Baseline Estradiol Research Articles

Baseline Endometrial Thickness or Endometrial Thickness Change in Response to Estrogen Is Not Predictive of Frozen Embryo Transfer Success in Medicated Cycles.

There is some consensus that endometrial thickness (EMT) needs to be at least 7mm on day of embryo transfer. However, the predictive role of baseline EMT and EMT change in response to estrogen is largely unknown. The objective of this study was to evaluate the role of endometrial thickness in frozen embryo transfer (FET) cycles. We analyzed the association of baseline endometrial thickness (EMTb-Day 3 of cycle) and endometrial thickness change (EMTΔ-from baseline to start of progesterone supplementation) with FET success in 121cycles. We also investigated whether baseline estradiol levels and body mass index (BMI) are associated with EMTb. No difference was observed in EMTb and EMTΔ in cycles resulting in clinical pregnancy compared to unsuccessful transfers (5.1 ± 2.2mm vs 5.0 ± 1.9mm; p= 0.92, and 4.7 ± 2.4mm vs. 4.4 ± 2.4mm; p= 0.56). When 7mm cut-off was used, endometrial thickness on the day of start of progesterone supplementation (EMTp) was also not different between groups (9.8 ± 2.9mm vs. 9.4 ± 2.5mm; p= 0.50). Multivariable logistic regression models did not demonstrate any predictive value of EMTb, EMTp, or EMTΔ in predicting success of FET cycles (p= 0.92, p= 0.80, and p= 0.84, respectively). There was no significant correlation between EMTb and baseline estradiol levels (r= -0.001; p= 0.985). BMI showed statistically significant weak positive linear relationship with EMTb (r= +0.29; p= 0.002). Our study did not demonstrate any significant relationship between baseline endometrial thickness or endometrial thickness change and clinical pregnancy rates in frozen embryo transfer cycles. Significant positive linear relationship of BMI with baseline endometrial thickness, despite no correlation between baseline estradiol and EMTb, points to the role of possible other mechanism affecting EMT besides estradiol in obese patients.

Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial.

The aim of the study was to quantify baseline estradiol (E2) and estrone (E1) concentrations according to selected patient characteristics in a substudy nested within the MAP.3 chemoprevention trial. E2 and E1 levels were measured in 4,068 postmenopausal women using liquid chromatography-tandem mass spectrometry. Distributions were described by age, years since menopause, race, body mass index (BMI), smoking status, and use and duration of hormone therapy using the Kruskal-Wallis test. Multivariable linear regression was also used to identify characteristics associated with estrogen levels. After truncation at the 97.5th percentile, the mean (SD)/median (IQR) values for E2 and E1 were 5.41 (4.67)/4.0 (2.4-6.7) pg/mL and 24.7 (14.1)/21 (15-31) pg/mL, respectively. E2 and E1 were strongly correlated (Pearson correlation [r] = 0.8, P < 0.01). The largest variation in E2 and E1 levels was by BMI; mean E2 and E1 levels were 3.5 and 19.1 pg/mL, respectively for women with BMI less than 25 and 7.5 and 30.6 pg/mL, respectively, for women with BMI greater than 30. E2 and E1 varied by age, BMI, smoking status, and prior hormone therapy in multivariable models (P < 0.01). There was large interindividual variability observed for E2 and E1 that varied significantly by participant characteristics, but with small absolute differences except in the case of BMI. Although the majority of participant characteristics were independently associated with E1 and E2, together, these factors only explained about 20% of the variation in E1 and E2 levels.

Obesity and Baseline Estradiol Levels Are Independent Predictors for Initiation of Anastrozole in Hypogonadal Men on Clomiphene Citrate.

