Repetitive ovarian reserve testing as a measure of natural fecundability

OVARIAN RESERVE P-305 Wednesday, October 19, 2011 THE EFFECT OF DIMINISHED OOCYTE RESERVE IN YOUNGER WOMEN (AGE %37) ON PREGNANCY RATES IN NATURAL CYCLES. J. H. Check, J. Liss. UMDNJ, Robert Wood Johnson Med. School at Camden, Cooper Hosp./Univ. Med Cntr., Dept. OB/GYN, Div. Repro. Endo. & Infertility, Marlton, NJ. OBJECTIVE: The objective of the present study was to determine the degree of adverse effect that a diminished oocyte reserve has on conception rate in natural cycles. DESIGN: Matched controlled study. MATERIALS AND METHODS: Women aged <37 with a day 3 serum follicle stimulating hormone (FSH) >15 mIU/mL were identified. If the semen analysis was suitable for intercourse or intrauterine insemination (IUI) and if the fallopian tubes were patent they were included in the study. Also required was to form a mature follicle with or without mild FSH stimulation. They were then matched to the next woman seeking infertility treatment with a serum FSH <8 mIU/mL who also met the same criteria. Only those matched pairs where they were both given at least 3 natural cycles of treatment were included. The goal of treatment was to attain a mature follicle of >18mm with a serum estradiol >200 pg/mL demonstrating a normal post-coital test or had IUI, would show oocyte release by ultrasound or were given therapy, e.g., human chorionic gonadotropin to achieve oocyte release and were given vaginal progesterone in the luteal phase. RESULTS: There were 24 women in both groups. For the high FSH group there were 10 (41.6%) clinical pregnancies (ultrasound evidence at 8 weeks) vs. 17 (70.8%) for those with normal FSH (P¼.08, chi-square analysis). The 10 pregnancies in the high FSH group took an average of 3.1 cycles to achieve vs. 3.2 cycles for those with normal FSH. There were two first trimester spontaneous abortions in both groups so the live delivery rates were 33.3% for the group with diminished oocyte reserve vs. 62.5% for normal ovarian reserve (P¼.08, Fisher’s exact test). CONCLUSION: Live delivery rates were almost twice as high in natural cycles in women with normal vs. marked depleted oocyte reserve. Nevertheless, this study shows that a reasonable pregnancy rate is seen even with natural cycles in women with marked diminished oocyte reserve.

P-306 Wednesday, October 19, 2011 ANTI MULLERIAN HORMONE SERUM LEVELS AND REPRODUCTIVE OUTCOME ARE NOT AFFECTED BY METHOTREXATE OR LAPAROSCOPIC SALPINGECTOMY FOR THE TREATMENT OF ECTOPIC PREGNANCY IN IVF PATIENTS. T. Singer, J. Kofinas, J. Huang, R. Elias, H.-C. Liu, G. L. Schattman, Z. Rosenwaks. The Center for Reproductive Medicine and Infertility, New York, NY; The Ronald O. Perelman & Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY. OBJECTIVE: To evaluate whether different treatment modalities for ectopic pregnancy (EP), namely Methotrexate (MTX) administration or laparoscopic salpingectomy, affects Anti Mullerian hormone (AMH) levels and reproductive outcome in women undergoing IVF. DESIGN: Retrospective study. SETTING: Academic medical center-based IVF practice MATERIALS AND METHODS: Thirty five women(age 26-44) diagnosed with EP between 1/08-12/10 following IVF were included in the study. 29 women were treated with MTX(1 mg/kg IM) and 6 treated surgically. Serum AMH levels were measured prior to the IVF which resulted in ectopic pregnancy and 2-8 months following the EP treatment. AMH levels, rate of tubal infertility, number of oocytes retrieved, number of mature oocytes, number of embryos transferred (ET), pregnancy outcome and gestational age (GA) at time the EP was treated were recorded. RESULTS: Patients’ age, BMI, tubal infertility, ET and GA did not differ between the 2 groups. AMH levels before and after EP treatment were similar in both the MTX group (2.32  1.94ng/mL before Vs. 2.04  1.56ng/mL after) and the surgery group (2.49  1.44ng/mL before Vs. 2.19  1.7ng/mL after). Time interval between serum AMH levels in the MTX group was longer by 6 weeks due to the time required to achieve negative serum bhcg. In the patients undergoing subsequent IVF treatment following the resolution of their EP, no differences in reproductive outcomes were seen.

