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Bone turnover in polycystic ovary syndrome (PCOS)
dopamine. It has been reported that dopamine negatively regulates follicle stimulating hormone (FSH) and insulin secretion through the D2 receptor, and this suggests that SLC18A2 might play a role in polycystic ovary syndrome (PCOS). Until now, however, there have been no studies on the association between SLC18A2 and PCOS. We investigated whether naturally occurring genetic variations at the human SLC18A2 locus are associated with the etiology of PCOS and/or with the FSH levels and insulin secretion seen in PCOS pataints. DESIGN: We undertook a systematic search for polymorphisms in SLC18A2 by resequencing the gene and investigated whether the common genetic variants are associated with PCOS in a large cohort (n¼539). And we also investigated the relationship between genetic variants and various kinds of metabolic traits in patients. Finally, we studied function of corresponding genetic variant by luciferase expression experiment in vitro. MATERIALS AND METHODS: We genotyped common single-nucleotide polymorphisms across the locus in 319 PCOS patients who were well phenotyped for several metabolic traits to determine associations between SLC18A2 variants and PCOS. We constructed wild-type and mutant plasmids into HeLa cell and investigated functional of different allele by measuring luciferase activity. RESULTS: We found two common genetic variants in the 3’-untranslated region(rs363282 and rs363238) that are strongly associated with serum FSH concentration (P¼0.0004 and P¼0.0001, respectively), insulin level at 0.5h after an oral glucose tolerance test (P¼0.032 and P¼0.009, respectively), and insulin level at 1h after the test (P¼0.007 and P¼0.005, respectively). Finally, we performed a functional study that showed that minor alleles of the two variants decreased expression from a transfected luciferase reporter/SLC18A23’-UTR expression plasmid. CONCLUSIONS: Our results strongly suggest that common genetic variants in SLC18A2 contribute to the phenotypic expression of PCOS and suggest novel pathophysiological links between the SLC18A2 locus and PCOS. Table1.The association of the phenotype and genotype of rs363282 and rs363238 in patients with PCOS.
Number Age (years) BMI (kg/m2) E2 (pmol/L) T (nmol/L) LH (IU/L) FSH (IU/L) FINS (mU/L) 0.5hINS (mU/L) 1hINS (mU/L)
Rs363282
Rs363282
Rs363282
Rs363238
Rs363238
Rs363238
AA+AG
GG
P-value
CC+AC
AA
P-value
245 26.02 0.40 25.60 0.33 188.39 9.10 2.83 0.05 8.91 0.35 7.14 0.16 16.57 0.88 89.48 3.16 110.97 3.70
72 240 24.66 0.68 0.135 25.94 0.41 25.15 0.67 0.667 25.43 0.33 190.89 17.98 0.930 195.25 19.33 2.72 0.09 0.211 2.84 0.05 10.31 0.87 0.102 8.91 0.35 8.17 0.25 0.0004 7.10 0.15 17.62 1.53 0.294 16.52 0.89 109.12 12.82 0.032 88.63 3.15 135.74 13.84 0.007 109.95 3.44
67 24.95 0.74 0.236 25.56 0.72 0.833 195.25 19.33 0.784 2.70 0.10 0.173 10.41 0.95 0.074 8.33 0.26 0.0001 17.97 1.65 0.288 114.46 14.09 0.009 139.92 15.22 0.005
Supported by: This work was Supported by the National Natural Science Foundation of China (Grants 81270747) and the Shanghai City Board of Education Scientific Research Innovation Key Projects (Grant 13ZZ001). P-54 Tuesday, October 20, 2015 IMPACT OF OVARIAN VOLUME-BASED ADJUSTED THERMAL DOSE VERSUS FIXED-PUNCTURE DOSAGE IN LAPAROSCOPIC OVARIAN DRILLING ON OVARIAN RESERVE IN CLOMIPHENE CITRATE-RESISTANT PCOS WOMEN. A. NASR. Obstetrics and Gynecology, Women’s Health Center, Assiut University, Assiut, Egypt. OBJECTIVE: To evaluate the impact of adjusted thermal dose on the basis of ovarian volume versus fixed-puncture