fresh embryo transfer (et) pregnancy rates are not compromised by freezing portion of embryos at 2...

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Supported by: grants from the Fund for Scientific Research, Flanders. P-73 Mathematical model predicts day 6 transfer outcomes. James R. Tri- marchi, Rick J. Hackett, Deborah J. Pierce, David L. Keefe. Women and Infants’ Hospital/Brown Univ, Providence, RI. Objective: Electronic medical record keeping is becoming prevalent and therefore the number of variables monitored and digitally tracked for each IVF cycle can be extensive. It is not feasible to design experiments testing the influence of each variable on IVF outcome. We are developing ap- proaches to analyze IVF databases to identify critical parameters that influence IVF outcome. Once retrospectively characterized, these key pa- rameters can be prospectively tailored to suit the particulars of individual patients and optimize the IVF process. We sought to identify the critical parameters that influence day 6 transfer success and develop a model capable of predicting day 6 transfer outcome. Design: A retrospective cohort study in a university setting Materials/Methods: 29 parameters broadly characterizing 46 day 6 trans- fer IVF cycles were entered into a multivariate regression analysis in Minitab. These parameters included patient demographics, stimulation re- gime, response properties, oocyte and embryo parameters and transfer variables. The variable with the least predictive power was sequentially removed from the regression equation until the R-squared (adjusted) had reached a maximum and the number of variables was less than 8. Standard stimulation, egg retrieval, fertilization, embryo culture and embryo transfer protocols were employed. Results: 56% of the 16 pregnancies resulting from 46 day 6 transfers could be uniquely distinguished from non-pregnant cycles by using a regression equation with only 7 IVF parameters; difference in E2 before and after the HCG trigger, number 19 mm follicles, number mature follicles (15–20 mm), percent mature follicles retrieved, number oocytes, number fertilized, number cleaved. Similarly, 23% of the unsuccessful cycles could be predicted using the same parameters. From these 7 identified parameters we constructed a model that can be employed prospectively to predict the probability of pregnancy and risk of multiples. Conclusions: Mathematical approaches are needed to analyze and utilize the increasing amount information gathered during each IVF cycle. Multi- variate analysis can identify some critical parameters that influence the IVF process, however, more powerful methods are being developed. Simple mathematical models should facilitate tailoring the IVF process to individ- ual patients and allow better management of patient’s expectations by predicting probabilities for success. We are presently applying this model prospectively and will report the results at the conference. Supported by: None provided. P-74 Can initial BHCG level predict a multiple ART pregnancy? Sophia Ouhilal, Staci E. Pollack, Barry R. Witt, Kelly Rimstidt, Nanette Santoro. Albert Einstein Coll of Medicine, Bronx, NY. Objective: To assess if the first beta human chorionic gonadotropin level (BHCG) measured post embryo transfer is sufficiently higher in multiple gestations to distinguish them from singleton pregnancies. We also sought to determine if the subsequent rate of rise of BHCG discriminates multiples from singletons, and whether either of these measurements is an accurate predictor of pregnancy status. Design: Retrospective chart review of 100 assisted reproductive technol- ogy (ART) cycles resulting in clinical intrauterine pregnancies documented by positive fetal heart visualization on ultrasound between January 1999 and January 2002. Materials/Methods: We identified 53 singleton pregnancies, 32 twin pregnancies and 15 high order multiples who had the BHCG measured in the Immuno-1 BHCG assay system (Bayer Diagnostics) at our center. Patient characteristics, date of embryo transfer, dates and levels of subse- quent BHCG measurements as well as ultrasound information were re- corded. Only women whose initial BHCG was done exactly 14 days from retrieval were used. Results: The 3 groups were compared using two tailed t-testing with Bonferroni correction factor for age, gravity, parity, infertility diagnosis and body mass index. The BHCG measured 14 days after retrieval level was highest in high order multiple pregnancies (273), followed by twin gesta- tions (229) and singleton pregnancies (95; p 0.0001). All twin and high order pregnancies had a BHCG above 100 14 days after retrieval. At this cut-off the specificity for singletons was 71.9%. A BHCG 14 days after retrieval greater than 230 was required to achieve 100% specificity, how- ever at this level the sensitivity for multiples was less than 50% (12/26). ROC curve analysis showed that BHCG on day 14 is highly predictive of multiple pregnancy (area under the curve of 0.932; p 0.0001). The doubling time was comparable between all 3 groups, and did not discrim- inate between singletons and multiples. Patient Characteristics, Initial BHCG and Doubling Time Age (years) Gravity Parity BMI (kg/m 2 ) Initial BHCG (mIU/ml) Doubling time (days) Singletons n 53 35.5 1.2 1.1 0.1 0.4 0.1 23.8 1.9 95.4 10.3 2.22 0.17 Twins n 32 34 0.5 1.2 0.2 0.5 0.1 25.6 3.3 229.1 18.2* 2.29 0.22 High order multiples n 15 34.5 0.6 1.2 0.5 0.21 0.1 24 6.1 273 23.3* 1.95 0.04 Data shown are mean SEM. * p 0.0001 (with 18 tests Bonferroni correc- tion 0.003) for multiples vs singletons. Conclusions: A high initial BHCG level 14 days after retrieval is predic- tive of multiple pregnancy. Levels less than 100 exclude the possibility of multiples, while levels greater than 230 rule out a singleton pregnancy. However, after the initial BHCG value singleton, twin and high order multiples double at the same rate. Supported by: N/A. P-75 Fresh embryo transfer (ET) pregnancy rates are not compromised by freezing portion of embryos at 2 pronuclear (2PN) stage. Shehua Shen, Christin Wong, Kitty Ho, Tracy L. Telles, Victor Y. Fujimoto, Marcelle I. Cedars. Univ of CA, San Francisco, San Francisco, CA. Objective: It is estimated that the cost of frozen embryo transfer (FET) is approximately a quarter of fresh IVF-ET cycle (Van Voorhis BJ et all, Fertil Steril 1995; 64:647–50). Damario et al reported high cumulative livebirth rates with embryo cryopreservation at the pronuclear stage and efficient embryo use by FET (Fertil Steril 2000; 73:767–73). Our program focused on determining optimal cumulative pregnancy rates from a single egg retrieval (ER) that could be obtained by 2 PN cryopreservation. For this study we examined clinical and cumulative pregnancy rates from our 2 PN freezing protocol. Design: A retrospective analysis of patients who had IVF-ET treatment at the UCSF In Vitro Fertilization program from July to December 2001. Materials/Methods: All patients were consulted before ER regarding the number of embryos for transfer. This exact number plus additional 2 to 5 embryos depending on patient age and other prognostic factors were cul- tured to day 3 for fresh ET, while remaining embryos were frozen at the 2 PN stage. During FET cycle, 2 PNs were thawed, cultured for 24 hours and transferred at the 2– 4 cell stage. The 2 PN freezing protocol has been utilized since July 2001. All ovum donor and hyperstimulation freeze-all cycles were excluded from this study. Clinical pregnancy was defined as the presence of a gestational sac on ultrasound examination. Chi square is used to analyze the freezing rate. Results: The freezing rate is significantly higher after the implementation of 2 PN freezing protocol (59%) compared to before (36%, p 0.002). Clinical pregnancy rates were higher in the cycles involved 2 PN freezing. The group with both 2 PN and D3 freezing had the highest pregnancy rate compared to the other groups. The cycles with frozen embryos generated higher cumulative pregnancy rates per egg retrieval. S140 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002

