- Email: [email protected]
Do intracytoplasmic sperm injection (ICSI) and extended embryo culture impact the need for genetic counseling?
women carrying C677T MTHFR and G20210A Prothrombin polymophisms (Od¼ 2.76, 95% CI 00.4- 71.5),on the other hand non significant risk for developing preeclampsia was found regarding C677T MTHFR polymorphism and G1691A Factor V Lieden polymorphism.Another non significant risk for developing severe preeclampsia with C677T MTHFR polymorphism. Regarding I/D of ACE non significant difference was found between preeclamptic and control groups (26.5%versus 15.135 resspectively) also the difference was not significant between mild and severe preeclampsia. CONCLUSIONS: C677T MTHFR, G1691A Factor V Lieden, and G20210A Prothrombin genes polymorphisms are risk factors for developing preeclamptic toxaemia in Egypt. A highly significant cumulative effect of the three polymorphism to develop preeclampsia and to determine the severity was detected. On the other hand I/D polymorphism of the ACE gene is not a useful marker to study the relationship between the ACE gene and preeclampsia. Supported by: None.
Wednesday, November 12, 2008 3:45 pm O-243 DOES FAMILY HISTORY OF CARDIOVASCULAR DISEASE PREDICT THE METABOLIC PROFILE OF PCOS PATIENTS? G. M. Davis, J. D. Lamb, L. A. Pasch, H. G. Huddleston, M. Hanna, M. I. Cedars. Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA; University of California, Berkeley, Berkeley, CA. OBJECTIVE: Women with PCOS are at risk for insulin resistance and the development of type 2 diabetes. In addition, they often have other risk factors for cardiovascular disease, including dyslipidemia, hypertension, obesity and central adiposity. Epidemiologic studies of cardiovascular events in women with PCOS have been inconclusive, despite the suggestion of a higher risk for cardiovascular disease. The aim of the present study was to determine whether a family history of cardiovascular or other metabolic dysfunction predicts the metabolic profile of patients with PCOS. DESIGN: A cross-sectional study of 56 patients presenting to a multidisciplinary PCOS clinic, with confirmed diagnosis of PCOS by Rotterdam criteria. MATERIALS AND METHODS: A three generation pedigree taken by a genetic counselor was analyzed for first degree relatives with a history of type 2 diabetes, myocardial infarction (MI) or cardiovascular disease (CVD), hypertension, dyslipidemia or overweight. Assessment of the metabolic profile included body mass index (BMI), waist-hip ratio (WHR), blood pressure, glucose tolerance (2 hour GTT) and lipid profile (LDL, HDL and triglycerides). Students t-test and chi square analysis were used as appropriate to determine whether family history predicts evidence of metabolic dysfunction in patients. RESULTS: BMI ranged from 18.9-47, with a mean of 30.9 (SD¼7.4); 24% of patients would be characterized as overweight and 43% as obese. Mean WHR was 0.80. Clinical hypertension was identified in 19% of our patients; 12% had impaired glucose tolerance; 20% had elevated LDL; 21% had elevated triglycerides and 13% percent had reduced HDL. Mean BMI was higher among patients with a positive family history of hypertension (33.3) than those without a family history of hypertension (27.9) (p< .01). Mean BMI was higher among patients with a positive family history of MI or CVD (35.4) than those without a family history of MI or CVD (29.6) (p< .05). An elevated LDL (above 130 mg/dl) was more frequent among patients with a positive family history of MI or CVD (50%) than those without a family history (12.8%) (p< .01). A positive family history of type 2 diabetes, dyslipidemia or overweight in first degree relatives was not associated with increased metabolic dysfunction. CONCLUSIONS: Our findings suggest that a history of cardiovascular disease in a first degree relative may be an important predictor of the risks of metabolic dysfunction in patients with PCOS. Supported by: Mt. Zion Health Fund.