PurposeTo assess the conversion rate from clomiphene citrate (CC) monotherapy to combination CC+anastrozole (AZ) therapy in hypogonadal men and the predictors associated with the initiation of AZ.Materials and MethodsA retrospective review of records from hypogonadal men treated with CC in a single fertility center was performed from 2013 to 2018. Patient age, body mass index (BMI), blood pressure, and reproductive hormones were obtained at baseline. Obesity was defined as BMI≥30 kg/m2. Cox proportional hazards models were used to identify predictors of switching to combination CC+AZ therapy.ResultsA total of 318 men on CC were included. Median (interquartile range) age was 34 years (30–39 years) and patients were followed for a median of 9 months (4–17 months). Of these, 97 (30.5%) were started on CC+AZ therapy. These patients had higher baseline BMI and estradiol, which in multivariable regression were significant predictors for switching to CC+AZ therapy. A threshold of 18.5 pg/mL for baseline estradiol provided the highest accuracy for predicting the addition of AZ after adjusting for baseline BMI and total testosterone levels.ConclusionsIn our practice, following CC monotherapy, 30% of men were initiated on CC+AZ. Obesity (BMI≥30 kg/m2) and baseline estradiol ≥18.5 pg/mL can predict the conversion to combination therapy with addition of AZ. This information can be used to counsel patients and also help to identify patients who can be started on combination therapy upfront.

377 Pretreatment Estradiol Does Not Predict Improvement in Serum Testosterone in Men Receiving Clomiphene Citrate

Since clomiphene citrate is a an estrogen receptor modulator and dosage in women is determined based on baseline estradiol level. We hypothesized that pre-treatment estradiol level in men is associated with greater total testosterone response to treatment with clomiphene citrate. Following IRB approval, a retrospective chart review was performed at two large academic centers for all men prescribed clomiphene citrate (25 mg every other day) between January 1, 2015 and December 31, 2018. Age, body mass index (BMI), and prescription date were recorded for all patients. Pre- and post-treatment estradiol (E), total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were recorded for all patients as well. Only men with pretreatment TT < 300 ng/dL were included in the analysis. Using SPSS, univariate linear regression analysis was performed to determinate the independent variables (i.e., age, BMI, pre and post treatment E, FSH, and LH serum levels) that may predict percent change in TT change following clomiphene citrate treatment. The unstandardized regression coefficient (B) and coefficient of determination (R2) were calculated for each independent variable.

Urinary bisphenol A concentration is correlated with poorer oocyte retrieval and embryo implantation outcomes in patients with tubal factor infertility undergoing in vitro fertilisation

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF.

Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency.

To evaluate the effect of ovarian biopsy and scratch on the resumption of ovarian function in women with premature ovarian insufficiency (POI), the follicle development and pregnancy outcome were retrospectively analyzed in women with POI after ovarian biopsy/scratch. Eighty patients with POI with secondary amenorrhea were accepted the laparoscopic surgery, and then hormone replacement treatment for 6 months was applied and in vitro fertilization and embryo transfer was suggested. No significant difference in clinical characteristics was observed before and after ovarian biopsy/scratch ( P > .05). After the ovarian surgery, 11 (13.75%) patients presented with ovarian function resumption spontaneously or with human menopausal gonadotropin stimulation. Three metaphases II oocytes were retrieved in 10 patients. Two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. Patients with follicle development had higher baseline estradiol compared to those without (78.20 [18.53-161.08] pg/mL vs 15.70 [8.40-43.80] pg/mL, P < .01). The technique of ovarian biopsy/scratch could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI. However, future improvement in efficiency and practice criteria is warranted.

Demographics and the Placebo Response in the REPLENISH TRIAL: A Study of Vasomotor Symptoms [16OP

INTRODUCTION: High placebo responses (up to 61%) are reported in studies evaluating therapeutic agents for vasomotor symptoms (VMS). Placebo response rates by subgroups from a recently completed positive trial of an investigational combination of 17β-estradiol and progesterone capsule (TX-001HR) are presented. METHODS: REPLENISH was a phase 3, randomized, double-blind, placebo-controlled trial that evaluated safety/efficacy of TX-001HR in postmenopausal women, who had ≥50 moderate to severe hot flushes at baseline. 767 women received one of four TX-001HR daily doses or placebo; frequency and severity of VMS at baseline and weeks 4 and 12 were recorded by diary. Secondary endpoints were responder analyses and menopause-specific quality of life (MENQOL) questionnaire. Subgroup analysis of efficacy was performed on demographics. RESULTS: The placebo response rate was high (55%). Significant differences were observed in the placebo response rates between White (51%) and African American (65%) women at 12 weeks (P=.049). Mean age was similar; more African American women had BMI≥30 kg/m2 (32.4%) vs White (18.7%). More African American women were current smokers than White (41.5% vs 17.6%). Significant differences in responders (≥50% and ≥75%) and the MENQOL Vasomotor Domain were observed for all groups compared to placebo in the White population; no differences noted in African Americans due to high placebo rate. Baseline estradiol levels and compliance rates for African American and White women were similar. CONCLUSION: Large placebo responses occurred and more frequently in African Americans. Understanding factors that contribute to placebo responses are important in designing and assessing the efficacy of medications in clinical trials.

