- Email: [email protected]
Superovulation does not increase embryonic aneuploidy: a prospective evaluation of aneuploidy in natural IVF cycles with comparison to 15,169 embryos from age controlled peers who had superovulation
CONCLUSION: Selective deletion of the Pten gene in theca cells leads to changes in growth factors TGF-b1 and FGF-7 along with changes in ovarian proteins OCLN, nectin-2, b-catenin, and a-E-catenin. Dysregulation of these growth factors may contribute to the PCOS-like ovarian phenotype of tPtenMT mice by causing an imbalance in structural proteins that may affect ovarian rigidity. When combined with recent studies suggesting the TGF-b signaling pathway may have the strongest genetic link to the etiology of PCOS1, the tPtenMT model may give insight into the pathogenesis of and treatment for PCOS in humans.
O-119 Tuesday, October 21, 2014 04:45 PM PROGRESSIVE FIBROSIS IN ENDOMETRIOSIS IS EPIGENETICALLY MEDIATED BY THE UBIQUITOUS CYTOKINE TGFBETA VIA TRANSCRIPTION FACTOR KLF11. L. Correa, Z. Khan, Y. Zheng, G. Daftary. OB/Gyn, Mayo Clinic, Rochester, MN. OBJECTIVE: Endometriosis is a debilitating disease affecting at least 10% reproductive aged women. A hallmark phenotype characterizing disease classification and severity is progressive fibrosis through all disease stages. Fibrosis usually accompanies such sequelae as pain and infertility and is difficult to treat. There is a critical need to develop novel translational research that targets pro-fibrotic molecular mechanisms. TGF-Beta (TGFB), a ubiquitous cytokine, elevated in peritoneal fluid in endometriosis is associated with fibrosis. TGFB signals intracellularly via conventional SMAD and alternative Kr€ uppel-like transcriptional factor (KLF) mechanisms. Specifically KLF11, associated with fibroids and endometriosis is a crucial candidate mediator of disease mechanisms. KLF11 recruits the epigenetic Histone acetyl transferase or Histone Deacetylases to target gene promoters such as scar tissue Collagen1 (COL1) to alter expression levels. DESIGN: Laboratory research. MATERIALS AND METHODS: Gene expression was evaluated by Luciferase and qPCR assays in the Ishikawa endometrial cell line and in a Klf11-/- mouse endometriosis model. Paired eutopic and ectopic endometrial samples from 28 patients with endometriosis were evaluated by immunohistochemistry. RESULTS: Loss of Klf11 in a mouse endometriosis model results in progressive fibrosis through epigenetic up-regulation of Collagen 1 expression. In TGFB treated Ishikawa cells, KLF11 was immediately up-regulated followed by sustained repression. KLF11 repressed TGF-B receptors and SMAD2 levels thereby silencing the conventional signaling pathway. Sustained KLF11 repression mimics the molecular dysregulation in the animal endometriosis model wherein loss of Klf11 is accompanied by epigenetic histone acetylation of the COL1 promoter, activated COL1 expression and fibrosis. We also found similar alterations in these genes in human endometriosis samples, corroborating their disease relevance. CONCLUSION: TGFB is a key cytokine implicated in fibrosis. We show here that KLF11 is a crucial mediator of pro-fibrotic TGFB signaling. Novel pharmacological approaches targeting TGFB and its downstream epigenetic histone mediated offer translational opportunities that significantly expand current therapeutic capability for this chronic disease. O-120 Tuesday, October 21, 2014 05:00 PM DONOR TSH LEVEL IS ASSOCIATED WITH IN VITRO FERTILIZATION OUTCOME AMONG OOCYTE DONATION CYCLES. A. E. Karmon, E. E. Cardozo, I. Souter, J. Gold, J. C. Petrozza, A. K. Styer. Vincent Obstetrics & Gynecology, Massachusetts General Hospital, Boston, MA. OBJECTIVE: To evaluate whether a TSH level of< 2.5mIU/L or R 2.5mIU/L among oocyte donors is related to recipient pregnancy outcome.
