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IVF Clinical Outcomes With 24-Chromosome Aneuploidy Testing Using Informatics-Enhanced SNP Microarrays
the high degree of mosaicism in Day 3 embryos complicates the interpretation of abnormal results. Given the major drawbacks of current aneuploidy detection METHODS and the far-reaching impact that Day 3 biopsy results have on embryo transfer decisions, it is important to understand how representative blastomeres biopsied on Day 3 are of embryos on Day 5. OBJECTIVE(S): To determine concordance between Day 3 and Day 5 PGD results using 24-chromosome microarray-based method. MATERIALS AND METHOD(S): Following Day 3 biopsy, single blastomeres were shipped on dry ice to a laboratory for aneuploidy screening. Embryos that were diagnosed as normal on Day 3 were either transferred or cryopreserved whereas embryos that tested as aneuploid were grown to blastocyst stage and re-biopsied on Day 5. RESULT(S): Sixty one embryos diagnosed with whole chromosome aneuploidy and/or structural abnormalities on Day 3 survived to Day 5 and were successfully re-biopsied. Of 51 embryos that had only fully aneuploid chromosomes on Day 3, 18 (35%) tested euploid on Day 5. Of 10 embryos that had one or more segmental errors, but no fully aneuploid chromosomes, on Day 3, eight (80%) tested euploid on Day 5. Of seven embryos that had both fully aneuploid chromosomes and del/dups on Day 3, four (57%) tested euploid on Day 5. Analysis of the sequential Day 3 and Day 5 biopsy results showed that 14 (23.0%) were completely concordant, 17 (27.9%) were partially concordant (having at least one abnormality in common), and 30 (49.2%) were completely discordant (having different type of abnormalities or being aneuploid on Day 3 and euploid on Day 5). CONCLUSION(S): The high rate of discordance between Day 3 and Day 5 biopsies is consistent with the hypothesis that a majority of Day 3 embryos are mosaic and can actually develop into euploid blastocysts prior to transfer. Therefore, Day 3 biopsy results must be interpreted in light of mosaicism to reduce the risk of discarding good embryos. These results also suggest that Day 5 biopsy may be more representative of the actual fetus. SUPPORT: None.
P-12 IVF Clinical Outcomes With 24-Chromosome Aneuploidy Testing Using Informatics-Enhanced SNP Microarrays. M. Rabinowitz,a A. Beltsos,b D. Potter,c M. Bush,d C. Givens,e D. Smotrich.f a Gene Security Network, Redwood City, CA; b Chicago IVF Center, Chicago, IL; c Huntington Reproductive Center; d Conceptions Reproductive Associates of Colorado, Littleton, CO; e Pacific Fertility Center, San Francisco, CA; f La Jolla IVF, La Jolla, CA. BACKGROUND: The majority of preimplantation genetic screening (PGS) outcome data was derived using fluorescence in situ hybridization (FISH) even though it tests only a fraction of chromosomes and has significant accuracy limitations. We present outcome data derived using a novel informatics enhanced microarray-based method that increases the scope of aneuploidy screening to 24 chromosomes with high accuracy, and holds the promise of improving clinical outcomes for couples undergoing in vitro fertilization. OBJECTIVE(S): To determine clinical benefit of an informatics-enhanced 24-chromosome aneuploidy screening technology in couples undergoing in vitro fertilization. MATERIALS AND METHOD(S): Patients (mean maternal age of 34) were referred for 24-chromosome aneuploidy screening for a variety of reasons that included prior aneuploid pregnancy, prior failed IVF cycle, recurrent pregnancy loss, or advanced maternal age. Following Day 3 biopsy, single blastomeres were shipped on dry ice to a laboratory, analyzed with the informatics enhanced microarray-based technology, and PGS results were reported by Day 5 to enable transfer decisions. RESULT(S): Outcomes have been collected on 261 euploid embryos transferred on Day 5/6 following 24-chromosome microarray-based aneuploidy screening on Day 3. Overall, the clinical pregnancy rate was 59%, the ongoing pregnancy rate is 56%, and the implantation rate was 48%. Stratification by age showed that these outcomes were comparable between women <36 years old versus R36 years old (62% vs 56%, 60% vs 52%, and 50% vs 46%, respectively). These results indicate that the informatics enhanced SNP-microarray PGS mitigates the causes of poor pregnancy rates associated with advanced maternal age (AMA). CONCLUSION(S): Our data suggest that 24-chromosome aneuploidy screening with microarray-based PGS improves IVF outcomes for women of advanced maternal age. A prospective, randomized clinical trial was initiated in 2010 to confirm the clinical benefit of this technology. SUPPORT: None.
