Baseline and cycle day 5 inhibin-b levels are useful adjuncts in assessing ovarian reserve of women of advanced reproductive age

evaluate the relationship between embryo quality and follicular fluid hormone concentrations. Women of different ages underwent IVF treatment cycles using either the short or long protocol with a GnRH agonist (GnRH-a). Design: Retrospective study. Materials and Methods: A total of 90 patients did not have the polycystic ovary syndrome (non-PCOS), while 10 were diagnosed as PCOS. A total of 100 patients underwent IVF (36 had c-IVF; 64 had ICSI). A total of 32 patients underwent the short protocol and 66 patients were treated by the long protocol. Follicular fluid (FF) estradiol (E2), progesterone (P4), total testosterone (TTE) and androstenedione (ASG) levels were compared in the two treatment groups (short and long) according to maternal age and oocyte or embryo quality. In 58 patients, inhibin B and hCG were measured in the FF. The initially retrieved, dominant follicles were used and hormonal assay was conducted. Results: No statistically significant difference was found in the FF volume of the PCOS and non-PCOS patients; however P4 was significantly lower in the PCOS group (P⬍0.01). No statistically significant difference was found in the six hormone levels analyzed in the short and long protocol groups. No statistically significant difference was found in the two groups in which four hormone levels were analyzed. The P4 of the younger age group was significantly lower than the older age group; conversely, significantly higher TTE and ASG were present in the younger group. The P4 was increased when a higher FF volume was preset; however, the difference was not significantly different. Inhibin B tended to decrease in relation to both age and embryo quality; however, this hormone concentration tended to increase if more follicles were present. Conclusion: FF P4 in the younger group was significantly lower, and TTE and ASG were significantly higher, when compared to that of the older group. Six hormone levels assayed were not significantly different in the short and long protocol groups. Furthermore, no statistically significant difference was found in either oocyte homology or embryo quality.

P-196 Effect of different doses of hCG on IVF outcomes. Hey-Joo Kang, Zev Rosenwaks, Glenn Schattman. Cornell Univ Medical Ctr, New York, NY; Director, The Cornell Institute for Reproductive Medicine, New York, NY; The Cornell Institute for Reproductive Medicine, New York, NY. Objective: The purpose of this study was to evaluate the effect of different doses of hCG on the rates of embryo transfer and implantation success in assisted reproductive pregnancies. Design: Retrospective chart review. Setting: The Cornell Institute for Reproductive Medicine. Materials and Methods: Two hundred forty-seven infertile couples utilizing a full luteal Lupron down-regulation undergoing IVF over a 6 month time period from January 2001 through June, 2001 were included. All patients underwent equivalent down-regulation with a GnRH analogue followed by stimulation with a mixed protocol of human menopausal gonadotropin and/or FSH. Ovulation was triggered by the administration of 3300, 4000, 5000, or 10,000 IU of hCG based on monitored estradiol levels on the day of hCG. Primary endpoints were the number of oocytes, E2/ oocyte, E2/mature oocyte, and fertilization rate. Secondary endpoints were number of embryos transferred and implantation rate. Results: There was no difference in average maternal age for each hCG group. The number of oocytes retrieved for each group using 3,300, 4000, 5000, or 10,000IU were 17.39, 15.23, 13.41, and 10.72, respectively (p⬍0.05). E2/oocyte values were as follows: 193, 191, 156, 127 (p⬍0.05). E2/mature oocyte with increasing hCG dose: 238, 240, 216, and 155 (p⬍0.05). There was a difference in fertilization rate in the group receiving 4,000 IU vs. 10,000 IU of hCG: 64% vs 73% respectively (p⫽0.04). There was no difference in fertilization rates in the 3,300 or 5,000 IU groups compared to the group recieving 10,000 IU (73%, 68%, 73% respectively). The average number of embryos transferred was not significantly different when using the different doses of hCG (3.30, 2.81, 2.86, 3.10 respectively). There was no difference in implantation rates with different hCG doses: 40.5%, 20.7%, 29.0%, 31.7% (p⫽0.76). Conclusion: The utilization of different doses of hCG to trigger ovulation does not negatively impact upon oocyte maturation or implantation rates. Using less hCG to trigger ovulation may decrease the risk of life-threatening ovarian hyperstimulation in patients at risk for this complication without affecting oocyte/embryo quality and outcome in IVF.