DESIGN: Cohort study. MATERIALS AND METHODS: Records from 220 consecutive fresh IVF donor oocyte cycles which occurred between 2004–2013 at the Massachusetts General Hospital Fertility Center were reviewed. There were 186 oocyte donors who underwent 215 oocyte donation cycles with complete donor thyroid stimulating hormone (TSH) data included in our analysis. The most recent TSH obtained prior to but within 12 months of a cycle was considered for analysis. Logistic regression models using generalized estimating equations (GEE) were fit to investigate the relationship between donor TSH and clinical pregnancy per oocyte retrieval while controlling for confounders and within-person correlations in cycle outcome. Multivariate results were adjusted for recipient TSH, donor age, recipient age, donor BMI, recipient BMI, donor antral follicle count, donor number of prior cycles, male factor infertility, and donor status (known vs. anonymous). RESULTS: Mean age of oocyte donors was 26.9 years and mean donor TSH was 1.9mIU/L at the time of first cycle. Donor TSH ranged from 0.4-9.0mIU/L in our sample. Crude clinical pregnancy rate per oocyte retrieval was 116/172 (67%) and 19/43 (44%) among cycles with donor TSH levels of < 2.5mIU/L and R 2.5mIU/L, respectively. There were no significant differences in rate of male factor or recipient uterine factor infertility among the two TSH groups (16% vs. 6% p¼0.17 and 3% vs. 0% p¼0.99, respectively, for TSH < and R 2.5mIU/L). In multivariate regression, odds of clinical pregnancy per oocyte retrieval were lower among cycles with donor TSH levels R 2.5mIU/L as compared to cycles with donor TSH levels < 2.5mIU/L (age-adjusted odds ratio 0.39, 95% CI 0.19-0.79, p<0.01, and multivariate odds ratio 0.37, 95% CI 0.3-0.8, p<0.01). Recipient TSH was not related to pregnancy outcome. CONCLUSION: Although a correlation between TSH concentration and pregnancy outcome has been well documented, its role prior to fertilization remains unclear. This analysis of oocyte donation cycles suggests that there may be relationship between TSH prior to fertilization and IVF outcome.
O-121 Tuesday, October 21, 2014 05:15 PM SUPEROVULATION DOES NOT INCREASE EMBRYONIC ANEUPLOIDY: A PROSPECTIVE EVALUATION OF ANEUPLOIDY IN NATURAL IVF CYCLES WITH COMPARISON TO 15,169 EMBRYOS FROM AGE CONTROLLED PEERS WHO HAD M. D. Werner,a,b SUPEROVULATION. K. H. Hong,a,b J. M. Franasiak,a,b E. J. Forman,a,b D. A. Gabriele,a M. Cheng,a R. T. Scott, Jr.,a,b aRMANJ, Basking Ridge, NJ; bDivision of Reproductive Endocrinology, Rutgers-RWJ Medical School, Basking Ridge, NJ. OBJECTIVE: The use of superovulation during IVF provides a greater number of mature oocytes and embryos per cycle and an overall increase in delivery rates when compared with natural cycles. However, some data suggest that superovulation may diminish oocyte quality. Of particular concern are limited animal and human data indicating increasing embryonic aneuploidy with increasing gonadotropin dose. Unfortunately, no data are available which systematically address aneuploidy rates in natural cycles where neither exogenous LH/FSH nor GnRH analogs prior to the mid-cycle surge have been administered. This study seeks to determine the embryonic aneuploidy rate during natural cycles and to compare them to rates observed in embryos from cycles employing superovulation. DESIGN: Prospective observational study. MATERIALS AND METHODS: All infertile patients with maternal ages 18 to 49 and regular ovulatory cycles lasting <39 days were offered study participation. Serial endocrine and ultrasound monitoring was performed. When a follicle reached R15mm in size, both hCG and GnRH
Aneuploidy rate by maternal age %(N)
Type of IVF cycle Natural Stimulated
Total embryos
%30
31-34