dosage in laparoscopic ovarian drilling (LOD) on reproductive outcome and ovarian reserve assessed by 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: Eighty women with CC-resistant PCOS who underwent LOD were recruited. They were randomized into two groups: group A [40 women; mean age: (SD) 27.7 (2.1) years], received an adjusted thermal dose based on ovarian volume with use of a new model for dose calculation (60 J/cm3 of ovarian tissue); group B [40 women; mean age: (SD) 28.5 (1.9) years], received 600 J per ovary through four ovarian holes regardless of size. A group of normally ovulating women; group C [40 women; mean age: (SD) 27.9 (2.2) years], served as controls. Basal serum
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ASRM Abstracts
AMH levels were measured in all three groups and six months after LOD in groups A and B. Women were followed-up for six months. 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. RESULTS: Changes in serum AMH levels, ovulation, conception and early abortion rates. In group A women, serum AMH levels showed a significant reduction, compared to preoperative values and controls (5.85 1.09 ng/ml; p <0.05). Similarly, in group B women LOD resulted in a significant reduction in serum AMH levels, compared to preoperative values and controls (6.34 1.31 ng/ml; p <0.05). However, there was no statistically significant difference between groups A and B serum AMH levels six months after LOD. The ovulation and pregnancy rates were significantly higher in group A than in group B (77.5% vs. 62.5% and 52.5% vs. 37.5%, respectively). There was no significant difference between groups in early miscarriage rate. CONCLUSIONS: Adjusted diathermy dose based on ovarian volume for LOD in PCOS women resulted in a similarly significant reduction of serum AMH levels, compared to fixed thermal dosage; postoperative values remained significantly higher than normally ovulating women. However, it resulted in a better reproductive outcome compared with fixed thermal dosage. References: Key Words: Polycystic ovary syndrome (PCOS); Laparoscopic ovarian drilling (LOD); Adjusted diathermy dose; Fixed thermal dosage; Anti-Mullerian hormone (AMH); Ovarian reserve; Randomized controlled trial. P-55 Tuesday, October 20, 2015 BONE TURNOVER IN POLYCYSTIC OVARY SYNDROME (PCOS). S. Lingaiah,a L. Morin-Papunen,a T. Piltonen,a J. Puurunen,a J. Risteli,b J. S. Tapanainen,c T. E. Vaskivuo.b aObstetrics and Gynaecology, Oulu University Hospital, Oulu, Finland; bClinical Chemistry, Oulu University Hospital, Oulu, Finland; cObstetrics and Gynaecology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland. OBJECTIVE: To evaluate the metabolic activity of bone in women with PCOS using bone turnover markers (BTMs). DESIGN: Case-control study. MATERIALS AND METHODS: 308 women with PCOS and 219 healthy women.Procollagen type I amino-terminal propeptide (PINP), osteocalcin (OC), carboxy-terminal telopeptide of type I collagen (CTX) and 25OHD (Vitamin D) were determined using IDS-iSYS Multi-Discipline Automated Analyzer. Subjects were divided into four groups (R 30 years, 31 - 40, premenopausal and postmenopausal) to compare the differences in BTMs. Statistical analysis was performed using SPSS Version 22.0. RESULTS: Concentrations of PINP and OC were significantly decreased (p<0.001; Age and BMI adjusted) in women with PCOS but no difference was observed for CTX and 25OHD. Age group analysis revealed no significant differences between women with PCOS and control women in all age groups for CTX and 25OHD. Significant difference was observed between PCOS and control