- Email: [email protected]
Evaluation of ‘Transport’ preimplantation genetic diagnosis (PGD) as a reproductive strategy for patients predisposed to an inherited disorder
DESIGN: Double blind randomized controlled trial. MATERIALS AND METHODS: Patients: 220 cycles in CC resistant PCOS cases randomized between 2 protocols of CC treatment. Intervention: 200 mg of CC given/day for 5 days versus 100 mg of CC given/ day for 10 days starting from day 5 of progestin induced withdrawal bleeding. Methods: transvaginal sonographic folliculometry, assay of serum FSH, and progesterone at specified times. Main outcome measures: Ovulation rate, time to ovulation, number of follicles, endometrial thickness at 18mm largest follicle diameter, mid-luteal progesterone, and pregnancy. RESULTS: The extended duration protocol resulted in significantly higher ovulation rate, higher number of dominant follicles, better endometrium at ovulation and ultimately higher pregnancy rates than the other protocol despite equal total dose of CC per cycle. CONCLUSION: The longer lower dose protocol is superior to higher dose protocol in CC resistant PCOS.
GENETIC COUNSELING O-309 Wednesday, October 19, 2011 03:45 PM PATIENT DESIRE FOR CHROMOSOME ANALYSIS OF PRODUCTS OF CONCEPTION FOLLOWING MISCARRIAGE: A NATIONAL SURVEY. R. B. Lathi, D. Huynh, J. Keller, J. Dikan, M. Rabinowitz. Stanford Fertility & Reproductive Medicine Center, Stanford University Medical Center, Palo Alto, CA; Department of Biological Sciences, College of Natural Sciences, CSU Stanislaus, Turlock, CA; Gene Security Network, Redwood City, CA. OBJECTIVE: Most first trimester miscarriages are due to fetal chromosome abnormalities. Karyotype analysis of products of conception (POC) can provide useful information regarding cause of loss and identify patients who need additional testing or counseling. Despite this, chromosome testing of POC is not routinely done. The objective of our study was to evaluate patient interest in testing and the frequency with which testing is currently performed. DESIGN: Anonymous web survey of patients with a history of miscarriage. MATERIALS AND METHODS: A web-based questionnaire was used to ask women about their miscarriage experience. Inclusion criteria were age R18 years, miscarriage within 1 year and US resident. Participants were recruited using Google AdWords advertisements, www.clinicaltrials.gov, www.genesecurity.net, and an advertisement flyer in local clinics. Only completed surveys of eligible patients were analyzed. RESULTS: 323 women consented to participate with the majority recruited through Google Adwords (300/323). 143 (48%) women from 41 states met inclusion criteria and completed the survey. On average, participants were 31 years old with 1.8 prior losses, completing the survey 3.8 months from time of loss. Only 10 participants (7%) reported receiving POC chromosome testing; 100% reported they would do it again. 65% without testing reported that they wished they could have had testing. Interestingly, although 65% reported being physically recovered from the miscarriage at the time of taking the survey only 27% reported feeling emotionally recovered. CONCLUSION: Chromosome testing of POC is rarely performed in the US, despite high patient satisfaction with testing and a frequent desire for testing. Our data suggests that emotional recovery after miscarriage takes longer than physical recovery. However, given the low numbers of patients who had testing done in our study, we were not able to assess whether performing a karyotype will shorten the time to emotional recovery from miscarriage. Supported by: California State University
O-310 Wednesday, October 19, 2011 04:00 PM EVALUATION OF ‘TRANSPORT’ PREIMPLANTATION GENETIC DIAGNOSIS (PGD) AS A REPRODUCTIVE STRATEGY FOR PATIENTS PREDISPOSED TO AN INHERITED DISORDER. S. Jaroudi, R. Prates, S. Tormasi, J. Sanchez-Garcia, G. Harton, D. Wells. Reprogenetics UK, Oxford, Oxfordshire, United Kingdom; Reprogenetics, Livingston, NJ; Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, Oxfordshire, United Kingdom. OBJECTIVE: PGD entails the genetic testing of cells biopsied from embryos created using in vitro fertilization (IVF), and aims to ensure that the embryos selected for uterine transfer are unaffected by specific familial disorders. The diagnosis should be sensitive, accurate and fast, providing patients with the greatest chance of pregnancy and the lowest risk of misdiagnosis. This study
