses on data generated since our center expanded its diagnostic services to include PGD single gene disorders approximately two and a half years ago. We aimed to examine factors such as amplification efficiency, incidence and origin of DNA contaminants, diagnostic accuracy, outcome of IVF cycles, speed of diagnosis and level of demand. These statistics were also broken down by referring center and analyzed in order to establish the importance of variations in methods of blastomere biopsy and cell preparation. DESIGN: Retrospective analysis of clinical diagnostic data. MATERIALS AND METHODS: Most PGD cases (83/107) involved the analysis of blastomeres transported from independent IVF laboratories. A total of 41 different laboratories sent cells for analysis. Diagnostic protocols involved the application of novel multiplex-PCR methods. Where possible the strategies involved the amplification of the following fragments: 1. the mutation site(s); 2. polymorphism(s) linked to the mutation*; 3. DNA fingerprint marker(s)**. *Analysis of both mutation site and linked polymorphism provides two opportunities to detect mutant alleles. **Analysis of a fingerprint marker revealed the presence of DNA contaminants. RESULTS: Diseases diagnosed: 26 different disorders were diagnosed in a total of 107 PGD cycles referred by 41 different IVF centers. Cystic fibrosis was the most common reason for referral (37 cases). Protocols for several disorders not previously subject to preimplantation testing were designed and/or clinically applied. Diagnostic efficiency and accuracy: A diagnosis was obtained from 82% of embryos tested. No misdiagnoses were recorded in any cycles. DNA contamination: 1) No DNA contamination was detected in any negative controls set up at our center (0/107); 2) Negative controls sent by the referring laboratories had a contamination rate varying from 2.1% to 27% (mean 8.7%); 3) DNA fingerprint analysis detected the presence of non-embryonic DNA in 6.7% of blastomere samples. In 57% of cases the contaminant gave a fingerprint that does not match the mother, father, or any of our PGD staff. It is most likely that the origin of such contaminants is the IVF lab. Cycle data: Of the 99 cycles that had oocyte retrieval only 5% had no transfer. The pregnancy rate per transfer is currently 43%. Speed of diagnosis: Diagnostic results were available 9-30 hours from receipt of all samples. CONCLUSION: PGD was shown to be an effective alternative to prenatal diagnosis for patients with an ethical/religious objection to pregnancy termination and for infertile patients carrying a genetic disorder. Demand for this service more than doubled each year that it was offered. Pregnancy rate per transfer was 43%. No misdiagnoses were recorded. The fingerprinting marker was found to be extremely effective, detecting half of all DNA
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