women in the postmenopausal group for OC and PINP (P < 0.05). CONCLUSIONS: Bone formation is slowed down in PCOS as reflected by the levels of PINP and OC, while bone resorption goes on at a normal pace as shown by the levels of CTX. This results in a negative bone balance in PCOS women. The difference is more pronounced in postmenopausal women with PCOS. Supported by: Sigrid Juselius Foundation, Medical Research Center Oulu, VTR funding, Jalmari and Rauha Ahokas Foundation, University of Oulu, Finland. P-56 Tuesday, October 20, 2015 IVM IS NOT EXPERIMENTAL METHOD, BUT CLINICALLY VALID WITHOUT RISK OF OHSS, ESPECIALLY FOR PCO PATIENTS, FROM OUR 10 YEARS OF EXPERIENCE. A. Fukuda,a R. Mori,a M. Ida,a Y. Morimoto.b aReproductive Endocrinology and Infertility, IVF Osaka Clinic, Higashiosaka City, Japan; bReproductive Endocrinology and Infertility, HORAC Grand Front Osaka Clinic, Osaka City, Japan. OBJECTIVE: The goal of clinical application of IVM is to eliminate or significantly reduce important drawbacks of controlled ovarian stimulation, such as drug costs, physical and emotional burden on patients, and the risk
Vol. 104, No. 3, Supplement, September 2015
Number Age (years) BMI (kg/m2) E2 (pmol/L) T (nmol/L) LH (IU/L) FSH (IU/L) FINS (mU/L) 0.5hINS (mU/L) 1hINS (mU/L)
Rs363282
Rs363282
Rs363282
Rs363238
Rs363238
Rs363238
AA+AG
GG
P-value
CC+AC
AA
P-value
245 26.02 0.40 25.60 0.33 188.39 9.10 2.83 0.05 8.91 0.35 7.14 0.16 16.57 0.88 89.48 3.16 110.97 3.70
72 240 24.66 0.68 0.135 25.94 0.41 25.15 0.67 0.667 25.43 0.33 190.89 17.98 0.930 195.25 19.33 2.72 0.09 0.211 2.84 0.05 10.31 0.87 0.102 8.91 0.35 8.17 0.25 0.0004 7.10 0.15 17.62 1.53 0.294 16.52 0.89 109.12 12.82 0.032 88.63 3.15 135.74 13.84 0.007 109.95 3.44
67 24.95 0.74 0.236 25.56 0.72 0.833 195.25 19.33 0.784 2.70 0.10 0.173 10.41 0.95 0.074 8.33 0.26 0.0001 17.97 1.65 0.288 114.46 14.09 0.009 139.92 15.22 0.005
Supported by: This work was Supported by the National Natural Science Foundation of China (Grants 81270747) and the Shanghai City Board of Education Scientific Research Innovation Key Projects (Grant 13ZZ001). P-54 Tuesday, October 20, 2015 IMPACT OF OVARIAN VOLUME-BASED ADJUSTED THERMAL DOSE VERSUS FIXED-PUNCTURE DOSAGE IN LAPAROSCOPIC OVARIAN DRILLING ON OVARIAN RESERVE IN CLOMIPHENE CITRATE-RESISTANT PCOS WOMEN. A. NASR. Obstetrics and Gynecology, Women’s Health Center, Assiut University, Assiut, Egypt. OBJECTIVE: To evaluate the impact of adjusted thermal dose on the basis of ovarian volume versus fixed-puncture dosage in laparoscopic ovarian drilling (LOD) on reproductive outcome and ovarian reserve assessed by 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: Eighty women with CC-resistant PCOS who underwent LOD were recruited. They were randomized into two groups: group A [40 women; mean age: (SD) 27.7 (2.1) years], received an adjusted thermal dose based on ovarian volume with use of a new model for dose calculation (60 J/cm3 of ovarian tissue); group B [40 women; mean age: (SD) 28.5 (1.9) years], received 600 J per ovary through four ovarian holes regardless of size. A group of normally ovulating women; group C [40 women; mean age: (SD) 27.9 (2.2) years], served as controls. Basal serum
e124
ASRM Abstracts