FERTILITY & STERILITYÒ
aimed to evaluate the diagnostic and clinical outcomes of PGD cycles carried out for patients at high risk of transmitting a single gene disorder. DESIGN: A retrospective review of 459 cases of PGD performed between September 2008 and April 2011 was carried out. MATERIALS AND METHODS: IVF and embryo biopsy took place in more than 60 different fertility clinics, with blastomeres sent to a single specialist PGD laboratory for analysis. Most diagnostic protocols were tailored to individual couples. The majority of protocols involved a multiplex polymerase chain reaction step to amplify the mutation site as well as linked polymorphisms. RESULTS: PGD was performed for a total of 3985 embryos. A diagnosis was obtained for 85% of cells tested. The accuracy of the diagnosis was predicted to be greater than 98% in most cases. A single misdiagnosis has been recorded to date. The linked polymorphisms allowed the detection of DNA contaminants and served as backups for diagnosis of the mutation, particularly when the mutation site was affected by allele dropout (ADO), resulting in increased rate of accuracy. The biochemical pregnancy rate per embryo transfer was 59.7% and the implantation rate (number of gestational sacs/number of embryos replaced) was 48%. The maternal age ranged between 26 and 39 years (mean 33.36). CONCLUSION: The results of this large study showed good rates of diagnosis, accuracy and pregnancy, indicating that transport PGD is an effective treatment option for patients requesting embryo diagnosis. Recommendations for best practice, based on in-depth analysis of our data, will be presented.
O-311 Wednesday, October 19, 2011 04:15 PM ELEVATED PREVALENCE OF 35-44 FMR1 TRINUCLEOTIDE REPEATS IN WOMEN WITH DIMINISHED OVARIAN RESERVE. L. M. Pastore, S. L. Young, V. L. Baker, L. B. Karns, C. D. Williams, L. M. Silverman. University of Virginia, Charlottesville, VA; University of North Carolina, Chapel Hill, NC; Stanford University, Stanford, CA; Reproductive Medicine & Surgery Center of VA, Charlottesville, VA. OBJECTIVE: Primary Ovarian Insufficiency (POI) is a spectrum of disorders of early ovarian aging ranging from diminished ovarian reserve (DOR, follicle stimulating hormone (FSH) > 10 mIU/mL and regular menses) to premature ovarian failure (POF, FSH > 40 mIU/mL and amenorrhea before age 40). The American College of Obstetrics & Gynecology and the American College of Medical Genetics all explicitly state that a CGG repeat count less than 45 in the fragile X mental retardation 1 (FMR1) gene has no clinical phenotype. A premutation range of FMR1 trinucleotide repeats (55 – 199 repeats) has been associated with POF. DESIGN: Genetic analysis of prospective cohort. MATERIALS AND METHODS: A cohort of 62 women with DOR were enrolled from four U.S. fertility centers and a venous blood sample was assayed for the FMR1 CGG repeat level. Eligibility required cycle day 2-5 FSH > 10 mIU/ mL and/or antral follicle count < 6, regular menses (22-35 day intercycle length), aged < 42, and no family history of Fragile X Syndrome or premutation. RESULTS: 14.5% of this cohort had 35-44 CGG repeats in the FMR1 gene. Limited comparison data from the literature imply that 3-6% of the general female population has 35-44 CGG repeats. Compared with the general female population, the odds of having DOR was 3.3 (95% CI 1.01 – 9.0) for 35-39 CGG repeats, 7.1 (95% CI 1.01 – 42.9) for 40-44 CGG repeats, and 4.2 (95% CI 1.6 – 10.0) for 35-44 CGG repeats. CONCLUSION: The serum FMR1 results in this cohort of 62 women with DOR suggest that CGG repeats of 35-44 are markedly over-represented in women with this phenotype (14.5% prevalence). These data suggest that the current clinical interpretation of ‘‘no abnormal phenotype’’ for an FMR1 CGG repeat count may be incorrect, and that indeed there may be an infertility phenotype associated with 35-44 triplet repeats. Supported by: National Institutes of Health R03 HD052768
O-312 Wednesday, October 19, 2011 04:30 PM GENETIC COUNSELING AND SCREENING OF SPERM DONORS IN THE UNITED STATES. L. Isley, P. Callum. Assisted Reproductive Technology and Infertility Special Interest Group, National Society of Genetic Counselors, Chicago, IL. OBJECTIVE: To evaluate how the genetic screening of donors is performed at semen banks in the United States. DESIGN: Twenty-six U.S. semen donor facilities were identified and invited to participate in an online survey about their genetic screening practices.
