The effect of serum inhibin B measurement for predicting ovarian reserve and treatment options in assisted reproduction

were either retrieved with no gonadotropins in the follicular phase (natural) or at most 150 IU FSH beginning day 5. Generally FSH was not added unless the serum FSH was <10 mIU/mL. Sometimes the FSH was brought down naturally by the rise in serum estradiol (E2) by the developing follicles and sometimes by exogenous use of ethinyl estradiol. No more than three embryos were transferred but these data included women with single embryo transfers. Embryos were transferred on day 3. No one in this group purposely chose a single embryo to be transferred. RESULTS: There were 93 transfers with a single embryo, 120 transfers with 2 embryos and 102 transfers with 3 embryos. The clinical PR per transfer for 3 embryos transferred was 24.5% (25/102) and the delivered PR per transfer was 17.6% (18/102). With two embryos transferred the clinical PR was 20.8% (25/120) and the delivered PR was 16.6% (20/120). Pregnancies were also achieved by women having single embryo transfer with a clinical pregnancy rate of 9.7% (9/93) and a live delivery rate of 6.5% (6/93) (P<.05 comparing single embryo transfers to 2 or 3). CONCLUSIONS: Obviously the use of donor oocytes would significantly improve the live delivery rate in this group of women. Nevertheless, these data can be presented to the couple and if they are willing to undergo the IVF procedure for these odds of success then they should be given the opportunity to proceed. We believe this is the largest series to date evaluating pregnancy outcome in women in this age group with elevated day 3 serum FSH. Supported by: None.

P-520 THE EFFECT OF AGE ON PREGNANCY RATES FOLLOWING IN VITRO FERTILIZATION-EMBRYO TRANSFER (IVF-ET) IN WOMEN WITH ELEVATED DAY 3 SERUM FOLLICLE STIMULATING HORMONE. B. Katsoff, J. H. Check, J. K. Choe, C. Wilson, J. Amui. Dept. OB/GYN, UMDNJ, Robert Wood Johnson Med. School at Camden, Camden, NJ. OBJECTIVE: To compare the pregnancy and implantation rates in women aged %35 vs. those 36–39 who have elevated day 3 serum follicle stimulating hormone (FSH). DESIGN: Previous studies in non-IVF cycles showed that advancing age has more of a negative impact on achieving a successful pregnancy than an elevated day 3 serum FSH. This retrospective IVF study was initiated to see if women in their mid to late 30’s with elevated day 3 serum FSH have a lower chance of successful conception than women in their early 30’s. MATERIALS AND METHODS: Women with elevated day 3 FSH (>12 mIU/mL) having IVF were treated with no more than 150 IU FSH. Sometimes minimal stimulation with 75 IU of FSH was used for a few days only when a dominant follicle was selected and some cycles were completely natural. RESULTS: The clinical (ultrasound evidence of pregnancy at 8 weeks) pregnancy rate (PR) per transfer was 47.4% (45/95), the delivered PR was 41.0% (39/95) for women aged %35 vs. 30.7% (44/143) and 25.9% (37/ 143) (P¼.014, P¼.02). The implantation rate for women %35 was 27.6% (67/242) vs. 15.6% (56/359) for women 36–39 (P¼.0005). CONCLUSIONS: These data clearly show that the presence of an elevated day 3 serum FSH should not warrant the suggestion by physician to patient that they should automatically consider the donor egg program especially in younger women. Even for women age 36–39 the PRs seemed adequate and this group should be advised that live delivery rates of about 25% are likely to occur if one does not use a high dose of gonadotropins for controlled ovarian hyperstimulation. The data do support the concept that age is more of an adverse factor than the actual day 3 FSH. Supported by: None.