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Supported by: grants from the Fund for Scientific Research, Flanders.

P-73

Mathematical model predicts day 6 transfer outcomes. James R. Tri-marchi, Rick J. Hackett, Deborah J. Pierce, David L. Keefe. Women andInfants’ Hospital/Brown Univ, Providence, RI.

Objective: Electronic medical record keeping is becoming prevalent andtherefore the number of variables monitored and digitally tracked for eachIVF cycle can be extensive. It is not feasible to design experiments testingthe influence of each variable on IVF outcome. We are developing ap-proaches to analyze IVF databases to identify critical parameters thatinfluence IVF outcome. Once retrospectively characterized, these key pa-rameters can be prospectively tailored to suit the particulars of individualpatients and optimize the IVF process. We sought to identify the criticalparameters that influence day 6 transfer success and develop a modelcapable of predicting day 6 transfer outcome.

Design: A retrospective cohort study in a university settingMaterials/Methods: 29 parameters broadly characterizing 46 day 6 trans-

fer IVF cycles were entered into a multivariate regression analysis inMinitab. These parameters included patient demographics, stimulation re-gime, response properties, oocyte and embryo parameters and transfervariables. The variable with the least predictive power was sequentiallyremoved from the regression equation until the R-squared (adjusted) hadreached a maximum and the number of variables was less than 8. Standardstimulation, egg retrieval, fertilization, embryo culture and embryo transferprotocols were employed.

