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A randomized double-blinded placebo-controlled trial on the effect of 16 weeks of dehydroepiandrosterone (DHEA) on ovarian reserve markers and IVF outcomes in normal responders
CONCLUSION: Inhibition of oocyte GSK-3 during oocyte growth and resumption of meiosis caused cardiovascular defects in offspring and neonatal death. This represents a novel developmental mechanism by which periconceptional hyperinsulinemia acts on the oocyte to influence offspring cardiovascular development and function. Supported by: NIH R01 HD046768. OVARIAN RESERVE O-371 Wednesday, October 16, 2013 04:00 PM FUNCTIONAL OVARIAN RESERVE ASSESSMENTS IN YOUNG OOCYTE DONORS BASED ON FMR1 GENOTYPES AND SUBE. Himaya,a,b D. H. Barad,a,c GENOTYPES. V. A. Kushnir,a A. Weghofer,a,d N. Gleicher.a,c aCenter for Human Reproduction, New York, NY; bCentre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada; cFoundation for Reproductive Medicine, New York, NY; dMedical University Vienna, Vienna, Austria. OBJECTIVE: Since ovarian aging patterns are associated with genotypes and sub-genotypes of the fragile X mental retardation 1 (FMR1) gene, we investigated if differences in functional ovarian reserve (FOR) are already apparent at young ages in healthy oocyte donors. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We assessed anti-M€ullerian hormone (AMH) in 233 egg donors in 355 measurements based on previously characterized FMR1 genotypes and sub-genotypes, which are based on normal range of CGG repeat numbers (n[thinsp]¼[thinsp]26–34), defining women as normal (norm), heterozygous (het) or homozygous (hom). Het and hom genotypes are subdivided into sub-genotypes, based on whether abnormal alleles are above (high) or below normal (low). With donors with norm FMR1 (both alleles in normal range) serving as controls, het and hom genotypes were compared. RESULTS: Mean age for the whole group was 24.33.3 years and did not vary based on FMR1. AMH for norm donors was 4.22.2 ng/mL. Pairwise comparison, adjusted for age, revealed significantly lower AMH in hom-low/low and hom-high/high donors (both P<0.001), while het-norm/low and het-norm/high donors showed significantly higher AMH (P¼0.037 and P¼0.004). Donors with hom-low/high had similar AMH levels to norm controls (P¼0.066). CONCLUSION: In the largest data set of FMR1-based FOR assessments in young oocyte donors so far, hom-low/low and hom-high/high sub-genotypes are associated with significantly lower FOR. Het sub-genotypes demonstrate higher FOR. These data confirm the importance of the FMR1 gene in predicting ovarian aging: Since het sub-genotypes demonstrate high FOR at young ages, such women deplete their total ovarian reserve relatively quickly. In contrast, young hom women, with lower FOR at this age, deplete slowly. FMR1 testing identifies young women who quickly deplete and likely are at potential risk for future premature ovarian senescence. Supported by: Foundation for Reproductive Medicine, Center for Human Reproduction and Centre Hospitalier de l’Universite de Montreal. O-372 Wednesday, October 16, 2013 04:15 PM IMPACT OF UNILATERAL VERSUS BILATERAL LAPAROSCOPIC OVARIAN DRILLING ON OVARIAN RESERVE IN CLOMIPHENE CITRATE-RESISTANT PCOS WOMEN. A. Nasr. Obstetrics & Gynecology, Assiut University, Assiut, Egypt. OBJECTIVE: To evaluate the impact of unilateral versus bilateral laparoscopic ovarian drilling (LOD) on serum anti-Mullerian hormone (AMH) in women with clomiphene citrate(CC)-resistant polycystic ovary syndrome (PCOS). DESIGN: A randomized controlled clinical trial. MATERIALS AND METHODS: The study was conducted at a universityaffiliated tertiary center. Eighty women with CC-resistant PCOS were randomized into two groups: group A [40 women; mean age: (SD) 28.4 (2.2)], underwent unilateral LOD; group B [40 women; mean age: (SD) 29.2 (1.9)], underwent bilateral LOD. A group of normally ovulatory women; group C [40 women; mean age: (SD) 27.6 (2.1)], served as controls. Serum AMH levels were measured before and six months after LOD. Assuming a 20% difference between the groups, with an a of 5% and a b of 20%, it was calculated that forty women are required in each arm of the study to detect a true difference at the 95% confidence level with 80% power. Statistical analysis was performed using SPSS software, version 17.0 (SPSS, Chicago, IL, USA). P <0.05 was considered statistically significant.