35-37
38-40
41-42
R43
119 15,169
23.8% (22) 25.1% (1,562)
37.5% (24) 31.1% (5,167)
39.0% (18) 37.4% (3,569)
76.0% (25) 52.7% (2,131)
89.4% (19) 71.2% (1,203)
90.9% (11) 84.7% (404)
FERTILITY & STERILITYÒ
e41
agonist were administered. Oocyte retrieval was performed 36 hours later. No LH, FSH, or GnRH antagonist was used. All mature oocytes underwent ICSI and the resulting embryos were cultured until they arrested or became blastocysts. Viable blastocysts were biopsied for aneuploidy screening. The aneuploidy data were then compared with a retrospective cohort of 15,169 embryos from stimulated IVF cycles employing aneuploidy screening. RESULTS: Sixty four of 119 (56.3%) embryos obtained from natural IVF cycles were aneuploid. Logistic regression controlling for maternal age demonstrated that the aneuploidy rates in natural and stimulated cycles were equivalent (P¼0.81). CONCLUSION: Embryonic aneuploidy rates in natural and stimulated IVF cycles do not differ. These data do not support a causative role for gonadotropin stimulation in embryonic aneuploidy. Data collection is ongoing. O-122 Tuesday, October 21, 2014 05:30 PM IMPORT AND EXPORT OF FROZEN DONOR OOCYTE BANK: DOES TRANSPORTATION AFFECT SURVIVAL AND PREGNANCY RATES? J. M. Cox,a K. Fru,a J. Lim,b T. Earl,c H. Hayes,c K. S. Richter,b B. Kaplan,d J. Frattarelli,e A. DeCherney,a M. Levy.b aPRAE, NICHD, NIH, Bethesda, MD; bShady Grove Fertility, Rockville, MD; cDonor Egg Bank USA, Rockville, MD; dFertility Centers of Illinois, Chicago, IL; eFertility Institute of Hawaii, Honolulu, HI. OBJECTIVE: To evaluate the difference in survival, fertilization, and pregnancy rates between internal freeze-internal thaw, internal freezeexternal thaw, and external freeze-internal thaw of donor frozen oocytes that were cryopreserved and banked at participating fertility centers. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Frozen donor oocyte banks used internally at our center, exported from our center, or imported to our center were identified between 2012- 2013. The frozen donor egg banks were categorized into 3 groups based on freeze-thaw locations: internal freeze-internal thaw(II), internal freeze-external thaw(IE), and external freeze-internal thaw(EI). Outcomes evaluated were: thaw survival, fertilization rates, cleavage rates, clinical pregnancy/embryo transfer (CP/ET), and ongoing pregnancy per thaw(OP/Thaw). RESULTS: While comparison of cleavage rates amongst II versus IE and II versus EI showed statistical significance, the survival of thaw and pregnancy outcomes from these comparisons showed no statistical significant difference (Table1). There was a trend towards higher pregnancy rates in the II group overall at 52.63% compared to IE at 41.92% and EI at 42.75%.
Survival % Fert % Clev % CP/ET OP/Thaw
II IE EI P-value P-value (N-thaw¼57) (N-thaw¼234) (N-thaw¼142) (II vs IE) (II vs EI) 90.20 75.56 84.68 58.18 52.63
89.94 76.78 95.86 49.55 41.92
85.55 74.93 89.91 51.52 42.75
0.88 0.68 <0.001 0.25 0.11
0.03 0.83 0.04 0.40 0.16
CONCLUSION: As donor egg banking becomes more popular, the transport of banked oocytes will also increase. Despite efforts to standardize oocyte vitrification and thaw techniques across the egg bank network, the variation seen in our results undoubtedly reflects variations in oocyte vitrification and culture conditions. This preliminary data shows a trend toward higher internal freeze-internal thaw pregnancy rates yet not statistically significant, possibly due to low numbers. However, this data also shows a relatively small decrease in success rates with oocyte importation and export, which is reassuring. While initial results are promising, further studies are warranted. Supported by: In part by PRAE/NICHD/NIH and Donor Egg Bank USA.
