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Effect of the duration of elevated progesterone (P) levels during in vitro fertilization (IVF) on pregnancy rates
O-170 Tuesday, October 15, 2013 4:20 PM TOTAL NUMBER OF OOCYTES RETRIEVED BUT NOT FOLLICLE STIMULATING HORMONE (FSH) DOSE VARIES ACROSS MULTIPLE CYCLES IN REPEAT OOCYTE DONORS. K. N. Fru,a M. J. Hill,a E. R. Bertone-Johnson,b A. H. DeCherney,a B. W. Whitcomb,b E. D. Levens.c aReproductive Endocrinology and Infertility Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child and Human Development/National Institutes of Health, Bethesda, MD; bDivision of Biostatistics and Epidemiology, University of Massachussetts School of Public Health and Health Sciences, Amherst, MA; cShady Grove Fertility Resproductive Science Center, Rockville, MD. OBJECTIVE: To evaluate the amount of variability across cycles among oocyte donors, we estimated the inter-cycle variability in oocyte yield and gonadotropin use.
these studies have evaluated the adverse effect of a single P measurement on the day of hCG trigger. This study assessed whether the duration of P elevation has an adverse effect on IVF outcomes. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Patients < 40 years of age who underwent IVF and embryo transfer cycles between 5/2010-3/2013 were included in the analysis. Pregnancy outcomes were compared in patients with P levels R1 ng/ dl for 0, 1, 2, and R3 days of elevation. ANOVAwas used for evaluation of continuous variables with Tukey’s HSD test for post-hoc evaluation. Categorical variables were analyzed using Chi-Squared test with post hoc pair-wise comparisons. RESULTS: A total of 982 cycles consisting of P elevation R1 ng/dl for 0, 1, 2, and R3 days duration were analyzed. Baseline characteristics and outcomes of stimulation between the four groups are shown in Table 1. The pregnancy rates were significantly lower with prolonged P elevation.
IVF outcomes by duration of P elevation.
Number of Days of P Elevation
Age (years) AMH (ng/ml) FSH (mIU/ml) Stimulation days (n) Peak E2 (pg/ml) P4 on day of hCG (ng/ml) # oocytes retrieved (n) Number embryos transferred (n) CPR (%) OPR (%) a, b,
0 (n¼559)
1 (n¼159)
2 (n¼152)
R3 (n¼112)
33.9 3.7a 2.7 3.2 7.0 2.7 8.8 2.0 11739 795a 0.6 0.1a 11.9 6.0a 1.8 0.6 62.1% (347/559)a 54.7% (306/559)a
34.9 3.5a 2.2 2.1 7.0 2.4 9.0 2.5 1906 745 1.1 0.2b 13.3 5.9 1.9 0.7 48.4% (77/159)b 41.5% (66/159)b
34.3 3.3 2.2 2.3 6.9 2.3 8.9 2.0 12073 816b 1.3 0.3c 13.4 5.9 1.8 0.6 36.8% (56/152)c 26.6% (42/152)c
34.0 3.9 2.5 2.8 6.4 2.3 9.3 1.8 12168 931b 1.4 0.4c 14.3 6.5b 1.9 0.6 27.7% (31/112)c 17.9% (20/112)c
and c are significantly different (p<0.05).
DESIGN: Retrospective cohort study. MATERIALS AND METHODS: In a large ART center, 117 donors contributing 220 donor oocyte retrieval cycles were evaluated. The 220 donor oocyte cycles were split among 461 recipients. Means and standard deviations (SD) were estimated for each characteristic. In order to evaluate the variability of cycle-level characteristics in oocyte donors seen for multiple retrievals, linear mixed models were used to estimate intraclass correlation coefficients (ICC), representing the proportion of all variability due to that between subjects. Characteristics considered included: total FSH dose, number of stimulation days, and number of oocytes retrieved. RESULTS: Cycles means SD were 2400 971 IU FSH, 10.8 1.6 stimulation days, and 22.5 8.7 oocytes retrieved. Total FSH dose varied minimally within donors across multiple cycles, with ICC¼ 0.79 (95%CI: 0.70-0.86), indicating that only 21% of all variability was due to that within donors. In contrast, the number of oocytes retrieved varied more across multiple retrieval cycles of the same donor (ICC¼0.51, 95%CI: 0.36 – 0.66). The proportion of variance due to that within donors was very high for days of stimulation (ICC 0.20, 95%CI: 0.060.50), though likely due to the very limited range in stimulation days. CONCLUSION: Using data from repeated retrieval cycles of the same donors, we observed minimal overall variability in stimulation days and minimal variability of FSH dose across repeated cycles. However, the number of oocytes retrieved varied moderately across multiple cycles of the same donor, as well as between donors. Cycle varying characteristics should be taken into consideration to better predict varying oocyte yield, and may be relevant for assessment of outcomes. Supported by: This work was Supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD.