Results: 56% of the 16 pregnancies resulting from 46 day 6 transferscould be uniquely distinguished from non-pregnant cycles by using aregression equation with only 7 IVF parameters; difference in E2 before andafter the HCG trigger, number 19 mm follicles, number mature follicles(15–20 mm), percent mature follicles retrieved, number oocytes, numberfertilized, number cleaved. Similarly, 23% of the unsuccessful cycles couldbe predicted using the same parameters. From these 7 identified parameterswe constructed a model that can be employed prospectively to predict theprobability of pregnancy and risk of multiples.

Conclusions: Mathematical approaches are needed to analyze and utilizethe increasing amount information gathered during each IVF cycle. Multi-variate analysis can identify some critical parameters that influence the IVFprocess, however, more powerful methods are being developed. Simplemathematical models should facilitate tailoring the IVF process to individ-ual patients and allow better management of patient’s expectations bypredicting probabilities for success. We are presently applying this modelprospectively and will report the results at the conference.

Supported by: None provided.

P-74

Can initial BHCG level predict a multiple ART pregnancy? SophiaOuhilal, Staci E. Pollack, Barry R. Witt, Kelly Rimstidt, Nanette Santoro.Albert Einstein Coll of Medicine, Bronx, NY.

Objective: To assess if the first beta human chorionic gonadotropin level(BHCG) measured post embryo transfer is sufficiently higher in multiplegestations to distinguish them from singleton pregnancies. We also soughtto determine if the subsequent rate of rise of BHCG discriminates multiplesfrom singletons, and whether either of these measurements is an accuratepredictor of pregnancy status.

Design: Retrospective chart review of 100 assisted reproductive technol-ogy (ART) cycles resulting in clinical intrauterine pregnancies documentedby positive fetal heart visualization on ultrasound between January 1999 andJanuary 2002.

Materials/Methods: We identified 53 singleton pregnancies, 32 twinpregnancies and 15 high order multiples who had the BHCG measured inthe Immuno-1 BHCG assay system (Bayer Diagnostics) at our center.Patient characteristics, date of embryo transfer, dates and levels of subse-quent BHCG measurements as well as ultrasound information were re-corded. Only women whose initial BHCG was done exactly 14 days fromretrieval were used.

Results: The 3 groups were compared using two tailed t-testing withBonferroni correction factor for age, gravity, parity, infertility diagnosis andbody mass index. The BHCG measured 14 days after retrieval level was

highest in high order multiple pregnancies (273), followed by twin gesta-tions (229) and singleton pregnancies (95; p �0.0001). All twin and highorder pregnancies had a BHCG above 100 14 days after retrieval. At thiscut-off the specificity for singletons was 71.9%. A BHCG 14 days afterretrieval greater than 230 was required to achieve 100% specificity, how-ever at this level the sensitivity for multiples was less than 50% (12/26).ROC curve analysis showed that BHCG on day 14 is highly predictive ofmultiple pregnancy (area under the curve of 0.932; p �0.0001). Thedoubling time was comparable between all 3 groups, and did not discrim-inate between singletons and multiples.

Patient Characteristics, Initial BHCG and Doubling Time

Age(years) Gravity Parity

BMI(kg/m2)

Initial BHCG(mIU/ml)

Doublingtime

(days)

Singletonsn � 53

35.5 � 1.2 1.1 � 0.1 0.4 � 0.1 23.8 � 1.9 95.4 � 10.3 2.22 � 0.17

Twinsn � 32

34 � 0.5 1.2 � 0.2 0.5 � 0.1 25.6 � 3.3 229.1 � 18.2* 2.29 � 0.22

High ordermultiplesn � 15

34.5 � 0.6 1.2 � 0.5 0.21 � 0.1 24 � 6.1 273 � 23.3* 1.95 � 0.04

Data shown are mean � SEM. * � p � 0.0001 (with 18 tests Bonferroni correc-tion � 0.003) for multiples vs singletons.

Conclusions: A high initial BHCG level 14 days after retrieval is predic-tive of multiple pregnancy. Levels less than 100 exclude the possibility ofmultiples, while levels greater than 230 rule out a singleton pregnancy.However, after the initial BHCG value singleton, twin and high ordermultiples double at the same rate.

Supported by: N/A.

P-75

Fresh embryo transfer (ET) pregnancy rates are not compromised byfreezing portion of embryos at 2 pronuclear (2PN) stage. Shehua Shen,Christin Wong, Kitty Ho, Tracy L. Telles, Victor Y. Fujimoto, Marcelle I.Cedars. Univ of CA, San Francisco, San Francisco, CA.