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RESULTS: There were no differences in age and body mass index between groups. AMH levels were significantly higher in PCOS women than in normally ovulatory women (8.56 +/- 1.67 ng/ml vs. 2.12 +/- 0.71 ng/ml; p <0.05). After unilateral LOD, serum AMH levels showed a significant reduction, compared to preoperative values and controls (6.24 +/-1.13 ng/ml; p <0.05). Similarly, bilateral LOD resulted in a significant reduction in serum AMH levels, compared to preoperative values and controls (5.98 +/-1.21 ng/ ml; p <0.05). However, there was no statistically significant difference in serum AMH levels six months after unilateral vs. bilateral LOD. CONCLUSION: Women with CC-resistant PCOS had higher serum AMH levels, compared to normally ovulatory women. Although unilateral and bilateral LOD resulted in a similarly significant reduction of serum AMH levels, postoperative values remained significantly higher than in normally ovulating women. O-373 Wednesday, October 16, 2013 04:30 PM A RANDOMIZED DOUBLE-BLINDED PLACEBO-CONTROLLED TRIAL ON THE EFFECT OF 16 WEEKS OF DEHYDROEPIANDROSTERONE (DHEA) ON OVARIAN RESERVE MARKERS AND IVF OUTCOMES IN NORMAL RESPONDERS. T. W. Y. Yeung, R. H. W. Li, V. C. Y. Lee, J. Chai, E. H. Y. Ng, P. C. Ho. Obstetrics and Gynaecology, University of Hong Kong, Hong Kong, Hong Kong. OBJECTIVE: To assess whether DHEA supplementation in women with normal responders improve ovarian reserve markers, ovarian response to standard dose gonadotrophins or IVF outcomes. DESIGN: Randomized double-blinded placebo-controlled study. MATERIALS AND METHODS: Normal responders (defined as AFC 515) were recruited in a university-affiliated reproductive unit between 10/ 2010 and 5/2012 and randomized into DHEA (n¼36) and placebo groups (n¼36) according to a computer generated randomization list. DHEA 25mg tds or placebo were started 12 weeks prior to IVF. Monthly ovarian reserve markers (AFC, AMH, FSH), ovarian response to standard dose HMG in 3rd month and IVF outcomes were compared. Sample size calculation was based on an increase of AFC by 3.0 being clinically significant with a test significance of 0.05 and power of 0.8. RESULTS: There was a trend towards higher AFC (10 vs 8, p¼0.955) after 12 weeks of DHEA use in DHEA group compared to placebo. There was no significant difference in FSH (8.4 vs 8.5 IU/L, p¼0.374), AMH (2.08 vs 2.42 ng/ml, p ¼0.534), duration (11 vs 10 days, p¼0.38) and dose (2100 vs 1950 IU, p¼0.428) of gonadogrophin use. There was higher number of follicles >10mm (2 vs 1, p ¼ 0.203) after standard dose HMG stimulation and higher number of top quality embryos (2 vs 1, p¼0.255) in DHEA group although they did not reach statistical significance. Similar clinical pregnancy rates (27.8 vs 41.1%, p¼0.347) and ongoing pregnancy rate (19.4 vs 29.4%, p¼0.521) were observed in DHEA and placebo groups. CONCLUSION: DHEA has been increasingly used in poor responders and there is no available in normal responders. Our study did not detect any significant difference in ovarian response markers and pregnancy outcomes after DHEA, although it suggested a trend of improved AFC, ovarian response with low dose HMG stimulation and top quality embryos. Routine use of DHEA in normal responders to improve ovarian response could not be recommended at this stage. Supported by: Committee on Research and Conference Grants, University of Hong Kong. O-374 Wednesday, October 16, 2013 04:45 PM VALIDATION OF THE POWER MODEL OF OVARIAN NONGROWING FOLLICLE DEPLETION ASSOCIATED WITH AGING. K. R. Hansen,a N. S. Knowlton,b N. M. Budrys,a M. T. Zavy,a L. B. Craig.a aDept. of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, University of Oklahoma Health Sciences Center, Oklahoma City, OK; bMolecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. OBJECTIVE: The primary determinant of reproductive aging in women is the progressive decline in ovarian non-growing follicles (NGFs). This pool of NGFs, inclusive of the ovarian primordial, intermediate and primary follicles, constitutes the ovarian reserve. Ultimately the depletion of the NGF pool results in menopause. We have previously characterized the decline in NGFs associated with aging, determining that a power model taking the form y ¼ axb + c, where a, b, and c are constants and y ¼ NGF count at age x, best characterizes the decline in the log-transformed NGF count associated with
Vol. 100, No. 3, Supplement, September 2013