O-171 Tuesday, October 15, 2013 4:40 PM EFFECT OF THE DURATION OF ELEVATED PROGESTERONE (P) LEVELS DURING IN VITRO FERTILIZATION (IVF) ON PREGNANCY RATES. T. H. Budinetz, M. H. Spiel, C. A. Benadiva, C. M. Sueldo, J. C. Nulsen, L. L. Engmann. Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT. OBJECTIVE: There are conflicting reports in the literature on the effect of premature P elevation on pregnancy outcomes during IVF. However, most of
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ASRM Abstracts
CONCLUSION: Prolonged P elevation R1ng/ml during the follicular phase progressively impairs pregnancy outcomes. O-172 Tuesday, October 15, 2013 05:00 PM A MOUSE MODEL FOR FRAGILE X- ASSOCIATED PRIMARY M. Ascano, Jr.,b OVARIAN INSUFFICIENCY. E. Mok-Lin,a Z. Rosenwaks,a T. Tuschl,b Z. Williams.c aThe Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY; bLaboratory of RNA Molecular Biology, The Rockefeller University, New York, NY; cDepartment of Obstetrics & Gynecology and Women’s Health, The Albert Einstein College of Medicine, Bronx, NY. OBJECTIVE: Fragile X is the most common known genetic cause of primary ovarian insufficiency (POI), accounting for up to 13% of familial cases. The mechanism is not known. The objective was to study the molecular basis and present a mouse model for Fragile X-associated POI (FXPOI). DESIGN: Prospective, controlled laboratory study. MATERIALS AND METHODS: Ovaries obtained from fragile X mental retardation 1 knockout (FMR1 KO) mice generated via homologous recombination using an exon-disrupted targeted vector with nil RNA or protein expression (n¼10) were examined at 3, 6, 9, 12 and 18 weeks of age and compared to ovaries from control, wild-type (WT) mice (n¼10). Ovarian morphology and weights were assessed prior to fixation with 4% paraformaldehyde in tris-buffered saline. 5mm sections stained in hematoxylin and eosin were analyzed and total numbers of primordial and activated (primary, secondary and antral) follicles were determined. Statistical analyses included t-tests and chi-squared tests. P<0.05 was deemed statistically significant. RESULTS: FMR1 KO had visibly and quantifiably larger ovaries than WT mice at and beyond 9 weeks of age, with increased ovarian weight and number of histologic sections. Histologic analysis revealed significantly higher numbers of activated follicles in the KO mice and a significantly smaller proportion of primordial follicles at 3 weeks (53% vs. 64%, P<0.0001), 9 weeks (34% vs. 50%, P<0.0001), and 18 weeks of age (20% vs. 62%, P<0.0001). CONCLUSION: FMR1 knockout mice exhibited increased ovarian size, increased number of activated follicles, and a decreased proportion of primordial follicles. This suggests premature activation of the primordial follicle pool, in the setting of Fragile X RNA and protein deficiencies, as the mechanism for
Vol. 100, No. 3, Supplement, September 2013
these studies have evaluated the adverse effect of a single P measurement on the day of hCG trigger. This study assessed whether the duration of P elevation has an adverse effect on IVF outcomes. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Patients < 40 years of age who underwent IVF and embryo transfer cycles between 5/2010-3/2013 were included in the analysis. Pregnancy outcomes were compared in patients with P levels R1 ng/ dl for 0, 1, 2, and R3 days of elevation. ANOVAwas used for evaluation of continuous variables with Tukey’s HSD test for post-hoc evaluation. Categorical variables were analyzed using Chi-Squared test with post hoc pair-wise comparisons. RESULTS: A total of 982 cycles consisting of P elevation R1 ng/dl for 0, 1, 2, and R3 days duration were analyzed. Baseline characteristics and outcomes of stimulation between the four groups are shown in Table 1. The pregnancy rates were significantly lower with prolonged P elevation.
IVF outcomes by duration of P elevation.
Number of Days of P Elevation
Age (years) AMH (ng/ml) FSH (mIU/ml) Stimulation days (n) Peak E2 (pg/ml) P4 on day of hCG (ng/ml) # oocytes retrieved (n) Number embryos transferred (n) CPR (%) OPR (%) a, b,
0 (n¼559)
1 (n¼159)
2 (n¼152)
R3 (n¼112)
33.9 3.7a 2.7 3.2 7.0 2.7 8.8 2.0 11739 795a 0.6 0.1a 11.9 6.0a 1.8 0.6 62.1% (347/559)a 54.7% (306/559)a
34.9 3.5a 2.2 2.1 7.0 2.4 9.0 2.5 1906 745 1.1 0.2b 13.3 5.9 1.9 0.7 48.4% (77/159)b 41.5% (66/159)b
34.3 3.3 2.2 2.3 6.9 2.3 8.9 2.0 12073 816b 1.3 0.3c 13.4 5.9 1.8 0.6 36.8% (56/152)c 26.6% (42/152)c
34.0 3.9 2.5 2.8 6.4 2.3 9.3 1.8 12168 931b 1.4 0.4c 14.3 6.5b 1.9 0.6 27.7% (31/112)c 17.9% (20/112)c
and c are significantly different (p<0.05).