FERTILITY & STERILITYÒ
Wednesday, November 12, 2008 4:00 pm O-244 PROFOUND TERATOSPERMIA DOES NOT INFLUENCE SEX CHROMOSOMAL ANEUPLOIDY RATES IN IVF-PGD CYCLES. D. Frankfurter, M. B. Dayal, D. Peak, A. Dubey, P. R. Gindoff. Fertility and IVF, George Washington Medical Faculty Associates, Washington, DC; George Washington Medical Faculty Associates, Washington. OBJECTIVE: Despite most autosomal aneuploidies resulting from maternal meiotic non-disjunction, meiotic errors in spermatogenesis cause a significant proportion of sex chromosomal aneuploidy. If sperm morphology correlates with genotype, then teratospermia should be associated with increased rates of sex chromosomal aneuploidy. The objective of this study was to determine if teratospermia is associated with sex chromosomal aneuploidy in IVF-PGD cycles. DESIGN: Retrospective observational study. MATERIALS AND METHODS: All initial IVF-PGD cycles between 1/1/ 04-5/6/08 were included in this study and were divided into two groups based on sperm morphology: Low Morphology Group (LMG) % 4 % morphologically normal sperm and Normal Morphology Group (NMG) > 4% morphologically normal sperm by Tygerberg strict criteria. Embryos were biopsied on day three (6-8 cells) and analyzed using FISH for chromosomes X and Y. Embryos with two signals for X or a single signal for both X and Y were considered normal. All other permutations were considered abnormal. RESULTS: 74 initial IVF-PGD cycles yielding 521 embryos were included. The incidence of 45, X did not differ between LMG and NMG (12% vs 9.5%, respectively; RR 1.40; 95%CI 0.69-2.83). Similarly, no difference in rates of sex chromosomal abnormalities were seen between LMG and NMG (31.6% vs 33.3%, respectively; RR 0.95; 95%CI 0.68-1.32). No differences between groups were noted regarding mean paternal age, maternal age, day3 FSH or the indication for PGD (Table 1). CONCLUSIONS: Errors in oocyte meiosis account for the vast majority of autosomal aneuploidy observed in human embryonic development. However, greater than 80% of monosomy X and many other sex aneuploidies can be traced to abnormal sperm. Some have argued that severe teratospermia is associated with increased rates of embryonic aneuploidy. This would predict a higher incidence of sex chromosomal aneuploidy and/or Turner Syndrome embryos in IVF-PGD cycles using profoundly teratospermic sperm. Our findings contradict this theory, suggesting that morphology does not correlate with sex chromosomal genotype. Further investigation is needed so that we may better understand the relationship between sperm morphology and embryo sex chromosomal aneuploidy. TABLE 1. Sex Chromosome Abnormalities as a Function of Sperm Morphology
%4% # embryos # cycles Mean Maternal Age Mean Paternal Age % Sex Chrom Abnl/Total # Embryos % 45, X/Total # Embryos
437 62 37.2 4.4 40.2 5.7 138/437 (31.6%) 53/437 (12.1)
>4% 84 12 36.1 3.8 39.4 4.0 28/84 (33.3%) 8/84 (9.5%)
Supported by: None.
Wednesday, November 12, 2008 4:15 pm O-245 DO INTRACYTOPLASMIC SPERM INJECTION (ICSI) AND EXTENDED EMBRYO CULTURE IMPACT THE NEED FOR GENETIC COUNSELING? O. Tan, A. E. Reh, L. Krey, S. Talebian, M. Perle, N. Noyes. NYU School of Medicine, New York, NY. OBJECTIVE: To compare pregnancy outcomes including the rates of aneuploidy, measured in products of conception, for patients with embryo transfer on D3 or D5, with or without ICSI, from 2000 - 2006.
