Body mass index and ART results. Results of a large cohort of patients

DESIGN: This is a study on samples from women (N¼16). MATERIALS AND METHODS: Women between the ages of 28-56 years with BMI (Body Mass Index) ranging from 42-63 kg/m were selected. Urine was collected before surgery and follow up visits at 1, 6, 12 and 24 mo (months). Urinary 2OHE levels were measured using an enzymeimmunoassay kit (Estramet, Immuna Care Inc.). The values were normalized against creatinine levels and expressed as nanograms per ml per mg of creatinine. Statistical analysis was done using Student’s T test. RESULTS: Urinary 2OHE mean levels increased from 18.1 2.6 before surgery to 25.9  5.9 nanograms per ml per mg of creatinine at 24 mo. BMI declined from 49.37  2.16 before surgery to 32  1.57 kg/m at 24 mo.Mean 2OHE levels at 12 mo (22.5  3.9) and 24 mo (25.9  5.6) was significantly higher than at 1 mo post surgery (8.2  1.28) (P<0.05). Analysis of related reproductive hormones in these study subjects is underway in our lab. CONCLUSIONS: $ Inverse changes in 2OHE and BMI levels may partially explain improved ovarian function reported after weight loss. $ Our model suggests that reduction in BMI may lead to a decrease in levels of adipocyte-secreted proinflammatory cytokines which in turn causes lowered expression/activity of COMT levels resulting in higher levels of 2OHE.These findings provide novel therapeutic targets for improving ovarian function in obese women. Supported by: # RO1HD046228.

P-47 Tuesday, October 20, 2009 EFFECTS OF TESTOSTERONE ON CARDIOMYOCYTE CALCIUM HOMEOSTASIS AND CONTRACTILE FUNCTION IN FEMALE RATS. R. D. Beesley, B. M. Palmer, M. J. Toth. University of Vermont, Burlington, VT. OBJECTIVE: The role of testosterone (T) in the regulation of cardiac function in post menopausal women is not well understood. Our goal was to assess sarcomere shortening dynamics and intracellular calcium signaling from intact compared to ovariectomized rats with various permutations of hormonal add-back to examine the role of (T) on cardiomyocyte biology. DESIGN: 20 wk old Sprague-Dawley female rats were studied. Animals (n¼6/group) were divided into four groups: 1) sham-operated controls 2) ovariectomized rats (OVX) 3) OVX rats given physiological (T) replacement and 4) OVX rats given (T) plus an aromatase inhibitor. The final group was added to rule out any effect from peripheral bioconversion to estradiol. Four weeks following surgery/pellet placement, sarcomere shortening dynamics and intracellular calcium transients were measured. MATERIALS AND METHODS: Cardiomyocytes were isolated using method previously described. Shortening dynamics and intracellular calcium transients were recorded at 2Hz and 6Hz, then at 6Hz with exposure to 300nM isoproterenol using sarcomere detection software (IonOptix, Milton, MA) and the calcium indicator dye Fura-2AM. RESULTS: Compared to controls, the OVX and groups receiving (T) gained more body weight and displayed significant uterine atrophy with no differences seen in total heart or heart/body weight ratios. There were no significant differences in baseline sarcomere length or any dynamic shortening/ relaxation parameters measured. Likewise, no differences were found in any of the intracellular calcium signaling dynamics. CONCLUSIONS: Our data do not support an effect of physiologic testosterone deficiency or replacement on female rat ventricular myocyte shortening/relaxation or intracellular calcium dynamics. Collectively, these results suggest that physiologic levels of testosterone may not have significant relevance with respect to cardiomyocyte function in sexually mature females. Supported by: UVM/FAHC Research Grant