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Abstracts
P-13 A Cytoarchitectural Analysis of the Effects of Cigarette Smoke Exposure on Human Oviductal Epithelium. B. Pier, L. Huston, K. Strenge, Z. Sundell, K. Wilson, R. Burney,. Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA. BACKGROUND: Despite the well-documented negative health consequences, approximately thirty percent of reproductive age women smoke cigarettes. Though the deleterious cardiovascular effects of smoking are well publicized, less appreciated is the impact of tobacco use on reproductive health. Women who smoke have an up to fourfold increased risk of ectopic pregnancy compared to women who never smoked, and a dose-response relationship has been demonstrated. The pathophysiologic basis for this epidemiologic finding is not well delineated, and studies investigating causality between tobacco use and ectopic pregnancy in human oviductal epithelium have not been reported. OBJECTIVE(S): To investigate the cytoarchitectural and molecular effects of cigarette smoking on human oviductal epithelium toward understanding the pathophysiology underlying the association between smoking and ectopic pregnancy. MATERIALS AND METHOD(S): Mid-isthmic oviductal segments were obtained at time of laparoscopic Pomeroy tubal sterilization from twelve women. Six women verbalized never using tobacco and six women endorsed current cigarette smoking. Serum levels of cotinine, a nicotine metabolite, were measured in smokers. Tubal segments were processed for immunohistochemical analysis using alpha tubulin and LHs28 monoclonal antibodies specific for cilia and ciliated epithelial cells, respectively. Color deconvolution was used to quantify immunohistochemical staining in the oviductal epithelial specimens. RESULT(S): Alpha tubulin signal localized to the cilia and LHs28 signal localized to the epithelial compartment of the oviduct. No significant differences were detected in density of ciliation or ciliated epithelium between smoking and non-smoking cohorts. Neither number of years of smoking nor pack year history correlated with density of ciliation. Among specimens from non-smoking women, cycle day at time of surgery correlated most with oviductal ciliation. CONCLUSION(S): This study is the first to evaluate the relationship between smoking and oviductal anatomy in human specimens. Cigarette smoking does not appear to result in quantitative differences in the density of ciliation or of ciliated epithelial cells. This finding suggests that other factors, perhaps physiologic rather than anatomic, contribute to the increased risk of ectopic pregnancy in women who smoke. Our tissue bank is well suited for investigation of differences at the molecular level, and a microarray study of alterations in oviductal epithelial gene expression between smokers and non-smokers is planned. SUPPORT: Departmental Funds.
P-14 Follow-up Survey of Cancer Survivors Who Underwent Ovarian Stimulation for Fertility Preservation. B. E. Friedman, K. O’Leary, L. M. Westphal,. Department of Obstetrics and Gynecology, Stanford Fertility and Reproductive Medicine Center, Palo Alto, CA, USA. OBJECTIVE(S): Ovarian stimulation can be challenging for patients diagnosed with cancer, and little data exists to guide clinicians in counseling them. Therefore, we investigated cancer survivors’ attitudes regarding their past attempts at fertility preservation. DESIGN: Chart review and questionnaire administered to cancer survivors who underwent ovarian stimulation for fertility preservation. MATERIALS AND METHOD(S): Telephone survey and chart review were conducted of cancer survivors who attempted fertility preservation from 2001-2009. We asked about cancer and reproductive history and current feelings regarding the decision to undergo fertility preservation. RESULT(S): We called 86 patients and reached 28, all of whom chose to participate. Of the 86 patients, eight (9.3%) underwent a frozen embryo transfer (FET) after their cancer treatment was complete, resulting in three pregnancies, and one live birth. Mean age of those undergoing FET was 37.3. Among those contacted, 14.3% had spontaneous pregnancies after chemotherapy and 78.6% plan to try to conceive in the future. The majority felt positively (92.8%) about their decision to undergo fertility preservation, with only one patient, diagnosed with metastatic cancer shortly after retrieval, expressing regret. 93.1% would refer a friend in a similar situation.
Vol. 95, No. 4, Supplement, March 15, 2011
P-12 IVF Clinical Outcomes With 24-Chromosome Aneuploidy Testing Using Informatics-Enhanced SNP Microarrays. M. Rabinowitz,a A. Beltsos,b D. Potter,c M. Bush,d C. Givens,e D. Smotrich.f a Gene Security Network, Redwood City, CA; b Chicago IVF Center, Chicago, IL; c Huntington Reproductive Center; d Conceptions Reproductive Associates of Colorado, Littleton, CO; e Pacific Fertility Center, San Francisco, CA; f La Jolla IVF, La Jolla, CA. BACKGROUND: The majority of preimplantation genetic screening (PGS) outcome data was derived using fluorescence in situ hybridization (FISH) even though it tests only a fraction of chromosomes and has significant accuracy limitations. We present outcome data derived using a novel informatics enhanced microarray-based method that increases the scope of aneuploidy screening to 24 chromosomes with high accuracy, and holds the promise of improving clinical outcomes for couples undergoing in vitro fertilization. OBJECTIVE(S): To determine clinical benefit of an informatics-enhanced 24-chromosome aneuploidy screening technology in couples undergoing in vitro fertilization. MATERIALS AND METHOD(S): Patients (mean maternal age of 34) were referred for 24-chromosome aneuploidy screening for a variety of reasons that included prior aneuploid pregnancy, prior failed IVF cycle, recurrent pregnancy loss, or advanced maternal age. Following Day 3 biopsy, single blastomeres were shipped on dry ice to a laboratory, analyzed with the informatics enhanced microarray-based technology, and PGS results were reported by Day 5 to enable transfer decisions. RESULT(S): Outcomes have been collected on 261 euploid embryos transferred on Day 5/6 following 24-chromosome microarray-based aneuploidy screening on Day 3. Overall, the clinical pregnancy rate was 59%, the ongoing pregnancy rate is 56%, and the implantation rate was 48%. Stratification by age showed that these outcomes were comparable between women <36 years old versus R36 years old (62% vs 56%, 60% vs 52%, and 50% vs 46%, respectively). These results indicate that the informatics enhanced SNP-microarray PGS mitigates the causes of poor pregnancy rates associated with advanced maternal age (AMA). CONCLUSION(S): Our data suggest that 24-chromosome aneuploidy screening with microarray-based PGS improves IVF outcomes for women of advanced maternal age. A prospective, randomized clinical trial was initiated in 2010 to confirm the clinical benefit of this technology. SUPPORT: None.