P-521 VALIDATION OFAGE-SPECIFIC CUT-OFFS FOR OVARIAN FUNCTION ASSESSMENT BY FSH LEVELS VIA A SECOND PATIENT POPULATION: INHERENT DIFFERENCES IN PATIENT POPULATIONS BETWEEN IVF-CENTERS. D. Barad, N. Gleicher, A. Weghofer, S. Chen, J. Cohen. The Center for Human Reproduction, New York; The University of Vienna Medical School, Vienna, Austria; The Institute for

FERTILITY & STERILITYÒ

Reproductive Medicine and Science at Saint Barnabas, Livingston, NJ; Tyho-Galileo Research Laboratories, Livingston, NJ. OBJECTIVE: We previously reported age-specific baseline (b-) FSH to define premature ovarian aging (POA; Obstet Gyncol, in press). The objective of this analysis was to validate these b-FSH levels, previously defined at one center (Clinic 1), in a second center’s (Clinic 2) unrelated patient population. DESIGN: Cross-sectional retrospective study. MATERIALS AND METHODS: 4,117 patients from Saint Barnabas (Clinic 2) demonstrated b-FSH levels %12 mIU/mL in their first IVF cycles. Age-specific b-FSH cut off levels were calculated based on the upper 95% confidence interval (CI) for each age group. We compared the odds of producing %4 oocytes for women with b-FSH levels above these age specific levels, to women with b-FSH within the 95% CI. We repeated this analysis using age specific b-FSH cut offs previously established in the CHR (Clinic 1) patient population. RESULTS: Table 1 presents age specific b-FSH and 95% CI of the mean, as established in this study for Clinic 2 patients. Normal patients with age specific b-FSH above the 95% CI produced significantly fewer oocytes in their first retrieval (17.5 9.4 vs. 14.2 7.7, P < 0.001). Table 2 compares percent of patients above the previously defined age-specific cutoffs of CHR (Clinic 1) and St Barnabas (Clinic 2). The Clinic 2 population had twice the odds of producing %4 oocytes if b-FSH was above previously defined age-specific levels for POA (OR 2.08, 1.3 to 3.6; P < 0.01). Patients with POA at Clinic 2 had similar odds of producing %4 oocytes to those previously reported in Clinic 1 (OR 2.8, 1.52 – 5.17) but the data also suggest overall less of an ovarian function impairment among Clinic 2 patients. TABLE 1. Baseline FSH (Clinic 2)

Age

N

Mean FSH mIU/mL

<33 R33 & <38 R38 & <41 R41 total

1141 1793 806 377 4117

5.72 6.17 6.33 6.41 6.10

95% C.I. 5.58 6.06 6.15 6.16 6.03

5.86 6.29 6.50 6.65 6.18

TABLE 2. Percent of patients with POA

Age Group <33 33 to 37 38 to 40

b-FSH

Clinic 1 (%)

Clinic 2 (%)

R7.0 and <12 R7.9 and <12 R8.4 and <12

50 43 28

30 20 18

CONCLUSIONS: Previously established b-FSH levels defining POA (Obstet Gynecol; In press) are significantly associated with poor ovarian response in both populations. Differences observed in b-FSH levels between the two clinics may reflect different prevalence of impaired ovarian function in these patient populations, or may be due laboratory assay variation. These data reemphasize why IVF outcomes between different IVF centers are not comparable. Supported by: Foundation for Reproductive Medicine.

P-522 THE EFFECT OF SERUM INHIBIN B MEASUREMENT FOR PREDICTING OVARIAN RESERVE AND TREATMENT OPTIONS IN ASSISTED REPRODUCTION. R. Wu, J. Du, Y. Liao, Y. Ye, Y. Du, G. Zhuang. Center for Reproductive Medicine, Zhongshan Boai Hospital, Zhongshan, Guangdong, China; Center for Reproductive Medicine, The First Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong, China. OBJECTIVE: To investigate the evaluation of the early follicular phase serum inhibin B levels as indicator of ovarian reserve and treatment options in the field of reproductive medicine. DESIGN: Retrospective analysis. MATERIALS AND METHODS: 361 women aged 21–42 years (mean 31) with different infertility etiologies of in vitro fertilization and embryo transfer (IVF-ET) were investigated. Serum levels of follicle stimulating