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RESULTS: There were no differences in age and body mass index between groups. AMH levels were significantly higher in PCOS women than in normally ovulatory women (8.56 +/- 1.67 ng/ml vs. 2.12 +/- 0.71 ng/ml; p <0.05). After unilateral LOD, serum AMH levels showed a significant reduction, compared to preoperative values and controls (6.24 +/-1.13 ng/ml; p <0.05). Similarly, bilateral LOD resulted in a significant reduction in serum AMH levels, compared to preoperative values and controls (5.98 +/-1.21 ng/ ml; p <0.05). However, there was no statistically significant difference in serum AMH levels six months after unilateral vs. bilateral LOD. CONCLUSION: Women with CC-resistant PCOS had higher serum AMH levels, compared to normally ovulatory women. Although unilateral and bilateral LOD resulted in a similarly significant reduction of serum AMH levels, postoperative values remained significantly higher than in normally ovulating women. O-373 Wednesday, October 16, 2013 04:30 PM A RANDOMIZED DOUBLE-BLINDED PLACEBO-CONTROLLED TRIAL ON THE EFFECT OF 16 WEEKS OF DEHYDROEPIANDROSTERONE (DHEA) ON OVARIAN RESERVE MARKERS AND IVF OUTCOMES IN NORMAL RESPONDERS. T. W. Y. Yeung, R. H. W. Li, V. C. Y. Lee, J. Chai, E. H. Y. Ng, P. C. Ho. Obstetrics and Gynaecology, University of Hong Kong, Hong Kong, Hong Kong. OBJECTIVE: To assess whether DHEA supplementation in women with normal responders improve ovarian reserve markers, ovarian response to standard dose gonadotrophins or IVF outcomes. DESIGN: Randomized double-blinded placebo-controlled study. MATERIALS AND METHODS: Normal responders (defined as AFC 515) were recruited in a university-affiliated reproductive unit between 10/ 2010 and 5/2012 and randomized into DHEA (n¼36) and placebo groups (n¼36) according to a computer generated randomization list. DHEA 25mg tds or placebo were started 12 weeks prior to IVF. Monthly ovarian reserve markers (AFC, AMH, FSH), ovarian response to standard dose HMG in 3rd month and IVF outcomes were compared. Sample size calculation was based on an increase of AFC by 3.0 being clinically significant with a test significance of 0.05 and power of 0.8. RESULTS: There was a trend towards higher AFC (10 vs 8, p¼0.955) after 12 weeks of DHEA use in DHEA group compared to placebo. There was no significant difference in FSH (8.4 vs 8.5 IU/L, p¼0.374), AMH (2.08 vs 2.42 ng/ml, p ¼0.534), duration (11 vs 10 days, p¼0.38) and dose (2100 vs 1950 IU, p¼0.428) of gonadogrophin use. There was higher number of follicles >10mm (2 vs 1, p ¼ 0.203) after standard dose HMG stimulation and higher number of top quality embryos (2 vs 1, p¼0.255) in DHEA group although they did not reach statistical significance. Similar clinical pregnancy rates (27.8 vs 41.1%, p¼0.347) and ongoing pregnancy rate (19.4 vs 29.4%, p¼0.521) were observed in DHEA and placebo groups. CONCLUSION: DHEA has been increasingly used in poor responders and there is no available in normal responders. Our study did not detect any significant difference in ovarian response markers and pregnancy outcomes after DHEA, although it suggested a trend of improved AFC, ovarian response with low dose HMG stimulation and top quality embryos. Routine use of DHEA in normal responders to improve ovarian response could not be recommended at this stage. Supported by: Committee on Research and Conference Grants, University of Hong Kong. O-374 Wednesday, October 16, 2013 04:45 PM VALIDATION OF THE POWER MODEL OF OVARIAN NONGROWING FOLLICLE DEPLETION ASSOCIATED WITH AGING. K. R. Hansen,a N. S. Knowlton,b N. M. Budrys,a M. T. Zavy,a L. B. Craig.a aDept. of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, University of Oklahoma Health Sciences Center, Oklahoma City, OK; bMolecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. OBJECTIVE: The primary determinant of reproductive aging in women is the progressive decline in ovarian non-growing follicles (NGFs). This pool of NGFs, inclusive of the ovarian primordial, intermediate and primary follicles, constitutes the ovarian reserve. Ultimately the depletion of the NGF pool results in menopause. We have previously characterized the decline in NGFs associated with aging, determining that a power model taking the form y ¼ axb + c, where a, b, and c are constants and y ¼ NGF count at age x, best characterizes the decline in the log-transformed NGF count associated with
Vol. 100, No. 3, Supplement, September 2013