e42
INFERTILITY AND THE INTERNET: ETHICAL CONCERNS IN MEDICAL MARKETING. J. L. Chan, S. B. Schon, K. E. O’Neill, P. Masson. University of Pennsylvania, Philadelphia, PA. OBJECTIVE: With an increasing number of patients seeking medical information on the Internet, there are concerns about information quality and content on patient-oriented websites. We sought to assess ethical issues related to information presented by fertility clinic websites, and evaluated them for completeness and adherence to ASRM guidelines. DESIGN: Cross-sectional evaluation. MATERIALS AND METHODS: Between 2/2014-4/4014, 396 Society of Assisted Reproductive Technologies (SART) member websites were evaluated by two independent researchers. Websites were surveyed for the following parameters: practice location, type and size, risks of IVF, egg donor traits, experimental procedures, advertising presence, sex selection, and presentation of success rates. X2 tests were used to assess for differences between groups. RESULTS: 98% (387/396) of clinics had a website, of which 80% were private and 20% academic. 26% of practices performed R500 cycles/year while 74% performed <500 cycles/year. Only 36% of websites discussed the risks of IVF, with no differences between academic and private practices (35 vs 39%, p¼ .49), or between small- and large-volume centers (35 vs. 45%, p¼ .07). Of the 259 practices that have egg donor availability, 14% provided public information on egg donor traits, however all of these websites abided by ASRM guidelines regarding the commodification of donors, and no additional fees were advertised for specific traits. Academic centers were more likely than private to offer experimental procedures such as ovarian tissue cryopreservation (44 vs.14%, p¼< .0001). Only 7% of practices had industry advertisements. ASRM guidelines suggest that success rates be reported as live births per cycles initiated, however, only 54% of websites reported both with large volume practices more likely to report both as compared to small practices (76 vs 50%, p< .0001). Meanwhile, there was no difference in success rate reporting between academic and private practices (55 vs 54%, p¼ .6). 25% of websites advertise elective sex selection. Private practices were more likely to advertise sex selection than their academic counterparts (31.2 vs. 2.5%, p< .0001), with no difference between large and small practices (26 vs 27%, p¼ .2). CONCLUSION: The majority of websites abide by ASRM advertising guidelines, however, there is still limited information regarding the risks of IVF and other experimental procedures. Moreover, there is considerable heterogeneity in success rate reporting along with promotion of controversial services such as elective sex selection on patient-oriented websites.
O-124 Tuesday, October 21, 2014 06:00 PM
TABLE 1. Outcomes
O-123 Tuesday, October 21, 2014 05:45 PM
ASRM Abstracts
MODIFIABLE ASPECTS OF ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) PROCEDURES LEAD TO ALTERATIONS IN PLACENTAL DNA METHYLATION. R. S. Weinerman,a J. Ghosh,b S. Song,b M. Truongcao,b C. Sapienza,b C. Coutifaris,a M. Mainigi.a aDivision of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, PA; bFels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA. OBJECTIVE: To determine if alterations in DNA methylation following in-vitro fertilization (IVF) can be attributed to modifiable aspects of ART procedures. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Full-term placentas from singleton deliveries were analyzed, 49 from in-vivo conceptions and 62 from IVF/ ICSI pregnancies: 40 from fresh embryo transfer (ET) cycles, 13 donor oocyte cycles, and 9 frozen embryo transfer (FET) cycles. Placental methylation was analyzed at 45 cytosine-phosphate-guanine (CpG) sites, representing 22 genes, by pyrosequencing. Methylation of an additional 51 placentas, 42 fresh and 9 donor, was analyzed for two placentation and growth related genes, MEST and GRB10. Percentage methylation at each CpG site was compared for the outcome measures, including fresh ET vs. FET, length of gonadotropin stimulation, and length of embryo culture.