FERTILITY & STERILITYÒ

MTX (29)

Surgery (6)

P

Age 37 35.6 0.3 BMI 25.3 23 0.78 Tubal factor% 14 17 0.73 AFC 11.5 12.1 0.82 #Oocytes 13.9 19.2 0.11 ET 3.1 3 0.44 Max HCG levels 2558 2347 0.59 GA (wks) 5.8 5.8 0.58 Repeat AMH (wks) 16.5 10 0.02 Pregnancy following 55 50 0.74 EP% Pre-EP Post-EP(18)p Pre-EP Post-EP(4)p #Oocyte 13.5 12.1 0.33 16.8 11 0.69 Mature oocytes 10.3 10.4 0.74 13 8.5 0.4 ET 3.5 3.8 0.58 3.3 3.5 0.99 AMH(ng/mL) 2.3 2 0.58 2.5 2.2 0.49

CONCLUSION: Single-dose MTX is a safe first line treatment for EP and does not seem to decrease AMH serum levels or affect the reproductive outcome in women undergoing subsequent IVF treatment Supported by: Institutional

P-307 Wednesday, October 19, 2011 THE ASSOCIATION OF URINARY PARABEN CONCENTRATIONS WITH MEASURES OF OVARIAN RESERVE AMONG PATIENTS FROM A FERTILITY CENTER. K. W. Smith, I. Dimitriadis, S. Ehrlich, J. Ford, K. F. Berry, I. Souter. Environmental Health, Harvard School of Public Health, Boston, MA; Obstetrics, Gynecology & Reproductive Biology, Massachusetts General Hospital - Harvard Medical School, Boston, MA; Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA. OBJECTIVE: Investigate the relationship of urinary paraben concentrations with measures of ovarian reserve. Parabens are preservatives with widespread exposure among the US population and in experimental studies are weakly estrogenic. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Female patients from a fertility center were included. Serum follicle stimulating hormone (FSH) was measured on day 3 of the menstrual cycle. Antral follicle count (AFC) and ovarian volume (OV) were measured by transvaginal ultrasound. Data from 182 women was analyzed and the number varied per outcome: FSH (102), AFC (135), and OV (102). Urine samples (mean 2.2 per woman collected 0 to 38 months before outcome) were analyzed for methyl- (MP), propyl- (PP), and butylparaben (BP) using on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry. Linear and Poisson regression were used to analyze the association of specific-gravity (SG) adjusted parabens with measures of ovarian reserve, adjusted for age. RESULTS: Mean values for day 3 FSH, AFC, and OV were 7.5  3.3 IU/ L, 12.3  7.0, and 5598  2931 mm3, respectively. SG-paraben levels ranged from 7.70-3641 mg/L (MP), 0.48-1091 mg/L (PP), 0.12-265 mg/L (BP). Higher PP was positively related to day 3 FSH (p, trend ¼ 0.1), with an average increase of 1.27 IU/L (P¼0.1) and 1.30 IU/L (P¼0.09) in tertiles 3 and 2, respectively, compared to the first tertile. Higher PP was negatively related to AFC (p, trend ¼ 0.05), with an average decrease of 17% (P¼0.05) and 5% (P¼0.7) in tertiles 3 and 2, respectively, compared to the first tertile. After excluding patients with ovulatory disorders the relationship was attenuated. There was no evidence of an association of MP or BP with day 3 FSH, AFC, or OV, or PP with OV. CONCLUSION: There was suggestive evidence for an association between PP and higher day 3 FSH, and lower AFC. Supported by: Grants ES009718, ES000002, and 2T32ES7069-31.

P-308 Wednesday, October 19, 2011 REPETITIVE OVARIAN RESERVE TESTING AS A MEASURE OF NATURAL FECUNDABILITY. A. Z. Steiner, D. L. Long, A. H. Herring. Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC; Biostatistics, University of North Carolina, Chapel Hill, NC. OBJECTIVE: Early follicular phase, urinary follicle stimulating hormone (FSH) is used as a measure of ovarian reserve and considered a potential

S197

fertility test. We sought to determine the value of repetitive urinary FSH testing in the prediction of natural fecundability. DESIGN: Prospective time-to pregnancy study. MATERIALS AND METHODS: Women (N ¼ 94), 30-44 years old, with no history of infertility, who had been trying to conceive for less than 3 months, were asked to provide early follicular phase urine in each menstrual cycle while trying to conceive. Women were followed until pregnancy or 6 months. Urine was analyzed for FSH and levels creatinine-corrected. Cox models were used to calculate fecundability ratios for the initial FSH value (first cycle of enrollment) and the maximum FSH value (over all enrollment cycles), adjusting for age and body mass index. RESULTS: Presented in table below.

