rupture of membranes, abnormal presentation, placental abruption, placentaprevia, and post-partum hemorrhage were similar between the two groups.Birth weight of singletons born to 50� mothers (3048 � 683 gm, mean �SD) was significantly lower than for singletons born to 40� mothers(3350 � 606 gm, p �0.05). However, overall and twin birth weights weresimilar between the two groups. There was a trend towards a higher risk oflow birth weight (LBW) in newborns of 50� mothers (35.1%) comparedwith newborns of 40� mothers (31.5%, p �0.05). Moreover, NICU admis-sions were higher in newborns of 50� mothers (23.3%) than for newbornsof 40� mothers (19.3%), but statistical significance was not achieved. Theaverage gestational age at delivery did not differ between 50� (37.6 � 2.9weeks) and 40� (37.4 � 3.3 weeks) recipients. Apgar scores at 1 and 5minutes were similar between newborns of 50� (8.4 � 0.9, 9.2 � 0.4) and40� (8.3 � 0.8, 8.9 � 0.5) mothers.

Conclusions: Among recipients of egg donation there is an age-relatedincreased risk for PIH, GDM, cesarean section for twins, and lower birthweights for singletons. Although outcomes were not significantly different,there appears to be a trend towards higher rates of LBW and NICUadmissions in recipients older than 50. Egg donation in women at the upperextreme of reproductive age appears to be associated with a satisfacoryoutcome, however, careful surveillance for common obstetrical and perina-tal conditions is warranted.

Supported by: University of Southern California Reproductive Endocri-nology and Infertility.

Tuesday, October 15, 20024:15 P.M.

O-134

The impact of peak follicular estradiol (E2) levels and its dramaticMid-Luteal decline on the outcome of IVF-ET. Shevach Friedler, A. L.Zimerman, M. Schachter, A. Raziel, D. Strassburger, R. Ron El. AssafHarofeh Medical Ctr, Zerifin, Israel.

Objective: Intense debate surrounds the influence of markedly elevatedE2 levels at the late follicular phase and its mid-luteal decline followingcontrolled ovarian hyperstimulation (COH) after pituitary suppression forIVF-ET (HR, 14:2777–82; 15:1903–8). Our objective was to quantify thedecline in E2 levels from the day of hCG administration to the mid-lutealphase and to evaluate the impact of the absolute E2 level and its declineupon IVF-ET outcome.

Design: A prospective study was conducted, of consecutive womentreated by a similar protocol, of mid-luteal pituitary down-regulation, usinga daily dose of GNRH-a, followed by ovarian stimulation in an individuallyadjusted step-up protocol and luteal support using micronized progesterone.Patients aged �39 years and receiving �3 embryos per transfer wereexcluded.

Materials/Methods: Serum E2 level was measured on the day of hCG(hCG-E2) and at the mid-luteal phase (hCG day �9) (ML-E2). E2 leveldrop was expressed as % of decline between hCG-E2 and ML-E2. Corre-lation between hCG-E2, ML-E2 values and % E2 decline and cycle out-come was evaluated. Various clinical and hormonal parameters were com-pared between conception (C) and non-conception (NC)cycles. Outcomemeasures included rates of implantation (IR), clinical pregnancy/ET (PR)and early spontaneous abortion (ESA).

Results: 100 patients met the inclusion criteria during the study period.Their characteristics (mean � S.D) included age: 30 � 5 years; hCG-E2:3414 � 1383pg/ml;# of mature oocytes retrieved: 16 � 7; fertilization rate50 � 20%. ET of 2 � 1 embryos led to conception of 35 clinical pregnan-cies,IR of 18% and an ESA rate of 17%. None of the patients developedOHSS. Among all cycles, a dramatic %E2 decline of 95 � 4.7% wasobserved. Comparing C to NC cycles, no significant differences were foundin various clinical and hormonal parameters, including age, dose and dura-tion of ovarian stimulation, # of oocytes retrieved, fertilized, # of embryostransferred, hCG-E2, ML-E2, % of E2 decline (Students T test). IR and PRdid not correlate to the absolute hCG-E2 or ML-E2 level or % E2 decline.Comparing normal and high responders (hCG-E2 of �2500pg/ml), PR(35% vs 35%), IR (20% vs 17%) and ESA (11% vs 19%) were similar.Comparing patients with ML E2 of �200 pg/ml, PR (31% vs 46%), IR(17% vs 22%) and ESA (18% vs 15%)were similar. Comparing patientswith �98% E2 decline, PR (35% vs 35%), IR (19% vs 15%) were similar,but a �98% E2 decline resulted in significantly higher ESA (57% vs 7%,

p � 0.01) (Chi-square test). More extreme E2 decline of �98% was moreprevalent in high than normal responders (p �0.01).