S89
DESIGN: Retrospective study at a university-based IVF program. MATERIALS AND METHODS: Data from 7398 IVF cycles were collected and grouped by age (<38y or R 38y), mode of fertilization (þICSI/non-ICSI), and day of fresh transfer (D3/D5). ICSI was performed only in cases of male factor or prior fertilization failure. PGD and cycles with a mixed cohort of transferred embryos resulting from both ICSI and insemination were excluded. Rates of pregnancy (sac on ultrasound; PR), miscarriage (loss after sac <24 weeks gestation; MC), and live birth (R24 weeks; LBR) were determined. Available cytogenetic results from products of conception were categorized as normal (46,XX and 46,XY) or aneuploid (trisomies, monosomies, translocations, microdeletions, etc.). X2 and relative risks with a 95% CI were performed as appropriate. RESULTS: In both age groups, D5 had a significantly higher PR (<38y: 64 vs. 49%, p<0.001; R38y: 47 vs. 32%, p<0.001) and LBR (<38y: 53 vs. 41%, p<0.001; R38y: 33 vs. 20%, p<0.0001) per cycle. D5 also had a lower miscarriage rate per pregnancy in R38y (37 vs. 25%, p<0.001), and showed a similar trend in <38y (15vs.12%, p¼0.06). The use of ICSI did not have a clinical impact on pregnancy outcome in either age group. PR/LBR/MC expressed as percentages were as follows: <38yþ ICSI: 56/45/17; <38y nonICSI: 59/50/13; R38y þICSI: 33/22/31; R38y non-ICSI: 37/24/35. A total of 200 cytogenetic results were available for analysis. There was a higher rate of aneuploidy in patients R38y than <38y (81 vs. 55%, RR 2.3, 1.5-3.6, p<0.001). There was no difference in the rate of aneuploidy between D3 and D5 in either age group (<38y: 59 vs. 53%; R38y: 82 vs. 77%), however higher aneuploidy was seen in non-ICSI R38y cycles (86 vs. 66%, RR 2.5, 1.3-4.9; p¼0.009). CONCLUSIONS: D5 cycles have higher pregnancy and live birth rates with a lower percentage of miscarriage, reflecting the selection of more developed, better quality embryos after extended culture. However, miscarriage and aneuploidy in this group still exist, showing that extended culture does not protect against these untoward outcomes. Conversely, ICSI does not increase the risk for these events. Counseling for miscarriage and aneuploidy risks should be individualized based on age, regardless of transfer day and fertilization method. Supported by: None.
Wednesday, November 12, 2008 4:30 pm O-246 THE FREQUENCY DISTRIBUTION OF ALLELIC VARIATION IN EXON 10 OF THE FSH RECEPTOR GENE IN INFERTILITY PATIENTS FROM DIFFERENT ETHNICAL BACKGROUNDS, A LARGE POPULATION STUDY FROM THE NETHERLANDS. E. A. Kuijper, M. A. Blankenstein, A. Overbeek, P. G. Hompes, J. W. Twisk, C. B. Lambalk. Reproductive Medicine, VUMC, Amsterdam, Netherlands; Clinical Chemistry, VUMC, Amsterdam, Netherlands. OBJECTIVE: Studies on the frequency distribution of the follicle stimulating hormone receptor (FSHR) polymorphisms report conflicting results not only within fertile and infertile populations, but also between males and females. It has been suggested that ethnicity might influence these outcomes. Therefore, the aim of this study was to determine the frequency distribution of the FHSR polymorphisms, at position 680 of exon 10, within a large group of infertility patients from different ethnical backgrounds. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We studied 2001 patients (1771 women and 230 men) of different ethnic origin (Caucasian, Asian, Hindustani, Creole and Mediterranean). FSH receptor single nucleotide polymorphisms (SNPs) at codon 680 of exon 10 were determined by restriction fragment length polymorphism of amplicons generated by PCR. Genotypes were compared with serum FSH levels and between different ethnical groups. RESULTS: We found a significantly lower percentage of Asians to have the Ser680Ser receptor variant compared to Caucasians and Mediterranean’s. FSH levels did not differ between either the various ethnical groups, or the different FSH receptor polymorphisms. CONCLUSIONS: In our study population the Ser680Ser receptor variant is less common in the Asian subgroup compared to Caucasians and Mediter-
S90
Abstracts
ranean’s. These data indicate that when comparing allelic frequency distributions of the FSHR polymorphism variants one should account at least for ethnical background. FSH levels did not differ between FSHR polymorphisms or between ethnical groups. Supported by: None.