MP07-02 BASELINE BODY MASS INDEX AND ESTRADIOL LEVELS PREDICT COMBINATION THERAPY WITH ANASTROZOLE IN HYPOGONADAL MEN TREATED WITH CLOMIPHENE CITRATE

You have accessJournal of UrologyInfertility: Therapy II1 Apr 2018MP07-02 BASELINE BODY MASS INDEX AND ESTRADIOL LEVELS PREDICT COMBINATION THERAPY WITH ANASTROZOLE IN HYPOGONADAL MEN TREATED WITH CLOMIPHENE CITRATE Sorena Keihani, Rachel Moses, Jeremy Myers, and James Hotaling Sorena KeihaniSorena Keihani More articles by this author , Rachel MosesRachel Moses More articles by this author , Jeremy MyersJeremy Myers More articles by this author , and James HotalingJames Hotaling More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3065AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clomiphene citrate (CC) is commonly used in the treatment of male hypogonadism/infertility as an off-label medication. CC can cause increased estradiol (E) levels and decreased testosterone to estradiol ratio (T/E) in some patients necessitating addition of aromatase inhibitors such as Anastrozole (AZ) to optimize E and T/E levels. Little data is available on the conversion rate from CC monotherapy to combination CC+AZ therapy and the predictors of this conversion. METHODS We retrospectively reviewed data of hypogonadal men treated with CC in our fertility center from 2010-2017. Data were gathered on patient age, race, body mass index (BMI) and laboratory values. Patients who were started on CC+AZ combination therapy in their follow up (due to increased E or decreased T/E levels) were identified. Patients with <1 month of follow up were excluded. Baseline values were compared between CC monotherapy and CC+AZ therapy groups. Logistic regression was used to find predictors of conversion to combination therapy. RESULTS 429 men were identified taking CC prescribed for hypogonadism/infertility. Mean age was 35.6±7.7 y and patients were followed up for a mean of 12.3±10.9 m. Following CC therapy, 106 (25%) men received combination therapy with CC+AZ. Baseline age and race were not different between CC monotherapy (323 patients) and combination therapy (106 patients). Patients who received combination therapy had higher baseline BMI (34.5±8.3 vs. 30.1±5.8; P<0.001), baseline E levels (22.9±9.8 vs. 18.0±9.0; P<0.001) and lower baseline T/E ratio (12.8±0.7 vs. 18.4±0.6; P<0.001). Other baseline lab values were similar in two groups (Table-1). In multivariable regression model (after controlling for baseline age and TT), BMI and E were significantly associated with conversion to combination therapy (OR: 1.07 95% CI: 1.01-1.13, P=0.006; and OR:1.07 95% CI: 1.02-1.12, P=0.003, respectively). CONCLUSIONS In our practice, following CC-therapy for male hypogonadism/infertility, 25% of men will receive combination therapy with AZ. Higher baseline BMI and estradiol levels predict the conversion to combination therapy. This information can be used to counsel patients and potentially help identify patients for whom initial combination therapy may be appropriate. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e88 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Sorena Keihani More articles by this author Rachel Moses More articles by this author Jeremy Myers More articles by this author James Hotaling More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition