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hormone (FSH), luteinizing hormone (LH) by chemiluminescent microparticle immunoassay and inhibin B by ELISA were measured in the third day of a spontaneous menstrual cycle, estradiol (E2) was measured on the day of HCG administration by the same way of FSH. Patients generally underwent gonadotrophin releasing hormone agonist down-regulation followed by exogenous gonadotrophin stimulation. These patients were classified into three groups including poor response (n ¼ 76), normal response (n ¼ 262), and over response (n ¼ 23) according to their response to ovary stimulation, which base on the number of oocytes retrieved (n % 4; 5 % n%19; n R 20). RESULTS: In three groups, inhibin B concentration, FSH level, E2 on HCG day, the number of retrieved oocytes, quality embryos, pregnancy rate, and the dosage of recombined FSH are different. In stepwise regression analysis, inhibin B and FSH, FSH/LH ratio correlate negatively (r ¼ 0.287, 0.451 respectively; P<0.05). While E2 on HCG day, the number of retrieved oocytes, quality embryos correlate positively with inhibin B serum concentrations (r ¼ 0.369, 0.454, 0.376 respectively; P<0.05). TABLE. Comparison of hormone levels, rFSH dosage and clinical results in three groups Groups

Inhibin B(pg/mL)

FSH(IU/L)

E2 on HCG Day(pg/mL)

Dosage of rFSH(IU)

No of oocytes

Pregnancy rate/cycle

TABLE 1. Correlation of antural follicle count and mean ovarian area with clinical characteristics and COH outcome parameters AFC

Age Body mass index Basal FSH Dose of gonadotropins used Serum estradiol on hCG day No. of oocytes retrieved No. of embryos transferred CES CES per transferred embryo

MOA

r

P-value

r

P-value

0.338 0.002 0.187 0.415 0.420 0.454 0.366 0.387 0.340

<0.001 NS 0.022 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

-0.277 0.060 -0.180 -0.255 0.489 0.373 0.196 0.259 0.344

0.008 NS NS 0.014 <0.001 <0.001 NS 0.013 0.001

AFC: Antral follicle count; MOA: Mean ovarian area; CES: Cumulative embryo score; r ¼ Person correlation coefficient.

TABLE 2. Comparison of clinical characteristics and outcomes of controlled ovarian hyperstimulation and IVF-ET according to mean ovarian area. P-value

Mean ovarian area (cm2)

Poor 28.2  15.6 10.2  4.7 2450.1  1408.3 3228.0  1398.0 3.3  1.4 response Normal 79.4  41.3* 7.7  4.2* 3460.9  2053.1* 2542.5  858.0* 11.8  3.5* response 99.3  69.1* 6.9  1.1* 8204.0  2574.2* 2093.3  461.3* 21.8  2.1* Over response

14.5

1

21.7

*P<0.05 vs. poor response group; 1 fresh embryo transfer was cancelled in 8.7% cycles of over response group because of ovarian hyperstimulation syndrome. CONCLUSIONS: During assisted reproductive cycles, inhibin B at baseline is associated with pregnancy, and being as strong predictive factor of ovary reverse, which is of clinic importance in the guidance of treatment options. Supported by: Zhongshan City Scientific Research Fund(2005A083).

P-523 MEAN OVARIAN AREA AS A PREDICTOR OF OVARIAN RESPONSE AND OUTCOMES OF IN VITRO FERTILIZATION AND EMBRYO TRANSFER. S. J. Ahn, S. H. Kim, J. R. Lee, C. S. Suh, Y. M. Choi, S. Y. Moon. Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea; Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, Korea. OBJECTIVE: Several studies have demonstrated the correlations between ovarian volume and ovarian response to controlled ovarian hyperstimulation (COH). However, there have been few studies about ovarian area, which is easier to measure and based on measures widely-used in routine practice. The aim of this study was to evaluate the day 3 mean ovarian area (MOA) as a predictor of ovarian responsiveness and treatment outcome in COH for IVF-ET. DESIGN: Retrospective comparative study. MATERIALS AND METHODS: A total of 151 women underwent COH for IVF-ET were included. On the day 3 of cycles, number of antral follicles (2–9 mm) and mean area of ovaries were assessed by ultrasonography. MOA was defined as the average value of areas of two ovaries, and each ovarian area was calculated by ellipsoid formula (area ¼ D1  D2  0.8) using two perpendicular diameters in the largest cross-sectional view of the ovary. Correlations were analyzed between antral follicle count (AFC), MOA, and COH outcome parameters. Then, subjects were divided into three groups with cut-off of lower and upper quartile values of or MOA, and compared differences of COH outcomes between the groups. RESULTS: Significant positive correlation was observed between MOA and AFC (r ¼ 0.634, P<0.001). Both MOA and AFC correlated significantly with age, serum estradiol level on hCG day, number of oocytes retrieved, and cumulative embryo score. Lower MOA (<2.9 cm2) was associated with poorer response and more risk of cancellation, and higher MOA (>5.2 cm2) had association with higher clinical pregnancy rate as well as lower risk of cancellation and poor response.