Fecundability Ratio for Initial Urinary FSH Value* Creatinine-corrected Urinary FSH <7 mIU/mg cr 7-12 mIU/mg cr >12 mIU/mg cr R11.5 mIU/mg cr vs.<11.5 mIU/mg cr£

Fecundability Ratio for Maximum Urinary FSH Value*

Unadjusted

Adjusted

Unadjusted

Adjusted

0.43 (0.21, 0.89) Reference 0.42 (0.17, 1.00) 0.70 (0.32, 1.5)

0.43 (0.21, 0.89) Reference 0.45 (0.18, 1.13) 0.72 (0.32, 1.6)

0.32 (0.14, 0.72) Reference 0.44 (0.19, 1.01) 0.89 (0.39, 2.02)

0.31 (0.14, 0.72) Reference 0.47 (0.19, 1.13) 0.91 (0.38, 2.21)

Results presented as fecundability ratio (95% confidence limits); £ Cut-off equivalent to 10mIU/ml serum FSH *

CONCLUSION: A single, elevated or low, early follicular phase, urinary FSH value appears to be a negative predictor of natural fecundability. Repetitive testing does not appear to strengthen the association between this measure of diminished ovarian reserve and reduced natural fecundability. Supported by: NIH R21 HD0602295 and K12 HD050113 (UNC WRHR)

P-309 Wednesday, October 19, 2011 FERTILITY-RELATED STRESS IN WOMEN WITH DIMINISHED OVARIAN RESERVE UNDERGOING FRAGILE X GENETIC TESTING. A. K. Schutt, L. M. Pastore. Obstetrics and Gynecology, University of Virginia, Charlottesville, VA. OBJECTIVE: Diminished ovarian reserve (DOR) is associated with significant patient stress, as there are few known causes and no treatments for this ovarian condition. This is the first attempt to analyze if the stress in DOR patients differs significantly from the general patient being evaluated for infertility. Additionally, this study attempts to identify risk factors for fertility stress in this population. DESIGN: Cross-sectional study. MATERIALS AND METHODS: 50 women diagnosed with DOR completed the fertility problem inventory (FPI) and underwent fragile X premutation testing. FPI scores were compared to other infertility cohorts. The association between FPI score and various covariates was analyzed using nonparametric tests and correlation statistics. RESULTS: The average age at diagnosis was 37.7 years, and 69% had previously achieved pregnancy. The overall global FPI score for this DOR cohort was 138.6 (SD ¼ 35.0) and did not differ significantly from the FPI validation data (mean score for global stress 134.4) or other general infertility patient groups (Peterson 2006, Slade 2007). The subscale scores were also similar to previous cohorts. There was no significant difference in global FPI score based on age at diagnosis (P¼0.32), race (P¼0.31), or previous pregnancy (P¼0.71). There was a positive association with anger at not learning earlier about fragile X potentially being related to their infertility (P¼0.018, R ¼ 0.35), but no association with regret at not having learned about fragile X earlier in their fertility attempts (P¼0.13). CONCLUSION: The results suggest that perceived infertility-related stress is similar in DOR patients as general infertility patients, and the stress was unrelated to selected demographic/reproductive history variables. Further analysis will be conducted on the potential relationship between fertility stress, their perception of fragile X and their self-esteem. Supported by: National Institutes of Health R03 HD052768