Objective: It is estimated that the cost of frozen embryo transfer (FET) isapproximately a quarter of fresh IVF-ET cycle (Van Voorhis BJ et all, FertilSteril 1995; 64:647–50). Damario et al reported high cumulative livebirthrates with embryo cryopreservation at the pronuclear stage and efficientembryo use by FET (Fertil Steril 2000; 73:767–73). Our program focusedon determining optimal cumulative pregnancy rates from a single eggretrieval (ER) that could be obtained by 2 PN cryopreservation. For thisstudy we examined clinical and cumulative pregnancy rates from our 2 PNfreezing protocol.

Design: A retrospective analysis of patients who had IVF-ET treatment atthe UCSF In Vitro Fertilization program from July to December 2001.

Materials/Methods: All patients were consulted before ER regarding thenumber of embryos for transfer. This exact number plus additional 2 to 5embryos depending on patient age and other prognostic factors were cul-tured to day 3 for fresh ET, while remaining embryos were frozen at the 2PN stage. During FET cycle, 2 PNs were thawed, cultured for 24 hours andtransferred at the 2–4 cell stage. The 2 PN freezing protocol has beenutilized since July 2001. All ovum donor and hyperstimulation freeze-allcycles were excluded from this study. Clinical pregnancy was defined as thepresence of a gestational sac on ultrasound examination. Chi square is usedto analyze the freezing rate.

Results: The freezing rate is significantly higher after the implementationof 2 PN freezing protocol (59%) compared to before (36%, p � 0.002).Clinical pregnancy rates were higher in the cycles involved 2 PN freezing.The group with both 2 PN and D3 freezing had the highest pregnancy ratecompared to the other groups. The cycles with frozen embryos generatedhigher cumulative pregnancy rates per egg retrieval.

S140 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002

Table 1. The result of IVF-ET cycles in groups by freezing status

Cycle type#

Case Age Egg # ET#Clinical

PregnancyCumulativePregnancy

No freezing 46 37.9 � 3.8 9.0 � 5.5 3.6 � 1.6 28% N/AD3 freezing

only30 37.1 � 4.2 14.6 � 5.2 3.4 � 1.2 40% 43%

2 PN freezingonly

14 33.8 � 4.4 23.3 � 9.6 3.6 � 1.0 57% 64%

2 PN � D3freezing

23 36.0 � 5.5 24.7 � 8.4 2.7 � 0.8 70% 83%

Conclusions: These data provide evidence that, with freezing portion ofembryos at 2-pronuclear stage, fresh embryo transfer pregnancy rates arenot compromised. Furthermore, the cycles with 2 PN freezing have greaterpotential of increasing cumulative pregnancy rates from a single egg re-trieval. Therefore, in our experience, IVF-ET outcome can be optimized in themost cost-effective manner allowing for a different strategy in IVF treatment.

Supported by: N/A.

P-76

Delivery rates in poor responders that decline cycle cancellation. Rich-ard A. Cochran, Mark L. Jutras, Mary T. Jutras. Reproductive Medicine andFertility Ctr, Orlando, FL.

Objective: Currently, most programs use a cutoff value of �500 pg/mlpeak serum concentration of estradiol, as well as a follicle count of at least3 follicles � 15 mm before proceeding to hCG injection and retrieval. Ifpatients fail to reach these criteria, the cycle is generally cancelled since itis believed that there is not a reasonable chance of success with that cycle.In this retrospective analysis, we present data collected over the last fiveyears with patients whose peak serum estradiol concentrations were �500pg/ml having at least 1 follicle �15 mm in diameter.

Design: Retrospective data analysis.Materials/Methods: Data were recorded for all IVF stimulation cycles in

our facility from January, 1996 through December, 2001 from a total of 380patients age 40 and under. Patients 40 years of age and under, whose peakserum estradiol concentrations were �500 pg/ml and who had at least 1follicle � 15 mm in diameter are included, regardless of stimulationprotocol or primary infertility diagnosis. All assays for serum estradiol wereperformed on the DPC Immulite analyzer. hCG was generally given whenthe lead follicle was � 18 mm. All embryo transfers were carried out onDay 2 or 3.

Results: The results from the data collected for patients age 40 and underwith peak E2 concentrations �500 pg/ml are presented in Table 1. Thedelivery rates were 25.9% per cycle start and 43.8% per retrieval. Thelowest peak serum E2 concentration with a delivery was 150 pg/ml and theoldest patient to deliver was 39.