Conclusions: Our results refutes the negative effect of the absolute E2level or its decline on implantation. Marked E2 decline might influence ESArate, especially in the high responder group suggesting an advantage ofmilder COH.

Supported by: none.

Tuesday, October 15, 20024:30 P.M.

O-135

The physician factor plays a significant role in the number of oocytesretrieved per case in a large assisted reproductive technology program.Brian M. Berger, Michael M. Alper. Boston IVF, Waltham, MA.

Objective: To examine the differences in the number of oocytes retrievedby 13 physicians in a large assisted reproductive technology program.

Design: Retrospective data analysis.Materials/Methods: The study population represented 7,733 IVF-ET vag-

inal oocyte retrievals that were performed consecutively at Boston IVFbetween January 1999 and December 2001. Patients who underwent oocytedonation or GIFT were not included in this study. All patients underwentcontrolled ovarian hyperstimulation using a combination of a GnRH agonist(Lupron�; Tap Pharmaceuticals, Deerfield, IL), or GnRH antagonists (Ce-trotide�; Serono, Norwell, MA and Antagon�; Organon, West Orange, NewJersey) and gonadotropins (Pergonal�, Fertinex� and Gonal-f�, Serono;Follistim�, Organon; Repronex�, Ferring, Tarrytown, New York). Cyclemonitoring with follicular ultrasound scans and measurement of E2levelswas performed in routine fashion, as was the administration of hCG and theretrieval of oocytes. For the most part, each physician supervised thestimulation of their own patients. Statistical analyses were performed usingthe Student’s t-test and paired samples t-test.

Results: The number of eggs retrieved for 1999, 2000, and 2001 wereanalyzed. For women under age 35, the number of oocytes per retrieval(mean � SD) for the three years was 12.3 � 1.2, 11.1 � 1.2, and 11.3 �1.2. For women from 35–40 years of age, the number of oocytes retrievedwas 9.8 � 1.2, 9.1 � 1.2, and 9.2 � 1.0. For women over the age of 40, thenumber of oocytes was 8.1 � 0.9, 7.4 � 1.1, and 7.5 � 0.9, respectively,within the years in question. There was a significant year-to-year correlationbetween the number of oocytes retrieved per individual physician forpatients less than age 35 (P �0.01) and age 35 to 40 (P �0.05). In addition,the same physicians consistently ranked highest or lowest in the meannumber of oocytes per retrieval each year. Analysis of the mean number ofoocytes retrieved by the 2 physicians with the greatest number of oocytesper retrieval each year showed a significant difference compared to the 2physicians with the lowest number of oocytes (P �0.05). There was nocorrelation between the number of oocytes retrieved and pregnancy rates(PR).

Conclusions: The data presented herein suggest the importance of thephysician factor on the number of oocytes retrieved in a large IVF-ETprogram with homogeneous stimulation protocols. Given the multiple fac-tors unrelated to oocyte number, it is not surprising that there was nocorrelation seen between mean oocyte number and PR from fresh embryotransfers. It remains possible that a correlation may have been detectedbetween pregnancy rates and oocyte numbers if we had combined preg-nancy rates from both fresh and frozen transfers resulting from the sameoocyte retrieval. These data strongly suggest that there are significantinter-physician technical differences leading to a significant difference inthe number of oocytes retrieved. Further study is needed to determine whatthese differences are and whether they might affect the PR when controllingfor other factors.

Supported by: None.

Tuesday, October 15, 20024:45 P.M.

O-136

The morphology of 2 pronuclear (2PN) embryos is related to the qualityof day 3 embryos. Shehua Shen, Christin Wong, Kitty Ho, Tracy L. Telles,

S52 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002

Victor Y. Fujimoto, Marcelle I. Cedars. Univ of CA, San Francisco, SanFrancisco, CA.