PEDIATRIC AND ADOLESCENT GYNECOLOGY SPECIAL INTEREST GROUP Wednesday, November 12, 2008 2:45 pm O-247 IMPROVEMENT IN QUALITY-OF-LIFE QUESTIONNAIRE MEASURES (PCOSQ) IN OBESE ADOLESCENT FEMALES WITH PCOS TREATED WITH LIFESTYLE CHANGE, ORAL CONTRACEPTIVES, WITH OR WITHOUT METFORMIN. M. Harris-Glocker, K. Davidson, L. Kochman, D. Guzick, K. Hoeger. Department of Obstetrics & Gynecology, Strong Memorial Hospital, Rochester, NY; University of Rochester, Strong Memorial Hospital, Rochester, NY; Strong Memorial Hospital, Rochester, NY. OBJECTIVE: To study the effect of a lifestyle modification program (LSM) combined with oral contraceptives (OC) with or without metformin (MET) on Quality of Life measures (PCOSQ) in adolescent obese females with PCOS. DESIGN: Prospective randomized placebo-controlled trial. MATERIALS AND METHODS: Subjects were obese, postmenarchal adolescent females, ages 12-18 years with PCOS. Subjects were randomized to OC (ethinyl estradiol þ drospirenone) with MET (2 g/day) versus OC with placebo (PL). All subjects were enrolled in a lifestyle change program. Outcome measures were PCOSQ at enrollment versus conclusion for five variables: Emotions, Weight, Menses, Body Hair, Infertility (Table 1). RESULTS: Mean BMI was 34.8 kg/m2 at baseline and BMI decreased 4% in PL (p¼0.008) and 5.2% (p¼0.001) in MET with no difference in weight reduction between groups. PCOSQ improved in both groups, however there was no significant difference between MET and PL. Changes in PCOSQ are shown, with 1 being worst (symptoms all of the time) and 7 best (symptoms none of the time). There was no correlation between baseline PCOSQ and reduction in BMI achieved during the LSM and a trend toward correlation between the reduction in BMI and increase in PCOSQ (p¼ 0.06). There was a statistically significant correlation between Ferriman-Gallway (FG) score and subject’s subjective view of hirsutism (p¼ < 0.001). CONCLUSIONS: Quality of life improves across all variables measured for obese adolescent women enrolled in a lifestyle program with OC regardless of MET administration. There is no correlation between initial PCOSQ and success in weight loss, suggesting adolescent women can respond to LSM regardless of baseline PCOSQ parameters. The trend in correlation between improved PCOSQ and change in BMI suggests an association between improvements in weight and quality of life in obese adolescent females with PCOS. Finally, FG scores of hirsutism in PCOS adolescents correlate with how subjects view themselves in terms of amount of facial and body hair present. TABLE 1.
PCOSQ
Emotions Weight Menses Body Hair Infertility
MET þ OC
(n¼16)
PL þ OC
(n¼16)
Pre
Post
p
Pre
Post
p
5.2 3.4 4.3 5.1 5.8
6.3 4.6 5.7 6.1 6.4
<0.001 .006 .001 .022 .067
4.7 2.9 4.4 4.6 4.8
5.8 4.2 5.5 5.7 5.7
<0.001 .001 .002 <0.001 .009
Supported by: In part by NIH grant K23 HD043881-01A1 (KMH) and Grant Number UL1 RR 024160 from the National Center for Research Resources (NCRR) to the University of Rochester.
Vol. 90, Suppl 1, September 2008
Wednesday, November 12, 2008 3:45 pm O-243 DOES FAMILY HISTORY OF CARDIOVASCULAR DISEASE PREDICT THE METABOLIC PROFILE OF PCOS PATIENTS? G. M. Davis, J. D. Lamb, L. A. Pasch, H. G. Huddleston, M. Hanna, M. I. Cedars. Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA; University of California, Berkeley, Berkeley, CA. OBJECTIVE: Women with PCOS are at risk for insulin resistance and the development of type 2 diabetes. In addition, they often have other risk factors for cardiovascular disease, including dyslipidemia, hypertension, obesity and central adiposity. Epidemiologic studies of cardiovascular events in women with PCOS have been inconclusive, despite the suggestion of a higher risk for cardiovascular disease. The aim of the present study was to determine whether a family history of cardiovascular or other metabolic dysfunction predicts the metabolic profile of patients with PCOS. DESIGN: A cross-sectional study of 56 patients presenting to a multidisciplinary PCOS clinic, with confirmed diagnosis of PCOS by Rotterdam criteria. MATERIALS AND METHODS: A three generation pedigree taken by a genetic counselor was analyzed for first degree relatives with a history of type 2 diabetes, myocardial infarction (MI) or cardiovascular disease (CVD), hypertension, dyslipidemia or overweight. Assessment of the metabolic profile included body mass index (BMI), waist-hip ratio (WHR), blood pressure, glucose tolerance (2 hour GTT) and lipid profile (LDL, HDL and triglycerides). Students t-test and chi square analysis were used as appropriate to determine whether family history predicts evidence of metabolic dysfunction in patients. RESULTS: BMI ranged from 18.9-47, with a mean of 30.9 (SD¼7.4); 24% of patients would be characterized as overweight and 43% as obese. Mean WHR was 0.80. Clinical hypertension was identified in 19% of our patients; 12% had impaired glucose tolerance; 20% had elevated LDL; 21% had elevated triglycerides and 13% percent had reduced HDL. Mean BMI was higher among patients with a positive family history of hypertension (33.3) than those without a family history of hypertension (27.9) (p< .01). Mean BMI was higher among patients with a positive family history of MI or CVD (35.4) than those without a family history of MI or CVD (29.6) (p< .05). An elevated LDL (above 130 mg/dl) was more frequent among patients with a positive family history of MI or CVD (50%) than those without a family history (12.8%) (p< .01). A positive family history of type 2 diabetes, dyslipidemia or overweight in first degree relatives was not associated with increased metabolic dysfunction. CONCLUSIONS: Our findings suggest that a history of cardiovascular disease in a first degree relative may be an important predictor of the risks of metabolic dysfunction in patients with PCOS. Supported by: Mt. Zion Health Fund.