S198

Abstracts

P-310 Wednesday, October 19, 2011 COMPARISON OF AGE-SPECIFIC SERUM ANTIMULLERIAN HORMONE CONCENTRATIONS BETWEEN YOUNG INFERTILE WOMEN AND OOCYTE DONORS. M. Bustillo, C. Goodman, J. Cortes, S. Merchant, C. B. Coulam. South Florida Institute for Reproductive Medicine, Miami, FL; Reproductive Medicine Institute, Evanston, IL; Unilab, Fort Lauderdale, FL. OBJECTIVE: To compare results of antimullerian hormone (AMH) concentrations among regularly menstruating infertile women ages 22 to 32 years with those of oocyte donors of the same age. DESIGN: Observational cohort study. MATERIALS AND METHODS: 90 infertile women and 31 oocyte donors aged 22-32 years with a history of regular menses had blood drawn for determination of AMH concentration. Serum AMH was measured by enzyme-linked immunosorbent assay using an AMH ELISA kit (Beckman Coulter, Chaska, MN, USA). RESULTS: Linear regression analysis revealed a significant association between age and AMH concentrations for both infertile women and oocyte donors (P< 0.001). In addition, Dunn’s Multiple comparison test confirmed a significant difference between AMH serum concentrations among infertile women and oocyte donors when age matched between 22 and 32 years (P<0.05). CONCLUSION: Some infertile women even those between the ages of 22 and 32 years have lower serum AMH concentrations than age-matched oocyte donors.

P-311 Wednesday, October 19, 2011 BMI INFLUENCES THE IMPACT OF ORAL CONTRACEPTIVE PILLS AND GNRH AGONISTS ON ANTRAL FOLLICLE COUNT (AFC) OVARIAN RESERVE SCREENS. A. K. Parker, N. Grindler, E. S. Jungheim, R. R. Odem, V. S. Ratts, A. R. Cooper. Obstetrics & Gynecology, Division of Reproductive Endocrinology & Infertility, Washington University, St. Louis, MO. OBJECTIVE: AFC is a popular ovarian reserve screen and predictor of response to gonadotropin stimulation. Yet, data regarding the impact of suppressive medications commonly used prior to in vitro fertilization (IVF) cycles and the influence of obesity on AFC, are scarce. Our aim was to compare AFC in women who underwent both controlled ovarian hyperstimulation (COH)/IUI cycles and then subsequent IVF cycles to determine the effect of ovarian suppression on AFC in obese and nonobese women. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Women who underwent both COH and IVF cycles <15 months apart were identified. Mean COH AFC (sum of bilateral 2-10mm follicles on transvaginal US, cycle day 2-4) was compared to each IVF AFC depending on uses of oral contraceptives (OCP) (21-35 days prior to IVF start), midluteal GnRH agonist (cycle day 21 or 4 day OCP overlap start), and obesity (BMI <30 or >30). Paired t-tests were done using SPSS. RESULTS: 88 IVF cycles (mean 4.6  1.7 months from COH) from 51 patients were included. Mean age was 33.7  4.7 yrs and BMI 28.3  7.3 (range 18.9-46.5). COH and IVF AFC in individual women are highly correlated (r ¼ 0.85; P<0.001). In the entire cohort, AFC measures were not impacted by midluteal GnRH (N ¼ 56, mean AFC 23  18 COH vs 24  16 IVF; P¼0.34), OCP use (N ¼ 36, 23  14 vs 24  14; P¼0.52) or a combination of both (N ¼ 27, 26  14 vs 28  14; P¼0.45), nor in the nonobese (P¼0.96, 0.81 & 0.78 respectively). In the obese, AFC was higher after midluteal GnRH agonist (N ¼ 21, 18  7 vs 21  10; P¼0.01) and combination of OCP and GnRH agonist (N ¼ 10, 22  7 vs 28  10; P¼0.015). CONCLUSION: Baseline AFC at IVF start is highly correlated to previous COH AFC measures and is not impacted by OCP or GnRH agonist use prior to IVF start in the nonobese. However, use of suppressive medications in the obese increases AFC during IVF, potentially by AFC cohort synchrony. The clinical significance of such warrants further research. Supported by: K12HD063086-01 (ARC)

P-312 Wednesday, October 19, 2011 THE ROLE OF ANTI-MULLERIAN HORMONE MEASUREMENT IN THE PREDICTION OF RESPONSE TO CONTROLLED OVARIAN STIMULATION: COMPARISON WITH THE ANTRAL FOLLICLE COUNT. T. Habara, R. Hirata, Y. Aoi, S. Terada, N. Yoshioka, N. Hayashi. Infertility, Okayama Couple’s Clinic, Okayama, Japan. OBJECTIVE: Anti-M€ullerian hormone (AMH) is a marker of ovarian reserve. We assessed the value of AMH as a test for predicting response to

Vol. 96., No. 3, Supplement, September 2011