The menopause transition and early postmenopausal period are associated with a 2- to 4-fold increased risk for clinically significant depressive symptoms. Although a few studies suggest that hormone therapy can effectively manage existing depression during this time, to our knowledge, there have been no studies testing whether hormone therapy can prevent the onset of perimenopausal and early postmenopausal depressive symptoms. To examine the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) in preventing depressive symptom onset among initially euthymic perimenopausal and early postmenopausal women. A secondary aim was to identify baseline characteristics predicting TE+IMP's beneficial mood effects. Double-blind, placebo-controlled randomized trial at the University of North Carolina at Chapel Hill from October 2010 to February 2016. Participants included euthymic perimenopausal and early postmenopausal women from the community, aged 45 to 60 years. Transdermal estradiol (0.1 mg/d) or transdermal placebo for 12 months. Oral micronized progesterone (200 mg/d for 12 days) was also given every 3 months to women receiving active TE, and identical placebo pills were given to women receiving placebo. Scores on the Center for Epidemiological Studies-Depression Scale (CES-D), assessed at baseline and months 1, 2, 4, 6, 8, 10, and 12 after randomization, and the incidence of clinically significant depressive symptoms, defined as a CES-D score of at least 16. Of 172 participants, 130 were white (76%), and 70 were African American (19%), with a mean household income of $50 000 to $79 999. The mean age was 51 years, and 43 developed clinically significant depressive symptoms. Women assigned to placebo were more likely than those assigned to TE+IMP to score at least 16 on the CES-D at least once during the intervention phase (32.3% vs 17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = .03) and had a higher mean CES-D score across the intervention period (P = .03). Baseline reproductive stage moderated the effect of treatment (β, -1.97; SEM, 0.80; P for the interaction = .03) such that mood benefits of TE+IMP vs placebo were evident among women in the early menopause transition (β, -4.2; SEM, 1.2; P < .001) but not the late menopause transition (β, -0.9; SEM, 0.3; P = .23) or among postmenopausal women (β, -0.3; SEM, 1.1; P = .92). Stressful life events in the 6 months preceding enrollment also moderated the effect of treatment on mean CES-D score such that the mood benefits of TE+IMP increased with a greater number of events (β, 1.22; SEM, 0.40; P = .003). Baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not moderate treatment effects. Twelve months of TE+IMP were more effective than placebo in preventing the development of clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women. clinicaltrials.gov Identifier: NCT01308814.

Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels

BACKGROUND AND OBJECTIVE Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin. DESIGN AND PATIENTS A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions. RESULTS SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P < 0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH. CONCLUSIONS Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.

Abstract P316: Reproductive Factors Associated With Subclinical Vascular Measures at Late Midlife: SWAN

Background: Sex-specific features, including adverse pregnancy outcomes (i.e., gestational hypertension, preeclampsia, gestational diabetes), have been associated with increased risk for CVD. However, there is limited research characterizing these associations with menopause features or with subclinical vascular measures at late midlife, when CVD risk increases. Objective: To evaluate associations between reproductive factors (i.e. gestational hypertension, preeclampsia, and gestational diabetes) with validated and reliable markers of subclinical vascular damage and remodeling; carotid intima-media thickness (cIMT), adventitial diameter (cAD), carotid plaque presence, and brachial-ankle pulse wave velocity (baPWV). Methods: A cross-sectional analysis was conducted with 1454 women (50% white, 31% black, 6% Hispanic, 13% Chinese) from the Study of Women’s Health Across the Nation (SWAN). Women were included if they completed a detailed reproductive history questionnaire and had a carotid ultrasound at visit 12 or 13. baPWV was performed at the same follow-up visit. Associations between reproductive history and subclinical CVD were tested using linear and logistic regression models adjusting for demographics and traditional CVD risk factors (age, site, race/ethnicity, financial strain, BMI, SBP, LDL-c, HDL-c, HOMA-IR). Additional models were adjusted for sex hormone levels and number of births. Results: Women were on average 60 years old and mostly postmenopausal (94%). Two hundred fifty-six women (18%) were nulliparous. Approximately 10% of parous women had a self-reported history of gestational hypertension or preeclampsia, and 4% reported gestational diabetes. Among parous women, gestational hypertension was associated with higher mean cIMT (β±SE=0.053±0.015mm; P=0.0003) and preeclampsia was associated with higher odds of plaque (OR=1.7; 95% CI: 1.1, 2.6; P=0.01) in fully adjusted models. History of gestational diabetes was related to higher baPWV (β±SE=64.6±28.4cm/s; P=0.009). Associations between adverse pregnancy outcomes and subclinical vascular measures remained significant after adjusting for baseline estradiol and number of births. Compared to nulliparous women, parity≥3 was associated with higher cAD (β±SE=0.10±0.05mm; P=0.02) when controlling for demographics, but not after adjustment for CVD risk factors. Age at menarche, age at menopause, hormone ever use, and bilateral oophorectomy were not associated with subclinical vascular measures at late midlife. Conclusions: Adverse pregnancy outcomes (i.e., gestational hypertension, preeclampsia, and gestational diabetes) converge to put women at excess risk for CVD, but may affect the vasculature through distinct pathways. Further studies are necessary to assess the joint effects of early and late midlife reproductive factors on future CVD.