Vol. 102, No. 3, Supplement, September 2014
O-119 Tuesday, October 21, 2014 04:45 PM PROGRESSIVE FIBROSIS IN ENDOMETRIOSIS IS EPIGENETICALLY MEDIATED BY THE UBIQUITOUS CYTOKINE TGFBETA VIA TRANSCRIPTION FACTOR KLF11. L. Correa, Z. Khan, Y. Zheng, G. Daftary. OB/Gyn, Mayo Clinic, Rochester, MN. OBJECTIVE: Endometriosis is a debilitating disease affecting at least 10% reproductive aged women. A hallmark phenotype characterizing disease classification and severity is progressive fibrosis through all disease stages. Fibrosis usually accompanies such sequelae as pain and infertility and is difficult to treat. There is a critical need to develop novel translational research that targets pro-fibrotic molecular mechanisms. TGF-Beta (TGFB), a ubiquitous cytokine, elevated in peritoneal fluid in endometriosis is associated with fibrosis. TGFB signals intracellularly via conventional SMAD and alternative Kr€ uppel-like transcriptional factor (KLF) mechanisms. Specifically KLF11, associated with fibroids and endometriosis is a crucial candidate mediator of disease mechanisms. KLF11 recruits the epigenetic Histone acetyl transferase or Histone Deacetylases to target gene promoters such as scar tissue Collagen1 (COL1) to alter expression levels. DESIGN: Laboratory research. MATERIALS AND METHODS: Gene expression was evaluated by Luciferase and qPCR assays in the Ishikawa endometrial cell line and in a Klf11-/- mouse endometriosis model. Paired eutopic and ectopic endometrial samples from 28 patients with endometriosis were evaluated by immunohistochemistry. RESULTS: Loss of Klf11 in a mouse endometriosis model results in progressive fibrosis through epigenetic up-regulation of Collagen 1 expression. In TGFB treated Ishikawa cells, KLF11 was immediately up-regulated followed by sustained repression. KLF11 repressed TGF-B receptors and SMAD2 levels thereby silencing the conventional signaling pathway. Sustained KLF11 repression mimics the molecular dysregulation in the animal endometriosis model wherein loss of Klf11 is accompanied by epigenetic histone acetylation of the COL1 promoter, activated COL1 expression and fibrosis. We also found similar alterations in these genes in human endometriosis samples, corroborating their disease relevance. CONCLUSION: TGFB is a key cytokine implicated in fibrosis. We show here that KLF11 is a crucial mediator of pro-fibrotic TGFB signaling. Novel pharmacological approaches targeting TGFB and its downstream epigenetic histone mediated offer translational opportunities that significantly expand current therapeutic capability for this chronic disease. O-120 Tuesday, October 21, 2014 05:00 PM DONOR TSH LEVEL IS ASSOCIATED WITH IN VITRO FERTILIZATION OUTCOME AMONG OOCYTE DONATION CYCLES. A. E. Karmon, E. E. Cardozo, I. Souter, J. Gold, J. C. Petrozza, A. K. Styer. Vincent Obstetrics & Gynecology, Massachusetts General Hospital, Boston, MA. OBJECTIVE: To evaluate whether a TSH level of< 2.5mIU/L or R 2.5mIU/L among oocyte donors is related to recipient pregnancy outcome.
