O-1

Hyperprolactinemia: guidelines for clinical assessment and pituitaryimaging. Aykut Bayrak, M.D., Peyman Saadat, M.D., Eliran Mor, M.D.,Rebecca Urwitz-Lane, M.D., Lisa Chong, B.S., Richard J. Paulson, M.D.,Rebecca Z. Sokol, M.D. Department of Obstetrics and Gynecology, Uni-versity of Southern California, Los Angeles, CA.

Background and Significance: The contemporary evaluation of hyperp-rolactinemia includes assessment of symptomatology, testing for presenceof thyroid disease, and imaging of the pituitary gland. However, controversyexists regarding the prevalence of clinical presenting symptoms, incidenceof co-existing thyroid disease, and the threshold value for ordering an MRI.

Objective: The purpose of this study was to establish guidelines for theevaluation of hyperprolactinemia and to determine a minimal prolactinvalue for ordering an MRI.

Materials and Methods: In this retrospective study, data were extractedfrom medical records of patients seen in the endocrine-infertility clinicbetween June 1997-August 2002. All patients with elevated prolactin levelswere included in the study. Symptomatology, prolactin levels, TSH valuesand tumor size on MRI were documented and analyzed. Data were analyzedusing x2 and correlation analysis as indicated.

Results: 98 patients were included in the study and of those 75 had MRIs.Mean (range) age of patients was 29.8 years (19–44). All patients werefound to be euthyroid. Mean prolactin value (range) was 151 ng/ml (23.5–1342.1). Prolactin levels and the corresponding tumor category are shownbelow. Patients’ presenting symptoms were as follows: Infertility 41.5%,headaches 40.5%, galactorrhea 27.7%, amenorrhea 18.8%, visual distur-bances 12.8%, oligomenorrhea 7.9%. Of the 75 patients, 51% had microad-enomas, 23% had macroadenomas and 26% had normal MRIs. Statisticallysignificant association was found between the prolactin levels (30–100ng/ml versus � 101 ng/ml) and the size of the tumor (micro versusmacroadenoma) p � 0.007; correlation coefficient � 0.71.

Prolactinlevels

Number ofpatients Microadenoma Macroadenoma

NormalMRI

20–30 1 0 0 131–40 7 5 1 141–50 6 3 0 351–60 9 4 0 561–70 4 2 0 271–80 3 2 0 181–90 3 0 0 391–100 5 3 1 1

101–200 23 16 5 2�201 14 3 10 1Total 75 38 17 20

Conclusion: The most common presenting symptom in our patients withhyperprolactinemia was infertility followed by headaches, galactorrhea, andamenorrhea. There were no cases of thyroid disease. Most patients werediagnosed with a pituitary tumor. Tumor size highly correlated with thelevel of prolactinemia. Pituitary tumors were identified with levels as low as30ng/ml. Although microadenomas were more likely with prolactin levelsbelow 200ng/ml and macroadenomas with prolactin levels greater than200ng/ml, overlap amongst diagnoses was not unusual. An MRI should beordered to identify a pituitary tumor in patients with a prolactin level above30ng/dl.

O-2

Use of a GnRH antagonist to rescue a unifollicular response to super-ovulation with gonadotropins. D.L. Gehlbach, D. Stewart, D. Chaffin.Shawnee Mission Medical Center, Shawnee Mission, KS.

Background and Objective: The success of gonadotropin therapy insuperovulation depends upon the production of multiple follicles. On occa-sion, the growth of one follicle exceeds that of the others and the physicianruns the risk of premature ovulation if gonadotropins are continued too long.The purpose of this study was to add a GnRH antagonist to gonadotropinstimulation in situations where one follicle appeared dominant in an attemptto allow secondary follicles to reach maturity.

Materials and Methods: Patients between ages 20–45 undergoing super-ovulation were started on a fixed dose of gonadotropins on Cycle Day 3; thedose was adjusted based on their ovarian response. If the lead follicle was �14 mm diameter and exceeded the size of the next largest follicle by 4 mmor more with at least 3 additional follicles � 10 mm, 250 �g of ganirelixacetate (Antagon™) was administered daily and continued until 2 or morefollicles reached 18 mm in diameter or there was no further growth of thesecondary follicles. Ovulation was triggered with 10,000 units of hCG andintrauterine insemination performed 36 hours later. Data were analyzed byMann-Whitney Rank Sum test or Fisher exact test.