THE VALUE OF PROGNOSTIC FACTORS IN CONTROLLED OVARIAN STIMULATION FOR IVF CYCLES

Objective: To evaluate prognostic values for ovarian response of age, AFC, baseline hormonal profile and Estradiol concentration in ovarian stimulation process for art cycles. Method: Retrospective cohort. Materials: Patients treated in vitro fertilization, is ovarian stimulated with antagonist protocol, at the Center for Reproductive Endocrinology and Infertility - Hue University Hospital, from 9/2013 to 9/ 2016. Results: Women with ≤5 oocytes retrieved had the average value of the parameters: AFC 6.0±3.04, FSH 9.01±2.95 mIU/ml, AMH 1.63±1.45 ng/ml, and E2N7 617.27±440.84 pg/ml. Those with &gt;15 oocytes retrieved had the average value of the parameters: AFC 12.91±4.52, FSH 6.06±2.03 mIU/ml, AMH 7.37±15.79 ng/ml, E2N7 1612.11±612.83 pg/ml, E2NhCG 2889.62±1732.98 pg/ml, and average number of follicles ≥12mm on day 7 was 7.70±6.35. Correlation coefficients between number of oocytes retrieved and AFC, AMH and FSH N2-3, age were 0.62; 0.48; -0.39; -0.22, respectively; and the correlation coefficients between number of oocytes retrieved and E2N7, number of follicles ≥12mm on day 7, number of follicles ≥14mm on day 9 were 0.58; 0.3; 0.7, respectively. Threshold value of E2 on day 7 ≤ 823 pg/ml predicted number of oocytes retrieved ≤5 with sensitivity 78.9%, specificity 65%. Threshold value of E2 on day 7 &gt; 1098 pg/ml predicted number of oocytes retrieved &gt;15 with sensitivity 81.0%, specificity 73.9%. Basal LH, E2 are not related to ovarian response. Conclusions: AFC, FSH on days 2-3 and AMH were prognostic values of number of oocytes retrieved in the ovarian stimulation cycle. Of which, AFC was the best prognostic factor in the same treatment cycle; age had lower level of prognosis than parameters evaluating ovarian reserve. E2 on day 7 was able to prognosis few or too many oocytes retrieved, number of follicles ≥12mm on day 7 was able to prognosis too many oocytes retrieved but not for few or moderate oocytes retrieved. Number of follicle ≥14mm and E2 on day 9 were good for prognosing all three levels of oocytes retrieved. Key words: Number of oocytes retrieved, AFC, AMH, FSH D2-3, estradiol D7, estradiol DhCG

Baseline ovarian cyst formation following gonadotropin-releasing hormone analogues: their prevalence and impact on in vitro fertilization outcome

