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Effectiveness of a letrozole escalation protocol in achieving ovulation in patients with polycystic ovary syndrome
RESULTS: PCOS subjects were younger with a higher mean BMI compared to controls (Table). Global and all individual EDEQ scores were significantly higher in PCOS subjects compared to controls. EDEQ Global Score inversely correlated with overall PCOSQ score (r¼-0.57, p¼0.001) and with all PCOSQ domains, particularly emotion (r¼ -0.51, p<0.001) and weight (r¼ -0.79, p<0.0001). Women with PCOS had an increased odds of abnormal EDEQ Global Score R 4 (OR¼6.87, 95% CI 0.8853.86, p¼0.04) however, the age and BMI-adjusted OR was 5.78 (CI 0.60–55.4, p<0.13). As expected, more women with PCOS had abnormal anxiety (41.7 vs 14%, p<0.001) and depressive scores (13.2 v. 3.5%, p¼0.06) compared to controls. Among PCOS patients with anxiety, the odds ratio of EDEQ R 4 was 9.70, 95%CI: 2.0, 46.1, p¼0.004 compared to those without anxiety. This association increased after controlling for age and BMI (AOR 19.6, 95%CI 2.4-158.7, p¼0.005). PCOS women with depression also had a greater odds of EDEQ R 4 (OR: 3.84, 95%CI: 1.014.6, p¼0.048; age and BMI AOR: 3.96, 95%CI 1.0-15.6, p¼0.049). The prevalences of bulimia, binge eating disorder, and night eating disorder in PCOS subjects were higher than in controls, but the differences were not statistically significant (Table). CONCLUSIONS: Our study demonstrates a significant increase in disordered eating attitudes and behaviors associated with decreased quality of life in women with PCOS. Further, it highlights the need to screen for eating disorders especially in women with PCOS and co-existing anxiety or depressive symptoms.
P-414 Wednesday, October 19, 2016
Eating disorders in women with PCOS and controls
PCOS PATIENTS CONTROLS (n¼121) (n¼57) p-VALUE Age (SD) BMI (SD) EDEQ Global Score (SD) EDEQ Restraint Score (SD) EDEQ Shape Concern Score (SD) EDEQ Weight Concern Score (SD) EDEQ Eating Concern Score (SD) EDEQ Global Score, Number R 4 (%) Bulimia Binge Eating Disorder Night Eating Disorder
28.08 (5.42) 33.56 (8.78) 2.33 (0.12)
33.26 (8.63) 25.40 (5.70) 1.24 (0.14)
0.0002 <0.0001 <0.0001
2.07 (0.12)
1.34 (0.19)
0.0009
3.22 (0.16)
1.87 (0.21)
<0.0001
2.91 (0.15)
1.47 (0.19)
<0.0001
1.11 (0.15)
0.25 (0.08)
0.0002
13 (10.92)
1 (1.75)
0.038
9 (7.44) 21 (17.4) 16 (13.3)
1 (1.75) 5 (8.8) 4 (7.02)
0.172 0.173 0.310
P-413 Wednesday, October 19, 2016 EFFECTIVENESS OF A LETROZOLE ESCALATION PROTOCOL IN ACHIEVING OVULATION IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME. T. L. Jones, C. C. Shenoy, J. Jensen, E. A. Stewart, G. S. Daftary, C. Coddington. Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, MN. OBJECTIVE: In the absence of follicular recruitment, immediate dose escalation is effective to achieve ovulation in oligo- or anovulatory women using clomiphene citrate. Limited data exist for using letrozole in a similar manner. We sought to determine if immediately increasing the letrozole dose during the same cycle is efficacious to achieve ovulation in oligo- or anovulatory women with polycystic ovary syndrome (PCOS). We also evaluated endometrial thickness and pregnancy rates in women undergoing the escalation protocol versus standard treatment. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Oligo- or anovulatory women with PCOS based on Rotterdam criteria undergoing their first cycle of ovulation induction with letrozole at Mayo Clinic in Rochester, MN, from January 1, 2014 to March 31, 2016 were selected. The escalation protocol was performed by administering letrozole at a starting dose of 2.5 mg for 5 days starting cycle day 3. A transvaginal ultrasound was performed on cycle day 10-12 to assess follicular recruitment. If no follicle(s) R10mm were observed, the dose was immediately increased by 2.5 mg of letrozole for an additional 5 days. This was repeated until a follicle was recruited or a maximum dose of 7.5 mg of letrozole was reached. Standard treatment consisted of admin-
FERTILITY & STERILITYÒ