DESIGN: Cohort study. MATERIALS AND METHODS: Records from 220 consecutive fresh IVF donor oocyte cycles which occurred between 2004–2013 at the Massachusetts General Hospital Fertility Center were reviewed. There were 186 oocyte donors who underwent 215 oocyte donation cycles with complete donor thyroid stimulating hormone (TSH) data included in our analysis. The most recent TSH obtained prior to but within 12 months of a cycle was considered for analysis. Logistic regression models using generalized estimating equations (GEE) were fit to investigate the relationship between donor TSH and clinical pregnancy per oocyte retrieval while controlling for confounders and within-person correlations in cycle outcome. Multivariate results were adjusted for recipient TSH, donor age, recipient age, donor BMI, recipient BMI, donor antral follicle count, donor number of prior cycles, male factor infertility, and donor status (known vs. anonymous). RESULTS: Mean age of oocyte donors was 26.9 years and mean donor TSH was 1.9mIU/L at the time of first cycle. Donor TSH ranged from 0.4-9.0mIU/L in our sample. Crude clinical pregnancy rate per oocyte retrieval was 116/172 (67%) and 19/43 (44%) among cycles with donor TSH levels of < 2.5mIU/L and R 2.5mIU/L, respectively. There were no significant differences in rate of male factor or recipient uterine factor infertility among the two TSH groups (16% vs. 6% p¼0.17 and 3% vs. 0% p¼0.99, respectively, for TSH < and R 2.5mIU/L). In multivariate regression, odds of clinical pregnancy per oocyte retrieval were lower among cycles with donor TSH levels R 2.5mIU/L as compared to cycles with donor TSH levels < 2.5mIU/L (age-adjusted odds ratio 0.39, 95% CI 0.19-0.79, p<0.01, and multivariate odds ratio 0.37, 95% CI 0.3-0.8, p<0.01). Recipient TSH was not related to pregnancy outcome. CONCLUSION: Although a correlation between TSH concentration and pregnancy outcome has been well documented, its role prior to fertilization remains unclear. This analysis of oocyte donation cycles suggests that there may be relationship between TSH prior to fertilization and IVF outcome.
O-121 Tuesday, October 21, 2014 05:15 PM SUPEROVULATION DOES NOT INCREASE EMBRYONIC ANEUPLOIDY: A PROSPECTIVE EVALUATION OF ANEUPLOIDY IN NATURAL IVF CYCLES WITH COMPARISON TO 15,169 EMBRYOS FROM AGE CONTROLLED PEERS WHO HAD M. D. Werner,a,b SUPEROVULATION. K. H. Hong,a,b J. M. Franasiak,a,b E. J. Forman,a,b D. A. Gabriele,a M. Cheng,a R. T. Scott, Jr.,a,b aRMANJ, Basking Ridge, NJ; bDivision of Reproductive Endocrinology, Rutgers-RWJ Medical School, Basking Ridge, NJ. OBJECTIVE: The use of superovulation during IVF provides a greater number of mature oocytes and embryos per cycle and an overall increase in delivery rates when compared with natural cycles. However, some data suggest that superovulation may diminish oocyte quality. Of particular concern are limited animal and human data indicating increasing embryonic aneuploidy with increasing gonadotropin dose. Unfortunately, no data are available which systematically address aneuploidy rates in natural cycles where neither exogenous LH/FSH nor GnRH analogs prior to the mid-cycle surge have been administered. This study seeks to determine the embryonic aneuploidy rate during natural cycles and to compare them to rates observed in embryos from cycles employing superovulation. DESIGN: Prospective observational study. MATERIALS AND METHODS: All infertile patients with maternal ages 18 to 49 and regular ovulatory cycles lasting <39 days were offered study participation. Serial endocrine and ultrasound monitoring was performed. When a follicle reached R15mm in size, both hCG and GnRH
Aneuploidy rate by maternal age %(N)
Type of IVF cycle Natural Stimulated
Total embryos
%30
31-34