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Abstracts

<2.9 (n¼23)

36.1* Age (years) Body mass index (kg/m2) Basal FSH (mIU/mL) Antral follicle count Dose of gonadotropins used (amp) Serum estradiol on hCG day (pg/mL) No. of oocytes retrieved No. of embryos transferred CES CES per embryo transferred Poor response rate (%) Cancellation rate (%) Clinical pregnancy rate(%)

>5.2 (n¼23)

a

37.0  5.2 35.0  5.2 20.7  1.5 22.0  3.2 7.9  18.9 4.5  3.2 8.2  6.9 10.7  5.2 35-3  12.9 33.0-  14.2

33.5  4.8 21.3  3.3 3.1  1.2 19.0  8.3 26.4  12.0

NS 0.034 NS 0.003 NS

1162.0  1126.2 7.5  7.1 2.5  1.9 55.3  44.8 15.8  12.2 47.8 (11/23) 30.4 (7/23) 17.4 (4/23)

3914.7 <0.001 <0.001  2347.6 17.2  9.2 0.003 0.003 3.4  0.9 NS NS 0.002 87.2  22.4 NS (0.054) 28.2  10.1 0.020 <0.001 4.3 (1/23) <0.001 0.036 0 (0/23) 0.009 0.033 43.5 (10/23) NS 0.011

2.9-5.2 (n¼46)

2160.9  1353.7 11.8  8.2 3.2  1.4 70.0  37.7 20.1  10.8 13.0 (6/46) 10.9 (5/46) 17.4 (8/46)

b

c

NS NS NS NS NS NS <0.001 <0.001 0.019 NS (0.66) <0.001 0.001 NS 0.015 0.001 0.001 0.008 0.040

Mean  S.D; Amp: ampules; CES: Cumulative embryo score; Poor response: <4 oocytes retrieved. a: between mean ovarian area < 2.9 and R 2.9. b: between mean ovarian area % 5.2 and > 5.2. c: between the three groups. CONCLUSIONS: MOA could be a useful marker to predict ovarian response to COH and outcomes of IVF-ET. It seems that MOA, which is easier to measure, could be used with AFC in practice for the prediction of ovarian response and treatment outcome. Supported by: None. P-524 WITHDRAWN P-525 DO ANTI-MULLERIAN HORMONE LEVELS PREDICT OVARIAN RESERVE IN SLE PATIENTS PRESENTING FOR HEMATOPOIETIC STEM CELL TRANSPLANT? H. Browne, A. Armstrong, R. Babb, G. Illei, J. Segars, S. Pavletic. Reproductive Biology and Medicine Branch, NICHD, NIH, Bethesda, MD; NCI, NIH, Bethesda, MD. OBJECTIVE: To assess the use of anti-mullerian hormone as a predictor of ovarian function in SLE patients undergoing non-myeolabalative, autologous hematopoietic stem cell transplantation. DESIGN: Retrospective analysis from a phase II study. MATERIALS AND METHODS: Six patients with systemic lupus erythematosis (SLE), 4 with Stage IV lupus nephritis and 2 with CNS lupus, were evaluated at the NIH as part of a non-myeloablative, autologous hematopoietic stem cell transplant (HSCT) protocol for refractory disease between January 2004 and October 2006. Prior to the transplantation, all patients received a conditioning regimen of methylprednisolone, cyclophosphamide, fludarabine, and rituximab. Records were reviewed and information was abstracted for menstrual and reproductive history, the use of hormonal medications prior to HSCT, and number of cycles of cyclophosphamide. Measures

Vol. 88, Suppl 1, September 2007