One known complication of gonadotropin-releasing hormone (GnRH) agonist treatment for in vitro fertilization (IVF) cycles is the formation of functional ovarian cysts. The effect of baseline ovarian cysts on the outcome of IVF treatment is controversial. No prior studies have compared the prevalence of cyst formation in GnRH agonist versus GnRH antagonist stimulation protocols. Our objective was to determine the prevalence and significance of baseline follicular cysts on the response to controlled ovarian hyperstimulation and the outcome of IVF in women treated with a GnRH agonist versus a GnRH antagonist. Retrospective case-controlled study. Three-hundred and eighteen consecutive IVF cycles performed between January 2010 and December 2014 were analyzed. The subjects were grouped according to stimulation protocol (GnRH agonist vs. GnRH antagonist) and by the presence or absence of baseline ovarian cysts. We compared baseline estradiol levels, total gonadotropin dose used, total number of days of ovulation induction, number of cycle cancellations, number of oocytes retrieved, and the clinical and live birth rates. There was no significant difference in the prevalence of baseline ovarian cysts using a GnRH agonist versus antagonist protocol (14% vs. 9.5%, p = 0.269). The average time delay to initiate an IVF cycle was 8.9 days for the agonist cycles and 10.2 days for the antagonist cycles (range 0-28 days). The number of oocytes retrieved was lower in the group of patients with a baseline cyst treated with the antagonist protocol (4.7 with a cyst vs. 10.2 without a cyst, p = 0.039) as well as a significantly higher cycle cancellation rate (36% vs. 8.4%, p = 0.028, OR 6.16, 95% CI 1.51-25.12). This effect was not seen with the GnRH agonist protocol. There was no difference in the number of ampules of gonadotropins used for stimulation or total days of stimulation for either protocol. Finally, there was no significant difference between the groups according to the clinical pregnancy rate or live birth rate. The presence of a baseline ovarian cyst delays the time to initiate an IVF cycle; however, there is no significant difference in the prevalence of cyst formation between GnRH agonist and GnRH antagonist protocols. Although presence of a baseline ovarian cyst was associated with a lower number of oocytes retrieved and higher cycle cancellation rate, there is no negative impact on pregnancy rates when compared to cycles without cyst formation. Larger prospective studies are needed to confirm these findings.

Circumventing the natural, frequent oestrogen waves of the female cheetah (Acinonyx jubatus) using oral progestin (Altrenogest).

Cheetah are induced ovulators, experiencing short, variable oestrogen waves year-round. Exogenous gonadotrophin administration induces ovulation, but success is variable and often improves if ovaries are quiescent. After affirming the presence of short-term oestrogenic waves, we examined the effect of the timing of administration of exogenous equine and human chorionic gonadotrophins (eCG-hCG) within the oestrogen concentration pattern on subsequent follicle development and oocyte and corpus luteum quality. We also investigated ovarian suppression using an oral progestin (Altrenogest, 7 days) and assessed whether Altrenogest moderated adrenal activity by reducing glucocorticoid metabolites. All cheetahs exhibited short (every ~7-10 days), sporadic, year-round increases in faecal oestradiol punctuated by unpredictable periods (4-10 weeks) of baseline oestradiol (anoestrous). Gonadotrophin (eCG-hCG) efficacy was not affected by oestradiol 'wave' pattern if administered ≥3 days after an oestrogen peak. Such cheetahs produced normative faecal progestagen patterns and higher numbers (P<0.06) of mature oocytes than females given gonadotrophins ≤2 days after an oestradiol peak. Altrenogest supplementation expanded the interval between oestradiol peaks to 12.9 days compared with 7.3 days without progestin pretreatment. Altrenogest-fed females excreted less (P<0.05) glucocorticoid metabolites than non-supplemented counterparts. Results show that Altrenogest is effective for suppressing follicular activity, may contribute to reduced glucocorticoid production and may result in more effective ovulation induction via gonadotrophin therapy.