Table 1

Age �35 35–37 38–40

N 10 10 7Mean Peak E2 (Range) 263 (75–477) 246 (93–473) 294 (104–496)Mean # Follicles/

Retrieval (Range)3.0 (1–5) 4.2 (3–8) 3.7 (3–4)

Mean # Embryos/Transfer (Range)

1.9 (1–4) 2.7 (2–4) 2.7 (2–4)

Delivered/Cycle Start 4/10 2/10 1/7Delivered/Retrieval 4/8 2/5 1/3Delivered/Transfer 4/6 2/3 1/3Cancelled 2/10 5/10 4/7

Conclusions: The data presented here suggests that the delivery rates aregood in patients 40 years of age and under with peak serum estradiolconcentrations �500 pg/ml and at least one follicle � 15 mm at the time ofhCG injection. Since many of the cycle expenses have already been incurredby the patient, retrieval should be offered to these patients. These findingssuggest a lack of importance of estradiol monitoring during the stimulationprocess.

Supported by: n/a.

P-77

Is ultrasound guidance or length of time to accomplish embryo transfermore important in achieving pregnancy in first cycle in vitro fertiliza-tion (IVF) patients? Stephanie B. McCulloch, Kay Sullivan, Victoria M.Sopelak, Randall S. Hines. Univ of Mississippi Medical Ctr, Jackson, MS.

Objective: Embryo transfer is the final critical step in the IVF process.Studies have looked at the impact that ease of transfer and the type ofcatheter have on pregnancy and implantation rates. In the present study, wespecifically evaluated the impact of 2 factors on pregnancy outcome: the useof ultrasound guidance to visualize catheter placement (used by one phy-sician) versus tactile only placement (used by another physician), in addi-tion to the length of time needed to accomplish transfer in first cycle IVFpatients of all ages.

Design: Retrospective analysis of pregnancy outcome was done on firstcycle IVF patients (N�82) of all ages, analyzed by use of ultrasound (USYes) or lack of ultrasound guidance (US No) and length of time to accom-plish transfer (� 2 minutes versus �2 minutes). Greater than 90% ofpatients had a trial transfer during the pre-cycle period. Transfers wereaccomplished using the Sydney IVF transfer set (Cook IVF)(N�68), theEdwards-Wallace catheter (SIMS Portex, UK)(N � 12) or the Jansen-Anderson catheter (Cook IVF)(N � 2).

Materials/Methods: All first cycle IVF patients having an embryotransfer were selected from our 2000 –2001 database irrespective of age(range � 23.8 to 45.6 years). At the time of embryo transfer, a stopwatchwas used to time the interval from removal of the embryos from theincubator until expulsion from the transfer catheter into the uterinecavity. Data regarding length of time for transfer were grouped as thoseaccomplished in � 2 minutes versus �2 minutes and analyzed byChi-square with a p �0.05 considered significant. Similarly, data wereregrouped and analyzed by use of ultrasound guidance and visualizationof catheter placement (US Yes) or no ultrasound (US No). Lastly,patients were regrouped by age (�35 versus �35) and pregnancyoutcome was analyzed. In instances where the oocytes were from adonor, the age of the oocyte donor was used. Values are expressed asMean � SEM. Data were analyzed by Chi-square and ANOVA statisticswhere appropriate, with a p �0.05 considered significant.

Results: The length of time to accomplish transfer (range � 60 to 973seconds) did not influence pregnancy outcome (see table). Similarly, therewere no significant differences in the pregnancies/transfer (%) in the USYes group which was 21/52 � 40.4% and in the US No group which was10/30 � 33.3%. However, the age of the patient had a significant impact onpregnancy outcome (p �0.05), with individuals �35 having a pregnancyrate/transfer of 43.4% compared to 27.6% in those � 35 years of age.

Demographics of patients with transfer time of �2 or 2 minutes

�2 minutes 2 minutes *P

N � patients with transfer 52 30Age 33.9 � 0.6 33.2 � 0.9 NSOocytes inseminated 8.6 � 0.6 8.5 � 0.8 NSFertilization rate (%) 74.4% 69.4% NSNumber of Pregnancies 20 11 NSPregnancy rate/transfer (%) 38.5% 36.6% NS

* Significantly different

Conclusions: In our retrospective study, neither the length of time toaccomplish embryo transfer or the use of ultrasound guidance had a signif-icant impact on pregnancy outcome. At our institution, patient age had thegreatest impact upon pregnancy outcome.

Supported by: Department of Obstetrics and Gynecology.

P-78

Obstetric and perinatal risks in IVF pregnancies conceived with ownoocytes or donor oocytes. Jose Gaytan, Carlos Troncoso, Luis PedroRossal, Ernesto Bosch, Antonio Pellicer, Jose Remohi. Inst Valenciano deInfertilidad, Valencia, Spain.

Objective: Determine if the obstetric and perinatal outcome of IVFpregnancies using patients own oocytes in the late reproductive years(around 35 years of age) differs from those obtained in patients of the same

FERTILITY & STERILITY� S141