35-37
38-40
41-42
R43
119 15,169
23.8% (22) 25.1% (1,562)
37.5% (24) 31.1% (5,167)
39.0% (18) 37.4% (3,569)
76.0% (25) 52.7% (2,131)
89.4% (19) 71.2% (1,203)
90.9% (11) 84.7% (404)
FERTILITY & STERILITYÒ
e41
agonist were administered. Oocyte retrieval was performed 36 hours later. No LH, FSH, or GnRH antagonist was used. All mature oocytes underwent ICSI and the resulting embryos were cultured until they arrested or became blastocysts. Viable blastocysts were biopsied for aneuploidy screening. The aneuploidy data were then compared with a retrospective cohort of 15,169 embryos from stimulated IVF cycles employing aneuploidy screening. RESULTS: Sixty four of 119 (56.3%) embryos obtained from natural IVF cycles were aneuploid. Logistic regression controlling for maternal age demonstrated that the aneuploidy rates in natural and stimulated cycles were equivalent (P¼0.81). CONCLUSION: Embryonic aneuploidy rates in natural and stimulated IVF cycles do not differ. These data do not support a causative role for gonadotropin stimulation in embryonic aneuploidy. Data collection is ongoing. O-122 Tuesday, October 21, 2014 05:30 PM IMPORT AND EXPORT OF FROZEN DONOR OOCYTE BANK: DOES TRANSPORTATION AFFECT SURVIVAL AND PREGNANCY RATES? J. M. Cox,a K. Fru,a J. Lim,b T. Earl,c H. Hayes,c K. S. Richter,b B. Kaplan,d J. Frattarelli,e A. DeCherney,a M. Levy.b aPRAE, NICHD, NIH, Bethesda, MD; bShady Grove Fertility, Rockville, MD; cDonor Egg Bank USA, Rockville, MD; dFertility Centers of Illinois, Chicago, IL; eFertility Institute of Hawaii, Honolulu, HI. OBJECTIVE: To evaluate the difference in survival, fertilization, and pregnancy rates between internal freeze-internal thaw, internal freezeexternal thaw, and external freeze-internal thaw of donor frozen oocytes that were cryopreserved and banked at participating fertility centers. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Frozen donor oocyte banks used internally at our center, exported from our center, or imported to our center were identified between 2012- 2013. The frozen donor egg banks were categorized into 3 groups based on freeze-thaw locations: internal freeze-internal thaw(II), internal freeze-external thaw(IE), and external freeze-internal thaw(EI). Outcomes evaluated were: thaw survival, fertilization rates, cleavage rates, clinical pregnancy/embryo transfer (CP/ET), and ongoing pregnancy per thaw(OP/Thaw). RESULTS: While comparison of cleavage rates amongst II versus IE and II versus EI showed statistical significance, the survival of thaw and pregnancy outcomes from these comparisons showed no statistical significant difference (Table1). There was a trend towards higher pregnancy rates in the II group overall at 52.63% compared to IE at 41.92% and EI at 42.75%.
Survival % Fert % Clev % CP/ET OP/Thaw
II IE EI P-value P-value (N-thaw¼57) (N-thaw¼234) (N-thaw¼142) (II vs IE) (II vs EI) 90.20 75.56 84.68 58.18 52.63
89.94 76.78 95.86 49.55 41.92
85.55 74.93 89.91 51.52 42.75
0.88 0.68 <0.001 0.25 0.11
0.03 0.83 0.04 0.40 0.16
CONCLUSION: As donor egg banking becomes more popular, the transport of banked oocytes will also increase. Despite efforts to standardize oocyte vitrification and thaw techniques across the egg bank network, the variation seen in our results undoubtedly reflects variations in oocyte vitrification and culture conditions. This preliminary data shows a trend toward higher internal freeze-internal thaw pregnancy rates yet not statistically significant, possibly due to low numbers. However, this data also shows a relatively small decrease in success rates with oocyte importation and export, which is reassuring. While initial results are promising, further studies are warranted. Supported by: In part by PRAE/NICHD/NIH and Donor Egg Bank USA.