FERTILITY & STERILITY威

ART: OVARIAN STIMULATION OF ABNORMAL RESPONDERS P-197 A four-year study of clomiphene citrate challenge test results. Jennifer W. Miller, George A. Hill, Christine M. Whitworth, Glenn A. Weitzman, Abby C. Eblen, Melanie R. Freeman. Nashville Fertility Ctr, Nashville, TN. Objective: The aim of this study was to review our clomiphene citrate challenge test (CCCT) results to determine whether borderline or abnormal test results are an adequate basis for denying admittance into an In Vitro Fertilization (IVF) program. Design: A retrospective study of 84 patients, excluding donor egg and donor embryo recipients, having had a CCCT and having undergone one or more IVF cycles between 1997 and 2001. Materials and Methods: CCCT was performed according to the following clinic guidelines: 1) Serum Estradiol and follicle stimulating hormone (FSH) levels were obtained on the third day of menses. 2) On cycle day five Clomiphene Citrate (100mg) was administered daily for a total of five days. 3) On cycle day 10 another serum FSH level was obtained. Serum Estradiol and FSH levels were determined by Enzyme-linked fluorescent immunoassay (ELFA). An abnormal CCCT was defined as a FSH level above 10.0 mIu/ml on day three or day 10 and/or an Estradiol level greater than 60 pg/ml on day three. The test results were reviewed for each patient and compared to the number of eggs retrieved and the outcome of each cycle. Results: Eighty-four patients undergoing 114 IVF cycles were divided into two groups, normal CCCT and abnormal CCCT, and compared to establish a correlation between the test result and achieving a pregnancy with IVF. No significant difference was noted between the abnormal and normal CCCT groups for patients’ age (35, range 27-44 vs. 34, range 27-44), or average number of oocytes retrieved (10.6 vs 10.8). Five of the cycles were cancelled due to poor stimulation. Two of the five had a normal CCCT and three had an abnormal test. Sixty-four retrievals were performed in the abnormal group with 32 (50%) achieving a positive serum pregnancy test, 27 (42%) having at least one gestational sac, and 20 (31%) having a live birth. Patients with an abnormal result achieving pregnancy included FSH levels on day three and day 10 ranging from 1.0-25.8 mIu/ml and Estradiol levels on day three ranging from 10-282 pg/ml. It is interesting to note that ten of the 12 patients (83%), who had a positive serum pregnancy test but did not deliver, failed the Estradiol portion of the CCCT. Fifteen of the 32 (47%) who had negative serum pregnancy tests also failed the Estradiol portion of the test. The normal CCCT group consisted of 44 retrievals with 19 (43%) achieving a positive serum pregnancy test, 16 (36%) having at least one gestational sac, and 13 (29%) having a live birth. Chi square and T-test analysis does not show this data to be significantly different. Conclusion: The clomiphene citrate challenge test, when used with other deciding factors such as microfollicle count, previous stimulation response, etc., can be a useful tool in patient education in IVF cycles. Used alone the CCCT is not a desirable selection criteria for denying admittance into an IVF program. Despite indications of diminished ovarian reserve, fifty percent of the abnormal CCCT patient group achieved positive serum pregnancy levels. There does appear to be a correlation between patients who fail the Estradiol portion of the test and increased rate of miscarriage. P-198 Baseline and cycle day 5 inhibin-b levels are useful adjuncts in assessing ovarian reserve of women of advanced reproductive age. Jane Ruman, Michel Ferin, Melvin H. Thornton II, Joseph E. Pen˜ a, Suzanne M. Kavic, Mark V. Sauer. Columbia Univ Coll of Physicians & Surgeons, New York, NY. Objective: Women aged 40 and older often have normal baseline concentrations of follicle stimulating hormone (FSH) and estradiol (E2), but nonetheless respond poorly to gonadotropin stimulation. We investigated the ability of both baseline and COH cycle day 5 inhibin-B levels to further predict ovarian response and cycle outcome in women ⱖ 40 years old. Design: A retrospective analysis. Materials and Methods: Seventy-five patients aged 40 to 45 years, underwent 103 IVF cycles using a GnRH antagonist for prevention of LH surge. Briefly, patients with normal baseline ultrasound, FSH ⱕ 15 IU/L

S187

and E2 ⱕ 80 pg/mL on day 2 of their menstrual cycle began stimulation with recombinant FSH or human menopausal gonadotropins. GnRH antagonists were given when the lead follicles were ⱖ 14mm or E2 ⱖ 400 pg/mL. HCG was administered when a minimum of 3 follicles were ⬎ 18 mm and E2 levels ⬎ 600 pg/mL, followed by oocyte retrieval 35 hours later. Cycles were cancelled if there were ⬍ 3 follicles with E2 ⬍ 500 pg/mL after 8 days of stimulation. Embryo transfer (ET) was performed on day 3. Serum samples collected at the time of baseline evaluation and after 4 days of gonadotropin stimulation were assayed in duplicate using an inhibin-B ELISA (Serotec, UK). Assay results were used to divide patients into four groups based on median inhibin values (baseline ⱕ 55 pg/mL vs. ⬎ 55 pg/mL, and day 5 ⱕ 300 pg/mL vs. ⬎ 300 pg/mL). Groups were then compared by age, baseline FSH and E2, oocyte number retrieved, number and quality of embryos transferred, and cycle pregnancy result. Statistical analysis was performed using Student’s t-test to compare means ⫾ SEM between groups. Results: Of 103 cycles, 64 (62.1%) were retrieved, and 39 (37.9%) were cancelled due to poor response. The overall clinical pregnancy rate per ET was 21.3% (13/61), with an ongoing pregnancy rate of 13.1% (8/61). Baseline inhibin and cycle day 5 levels ranged from 15 to 256 pg/mL, and 15 to 2500 pg/mL, respectively. Baseline inhibin levels ⱕ 55 pg/mL and day 5 inhibin levels ⱕ 300 pg/mL were associated with significantly higher cancellation rates, and extremely low pregnancy rates (see table). There was no statistical difference detected amongst groups in age, baseline E2, number of oocytes, and embryo number and quality. Cycle results according to inhibin-B levels.