FERTILITY & STERILITYÒ
Wednesday, November 12, 2008 4:00 pm O-244 PROFOUND TERATOSPERMIA DOES NOT INFLUENCE SEX CHROMOSOMAL ANEUPLOIDY RATES IN IVF-PGD CYCLES. D. Frankfurter, M. B. Dayal, D. Peak, A. Dubey, P. R. Gindoff. Fertility and IVF, George Washington Medical Faculty Associates, Washington, DC; George Washington Medical Faculty Associates, Washington. OBJECTIVE: Despite most autosomal aneuploidies resulting from maternal meiotic non-disjunction, meiotic errors in spermatogenesis cause a significant proportion of sex chromosomal aneuploidy. If sperm morphology correlates with genotype, then teratospermia should be associated with increased rates of sex chromosomal aneuploidy. The objective of this study was to determine if teratospermia is associated with sex chromosomal aneuploidy in IVF-PGD cycles. DESIGN: Retrospective observational study. MATERIALS AND METHODS: All initial IVF-PGD cycles between 1/1/ 04-5/6/08 were included in this study and were divided into two groups based on sperm morphology: Low Morphology Group (LMG) % 4 % morphologically normal sperm and Normal Morphology Group (NMG) > 4% morphologically normal sperm by Tygerberg strict criteria. Embryos were biopsied on day three (6-8 cells) and analyzed using FISH for chromosomes X and Y. Embryos with two signals for X or a single signal for both X and Y were considered normal. All other permutations were considered abnormal. RESULTS: 74 initial IVF-PGD cycles yielding 521 embryos were included. The incidence of 45, X did not differ between LMG and NMG (12% vs 9.5%, respectively; RR 1.40; 95%CI 0.69-2.83). Similarly, no difference in rates of sex chromosomal abnormalities were seen between LMG and NMG (31.6% vs 33.3%, respectively; RR 0.95; 95%CI 0.68-1.32). No differences between groups were noted regarding mean paternal age, maternal age, day3 FSH or the indication for PGD (Table 1). CONCLUSIONS: Errors in oocyte meiosis account for the vast majority of autosomal aneuploidy observed in human embryonic development. However, greater than 80% of monosomy X and many other sex aneuploidies can be traced to abnormal sperm. Some have argued that severe teratospermia is associated with increased rates of embryonic aneuploidy. This would predict a higher incidence of sex chromosomal aneuploidy and/or Turner Syndrome embryos in IVF-PGD cycles using profoundly teratospermic sperm. Our findings contradict this theory, suggesting that morphology does not correlate with sex chromosomal genotype. Further investigation is needed so that we may better understand the relationship between sperm morphology and embryo sex chromosomal aneuploidy. TABLE 1. Sex Chromosome Abnormalities as a Function of Sperm Morphology
%4% # embryos # cycles Mean Maternal Age Mean Paternal Age % Sex Chrom Abnl/Total # Embryos % 45, X/Total # Embryos
437 62 37.2 4.4 40.2 5.7 138/437 (31.6%) 53/437 (12.1)
>4% 84 12 36.1 3.8 39.4 4.0 28/84 (33.3%) 8/84 (9.5%)
Supported by: None.