DESIGN: Prospective cohort study. MATERIALS AND METHODS: 39 obese anovulatory women(20-38 years of age,BMI > 29 kg/m) followed a 3 months weight loss program. After excluding drop-outs and pregnancies, the remaining 25 women that did loose weight, kept a basal body temperature chart. A midluteal progesterone level was assessed 7-10 days after the temperature rise. Ovulation was defined by a progesterone level > 15 nmol/l. At inclusion and after 3 months all women underwent waist circumference (Wc) measurement, whole body DEXA scan(DEXA) and a single sliced CT scan(ssCT) at the level of the umbilicus. Data were compared between the ovD and ov- group using the Paired student t-test and the Wilcoxon-signed-rank-test with SPSS version 14.0. RESULTS: There were no significant baseline differences between the 7 ovD women and the 18 ov- women regarding mean age(29 years), BMI(38 kg/m), Wc(114,5 cm), total body fat on DEXA(47,5kg), subcutaneous abdominal fat(SAF) on ssCT(968cm) and IAF on ssCT(201cm). The percentage weight loss(ovD [ 4,8% vs ov- ¼ 4,2%; p¼0,67), decrease in Wc(ovD [ 6,2cm vs ov- ¼ 2,5cm; p¼0,11), decrease in total body fat on DEXA(ovD [ 3,1kg vs ov- ¼ 2,5kg; p¼0,28) and percentage loss of trunk fat on DEXA(ovD [ 8,1% vs ov- ¼ 4,6%; P¼0,19), were not significantly different. The percentage loss of abdominal fat on DEXA(ovD [ 9,6% vs ov- ¼ 5,6%; P¼0,04), was significantly increased in women who resumed ovulation. The percentage loss of IAF on ssCT showed a trend of more loss in women who resumed ovulation(ovD [ 16,6% vs ov- ¼ 6,2%; P¼0,085). CONCLUSIONS: These data show that anovulatory obese women who resume ovulation during weight loss, loose significantly more abdominal fat on DEXA and show a trend of loosing more IAF on ssCT compared to those women who remain anovulatory despite the same amount of weight loss.

P-49 Tuesday, October 20, 2009 BODY MASS INDEX AND ART RESULTS. RESULTS OF A LARGE COHORT OF PATIENTS. J. de Mouzon, S. Belloc, M. Dumont, A.M. Junca, Y. Menezo, P. Cohen-Bacrie. INSERM, Paris, France; AMP EYLAU, UNILABS, Paris, France; AMP EYLAU, UNILABS, Paris, France; AMP EYLAU, UNILABS, Paris, France; AMP EYLAU, UNILABS, Paris, France; AMP EYLAU, UNILABS, Paris, France. OBJECTIVE: Obesity is known to be associated with sub-optimal reproductive performance but its direct effect on the outcome of assisted reproduction techniques (ART) is less clear. DESIGN: Retrospective analysis of a continuous series. MATERIALS AND METHODS: A continuous series of 1664 ART cycles performed in 2007 / 2008 in one ART centre, with information on patients’ height and weight were included. The relationships between body mass index (BMI) and main characteristics of women and of ART cycles were analyzed. Then, the clinical pregnancy rate (PR) per aspiration was compared between 3 groups of BMI, less than 19, 20-25 and more than 25 kg/m2. A multivariate logistic regression (LR) was finally conducted.

TABLE 1. Results

BMI

OBESITY AND METABOLISM P-48 Tuesday, October 20, 2009 RESUMPTION OF OVULATION OCCURS IN OBESE WOMEN WHO LOOSE ABDOMINAL FAT WITH PREFERENTIAL LOSS OF INTRA ABDOMINAL FAT (IAF). W. K. Kuchenbecker, H. Groen, A. H. Bolster, J. A. Land, A. Hoek. Obstetrics and Gynecology, Isala Clinics, Zwolle, Overijssel, Netherlands; Obstetrics and Gynecology, University Medical Center Groningen, Groningen, Netherlands; Clinical Epidemiology, University Medical Center Groningen, Groningen, Netherlands. OBJECTIVE: We aimed to compare the changes in body fat distribution between obese anovulatory women that resume ovulation(ovD) and those that remain anovulatory (ov-) after weight loss.

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Abstracts

Age FSH Day 3 E2 Day 3 LH Day 3 PRL Day 3 Inhibin B Day 3 AMH Day 3 Collected oocytes Inseminated oocytes Cleaved embryos Day 24.5  3.8 Cleavage rate PR / aspiration

<19

19-25

>25

p

34.6  4.1 7.0  2.9 36.5  25.9 5.1  4.1 13.8  16.3 58.9  16.2 3.8  3.2 9.1  6.3 7.3  5.4 4.5  3.8

35.5  4.2 7.1  2.8 37.9  42.7 4.9  3.3 13.7  16.2 59.7  18.1 3.4  3.4 8.8  5.6 7.5  5.1 4.9  3.9