Objective: It has been reported that 2 PN morphology is positively relatedto blastocyst development and implantation; thus, zygote scoring may beuseful as an efficient tool for embryo selection. The 2 PN score is generatedfrom the grading of pronuclear (size and alignment), nucleoli (alignmentand distribution) and cytoplasmic halo (with or without). However, therelationship between each individual factor and day 3 embryo quality hasnot been studied. The predictive value of zygote morphology for embryoselection needs further investigation.

Design: A retrospective analysis of 706 zygote embryos from 97 patientswho had IVF-ET treatment at UCSF In Vitro Fertilization program in 2001.

Materials/Methods: Each embryo in this study was scored on both day 1and day 3. 2 PN score was the sum of three scores: pronuclear (1 or 5),nucleoli (3, 4, 5) and cytoplasmic halo (3 or 5). Day 3 embryo scoreincluded cell number, fragmentation and compacting. Regression analysisand logistic regression analysis were used to find the predictive componentsin the 2 PN scoring system for cell number and compacting, respectively.

Results: Regression analysis showed that the cytoplasmic halo (p �0.005) and nucleoli scores (p � 0.004) were predictive of day 3 embryo cellnumber. Logistic regression analysis showed that both patient age (p �0.014) and nucleoli scores (p � 0.015) were predictive of the compactingphenomenon. The pronuclear component was not predictive of both day 3cell number and compacting.

Conclusions: We found that the cytoplasmic halo and nucleoli scoreswere predictive of day 3 embryo cell cleavage. Both patient age and nucleoliscore were related to compacting phenomenon. These data confirmed thepredictive value of 2 PN grading.

Supported by: N/A.

ART: OVARIAN STIMULATION

Tuesday, October 15, 20022:00 P.M.

O-137

Continuation of gonadotropin releasing hormone agonist during theluteal phase in in vitro fertilization patients: Is it beneficial? KemalOzgur, Mete Isikoglu, Murat Seleker. Antalya IVF Ctr, Antalya, Turkey.

Objective: The aim of this study was to investigate the effect of contin-uous administration of GnRH agonist during the luteal phase on outcomeparameters in an ovarian stimulation programme for intracytoplasmic sperminjection (ICSI).

Design: Prospective randomized study.Materials/Methods: Ninety-one patients who were enrolled ICSI pro-

gramme between March 2001 and March 2002 were randomized into twogroups. All patients underwent a down-regulation protocol of GnRH agonistadministered from the 21st day of the cycle. The dosage was reduced to halfon the third day of the next cycle and the first group of patients with an oddID number were administered GnRHa until 12th day after embryo transferwhile the second group with even ID numbers were administered GnRHauntil the day of human chorionic gonadotrophin (hCG) administration.Gonadotropin stimulation including FSH and hMG was commenced on the3rd day and dosage was individualized according to the predeterminedovarian reserve. 10.000 IU hCG was administered im when at least twofollicles �19mm have been detected followed 35 hours later by oocyteretrieval. ICSI procedures were performed immediately after ovum pick-up(OPU). Three to five cleaved embryos were transferred into the uterinecavity of each patient 50 hours after OPU. Progesterone in oil 50 mg/daywas administered im for the luteal phase support until the day of beta hCGassay. Implantation rates and clinical pregnancy rates were determined asoutcome parameters. Chi-square test was used to analyse the data. A p-value�0.05 was considered significant.

Results: Group I consisted of 45 patients while group II confined 46patients. The age of the women, age of the husbands, number of previousART attempts, distribution of etiologic reasons of infertility, number of MIIoocytes, cycle cancellation rates, total ampules of gonadotropins used wereall similar in both groups. Clinical pregnancy rates of 57.14% for the firstgroup and 53.57% for the second group were not statistically significantfrom each other. Implantation rate of the first group (28.32%) was higher

than the second group (21.95) but the difference was not statisticallysignificant. One of the Patients from the 2nd group had ectopic pregnancy.

Conclusions: Preliminary results of this current study revealed that pro-longing the GnRHa treatment beyond hCG injection does not increase thepregnancy or implantation rates. Nevertheless, we believe that additionalrandomized prospective studies will help deciding whether to change theclassical long protocol or not.