Results: Results for primary outcomes (number of follicles on day ofhCG) and secondary outcomes (FSH dose, stimulation days, and pregnancy)are presented in Table 1. Values are medians unless otherwise indicated.

Table 1:

Parameter Study Control P

N 19 38Age 32 33 0.7718 mm follicles 2 2.5 0.25Range 1 to 4 1 to 615–17 mm follicles 1 1 0.43Range 0 to 5 0 to 6Total Dose FSH (vials) 20 16 0.01Total Stim Days 9 8 0.01Pregnancy 5/19 � 26.3% 11/38 � 28.9% 1.00

Compared to an age-matched control group of 38 women undergoinggonadotropin superovulation with a multifollicular response, the ganirelixacetate-treated group had similar numbers of mature [2 (1–4) versus 2.5 (1–6)] and medium [1 (0–5) versus 1 (0–6)] follicles on the day of hCG. Asimilar pregnancy rate between the two groups was also observed (26.3%versus 28.9%).

Conclusions: When superovulation with gonadotropins begins with anapparent unifollicular response, the addition of ganirelix acetate may allowa greater number of follicles to reach maturity and restore a respectablepregnancy rate.

O-3

Evaluation of mixed protocols with Bravelle (hFSH) and Repronex(hMG) to assess clinical efficacy (EMBRACE II) in patients (34–40years) undergoing in vitro fertilization. W.R. Keye, Jr.1, M.W. Surrey2,B.J. Van Voorhis3, D.J. Kenigsberg4, J.H. Check5, P.M. McShane6, J.Eisermann7, M.D. Scheiber8, L.M. Westphal9, D.C. Marshall10 for theEMBRACE Study Group. 1William Beaumont Hospital, Royal Oak, MI;2Southern California Reproductive Center, Beverly Hills, CA; 3Universityof Iowa Hospital and Clinic, Iowa City, IA; 4Long Island IVF, LakeSuccess, NY; 5Cooper Institute, Marlton, NJ; 6Reproductive Science Cen-ter, Waltham, MA; 7South Florida Institute for Reproductive Medicine,Miami, FL; 8Institute for Reproductive Health, Cincinnati, OH; 9StanfordUniversity School of Medicine, Stanford, CA; 10Ferring PharmaceuticalsInc., Suffern, NY.

Principal Author: Dennis C. Marshall, Ph.D., Ferring Pharmaceuticals,Inc., 120 White Plains Road, Suite 400, Tarrytown, NY 10591. Phone:914.333.8985. Fax: 914.631.5120. Email: marshall@ferringusa.com

Presenting Author: William R. Keye, MD, Director, Division Reproduc-tive Endocrinology, William Beaumont Hospital In Vitro Fertility Clinic,3535 Thirteen Mile Road, Royal Oaks, MI 48073. Phone: (248) 551-0515.(248) 551-3616. Email: wkeye@beaumont.edu

Introduction: There is widespread use of combined FSH and hMG (mixedprotocols) in controlled ovarian hyperstimulation (COH) for in vitro fertil-ization (IVF). However, there have been no systematic efficacy and safetystudies examining various ratios of FSH and hMG mixed in a single dailydose.

Objective: To assess the therapeutic efficacy and safety of continuous andsequential dose ratios of FSH:hMG (Bravelle, highly purified FSH andRepronex, hMG) combined in the same syringe and administered subcuta-neously, once daily, in COH-IVF patients 34–40 years of age.

