Faculty Bibliography

PURPOSE: To investigate production of progesterone's precursor, pregnenolone, in the early oocyte donation pregnancy. METHODS: Pregnenolone and progesterone were measured on luteal days 21, 28, 35, 60 and 80. Progesterone was measured via the Immulite system, pregnenolone by liquid chromatography separation with tandem mass spectrometric detection. RESULTS: Progesterone rose significantly from days 35 today 60. Pregnenolone likewise rose significantly from days 35-60, but at a much higher rate, with an increase of 57 % by day 60, 75 % to day 80. The increase in pregnenolone was statistically more significant than the increase in progesterone (p < .05). CONCLUSIONS: This is the first report describing that progesterone's precursor, pregnenolone, increases with time in the very early pregnancy. Because no corpus luteum is present in oocyte recipients, the main source of pregnenolone is the early placenta. Measurements of pregnenolone may provide information concerning early trophoblast function and may represent a method of assessing placental competency.

The timing of the luteoplacental shift has been eloquently studied,however there has been little new information brought forth on the subject over the past 2 decades. OD provides a unique model to study this phenomenon,as women who become pregnant do so in the absence of a CL.The timing of the LPS in oocyte recipients using changes in progesterone(Prog) levels can only be extrapolated because exogenous Prog is always given. Pregnenolone(Preg) is the Prog precursor made by the placenta and is without an exogenous source. Measurements of Preg may provide better information about the timing and even the quality of placental maturation. Methods.Recipients' serum was drawn on luteal days 21,28,35,60and80.Prog was measured using the Immulite system,an immunoassay utilizing polystyrene bead solid phase and a chemiluminescent substrate.The intra and inter assay imprecision is 7-10% and 9-12%. 50 delivered patients were selected, 36 of whom had Prog levels for all days listed. Stored frozen serum samples from 6 delivered DE recipients were used for the Preg analysis.This number was low due to the high cost of each test.Analysis was performed by Endocrine Sciences using liquid chromatography separation with tandem mass spectrometric detection (LC-MS/MS). An MDS-Sciex API5000 triple quadrupole mass spectrometer was used and quantification of analyte and standard was performed in selected reaction monitoring mode(SRM).The intra-day imprecision is 2-3%.Using random effects models to fit to the longitudinal data, the significant differences between Preg and Prog were evaluated. Results. Preg levels rise in the very early DE pregnancy, and this rise is significantly different from the changes in Prog(p<.05 linear mixed model). (Figure Presented) Box plots at individual days respect to their longitudinal measurements. Concl.These results provide valuable new information and ignite interest in further study of the developing placenta.Future work related to the timing and amplitude of this rise in pregnenolone c!

OBJECTIVE: To review a center's experience with cryopreserved embryos generated from donor eggs and to analyze their long-term disposition. DESIGN: Retrospective analysis of donor egg cycles with cryopreserved embryos. SETTING: University-based IVF program. PATIENT(S): Eight hundred twenty-nine women undergoing oocyte donation. INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): Factors affecting the decision regarding disposition of donor frozen embryo transfer (dFET) and the association between fresh and dFET cycles. RESULT(S): From January 2000 to December 2004, donor egg recipients underwent 829 fresh embryo transfer cycles that resulted in a 54% live birth rate. Of the 444 recipients who delivered, 177 (40%) also cryopreserved embryos at transfer; however, only 37 (21%) returned for a dFET by August 2009 and only 18 women had children from fresh and frozen transfers. In contrast, 128 of the 385 recipients who failed the fresh transfer (33%) cryopreserved embryos and 111 (87%) returned for a dFET. Of these, 44 had children from the dFET. Frozen cycle success rates between these recipient groups did not depend on fresh cycle outcome or prior parity. CONCLUSION(S): Donor oocyte recipients often initiate treatment with a desire to cryopreserve embryos for future use and family expansion. However, our data demonstrates that most recipients with a child from the fresh transfer do not return to use their cryopreserved embryos. Although fresh transfer success correlated with embryo disposition, it did not correlate with the outcome of thawed embryo transfer

BACKGROUND To minimize the potential for harmful inheritable conditions, donors are rigorously screened according to standard guidelines, yet such guidelines may not be sufficient to exclude egg donors with certain known inheritable conditions. We compared universal screening of oocyte donors with Tay-Sachs, Fragile X, karyotype and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) versus standard American Society of Reproductive Medicine (ASRM) guidelines that do not include such testing. METHODS In this 12 year retrospective cohort study, results of enhanced universal screening of all anonymous oocyte donor candidates from 1997 to 2008 at a university hospital oocyte donation program were reviewed. Primary outcomes were the frequency of oocyte donor candidates excluded as a result of enhanced universal screening (Tay-Sachs, Fragile X, karyotypic analysis and MMPI-2) versus basic screening according to ASRM guidelines. RESULTS Of 1303 candidates who underwent on-site evaluation, 47% passed the screening process, 23% were lost to follow-up and 31% were excluded. Genetic and psychological factors accounted for the most common reasons for candidate exclusion. Enhanced genetic screening excluded an additional 25 candidates (19% of all genetic exclusions) and enhanced psychological screening excluded an additional 15 candidates (12% of all psychological exclusions). Altogether enhanced screening accounted for 40 candidates (10%) of the total pool of excluded candidates. CONCLUSIONS Although our study is limited by its retrospective nature and center-specific conclusions, we show that enhanced comprehensive screening can exclude a significant number of candidates from an oocyte donor program and should be encouraged to assure optimal short-term and long-term outcomes for pregnancies achieved through oocyte donation