Wednesday, November 12, 2008 4:15 pm O-245 DO INTRACYTOPLASMIC SPERM INJECTION (ICSI) AND EXTENDED EMBRYO CULTURE IMPACT THE NEED FOR GENETIC COUNSELING? O. Tan, A. E. Reh, L. Krey, S. Talebian, M. Perle, N. Noyes. NYU School of Medicine, New York, NY. OBJECTIVE: To compare pregnancy outcomes including the rates of aneuploidy, measured in products of conception, for patients with embryo transfer on D3 or D5, with or without ICSI, from 2000 - 2006.
S89
DESIGN: Retrospective study at a university-based IVF program. MATERIALS AND METHODS: Data from 7398 IVF cycles were collected and grouped by age (<38y or R 38y), mode of fertilization (þICSI/non-ICSI), and day of fresh transfer (D3/D5). ICSI was performed only in cases of male factor or prior fertilization failure. PGD and cycles with a mixed cohort of transferred embryos resulting from both ICSI and insemination were excluded. Rates of pregnancy (sac on ultrasound; PR), miscarriage (loss after sac <24 weeks gestation; MC), and live birth (R24 weeks; LBR) were determined. Available cytogenetic results from products of conception were categorized as normal (46,XX and 46,XY) or aneuploid (trisomies, monosomies, translocations, microdeletions, etc.). X2 and relative risks with a 95% CI were performed as appropriate. RESULTS: In both age groups, D5 had a significantly higher PR (<38y: 64 vs. 49%, p<0.001; R38y: 47 vs. 32%, p<0.001) and LBR (<38y: 53 vs. 41%, p<0.001; R38y: 33 vs. 20%, p<0.0001) per cycle. D5 also had a lower miscarriage rate per pregnancy in R38y (37 vs. 25%, p<0.001), and showed a similar trend in <38y (15vs.12%, p¼0.06). The use of ICSI did not have a clinical impact on pregnancy outcome in either age group. PR/LBR/MC expressed as percentages were as follows: <38yþ ICSI: 56/45/17; <38y nonICSI: 59/50/13; R38y þICSI: 33/22/31; R38y non-ICSI: 37/24/35. A total of 200 cytogenetic results were available for analysis. There was a higher rate of aneuploidy in patients R38y than <38y (81 vs. 55%, RR 2.3, 1.5-3.6, p<0.001). There was no difference in the rate of aneuploidy between D3 and D5 in either age group (<38y: 59 vs. 53%; R38y: 82 vs. 77%), however higher aneuploidy was seen in non-ICSI R38y cycles (86 vs. 66%, RR 2.5, 1.3-4.9; p¼0.009). CONCLUSIONS: D5 cycles have higher pregnancy and live birth rates with a lower percentage of miscarriage, reflecting the selection of more developed, better quality embryos after extended culture. However, miscarriage and aneuploidy in this group still exist, showing that extended culture does not protect against these untoward outcomes. Conversely, ICSI does not increase the risk for these events. Counseling for miscarriage and aneuploidy risks should be individualized based on age, regardless of transfer day and fertilization method. Supported by: None.
Wednesday, November 12, 2008 4:30 pm O-246 THE FREQUENCY DISTRIBUTION OF ALLELIC VARIATION IN EXON 10 OF THE FSH RECEPTOR GENE IN INFERTILITY PATIENTS FROM DIFFERENT ETHNICAL BACKGROUNDS, A LARGE POPULATION STUDY FROM THE NETHERLANDS. E. A. Kuijper, M. A. Blankenstein, A. Overbeek, P. G. Hompes, J. W. Twisk, C. B. Lambalk. Reproductive Medicine, VUMC, Amsterdam, Netherlands; Clinical Chemistry, VUMC, Amsterdam, Netherlands. OBJECTIVE: Studies on the frequency distribution of the follicle stimulating hormone receptor (FSHR) polymorphisms report conflicting results not only within fertile and infertile populations, but also between males and females. It has been suggested that ethnicity might influence these outcomes. Therefore, the aim of this study was to determine the frequency distribution of the FHSR polymorphisms, at position 680 of exon 10, within a large group of infertility patients from different ethnical backgrounds. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We studied 2001 patients (1771 women and 230 men) of different ethnic origin (Caucasian, Asian, Hindustani, Creole and Mediterranean). FSH receptor single nucleotide polymorphisms (SNPs) at codon 680 of exon 10 were determined by restriction fragment length polymorphism of amplicons generated by PCR. Genotypes were compared with serum FSH levels and between different ethnical groups. RESULTS: We found a significantly lower percentage of Asians to have the Ser680Ser receptor variant compared to Caucasians and Mediterranean’s. FSH levels did not differ between either the various ethnical groups, or the different FSH receptor polymorphisms. CONCLUSIONS: In our study population the Ser680Ser receptor variant is less common in the Asian subgroup compared to Caucasians and Mediter-
S90
Abstracts
ranean’s. These data indicate that when comparing allelic frequency distributions of the FSHR polymorphism variants one should account at least for ethnical background. FSH levels did not differ between FSHR polymorphisms or between ethnical groups. Supported by: None.