Materials and Methods: Eligible patients received leuprolide acetate (LA,0.5 mg, OD, SC) starting seven days before onset of menses and continued

S6 Abstracts Vol. 79, Suppl. 2, April 2003

for � 20 days until estradiol (E2) was � 40 pg/ml with endometrial lining� 6 mm. Thereafter, LA was reduced to 0.25 mg/d and continued until theday before hCG administration. Patients were randomized to treatmentgroups A, B, or C, and gonadotropin stimulation began for � 15 days. TheFSH:hMG vial ratios were: Group A had a 1:1 ratio throughout; Group Bbegan with FSH only then changed to and maintained a 1:1 ratio after day5 of gonadotropins; Group C had a 2:1 ratio that, after day 5 of gonado-tropins, was sequentially adjusted to 3:1, 4:1 or 5:1 as needed to maximumFSH dose of 450 IU. When ultrasound showed � 3 follicles with diametersof � 16 mm, and acceptable E2 levels, gonadotropins were stopped andhCG (10,000 IU IM) was administered; oocytes were retrieved 34–36 hrslater. Primary efficacy was the number of oocytes retrieved.

Results: Implantation rates and continuing pregnancy rates were high inall three groups. There were, however, no significant differences amonggroups in any efficacy parameter assessed. There were no differences amonggroups with respect to adverse events.

Patient Demographics, Efficacy Results and Safety Data: EMBRACE II

ParameterTreatment A

(n � 38)Treatment B

(n � 36)Treatment C

(n � 36) P-value

Age (mean � SD; yrs) 36.3 (2.0) 36.8 (1.9) 36.8 (1.9) 0.435BMI (kg/m2) 24.9 (4.3) 24.9 (4.9) 24.2 (4.4) 0.751Duration of treatment

(mean days � SD)9.5 (1.8) 9.5 (2.0) 9.2 (1.9) 0.603

Total gonadotropin dose(mean IU � SD)

2488.7 (909.0) 2556.5 (905.6) 2465.4 (840.0) 0.893

Peak serum E2 levels(mean � SD; pg/ml)

1809.6 (1081.4) 1768.2 (1475.8) 1428.7 (1114.3) 0.364

Patients with oocyteretrieval and embryotransfer (%)

37 (97.4) 32 (88.9) 34 (94.4) 0.300

Total oocytes retrieved(mean � SD)

11.5 (6.7) 11.4 (5.5) 9.6 (6.8) 0.333

Mature oocytes(mean � SD)

8.2 (4.4) 8.8 (5.2) 8.0 (6.3) 0.790

Oocytes with normalfertilization(mean � SD)

6.4 (4.0) 6.1 (4.5) 6.0 (4.0) 0.893

Embryos transferred(mean � SD)

2.6 (1.0) 2.4 (1.2) 2.3 (1.1) 0.454

Implantation rate (%) 31.0 25.0 30.1 0.629Patients with chemical

pregnancy (%)20 (52.6) 18 (50.0) 21 (58.8) 0.769

Patients with clinicalpregnancy (%)

18 (47.4) 15 (41.7) 20 (55.6) 0.494

Patients with continuingpregnancy (%)

17 (44.7) 15 (41.7) 16 (44.4) 0.958

Patients with any adverseevent (%)

18 (43.9) 23 (57.5) 19 (50.0) 0.472

Patients with seriousadverse events (%)

1 (2.4) 2 (5.0) 0 (0.0) 0.653

O-4

An alternate approach to the culture and cryopreservation of humanembryos to maximize IVF pregnancy rates per oocyte retrieval. D.G.Hammitt, C.A. Sattler, J.A. Rebert, P.B. Peat, A.P. Singh. Division ofReproductive Endocrinology and Infertility, Mayo Clinic Scottsdale, Scotts-dale, AZ.

Objective: To optimize pregnancy rates/retrieval (R) it is necessary todevelop embryo selection methods that permit transfer of the best embryosin the fresh cycle (FrT) and cryopreservation techniques that produce highsurvival rates. Studies have shown that embryos with certain pronuclear-stage (PNS) features implant at high rates. Frozen embryo transfer (FET)rates appear to be highest for embryos cryopreserved at PNS. Based on thesestudies, we developed a unique approach to embryo culture and cryopreser-vation that may provide for higher rates of pregnancy/R than other culturestrategies. Our approach involves selection of embryos for FrT at PNS andPNS cryopreservation of embryos in excess of the number selected for FrT.The objective was to examine FrT, FET and cumulative delivery rates perretrieval (CDR/R), using this approach.