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GENETIC COUNSELING O-309 Wednesday, October 19, 2011 03:45 PM PATIENT DESIRE FOR CHROMOSOME ANALYSIS OF PRODUCTS OF CONCEPTION FOLLOWING MISCARRIAGE: A NATIONAL SURVEY. R. B. Lathi, D. Huynh, J. Keller, J. Dikan, M. Rabinowitz. Stanford Fertility & Reproductive Medicine Center, Stanford University Medical Center, Palo Alto, CA; Department of Biological Sciences, College of Natural Sciences, CSU Stanislaus, Turlock, CA; Gene Security Network, Redwood City, CA. OBJECTIVE: Most first trimester miscarriages are due to fetal chromosome abnormalities. Karyotype analysis of products of conception (POC) can provide useful information regarding cause of loss and identify patients who need additional testing or counseling. Despite this, chromosome testing of POC is not routinely done. The objective of our study was to evaluate patient interest in testing and the frequency with which testing is currently performed. DESIGN: Anonymous web survey of patients with a history of miscarriage. MATERIALS AND METHODS: A web-based questionnaire was used to ask women about their miscarriage experience. Inclusion criteria were age R18 years, miscarriage within 1 year and US resident. Participants were recruited using Google AdWords advertisements, www.clinicaltrials.gov, www.genesecurity.net, and an advertisement flyer in local clinics. Only completed surveys of eligible patients were analyzed. RESULTS: 323 women consented to participate with the majority recruited through Google Adwords (300/323). 143 (48%) women from 41 states met inclusion criteria and completed the survey. On average, participants were 31 years old with 1.8 prior losses, completing the survey 3.8 months from time of loss. Only 10 participants (7%) reported receiving POC chromosome testing; 100% reported they would do it again. 65% without testing reported that they wished they could have had testing. Interestingly, although 65% reported being physically recovered from the miscarriage at the time of taking the survey only 27% reported feeling emotionally recovered. CONCLUSION: Chromosome testing of POC is rarely performed in the US, despite high patient satisfaction with testing and a frequent desire for testing. Our data suggests that emotional recovery after miscarriage takes longer than physical recovery. However, given the low numbers of patients who had testing done in our study, we were not able to assess whether performing a karyotype will shorten the time to emotional recovery from miscarriage. Supported by: California State University
O-310 Wednesday, October 19, 2011 04:00 PM EVALUATION OF ‘TRANSPORT’ PREIMPLANTATION GENETIC DIAGNOSIS (PGD) AS A REPRODUCTIVE STRATEGY FOR PATIENTS PREDISPOSED TO AN INHERITED DISORDER. S. Jaroudi, R. Prates, S. Tormasi, J. Sanchez-Garcia, G. Harton, D. Wells. Reprogenetics UK, Oxford, Oxfordshire, United Kingdom; Reprogenetics, Livingston, NJ; Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, Oxfordshire, United Kingdom. OBJECTIVE: PGD entails the genetic testing of cells biopsied from embryos created using in vitro fertilization (IVF), and aims to ensure that the embryos selected for uterine transfer are unaffected by specific familial disorders. The diagnosis should be sensitive, accurate and fast, providing patients with the greatest chance of pregnancy and the lowest risk of misdiagnosis. This study
FERTILITY & STERILITYÒ
aimed to evaluate the diagnostic and clinical outcomes of PGD cycles carried out for patients at high risk of transmitting a single gene disorder. DESIGN: A retrospective review of 459 cases of PGD performed between September 2008 and April 2011 was carried out. MATERIALS AND METHODS: IVF and embryo biopsy took place in more than 60 different fertility clinics, with blastomeres sent to a single specialist PGD laboratory for analysis. Most diagnostic protocols were tailored to individual couples. The majority of protocols involved a multiplex polymerase chain reaction step to amplify the mutation site as well as linked polymorphisms. RESULTS: PGD was performed for a total of 3985 embryos. A diagnosis was obtained for 85% of cells tested. The accuracy of the diagnosis was predicted to be greater than 98% in most cases. A single misdiagnosis has been recorded to date. The linked polymorphisms allowed the detection of DNA contaminants and served as backups for diagnosis of the mutation, particularly when the mutation site was affected by allele dropout (ADO), resulting in increased rate of accuracy. The biochemical pregnancy rate per embryo transfer was 59.7% and the implantation rate (number of gestational sacs/number of embryos replaced) was 48%. The maternal age ranged between 26 and 39 years (mean 33.36). CONCLUSION: The results of this large study showed good rates of diagnosis, accuracy and pregnancy, indicating that transport PGD is an effective treatment option for patients requesting embryo diagnosis. Recommendations for best practice, based on in-depth analysis of our data, will be presented.
