Luteinizing hormone pulsatility in vervet monkeys (chlorocebus aethiops): normative data for modeling the impact of body mass on pituitary function

mineral density (BMD) in hypoestrogenic women in the reproductive age range. There are currently no data to determine whether bone protection in these younger women is better with HRT or OC use. DESIGN: A prospective randomized controlled trial. MATERIALS AND METHODS: One hundred women aged 20-45 years with chronic hypoestrogenism due to various medical problems were randomized to either standard dose oral contraception (ethinyl estradiol 0.03 mg, levonorgestrel 0.15 mg for 21 days with 7 lactose tablets) or standard dose hormone replacement therapy (oestradiol 2 mg daily for 14 days, oestradiol 2 mg plus dydrogesterone 10 mg daily for 14 days) for a minimum of 12 months. The primary outcome marker was the change in BMD. The secondary outcome marker was the change in biochemical markers of bone turnover. RESULTS: These data are from 76 of the 100 women recruited into the study. Over only a 12 month period of treatment, increases in BMD were greater in all areas of the lumbar sprine and hip in the HRT group compared with the OC group. The differences were statistically significant at L2 (P<0.01), L3 (P<0.001), L4 (P<0.01) and for total spine (P<0.01). Whilst the trend was the same for all areas of the hip, the changes were not statistically significant. Biochemical markers can not be run until all 100 subjects have completed the study. CONCLUSION: In both the hip and lumbar spine, women on HRT showed improvement in BMD compared with those on an OC in only 12 months of treatment. We keenly await the final BMD measurements and the results of bone markers. If the above findings are confirmed, then we may need to rethink our plan to extend the study. These findings are of great significance to a huge number of hypoestrogenic women currently using either an OC or HRT to prevent osteoporosis. Supported by: This study was supported by a Direct Grant for Research. P-293 Tuesday, October 23, 2012 LUTEINIZING HORMONE PULSATILITY IN VERVET MONKEYS (CHLOROCEBUS AETHIOPS): NORMATIVE DATA FOR MODELING THE IMPACT OF BODY MASS ON PITUITARY FUNCTION. S. M. Stephens,a K.-Y. F. Pau,b T. M. Yalcinkaya,c S. L. Berga,c S. E. Appt,d A. J. Polotsky.a aReproductive Endocrinology, University of Colorado Denver, Aurora, CO; bOregon National Primate Research Center, Beaverton, OR; cObstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC; dPathology/Comparative Medicine, Wake Forest School of Medicine and Primate Center, WinstonSalem, NC. OBJECTIVE: Reduced LH pulse amplitude is linked to obesity-related subfertility in ovulatory women. Vervet monkeys develop obesity and have a 28-30 day menstrual cycle. We sought to obtain normative data on vervet LH pulses. DESIGN: Prospective. MATERIALS AND METHODS: 12 sexually mature and normal weight monkeys (4.90.8 kg) were followed with daily vaginal swabs to document menses. Ovulation was confirmed by luteectomy in the cycle under study. Serum was collected remotely q10 min for 4h by a tether device in conscious, freely moving females on CD 3-6. Monkey LH RIA was done using a NHPP kit. Follicular phase daily serum estradiol (E2) was assayed by chemiluminescence, Immulite 1000. The day of low (<100pg/ml) E2 after the midcycle peak was used as luteal day#1. For comparison, we used data from 12 ovulatory women (BMI 20.80.5kg/m2) who had LH drawn q15 min on CD 2-7. Human LH was assayed by immunofluorometry, DELFIA. 8 am study start & pulse analysis method were identical in all monkeys and women. To account for different assays,% increase from baseline was calculated. RESULTS: Normal vervet % body fat was confirmed by DXA with a mean of 16.44.1%. Each monkey had LH pulses; mean pulse amplitude of 0.220.05 ng/ml, and mean LH of 0.260.05 ng/ml. Vervet peak E2 of 487304 pg/ml occurred on CD 14.73.0 (menstrual cycle length 30.04.1 days). LH Parameters in Vervets and Women

Parameter Number of LH pulses/4 hrs LH pulse mass, % increase from baseline

Vervets

Women

P value

2.8 (0.7) 123.2 (27.4)

2.3 (0.7) 60.9 (14.9)

0.43 <0.01

Data presented as mean (st. dev).