Design: All � 39 R patients undergoing day 3 IVF-ET from 1/1/01 to12/31/01 were included. Patients were divided into 3 groups (G): AOD(G-I), women � 35 (G-II), and women 35–38 (G-III).

Materials and Methods: Patients consented for cryopreservation of PNSembryos in excess of the number chosen for FrT. G-I and G-II consented to2–3, and G-III to 3–4, embryos for FrT. For FET, G-I-III usually consentedto transfer 3, 3, and 4 zygotes, respectively. The best embryos were selectedfor FrT using PNS grading. If � 2 embryos were good quality, the lowernumber of embryos consented for were transferred.

Results: For embryos TRS to date CDR/R were 76.5%, 71.8%, and58.6% for G-I-III.

FrTAOD

FrT� 35

FrT35–38

FETAOD

FET� 35

FET35–38

Age at retrieval* 29.4 31.5 37.2 — — —# of 2PN* 13.1 8.3 7.1 — — —Cycles with CSE

(%)100 65 59 — — —

FrT or FETThaws

17 39 29 12 12 5

# oocytes R or #thawed*

19.2 13.4 10.8 3.7 3.7 3.8

# 2PN for freshculture*

3.1 3.2 3.6 — — —

# embryos TRS* 2.2 2.4 3.0 3.0 2.3 2.8Clinical rate (%) 70.6 69.2 58.6 41.7 41.7 40.0Implantation rate

(%)54.0 39.8 29.5 16.7 21.4 21.4

Delivery rate(%)**

52.9 61.5 51.7 33.3 33.3 40.0

* Numbers are averages** FET-3 ongoing pregnancies

Conclusions: High delivery rates were obtained in FrT and FET cyclesalong with a low incidence of high-order multiple pregnancy (2 triplets/68pregnancies–2.9%). These results suggest that PNS selection and cryo-preservation of extra embryos is a viable alternate method to the moretypical method of culturing all embryos to day 3 or 5 and cryopreservationat the cleavage or blastocyst stages. Our approach optimizes the chance ofa pregnancy from one oocyte R, results in a high percentage of R with CSE,and provides many patients with an opportunity for delivery of more thanone pregnancy per R.

O-5

A new insulin sensitivity index obtained from the oral glucose tolerancetest (OGTT) is applicable for evaluating women with polycystic ovarysyndrome (PCOS). K. Elkind-Hirsch, B. Webster. Woman’s Health Re-search Institute, Baton Rouge, LA.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneousendocrine disorder frequently associated with insulin resistance (IR) andadiposity.

Objective: To compare various insulin sensitivity indices derived fromthe oral glucose tolerance test (OGTT) in women with PCOS and normo-ovulatory controls in order to identify the best single predictor of insulinsensitivity.

Materials and Methods: Premenopausal women with PCOS (n � 12) and6 age-matched controls (BMI 20–48 kg/m2) with normal glucose tolerancewere evaluated. After an overnight fast, all women were administered 75 gglucola for assessment of glucose (G) and insulin (I) at 0, 30, 60, and 120minutes. An index of whole-body insulin sensitivity (SI) was derived fromthe OGTT (10,000/square root of [fasting G � fasting I] � [mean G �mean I during an OGTT]). Homeostasis model assessment (HOMA) ofinsulin sensitivity was calculated from fasting G and I level. Estimation ofinsulin sensitivity was also determined using G:I ratios in a fasting sample(FG/I) and 2 hours after OGTT (G/I 2-h). Levels of testosterone, SHBG,androstenedione, and DHEAS were assayed from baseline samples.

Results: Significantly elevated androgen levels, lower SHBG concentra-tions, higher BMI, and greater insulin resistance was found in women withPCOS (p � 0.01). BMI correlated negatively with all insulin sensitivityparameters in women with PCOS (p � 0.02) but was not predictive ofinsulin sensitivity in controls. SHBG was directly related to SI (r � 0.84)and inversely correlated with HOMA (r � �0.87) in women with PCOSwhereas neither measure correlated with SHBG (r � 0.3) in ovulatory

FERTILITY & STERILITY� S7