serum FSH and/or inhibin B levels (n⫽47) or repeated embryo implantation failures (REIF) defined as ⫽10 embryos transferred (n⫽19). Patients were offered up to 3 IVF-ET using naturally-selected dominant follicle cycles. Treatment was scheduled as follows: from cycle day 8 onward the selection of the dominant follicle was monitored by ultrasound and hormonal measurements. When dominant follicle diameter exceeded 13 mm, patients received GnRH antagonist and, thereafter, exogenous gonadotropins to support further follicular development. Oocyte pickups (OPU) were performed 36 hours after hCG administration. Results:

Conclusions: (i) IVF-ET using naturally-selected dominant follicle appeared very selective to poor prognosis patients (55% and 54% of cycles failed to go through ET, in AOFS and REIF groups, respectively). (ii) High cycle selectivity may be considered as a major advantage of this approach over COH and constitutes a plausible explanation to the encouraging IVF-ET outcome observed among patients undergoing ET. (iii) Prospective, randomized studies versus COH are however needed to challenge clinical soundness of IVF-ET using naturally-selected dominant follicle in the management of poor prognosis patients. P-200 Comparison of GnRH antagonist cycles with and without oral contraceptive pill pretreatment in poor responders. Kristin Bendikson, Amin A. Milki, Andrea Speck-Zulak, Lynn M. Westphal. Stanford, Stanford, CA.

* P ⬍.05 Conclusion: Both baseline and cycle day 5 inhibin-B levels are useful additions to traditional ovarian reserve measurements in predicting ovarian response and cycle outcome in women over 39, and may be helpful in counseling patients regarding opportunity for IVF success. P-199 IVF-ET using naturally-selected dominant follicle for poor prognosis patients: A hypothesis. Jacques J. K. Kadoch, Nelly N. F. Frydman, Altina A. C. Castelo Branco, Nathalie N. L. Le´ de´ e Bataille, Renato R. F. Fanchin, Rene´ R. F. Frydman. Hosp Antoine be´ cle`re, Clamart, France. Objective: Controlled ovarian hyperstimulation (COH) is widely used to improve embryo selection and pregnancy rates of IVF-ET candidates. Unfortunately, refractoriness to these conventional treatments due to ovarian or endometrial status defects is not rare. It is conceivable that COH itself may contribute directly or indirectly to exacerbate preexisting follicular and endometrial abnormalities. Also, the COH-induced multiplication in the number of follicles may conceal follicular defects that would be otherwise noticeable during mono-dominant cycles. To rule out these potential, unwanted consequences of COH, we conducted a pilot investigation on IVF-ET using naturally-selected dominant follicle for poor prognosis patients. Design: Prospective study in Unity of Reproductive Medicine, Hoˆ p. A. Be´ cle`re, Clamart, France Material and Methods: We studied 66 infertile women who presented either altered ovarian follicular status (AOFS) defined as previous cycle cancellations due to poor ovarian response to COH and/or abnormal day-3

S188

Abstracts

Objective: One of the most difficult challenges in the practice of assisted reproductive technologies is the management of poor responders. Previous studies examining the use of oral contraceptive pills (OCPs) with in vitro fertilization (IVF) cycles have reported positive benefits: a decrease in time needed for suppression, decrease in the amount of gonadotropins needed for stimulation, elimination of premature LH surges, and possible improvement in pregnancy rates. However, these studies examining the effects of OCPs have all been performed with GnRH agonists using either a long or flare protocol. In the present study, we seek to compare IVF outcomes in poor responders undergoing GnRH antagonist cycles with and without the use of oral contraceptive pills before ovarian stimulation. Design: Retrospective study of patients undergoing IVF August 2001August 2002. Materials and Methods: We evaluated records from 194 cycles in which GnRH antagonists were used in patients identified as poor responders. Medical charts were evaluated for patient characteristics, cycle types, as well as pregnancy outcomes. Use of OCP pretreatment was based on scheduling availability or patient preference. Results: During the study period, 138 patients underwent 194 antagonist cycles, both with oral contraceptive pills (n⫽146) and without oral contraceptive pills (n⫽48). The two groups did not differ in age, gravity, parity, day 3 FSH, number of previous cycles or cause of infertility. Patients that used oral contraceptive pills required more total ampules of gonadotropins (5888 v. 4410 IU, p⫽0.009). The two groups of patients did not differ in number of follicles produced, oocytes retrieved or number of embryos. The pregnancy rate did not differ between the two groups.

Conclusion: In this patient population of poor responders, pregnancy outcomes were the same whether or not OCP pretreatment was used. Since there is no difference in pregnancy outcome, the use of OCP pretreatment

Vol. 80, Suppl. 3, September 2003