Supported by: None.

Tuesday, October 15, 20022:15 P.M.

O-138

Elevated efficacy of highly purified human menopausal gonadotropin(HP hMG) for intracytoplasmic sperm injection (ICSI): Results of aprospective, randomized, controlled trial comparing HP hMG to re-combinant Follicle-Stimulating hormone (r-hFSH). Zaid Kilani, AmalDakkak, Samer Ghunaim, Graciela Estela Cognigni, Silvia Melappioni,Marco Filicori. Farah Hosp, Amman, Jordan; Univ of Bologna, Bologna,Italy.

Objective: HP hMG is becoming available worldwide, but limited infor-mation exists on the endocrine profile and clinical efficacy of this newgonadotropin preparation in ovulation induction and assisted reproduction(ART). Lower cost compared to r-hFSH, combined FSH and luteinizinghormone (LH) activity content, and the possibility of subcutaneous admin-istration, make HP hMG an attractive compound for ART. Thus, for the firsttime we elected to prospectively compare HP hMG and r-hFSH in ICSI.

Design: Prospective, randomized, controlled comparison of fixed dosegonadotropin regimens consisting of equal FSH and different LH activityamounts in ICSI patients.

Materials/Methods: One hundred infertile women were randomized toreceive HP hMG (Menopur, Ferring; 48 patients) or r-hFSH (Gonal-F,Serono; 52 patients) at Farah Hospital, Jordan. All subjects had normal:menstrual cycles, body weight, ovaries at ultrasound (U/S), and hormones.Baseline biometric and endocrine profiles did not significantly differ in the2 groups. Following gonadotropin-releasing hormone agonist suppression(long regimen) all patients received the same daily FSH dose (150 IU, aseither HP hMG or r-hFSH) until �3 follicles �17mm and estradiol (E2)levels �600 pg/mL were reached. Gonadotropin dose increments wereallowed only after 14 days of unsuccessful treatment. Thereafter, 10,000 IUhuman chorionic gonadotropin (hCG) were administered, and ICSI wasperformed. Patients were monitored with daily LH, FSH, hCG, E2, proges-terone (P), and testosterone (T) measurements; and alternate day U/S.Hormone levels were reported as area under the curve (AUC) during theinitial 14 fixed FSH dose treatment days. Statistical assessment: parametricand non-parametric tests, as appropriate.

Results: Cycle cancellation rates were not significantly different (HPhMG 15% vs. r-hFSH 19%). Duration of treatment (11.1 � 0.4 vs. 12.7 �0.5 days, p �0.05) and gonadotropin dose (22.6 � 1.0 vs. 26.6 � 1.4ampoules, p �0.05) were lower in the HP hMG group. Peak preovulatoryE2 (1,255 � 127 vs. 907 � 112 pg/mL, p �0.01); and AUC of E2 (3,458 �356 vs. 2,677 � 347 pg/mL.day, p �0.05) and hCG (1.5 � 0.3 vs. 0.3 �0.2 IU/L.day, p �0.001) during treatment were higher in the HP hMGgroup. Unexpectedly, serum FSH was also higher in the HP hMG group(64.9 � 2.1 vs. 50.6 � 2.2 IU/L.day, p �0.001), despite matched daily FSHactivity administration. Serum LH, P, and T AUC, and the ovarian follicledevelopment pattern did not differ. Transferred embryo number; pregnancyrates (U/S detected heartbeat) per started cycle (HP hMG 31% vs. r-hFSH25%) and per oocyte retrieval (37% vs. 31%); and abortion rates (20% vs.15%) were not significantly different.

Conclusions: When HP hMG and r-hFSH COS regimens during ICSIwere compared under conditions of matched daily FSH activity adminis-tration, HP hMG was associated with: 1. A more efficient patient response,as reflected by reduced treatment duration and gonadotropin requirements;2. Pregnancy and abortion rates comparable to r-hFSH; 3. Higher peripheralFSH levels, despite administration of the same amounts of exogenous FSHactivity; 4. Increased preovulatory E2, and serum E2 and hCG levels duringtreatment.

Supported by: a Ferring Pharmaceuticals A/S grant.

FERTILITY & STERILITY� S53