e42
INFERTILITY AND THE INTERNET: ETHICAL CONCERNS IN MEDICAL MARKETING. J. L. Chan, S. B. Schon, K. E. O’Neill, P. Masson. University of Pennsylvania, Philadelphia, PA. OBJECTIVE: With an increasing number of patients seeking medical information on the Internet, there are concerns about information quality and content on patient-oriented websites. We sought to assess ethical issues related to information presented by fertility clinic websites, and evaluated them for completeness and adherence to ASRM guidelines. DESIGN: Cross-sectional evaluation. MATERIALS AND METHODS: Between 2/2014-4/4014, 396 Society of Assisted Reproductive Technologies (SART) member websites were evaluated by two independent researchers. Websites were surveyed for the following parameters: practice location, type and size, risks of IVF, egg donor traits, experimental procedures, advertising presence, sex selection, and presentation of success rates. X2 tests were used to assess for differences between groups. RESULTS: 98% (387/396) of clinics had a website, of which 80% were private and 20% academic. 26% of practices performed R500 cycles/year while 74% performed <500 cycles/year. Only 36% of websites discussed the risks of IVF, with no differences between academic and private practices (35 vs 39%, p¼ .49), or between small- and large-volume centers (35 vs. 45%, p¼ .07). Of the 259 practices that have egg donor availability, 14% provided public information on egg donor traits, however all of these websites abided by ASRM guidelines regarding the commodification of donors, and no additional fees were advertised for specific traits. Academic centers were more likely than private to offer experimental procedures such as ovarian tissue cryopreservation (44 vs.14%, p¼< .0001). Only 7% of practices had industry advertisements. ASRM guidelines suggest that success rates be reported as live births per cycles initiated, however, only 54% of websites reported both with large volume practices more likely to report both as compared to small practices (76 vs 50%, p< .0001). Meanwhile, there was no difference in success rate reporting between academic and private practices (55 vs 54%, p¼ .6). 25% of websites advertise elective sex selection. Private practices were more likely to advertise sex selection than their academic counterparts (31.2 vs. 2.5%, p< .0001), with no difference between large and small practices (26 vs 27%, p¼ .2). CONCLUSION: The majority of websites abide by ASRM advertising guidelines, however, there is still limited information regarding the risks of IVF and other experimental procedures. Moreover, there is considerable heterogeneity in success rate reporting along with promotion of controversial services such as elective sex selection on patient-oriented websites.
O-124 Tuesday, October 21, 2014 06:00 PM
TABLE 1. Outcomes
O-123 Tuesday, October 21, 2014 05:45 PM
ASRM Abstracts
MODIFIABLE ASPECTS OF ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) PROCEDURES LEAD TO ALTERATIONS IN PLACENTAL DNA METHYLATION. R. S. Weinerman,a J. Ghosh,b S. Song,b M. Truongcao,b C. Sapienza,b C. Coutifaris,a M. Mainigi.a aDivision of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, PA; bFels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA. OBJECTIVE: To determine if alterations in DNA methylation following in-vitro fertilization (IVF) can be attributed to modifiable aspects of ART procedures. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Full-term placentas from singleton deliveries were analyzed, 49 from in-vivo conceptions and 62 from IVF/ ICSI pregnancies: 40 from fresh embryo transfer (ET) cycles, 13 donor oocyte cycles, and 9 frozen embryo transfer (FET) cycles. Placental methylation was analyzed at 45 cytosine-phosphate-guanine (CpG) sites, representing 22 genes, by pyrosequencing. Methylation of an additional 51 placentas, 42 fresh and 9 donor, was analyzed for two placentation and growth related genes, MEST and GRB10. Percentage methylation at each CpG site was compared for the outcome measures, including fresh ET vs. FET, length of gonadotropin stimulation, and length of embryo culture.
Vol. 102, No. 3, Supplement, September 2014