Fertility Preservation Decisions Among Newly Diagnosed Oncology Patients

To evaluate fertility preservation decisions and compare controlled ovarian stimulation (COS) and assisted reproductive technology (ART) outcomes between newly diagnosed cancer patients and age-matched healthy controls. Our retrospective study was conducted at Columbia University's Center for Women's Reproductive Care between 2005 and 2012. Forty-nine women elected to undergo ART with COS for either oocyte or embryo cryopreservation before commencement of cancer therapy. Demographic and descriptive characteristics were collected from the cohort of patients. Treatment outcomes were compared with randomly selected, healthy, age-matched controls undergoing ART with COS during the same time period. Single women began fertility preservation cycles in half the time of married women (10.4 vs. 22.9 d). All 21 married women chose embryo cryopreservation, whereas 17 of the 28 (61%) single women chose embryo over oocyte cryopreservation. Baseline anti-Mullerian hormone levels and body mass indices were similar among fertility preservation patients and controls. Despite elevated baseline estradiol (E2) levels and luteal phase cycle starts in some cycles to avoid delay of cancer treatment, no significant differences were noted when comparing days of stimulation, total gonadotropins prescribed, numbers of oocytes and mature oocytes retrieved, fertilization rate, or cancellation rate to controls. Our experience shows that, with appropriate counseling and multidisciplinary care, newly diagnosed cancer patients desiring fertility preservation experience similar outcomes as age-matched healthy controls. These women can pursue oocyte or embryo cryopreservation with likely minimal disruption to the flow of their oncologic care.

Timing of polar body extrusion is associated with body mass index, a pilot study using time lapse video microscopy

To determine timing of oocyte maturation by observing polar body extrusion in a closed time lapse incubator system, as well as to correlate the observed times to patient derived factors. Retrospective Analysis. 21 patients (57 oocytes) undergoing either elective oocyte cryopreservation (OC) or intra-cytoplasmic sperm injection (ICSI) at our center were included in this study. Patients that had not signed research consent or if no immature oocytes were available after retrieval were excluded. 20 patients underwent gonadotropin/antagonist cycles and one patient underwent estrogen priming. Patients were triggered as per our protocol when the lead follicles were 18-19 mm and all follicles were retrieved at the time of egg retrieval. GV oocytes were then placed in a time lapse/stage top incubator which maintains constant temp of 37 degrees C and 5% C02 in air and 95% humidity levels as a conventional incubator. Images were obtained every 5 minutes for a total of 48 hours. All times were normalized to time of hcg trigger. Oocytes were left in Global for fertilization (Lifeglobal) media (G2), which is the media the oocytes were placed in after retrieval. Average age of all participants was 38.1 +/-3.4 years. Average baseline estradiol (E2) and follicle stimulating hormone (FSH) were 49.3 +/-14.6 (pg/ml) and 6.4+/-2 (mIU/ml) respectively. Average gonadotropin dosage (IU), E2 at trigger and number of oocytes retrieved were 3778.6 +/- 1576, 3349.3 +/-1334.7 and 21.9 +/-12.6, respectively. AMH and BMI were 3.34 +/- 2.1 and 20.1 +/- 8.5 respectively. Average time to oocyte polar body (PB) extrusion (in relation to trigger time) was 3495.3 +/- 253.9 minutes. Oocytes matured in 1104.6 +/- 274.5 minutes on average once placed in the time lapse incubator. 34/57 (60%) GV oocytes matured to metaphase 2 in vitro. Multiple linear regression revealed that the time to polar body extrusion was associated with BMI but not with AMH or percent of retrieved oocytes that were mature. Time to PB extrusion (TPBe) declined with BMI according to the equation: TPBe = -35.031 (BMI) + 4290.8 (minutes). Maturation rates of 60% were seen with the above protocol, which is comparable to published rates of IVM specific media. Although age and AMH did not show significance, higher BMI did show shorter maturation rates of GV oocytes in vitro. Further studies are needed to confirm these findings.

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years

The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. This is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m2). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively). Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men.

Preclinical laboratory assessments of predictors of social rank in female cynomolgus monkeys.

Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups (n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. © 2015 Wiley Periodicals, Inc.