AMH levels were measured in all three groups and six months after LOD in groups A and B. Women were followed-up for six months. 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. RESULTS: Changes in serum AMH levels, ovulation, conception and early abortion rates. In group A women, serum AMH levels showed a significant reduction, compared to preoperative values and controls (5.85 1.09 ng/ml; p <0.05). Similarly, in group B women LOD resulted in a significant reduction in serum AMH levels, compared to preoperative values and controls (6.34 1.31 ng/ml; p <0.05). However, there was no statistically significant difference between groups A and B serum AMH levels six months after LOD. The ovulation and pregnancy rates were significantly higher in group A than in group B (77.5% vs. 62.5% and 52.5% vs. 37.5%, respectively). There was no significant difference between groups in early miscarriage rate. CONCLUSIONS: Adjusted diathermy dose based on ovarian volume for LOD in PCOS women resulted in a similarly significant reduction of serum AMH levels, compared to fixed thermal dosage; postoperative values remained significantly higher than normally ovulating women. However, it resulted in a better reproductive outcome compared with fixed thermal dosage. References: Key Words: Polycystic ovary syndrome (PCOS); Laparoscopic ovarian drilling (LOD); Adjusted diathermy dose; Fixed thermal dosage; Anti-Mullerian hormone (AMH); Ovarian reserve; Randomized controlled trial. P-55 Tuesday, October 20, 2015 BONE TURNOVER IN POLYCYSTIC OVARY SYNDROME (PCOS). S. Lingaiah,a L. Morin-Papunen,a T. Piltonen,a J. Puurunen,a J. Risteli,b J. S. Tapanainen,c T. E. Vaskivuo.b aObstetrics and Gynaecology, Oulu University Hospital, Oulu, Finland; bClinical Chemistry, Oulu University Hospital, Oulu, Finland; cObstetrics and Gynaecology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland. OBJECTIVE: To evaluate the metabolic activity of bone in women with PCOS using bone turnover markers (BTMs). DESIGN: Case-control study. MATERIALS AND METHODS: 308 women with PCOS and 219 healthy women.Procollagen type I amino-terminal propeptide (PINP), osteocalcin (OC), carboxy-terminal telopeptide of type I collagen (CTX) and 25OHD (Vitamin D) were determined using IDS-iSYS Multi-Discipline Automated Analyzer. Subjects were divided into four groups (R 30 years, 31 - 40, premenopausal and postmenopausal) to compare the differences in BTMs. Statistical analysis was performed using SPSS Version 22.0. RESULTS: Concentrations of PINP and OC were significantly decreased (p<0.001; Age and BMI adjusted) in women with PCOS but no difference was observed for CTX and 25OHD. Age group analysis revealed no significant differences between women with PCOS and control women in all age groups for CTX and 25OHD. Significant difference was observed between PCOS and control women in the postmenopausal group for OC and PINP (P < 0.05). CONCLUSIONS: Bone formation is slowed down in PCOS as reflected by the levels of PINP and OC, while bone resorption goes on at a normal pace as shown by the levels of CTX. This results in a negative bone balance in PCOS women. The difference is more pronounced in postmenopausal women with PCOS. Supported by: Sigrid Juselius Foundation, Medical Research Center Oulu, VTR funding, Jalmari and Rauha Ahokas Foundation, University of Oulu, Finland. P-56 Tuesday, October 20, 2015 IVM IS NOT EXPERIMENTAL METHOD, BUT CLINICALLY VALID WITHOUT RISK OF OHSS, ESPECIALLY FOR PCO PATIENTS, FROM OUR 10 YEARS OF EXPERIENCE. A. Fukuda,a R. Mori,a M. Ida,a Y. Morimoto.b aReproductive Endocrinology and Infertility, IVF Osaka Clinic, Higashiosaka City, Japan; bReproductive Endocrinology and Infertility, HORAC Grand Front Osaka Clinic, Osaka City, Japan. OBJECTIVE: The goal of clinical application of IVM is to eliminate or significantly reduce important drawbacks of controlled ovarian stimulation, such as drug costs, physical and emotional burden on patients, and the risk
Vol. 104, No. 3, Supplement, September 2015