istering 10 days of oral progestin to induce a withdrawal bleed if there was no follicular recruitment on CD 10-12 ultrasound, followed by an increased dose of letrozole in the subsequent cycle. Ovulation was determined by detection of urinary luteinizing hormone surge or by administering human chorionic gonadotropin when a dominant follicle reached 20 mm. Clinical pregnancy was defined by a positive hCG and by fetal cardiac activity on ultrasound. Statistical analysis was performed using the Wilcoxon Rank Sum and Fisher Exact tests where appropriate. RESULTS: Forty six PCOS patients with ovulatory dysfunction were identified; 11 utilized the escalation protocol. There were no differences in baseline age, body mass index, and ovarian reserve between the two groups. Of the 35 patients using the standard protocol, 72% ovulated versus 100% of the 11 using the escalation protocol (p¼0.042). There were no differences in mean follicular recruitment (2.1 1.6 vs 2.4 1.6, p¼0.62) or endometrial thickness (5.8 2.1 vs 5.7 2.4 mm, p 0.90) between standard and escalation protocol, respectively. There were no statistical difference in clinical pregnancies 3 (11%) in the standard and 1 (9%) in the escalation group. CONCLUSIONS: The escalation protocol increases ovulation rates in patients with PCOS by effectively identifying the letrozole dose necessary to achieve follicular recruitment during the initial ovulation induction cycle. Immediately increasing the dose of letrozole in a single cycle does not exhibit detrimental effects on the number of follicles recruited, endometrial development or pregnancy rates.
SEXUAL FUNCTION AND POLYCYSTIC OVARY SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS. D. Lizneva,a W. J. Walker,a L. Gavrilova-Jordan,a M. P. Diamond,b R. Azziz,a L. Suturina,c I. Atabyekov,c S. Brakta.b aObstetrics and Gynecology, Augusta University, Augusta, GA; bAugusta University, Augusta, GA; cReproductive Health Protection, Scientific Center of Family Health and Human Reproduction, Irkutsk, Russian Federation. OBJECTIVE: Changes in self-image related to obesity, hirsutism, acne, as well as depression and anxiety associated with PCOS appear to have negative effects on sexual health. Alternatively, higher androgen levels found in PCOS women may actually improve libido. Unfortunately, currently published data are based on under-powered studies and results are often inconclusive; therefore, pooled data is needed. The purpose of our study is to determine differences in sexual function between women with and without PCOS. DESIGN: Systematic review and meta-analysis MATERIALS AND METHODS: Electronic databases (MEDLINE through PubMed, EMBASE, Web of Science, LILACS, Cochrane Library, CINAHL, and PsycINFO) were searched through October 2015. Search terms included: polycystic ovarian syndrome, PCOD, PCOS, quality of life, sexual dysfunction, sexual function, sexual dissatisfaction, sexual comfort, sexual intercourse, libido, arousal, orgasm, dyspareunia, satiation, craving, lubrication, coitus, desire, excitement, and sexarche. Observational studies (crosssectional, case-control, cohort) reporting sexual function of PCOS vs unaffected subjects were considered. Data was extracted using a web-based, piloted form. The inverse variance method, based on a random- or fixed-effects model (Review Manager, Version 5) was used to analyze the data. Data from eligible studies was independently extracted by two reviewers. RESULTS: The original search yielded 880 publications. Hand searching of titles and abstracts was conducted to exclude articles which did not focus on PCOS and quality of life or sexual function, and duplicates were removed, yielding a total of 431 articles. These articles were reviewed, and eight comparative studies were included (428 PCOS women and 423 controls) in the systematic review. The polled analysis revealed no significant differences between PCOS and controls in sexual desire (SMD -0.01; 95% CI: -0.43, 0.42; Z¼0.02, p¼0.98); lubrication during intercourse (SMD -0.20; 95% CI -0.43, 0.03; Z¼1.73, p¼0.08); orgasm (SMD -0.11; 95% CI -0.34, 0.12; Z¼0.95, p¼0.34); satisfaction (SMD -0.40; 95% CI -0.94, 0.14; Z¼1.45, p¼0.15); pain during intercourse (SMD -0.12; 95% CI -0.25, 0.48; Z¼0.62, p¼0.53); and total sexual function score (SMD -0.20; 95% CI -0.43, 0.03; Z¼1.73, p¼0.08). PCOS patients had less arousal scores then controls (SMD -0.26; -0.49,-0.04; Z¼2.27, p¼0.02). CONCLUSIONS: Our systematic review based on the limited comparative data published thus far suggests that women with PCOS, compared to controls, have some degree of impairment in the domain of sexual arousal, but little evidence of any other sexual dysfunction. Additional well designed studies are needed. Supported by: Partial funding from MD Medical Group, MDMED00001, ‘‘The Epidemiology and Phenotype of PCOS in Women’’.