DESIGN: Retrospective cohort study. MATERIALS AND METHODS: In a large ART center, 117 donors contributing 220 donor oocyte retrieval cycles were evaluated. The 220 donor oocyte cycles were split among 461 recipients. Means and standard deviations (SD) were estimated for each characteristic. In order to evaluate the variability of cycle-level characteristics in oocyte donors seen for multiple retrievals, linear mixed models were used to estimate intraclass correlation coefficients (ICC), representing the proportion of all variability due to that between subjects. Characteristics considered included: total FSH dose, number of stimulation days, and number of oocytes retrieved. RESULTS: Cycles means SD were 2400 971 IU FSH, 10.8 1.6 stimulation days, and 22.5 8.7 oocytes retrieved. Total FSH dose varied minimally within donors across multiple cycles, with ICC¼ 0.79 (95%CI: 0.70-0.86), indicating that only 21% of all variability was due to that within donors. In contrast, the number of oocytes retrieved varied more across multiple retrieval cycles of the same donor (ICC¼0.51, 95%CI: 0.36 – 0.66). The proportion of variance due to that within donors was very high for days of stimulation (ICC 0.20, 95%CI: 0.060.50), though likely due to the very limited range in stimulation days. CONCLUSION: Using data from repeated retrieval cycles of the same donors, we observed minimal overall variability in stimulation days and minimal variability of FSH dose across repeated cycles. However, the number of oocytes retrieved varied moderately across multiple cycles of the same donor, as well as between donors. Cycle varying characteristics should be taken into consideration to better predict varying oocyte yield, and may be relevant for assessment of outcomes. Supported by: This work was Supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD.
O-171 Tuesday, October 15, 2013 4:40 PM EFFECT OF THE DURATION OF ELEVATED PROGESTERONE (P) LEVELS DURING IN VITRO FERTILIZATION (IVF) ON PREGNANCY RATES. T. H. Budinetz, M. H. Spiel, C. A. Benadiva, C. M. Sueldo, J. C. Nulsen, L. L. Engmann. Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT. OBJECTIVE: There are conflicting reports in the literature on the effect of premature P elevation on pregnancy outcomes during IVF. However, most of
S52
ASRM Abstracts
CONCLUSION: Prolonged P elevation R1ng/ml during the follicular phase progressively impairs pregnancy outcomes. O-172 Tuesday, October 15, 2013 05:00 PM A MOUSE MODEL FOR FRAGILE X- ASSOCIATED PRIMARY M. Ascano, Jr.,b OVARIAN INSUFFICIENCY. E. Mok-Lin,a Z. Rosenwaks,a T. Tuschl,b Z. Williams.c aThe Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY; bLaboratory of RNA Molecular Biology, The Rockefeller University, New York, NY; cDepartment of Obstetrics & Gynecology and Women’s Health, The Albert Einstein College of Medicine, Bronx, NY. OBJECTIVE: Fragile X is the most common known genetic cause of primary ovarian insufficiency (POI), accounting for up to 13% of familial cases. The mechanism is not known. The objective was to study the molecular basis and present a mouse model for Fragile X-associated POI (FXPOI). DESIGN: Prospective, controlled laboratory study. MATERIALS AND METHODS: Ovaries obtained from fragile X mental retardation 1 knockout (FMR1 KO) mice generated via homologous recombination using an exon-disrupted targeted vector with nil RNA or protein expression (n¼10) were examined at 3, 6, 9, 12 and 18 weeks of age and compared to ovaries from control, wild-type (WT) mice (n¼10). Ovarian morphology and weights were assessed prior to fixation with 4% paraformaldehyde in tris-buffered saline. 5mm sections stained in hematoxylin and eosin were analyzed and total numbers of primordial and activated (primary, secondary and antral) follicles were determined. Statistical analyses included t-tests and chi-squared tests. P<0.05 was deemed statistically significant. RESULTS: FMR1 KO had visibly and quantifiably larger ovaries than WT mice at and beyond 9 weeks of age, with increased ovarian weight and number of histologic sections. Histologic analysis revealed significantly higher numbers of activated follicles in the KO mice and a significantly smaller proportion of primordial follicles at 3 weeks (53% vs. 64%, P<0.0001), 9 weeks (34% vs. 50%, P<0.0001), and 18 weeks of age (20% vs. 62%, P<0.0001). CONCLUSION: FMR1 knockout mice exhibited increased ovarian size, increased number of activated follicles, and a decreased proportion of primordial follicles. This suggests premature activation of the primordial follicle pool, in the setting of Fragile X RNA and protein deficiencies, as the mechanism for
Vol. 100, No. 3, Supplement, September 2013