36.0  4.5 6.8  3.6 35.2  24.7 4.5  4.2 19.6  34.5 56.9  22.9 3.6  3.7 8.4  5.6 6.5  4.7 4.1  3.6

0.001 0.31 0.62 0.21 0.01 0.29 0.40 0.35 0.02 0.01

61.3  28.6 24.8 %

64.1  27.8 22.5 %

64.1  30.5 15.9 %

0.37 0.01

Vol. 92., No. 3, Supplement, September 2009

RESULTS: In total, 16.6% of patients had a high BMI. High BMI was associated with older age and higher prolactin levels (table 1). The number of collected oocytes was similar, but mature oocytes and embryos were less numerous. PR was far lower. This was confirmed by LR taking in account women’s age (OR¼0.69, 95% CI: 0.49-0.99, p<0.05). CONCLUSIONS: Elevated BMI is associated with an important decrease in pregnancy chances. This must be considered when treating these patients, by trying to decrease the weight previously to ART and/or by adapting the stimulation regimen

MATERIALS AND METHODS: A total of 69 donors were analyzed. Controlled ovarian hyperstimulation was carried out by recombinant FSH and late-luteal phase GnRH agonist down-regulation with leuprolide acetate at a dose of 1mg daily reduced to 0.5mg at the start of stimulation.Statistical analyses were made by SPSS software. RESULTS: Statistically significant relationship were found between total dose of gonadotropins (IU) required for ovarian stimulation and BMI (p< 0.01) and mature oocytes retrieved (Metaphase II) (p<0.05). Levels of estradiol on day 10 had no direct relation on the body mass index and there was a trend towards higher number of total oocytes retrieved in donors with normal BMI.

P-50 Tuesday, October 20, 2009

TABLE 1. Patients Characteristics

INCREASED BMI AND FASTING INSULIN ARE ASSOCIATED WITH DECREASED NUMBERS OF LARGE ANTRAL FOLLICLES. E. B. Johnstone, C. Addauan-Andersen, D. Trevithick, B. Sternfeld, M. P. Rosen, M. I. Cedars. Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, San Francisco, CA; Division of Research, Kaiser Permanente, Oakland, CA. OBJECTIVE: Obesity is associated with decreased antral follicle count (AFC) and antimullerian hormone (AMH) (Su 2008; Freeman 2007). We examined relationships among body mass index (BMI), insulin, age, and elements of ovarian reserve. DESIGN: Population-based cross-sectional study MATERIALS AND METHODS: 459 women aged 25-45 with regular menses enrolled in the OVA (Ovarian Aging) study underwent body measurements, and transvaginal ultrasound and fasting blood tests on cycle day 2-4. Relationships among continuous variables were assessed with Spearman rank correlations. Stepwise linear regression models predicted follicle number. RESULTS: Spearman correlations are in Table 1. Neither BMI nor fasting insulin relates to 2-4.9 mm follicle number, while both are associated with fewer 5-10mm follicles and lower AMH. In the regressions, BMI was retained as a positive predictor of 2-4.9 mm follicle number, and a negative predictor of 9-10 mm follicles. TABLE 1. Spearman’s rank correlations (r) of BMI and insulin with markers of ovarian age

Age FSH AMH Testosterone Follicles 2-4.9 mm Follicles 5-8.9 mm Follicles 9-10 mm Total AFC

r with BMI

P-value

r with insulin

P-value

0.17 -0.03 -0.24 -0.09 -0.02 -0.20 -0.12 -0.11

0.0004 NS <0.0001 0.049 NS <0.0001 0.009 0.02

0.07 -0.08 -0.12 -0.04 0.05 -0.17 -0.10 -0.05

NS NS 0.01 NS NS 0.0004 0.04 NS

CONCLUSIONS: The decreased AFC seen in obese women appears to be due to decreased numbers of larger antral follicles. This decrease in larger follicles is associated with increased insulin. We propose a role for BMI and insulin in suppressing growth of antral follicles in the follicular phase. This mechanism is evident in increasing menstrual cycle length in normal women, and may contribute to anovulation in PCOS. Supported by: NIH RO1-HD044876; T32 – HD040135-06