FERTILITY & STERILITYÒ

CONCLUSION: To the best of our knowledge, this is the first report of LH pulse analysis in vervets. Follicular phase LH patterns are similar to humans and the luteal phase is easily timed by daily serum E2. Although the absolute increase for LH pulse amplitude appeared to be greater for vervets than for women, this is a suitable platform to follow LH pulse dynamics longitudinally in studies of diet-induced obesity. Supported by: SEA & AJP contributed equally See disclosures for grant support. P-294 Tuesday, October 23, 2012 CHANCES OF PREGNANCY AT EXTREME OF AGE: DOES ANTIMULLERIAN HORMONE (AMH) MATTER? A. Aelion Brauer, E. Mok-Lin, L. Meyer, S. D. Spandorfer, Z. Rosenwaks. Ronald O Perelman and Claudia Cohen Center for Reproductive Medicine/Weill Cornell Medical College, New York, NY. OBJECTIVE: To determine whether womenR43 years of age demonstrate live birth potential with autologous in vitro fertilization (IVF) and whether such potential can be enhanced by having normal AMH levels. DESIGN: Retrospective analysis. MATERIALS AND METHODS: All patientsR43 years of age who underwent IVF treatment between 1/2009 and 12/2011 with a documented AMH were included. Patients with severe male factor or an abnormal uterine cavity were excluded. The primary outcome was live birth rate. Secondary outcomes included cancellation rate, number of oocytes retrieved, mature oocytes, oocytes fertilized, implantation rate, and total pregnancy rate. Kruskal-Wallis and chi squared tests were used in analyses. P<0.05 was considered statistically significant. RESULTS: 191 patients undergoing 266 cycles of IVF met inclusion criteria. Results are shown in Table 1. CONCLUSION: PatientsR43 years of age can still achieve live birth, albeit at a very low rate. While chronologically older patients with a normal AMH did have a better response to stimulation, were able to have more embryos transferred and had a higher total pregnancy rate, live birth rates were not significantly enhanced. PatientsR43 with undetectable AMH did not have a chance of delivery in this preliminary work. P-295 Tuesday, October 23, 2012 FALLING HUMAN CHORIONIC GONADOTROPIN (hCG) CURVES IN PREGNANCIES OF UNKNOWN LOCATION: DEFINING THE WINDOW OF CONCERN. K. E. Dillon,a M. Sammel,a S. Senapati,a P. Takacs,b K. Chung,c K. T. Barnhart.a aObstetrics and Gynecology, University of Pennslyvania School of Medicine, Philadelphia, PA; bObstetrics and Gynecology, University of Miami School of Medicine, Miami, FL; cObstetrics and Gynecology, University of Southern California, Los Angeles, CA.

Cycle Characteristics and Outcomes

N Age AMH BMI Prior attempts % Cancelled Oocytes retrieved Mature 2PN Embryos per ET* Implantation rate Total pregnancies (%/cycle) Clinical pregnancies (%/cycle) Live Birth/Ongoing (%/cycle)

AMH<0.2

AMH 0.2-0.79

AMH 0.8-10

P-value

39 44.191.26 0.140.04 23.373.19 1.191.52 43.59 3.501.85 2.861.64 2.27+1.52 2.321.29 1.325.74 2(5.13)

165 43.760.95 .38.16 23.816.64 2.713.34 33.33 5.923.88 4.553.07 3.17+2.36 3.221.59 4.7913.45 25(15.15)

62 43.610.79 1.771.18 25.145.14 1.92.23 3.22 11.595.25 9.564.57 7.19+3.74 4.291.49 2.8410.39 14(22.58)

NS 0.0001 NS 0.045 0.0001 0.0001 0.0001 0.0001 0.0001 NS 0.008

2(5.13)

13(7.88)

6(9.68)

NS

0

7(4.24)

4(6.45)

NS

* Embryo transfer (ET).

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