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P-414 Wednesday, October 19, 2016
Eating disorders in women with PCOS and controls
PCOS PATIENTS CONTROLS (n¼121) (n¼57) p-VALUE Age (SD) BMI (SD) EDEQ Global Score (SD) EDEQ Restraint Score (SD) EDEQ Shape Concern Score (SD) EDEQ Weight Concern Score (SD) EDEQ Eating Concern Score (SD) EDEQ Global Score, Number R 4 (%) Bulimia Binge Eating Disorder Night Eating Disorder
28.08 (5.42) 33.56 (8.78) 2.33 (0.12)
33.26 (8.63) 25.40 (5.70) 1.24 (0.14)
0.0002 <0.0001 <0.0001
2.07 (0.12)
1.34 (0.19)
0.0009
3.22 (0.16)
1.87 (0.21)
<0.0001
2.91 (0.15)
1.47 (0.19)
<0.0001
1.11 (0.15)
0.25 (0.08)
0.0002
13 (10.92)
1 (1.75)
0.038
9 (7.44) 21 (17.4) 16 (13.3)
1 (1.75) 5 (8.8) 4 (7.02)
0.172 0.173 0.310
P-413 Wednesday, October 19, 2016 EFFECTIVENESS OF A LETROZOLE ESCALATION PROTOCOL IN ACHIEVING OVULATION IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME. T. L. Jones, C. C. Shenoy, J. Jensen, E. A. Stewart, G. S. Daftary, C. Coddington. Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, MN. OBJECTIVE: In the absence of follicular recruitment, immediate dose escalation is effective to achieve ovulation in oligo- or anovulatory women using clomiphene citrate. Limited data exist for using letrozole in a similar manner. We sought to determine if immediately increasing the letrozole dose during the same cycle is efficacious to achieve ovulation in oligo- or anovulatory women with polycystic ovary syndrome (PCOS). We also evaluated endometrial thickness and pregnancy rates in women undergoing the escalation protocol versus standard treatment. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Oligo- or anovulatory women with PCOS based on Rotterdam criteria undergoing their first cycle of ovulation induction with letrozole at Mayo Clinic in Rochester, MN, from January 1, 2014 to March 31, 2016 were selected. The escalation protocol was performed by administering letrozole at a starting dose of 2.5 mg for 5 days starting cycle day 3. A transvaginal ultrasound was performed on cycle day 10-12 to assess follicular recruitment. If no follicle(s) R10mm were observed, the dose was immediately increased by 2.5 mg of letrozole for an additional 5 days. This was repeated until a follicle was recruited or a maximum dose of 7.5 mg of letrozole was reached. Standard treatment consisted of admin-
FERTILITY & STERILITYÒ
istering 10 days of oral progestin to induce a withdrawal bleed if there was no follicular recruitment on CD 10-12 ultrasound, followed by an increased dose of letrozole in the subsequent cycle. Ovulation was determined by detection of urinary luteinizing hormone surge or by administering human chorionic gonadotropin when a dominant follicle reached 20 mm. Clinical pregnancy was defined by a positive hCG and by fetal cardiac activity on ultrasound. Statistical analysis was performed using the Wilcoxon Rank Sum and Fisher Exact tests where appropriate. RESULTS: Forty six PCOS patients with ovulatory dysfunction were identified; 11 utilized the escalation protocol. There were no differences in baseline age, body mass index, and ovarian reserve between the two groups. Of the 35 patients using the standard protocol, 72% ovulated versus 100% of the 11 using the escalation protocol (p¼0.042). There were no differences in mean follicular recruitment (2.1 1.6 vs 2.4 1.6, p¼0.62) or endometrial thickness (5.8 2.1 vs 5.7 2.4 mm, p 0.90) between standard and escalation protocol, respectively. There were no statistical difference in clinical pregnancies 3 (11%) in the standard and 1 (9%) in the escalation group. CONCLUSIONS: The escalation protocol increases ovulation rates in patients with PCOS by effectively identifying the letrozole dose necessary to achieve follicular recruitment during the initial ovulation induction cycle. Immediately increasing the dose of letrozole in a single cycle does not exhibit detrimental effects on the number of follicles recruited, endometrial development or pregnancy rates.