O-311 Wednesday, October 19, 2011 04:15 PM ELEVATED PREVALENCE OF 35-44 FMR1 TRINUCLEOTIDE REPEATS IN WOMEN WITH DIMINISHED OVARIAN RESERVE. L. M. Pastore, S. L. Young, V. L. Baker, L. B. Karns, C. D. Williams, L. M. Silverman. University of Virginia, Charlottesville, VA; University of North Carolina, Chapel Hill, NC; Stanford University, Stanford, CA; Reproductive Medicine & Surgery Center of VA, Charlottesville, VA. OBJECTIVE: Primary Ovarian Insufficiency (POI) is a spectrum of disorders of early ovarian aging ranging from diminished ovarian reserve (DOR, follicle stimulating hormone (FSH) > 10 mIU/mL and regular menses) to premature ovarian failure (POF, FSH > 40 mIU/mL and amenorrhea before age 40). The American College of Obstetrics & Gynecology and the American College of Medical Genetics all explicitly state that a CGG repeat count less than 45 in the fragile X mental retardation 1 (FMR1) gene has no clinical phenotype. A premutation range of FMR1 trinucleotide repeats (55 – 199 repeats) has been associated with POF. DESIGN: Genetic analysis of prospective cohort. MATERIALS AND METHODS: A cohort of 62 women with DOR were enrolled from four U.S. fertility centers and a venous blood sample was assayed for the FMR1 CGG repeat level. Eligibility required cycle day 2-5 FSH > 10 mIU/ mL and/or antral follicle count < 6, regular menses (22-35 day intercycle length), aged < 42, and no family history of Fragile X Syndrome or premutation. RESULTS: 14.5% of this cohort had 35-44 CGG repeats in the FMR1 gene. Limited comparison data from the literature imply that 3-6% of the general female population has 35-44 CGG repeats. Compared with the general female population, the odds of having DOR was 3.3 (95% CI 1.01 – 9.0) for 35-39 CGG repeats, 7.1 (95% CI 1.01 – 42.9) for 40-44 CGG repeats, and 4.2 (95% CI 1.6 – 10.0) for 35-44 CGG repeats. CONCLUSION: The serum FMR1 results in this cohort of 62 women with DOR suggest that CGG repeats of 35-44 are markedly over-represented in women with this phenotype (14.5% prevalence). These data suggest that the current clinical interpretation of ‘‘no abnormal phenotype’’ for an FMR1 CGG repeat count may be incorrect, and that indeed there may be an infertility phenotype associated with 35-44 triplet repeats. Supported by: National Institutes of Health R03 HD052768
O-312 Wednesday, October 19, 2011 04:30 PM GENETIC COUNSELING AND SCREENING OF SPERM DONORS IN THE UNITED STATES. L. Isley, P. Callum. Assisted Reproductive Technology and Infertility Special Interest Group, National Society of Genetic Counselors, Chicago, IL. OBJECTIVE: To evaluate how the genetic screening of donors is performed at semen banks in the United States. DESIGN: Twenty-six U.S. semen donor facilities were identified and invited to participate in an online survey about their genetic screening practices.
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