P-51 Tuesday, October 20, 2009 THE IMPACT OF BODY MASS INDEX (BMI) ON OVARIAN STIMULATION IN YOUNG OOCYTE DONORS. I. Obeso, R. Santos, P. Galache, J. Sepulveda, P. Diaz, P. Patrizio. Centro de Fertilidad IECH, Instituto para el Estudio de la Concepcion Humana, Monterrey, Nuevo Leon, Mexico; Yale Fertility Center, New Haven, CT. OBJECTIVE: Excess weight has been associated with reduced fertility, increased gonadotropin requirements, insufficient follicle development and lower oocyte numbers and pregnancy rates. To remove potentially confounding variables due to other, non weight-related, issues, we used the oocyte donation model to assess the impact of BMI on ovarian stimulation outcome. DESIGN: A retrospective analysis from 1st January 2006 to December 2008.

FERTILITY & STERILITYÒ

Variable BMI

Normal Overweight (>18.5-24.9) (>25-29.9)

Obese (>30)

p value

Number of patients 27 23 19 Mean BMI SD 22.5 1.7 27.31.3 33.23.6 <0.01 Age  SD 25.13.4 25.63.2 25.33.2 0.86 Total dose of 2624638 3166.3634 3134.2756 <0.01 gonadotropins (IU) Estradiol day 10 3358.81966 2981.31343 30741799 0.72 Follicle > 18mm 8.13.9 7.43.9 7.055.08 0.67 Oocyte retrieved 18.410 16.529.3 12.55.7 0.08 Metaphase II 15.98.6 13.748.5 10.24.8 <0.05

CONCLUSIONS: Young donor patients with high BMI require higher total doses of gonadotropins and produce fewer total and mature oocytes. Overweight and obese patients may reduce the rate of success and increase the cost of oocyte donation programs. Prior to being accepted as oocyte donors, overweight and obese should be screened.

P-52 Tuesday, October 20, 2009 THE IMPACT OF OBESITY ON IMPLANTATION RATES AND THE OUTCOMES OF FIRST TRIMESTER PREGNANCIES AFTER ASSISTED REPRODUCTIVE TREATMENT. V. Seneclauze-Seguin, P. Olivier, O. Jeanine, W. Christiane, N. Israe¨l. Department of Obstetrics and Gynecology, University of Medicine, Strasbourg, Alsace, France; Department of Obstetrics and Gynecology, University of Medicine, Strasbourg, Alsace, France; Department of Obstetrics and Gynecology, University of Medicine, Strasbourg, Alsace, France; ART Unit CMCO, Schiltigheim, Alsace, France; Department of Obstetrics and Gynecology, University of Medicine, Strasbourg, Alsace, France. OBJECTIVE: Given the constant increase in requests for management of obese patients, our aim was to evaluate the chances for success of IVF/ICSI attempts. The elements taken into account were Body Mass Index (BMI) and ‘‘initial prognosis’’, based on the association of age and FSH concentrations on the 3rd day of the patients’ cycles. DESIGN: Retrospective study looking at all first attempts at IVF/ICSI made between January 2006 and June 2008. MATERIALS AND METHODS: The population was divided into 5 BMI groups (kg/m2): A (BMI<20), B (20%BMI<25), C (25%BMI<30), D (30%BMI<35) and E (BMIR35). Observation of the results, first in the general population and then in three other populations: good responders (age<38 years AND FSH< 10 UI/l), poor responders (ageR 38 years OR FSHR 10 UI/l) and very poor responders (ageR 38 years AND FSHR 10 UI/l). RESULTS: 831 cycles of IVF/ICSI with embryo transfer were included: 571 were in good responders, 232 poor responders and 28 very poor responders. Obese patients represented 10.65% of the total population, with 56 patients in group D and 31 patients in group E. The best results in terms of clinical pregnancy in the general population were obtained with the long agonist protocol in patients with a BMI<25. In the good responders population, the highest implantation failure rates were observed in patients whose BMI>30. However, the number of early spontaneous miscarriages was no higher in the obese patients. No pregnancy was obtained from 14 attempts in the patients with morbid obesity (BMIR35). Only 2 pregnancies were obtained in the very poor responders population: both with an antagonist protocol in patients whose BMI<30 and both ended with a spontaneous miscarriage at 8 and 10 weeks of amenorrhoea.

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