PEDIATRIC AND ADOLESCENT GYNECOLOGY SPECIAL INTEREST GROUP Wednesday, November 12, 2008 2:45 pm O-247 IMPROVEMENT IN QUALITY-OF-LIFE QUESTIONNAIRE MEASURES (PCOSQ) IN OBESE ADOLESCENT FEMALES WITH PCOS TREATED WITH LIFESTYLE CHANGE, ORAL CONTRACEPTIVES, WITH OR WITHOUT METFORMIN. M. Harris-Glocker, K. Davidson, L. Kochman, D. Guzick, K. Hoeger. Department of Obstetrics & Gynecology, Strong Memorial Hospital, Rochester, NY; University of Rochester, Strong Memorial Hospital, Rochester, NY; Strong Memorial Hospital, Rochester, NY. OBJECTIVE: To study the effect of a lifestyle modification program (LSM) combined with oral contraceptives (OC) with or without metformin (MET) on Quality of Life measures (PCOSQ) in adolescent obese females with PCOS. DESIGN: Prospective randomized placebo-controlled trial. MATERIALS AND METHODS: Subjects were obese, postmenarchal adolescent females, ages 12-18 years with PCOS. Subjects were randomized to OC (ethinyl estradiol þ drospirenone) with MET (2 g/day) versus OC with placebo (PL). All subjects were enrolled in a lifestyle change program. Outcome measures were PCOSQ at enrollment versus conclusion for five variables: Emotions, Weight, Menses, Body Hair, Infertility (Table 1). RESULTS: Mean BMI was 34.8 kg/m2 at baseline and BMI decreased 4% in PL (p¼0.008) and 5.2% (p¼0.001) in MET with no difference in weight reduction between groups. PCOSQ improved in both groups, however there was no significant difference between MET and PL. Changes in PCOSQ are shown, with 1 being worst (symptoms all of the time) and 7 best (symptoms none of the time). There was no correlation between baseline PCOSQ and reduction in BMI achieved during the LSM and a trend toward correlation between the reduction in BMI and increase in PCOSQ (p¼ 0.06). There was a statistically significant correlation between Ferriman-Gallway (FG) score and subject’s subjective view of hirsutism (p¼ < 0.001). CONCLUSIONS: Quality of life improves across all variables measured for obese adolescent women enrolled in a lifestyle program with OC regardless of MET administration. There is no correlation between initial PCOSQ and success in weight loss, suggesting adolescent women can respond to LSM regardless of baseline PCOSQ parameters. The trend in correlation between improved PCOSQ and change in BMI suggests an association between improvements in weight and quality of life in obese adolescent females with PCOS. Finally, FG scores of hirsutism in PCOS adolescents correlate with how subjects view themselves in terms of amount of facial and body hair present. TABLE 1.
PCOSQ
Emotions Weight Menses Body Hair Infertility
MET þ OC
(n¼16)
PL þ OC
(n¼16)
Pre
Post
p
Pre
Post
p
5.2 3.4 4.3 5.1 5.8
6.3 4.6 5.7 6.1 6.4
<0.001 .006 .001 .022 .067
4.7 2.9 4.4 4.6 4.8
5.8 4.2 5.5 5.7 5.7
<0.001 .001 .002 <0.001 .009
Supported by: In part by NIH grant K23 HD043881-01A1 (KMH) and Grant Number UL1 RR 024160 from the National Center for Research Resources (NCRR) to the University of Rochester.
Vol. 90, Suppl 1, September 2008