S12
Abstracts
P-13 A Cytoarchitectural Analysis of the Effects of Cigarette Smoke Exposure on Human Oviductal Epithelium. B. Pier, L. Huston, K. Strenge, Z. Sundell, K. Wilson, R. Burney,. Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA. BACKGROUND: Despite the well-documented negative health consequences, approximately thirty percent of reproductive age women smoke cigarettes. Though the deleterious cardiovascular effects of smoking are well publicized, less appreciated is the impact of tobacco use on reproductive health. Women who smoke have an up to fourfold increased risk of ectopic pregnancy compared to women who never smoked, and a dose-response relationship has been demonstrated. The pathophysiologic basis for this epidemiologic finding is not well delineated, and studies investigating causality between tobacco use and ectopic pregnancy in human oviductal epithelium have not been reported. OBJECTIVE(S): To investigate the cytoarchitectural and molecular effects of cigarette smoking on human oviductal epithelium toward understanding the pathophysiology underlying the association between smoking and ectopic pregnancy. MATERIALS AND METHOD(S): Mid-isthmic oviductal segments were obtained at time of laparoscopic Pomeroy tubal sterilization from twelve women. Six women verbalized never using tobacco and six women endorsed current cigarette smoking. Serum levels of cotinine, a nicotine metabolite, were measured in smokers. Tubal segments were processed for immunohistochemical analysis using alpha tubulin and LHs28 monoclonal antibodies specific for cilia and ciliated epithelial cells, respectively. Color deconvolution was used to quantify immunohistochemical staining in the oviductal epithelial specimens. RESULT(S): Alpha tubulin signal localized to the cilia and LHs28 signal localized to the epithelial compartment of the oviduct. No significant differences were detected in density of ciliation or ciliated epithelium between smoking and non-smoking cohorts. Neither number of years of smoking nor pack year history correlated with density of ciliation. Among specimens from non-smoking women, cycle day at time of surgery correlated most with oviductal ciliation. CONCLUSION(S): This study is the first to evaluate the relationship between smoking and oviductal anatomy in human specimens. Cigarette smoking does not appear to result in quantitative differences in the density of ciliation or of ciliated epithelial cells. This finding suggests that other factors, perhaps physiologic rather than anatomic, contribute to the increased risk of ectopic pregnancy in women who smoke. Our tissue bank is well suited for investigation of differences at the molecular level, and a microarray study of alterations in oviductal epithelial gene expression between smokers and non-smokers is planned. SUPPORT: Departmental Funds.
P-14 Follow-up Survey of Cancer Survivors Who Underwent Ovarian Stimulation for Fertility Preservation. B. E. Friedman, K. O’Leary, L. M. Westphal,. Department of Obstetrics and Gynecology, Stanford Fertility and Reproductive Medicine Center, Palo Alto, CA, USA. OBJECTIVE(S): Ovarian stimulation can be challenging for patients diagnosed with cancer, and little data exists to guide clinicians in counseling them. Therefore, we investigated cancer survivors’ attitudes regarding their past attempts at fertility preservation. DESIGN: Chart review and questionnaire administered to cancer survivors who underwent ovarian stimulation for fertility preservation. MATERIALS AND METHOD(S): Telephone survey and chart review were conducted of cancer survivors who attempted fertility preservation from 2001-2009. We asked about cancer and reproductive history and current feelings regarding the decision to undergo fertility preservation. RESULT(S): We called 86 patients and reached 28, all of whom chose to participate. Of the 86 patients, eight (9.3%) underwent a frozen embryo transfer (FET) after their cancer treatment was complete, resulting in three pregnancies, and one live birth. Mean age of those undergoing FET was 37.3. Among those contacted, 14.3% had spontaneous pregnancies after chemotherapy and 78.6% plan to try to conceive in the future. The majority felt positively (92.8%) about their decision to undergo fertility preservation, with only one patient, diagnosed with metastatic cancer shortly after retrieval, expressing regret. 93.1% would refer a friend in a similar situation.
Vol. 95, No. 4, Supplement, March 15, 2011