SEXUAL FUNCTION AND POLYCYSTIC OVARY SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS. D. Lizneva,a W. J. Walker,a L. Gavrilova-Jordan,a M. P. Diamond,b R. Azziz,a L. Suturina,c I. Atabyekov,c S. Brakta.b aObstetrics and Gynecology, Augusta University, Augusta, GA; bAugusta University, Augusta, GA; cReproductive Health Protection, Scientific Center of Family Health and Human Reproduction, Irkutsk, Russian Federation. OBJECTIVE: Changes in self-image related to obesity, hirsutism, acne, as well as depression and anxiety associated with PCOS appear to have negative effects on sexual health. Alternatively, higher androgen levels found in PCOS women may actually improve libido. Unfortunately, currently published data are based on under-powered studies and results are often inconclusive; therefore, pooled data is needed. The purpose of our study is to determine differences in sexual function between women with and without PCOS. DESIGN: Systematic review and meta-analysis MATERIALS AND METHODS: Electronic databases (MEDLINE through PubMed, EMBASE, Web of Science, LILACS, Cochrane Library, CINAHL, and PsycINFO) were searched through October 2015. Search terms included: polycystic ovarian syndrome, PCOD, PCOS, quality of life, sexual dysfunction, sexual function, sexual dissatisfaction, sexual comfort, sexual intercourse, libido, arousal, orgasm, dyspareunia, satiation, craving, lubrication, coitus, desire, excitement, and sexarche. Observational studies (crosssectional, case-control, cohort) reporting sexual function of PCOS vs unaffected subjects were considered. Data was extracted using a web-based, piloted form. The inverse variance method, based on a random- or fixed-effects model (Review Manager, Version 5) was used to analyze the data. Data from eligible studies was independently extracted by two reviewers. RESULTS: The original search yielded 880 publications. Hand searching of titles and abstracts was conducted to exclude articles which did not focus on PCOS and quality of life or sexual function, and duplicates were removed, yielding a total of 431 articles. These articles were reviewed, and eight comparative studies were included (428 PCOS women and 423 controls) in the systematic review. The polled analysis revealed no significant differences between PCOS and controls in sexual desire (SMD -0.01; 95% CI: -0.43, 0.42; Z¼0.02, p¼0.98); lubrication during intercourse (SMD -0.20; 95% CI -0.43, 0.03; Z¼1.73, p¼0.08); orgasm (SMD -0.11; 95% CI -0.34, 0.12; Z¼0.95, p¼0.34); satisfaction (SMD -0.40; 95% CI -0.94, 0.14; Z¼1.45, p¼0.15); pain during intercourse (SMD -0.12; 95% CI -0.25, 0.48; Z¼0.62, p¼0.53); and total sexual function score (SMD -0.20; 95% CI -0.43, 0.03; Z¼1.73, p¼0.08). PCOS patients had less arousal scores then controls (SMD -0.26; -0.49,-0.04; Z¼2.27, p¼0.02). CONCLUSIONS: Our systematic review based on the limited comparative data published thus far suggests that women with PCOS, compared to controls, have some degree of impairment in the domain of sexual arousal, but little evidence of any other sexual dysfunction. Additional well designed studies are needed. Supported by: Partial funding from MD Medical Group, MDMED00001, ‘‘The Epidemiology and Phenotype of PCOS in Women’’.
e261