127 THYROID STIMULATING HORMONE LEVEL CHANGE DURING CONTROLLED OVARIAN STIMULATION

Women who undergo assisted reproductive technology (ART) are exposed to a supra-physiological hormonal environment, which can affect the hypothalamus-pituitary-thyroid axis. Understanding these changes can help us improve the outcomes of ART. In this study we discuss the changes of thyroid hormone levels during ovarian stimulation as part of intrauterine insemination (IUI) and compare hypothyroid and euthyroid patients. Fifty-two infertile women aged 22 to 40 who underwent induction ovulation (I/O) as part of IUI were enrolled in this study. Out of 52 patients, 13 had underlying thyroid disease receiving levothyroxine treatment, and their thyroid test results were normal (&lt;2.5) for more than 6 weeks and had taken fixed levels of levothyroxine for more than 6 weeks. The TSH levels were measured by electrochemiluminescence at 3 times: baseline TSH (before starting of I/O), the day of HCG administration, and 4 weeks after. The change of TSH levels during this period and its relationship with baseline hypothyroidism, oestradiol levels, and I/O and pregnancy outcome were studied. Mean central index, frequency percentage, the median, and dispersion of standard deviation and interquartile range (IQR) were used to describe the data. Statistical tests, including t-test and chi-square, were used to analyse the data. Mean difference and relative risk indices were used to measure the differences. There was a significant increase in TSH level at the time of hCG injection compared with basal TSH in hypothyroid patients under treatment, TSH increased from 1.61 ± 0.81 to 2.75 ± 1.86 (P = 0.045), and this increase was seen in TSH 4 weeks later from 1.61 ± 0.81 to 2.12 ± 0.87 (P = 0.026). However, there were not significant changes in thyroid hormone level during treatment in euthyroid patients. In hypothyroid patients who got pregnant, there was no significant increase in 3 TSH measurements. But for the patients with an unsuccessful cycle this increase was seen at the time of HCG injection and 4 weeks later in comparison with basal TSH, which was statistically significant: 1.55 ± 0.83 v. 2.97 ± 2.09 (P = 0.05) and 1.55 ± 0.83 v. 2.14 ± 0/99 (P = 0.039). But this change was not seen in euthyroid patients with successful and unsuccessful cycle results. The relationship between TSH level with oestradiol in both euthyroid and hypothyroid patients was not significant. There was not a significant correlation between the number of follicles bigger than 16 mm, the mean size of follicles, and endometrial thickness with TSH at the time of HCG injection in both hypothyroid and euthyroid patients. There was a negative and reverse correlation between endometrial thickness and TSH at the time of HCG injection, but it was not significantly different. (P = 0.05). In euthyroid patients who undergo I/O as part of IUI, we did not observe significant TSH level changes during I/O, but in controlled hypothyroid patients a rise in serum TSH levels was observed. The pregnancy rate between 2 euthyroid and controlled hypothyroid groups was not different.

Sex Steroid Hormone Levels May Not Explain Gender Differences in Development of Nephrolithiasis.

To determine whether serum sex steroid hormone levels, or the subsequent change in those levels over time, represent a risk factor for the development of nephrolithiasis in men. We retrospectively identified patients participating in a long-term cohort study (Rochester Epidemiology Project) in Olmsted County, Minnesota. Patients had previously undergone baseline detailed clinical examination and sex steroid hormone studies, including estradiol, testosterone, and bioavailable testosterone. Patients were followed on a biennial basis. Records were then reviewed to assess for formation of nephrolithiasis. We identified 684 patients, with a median follow-up for stone formation of 12.8 years. All 684 patients had measurement of testosterone, of which 78.9% were in normal range. Five hundred eighteen men had baseline-free testosterone, of whom 88.6% were normal. Three hundred seventy-one patients had baseline estradiol, of whom 88.7% were normal. One hundred two men (14.9%) were found to have stones, with 61 of those (59.8%) occurring before first hormone measurement and 41 (40.2%) occurring after. On multivariate analysis, there was no significant association of serum hormones with nephrolithiasis, although a trend toward higher baseline testosterone and stones was seen (odds ratio [OR] 1.29; 95% confidence intervals [CI] 0.71, 2.33). Using a time-to-event for incident stone formation, we found no significant association of baseline hormones or percentage change in hormone levels over time with risk of stones. We found no significant association of sex steroid hormone levels with the risk of nephrolithiasis formation in men, although a weak trend toward an increased risk with elevated testosterone was seen.