Faculty Bibliography

OBJECTIVE: To determine whether there is a difference in pregnancy outcomes, stratified by age, between women undergoing elective single blastocyst transfer (eSBT) versus those undergoing double blastocyst transfer (2BT). DESIGN: Retrospective analysis. SETTING: University IVF center. PATIENT(S): A total of 1,141 nondonor IVF cycles in women aged <40 years from January 2004-March 2007. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Eggs retrieved, embryos cryopreserved, implantation rates, clinical pregnancy rates (PR), live birth rates (LBR), spontaneous abortion rates (SAB). RESULT(S): Pregnancy outcomes in 52 cycles of women <40 years of age who underwent eSBT were compared with 1,086 cycles of women who underwent 2BT in fresh IVF cycles from January 2004-March 2007. Overall, the eSBT was associated with a statistically significant 92% reduction in the twinning rate (from 25%-2%) while maintaining a high clinical PR (63% in the eSBT group vs. 61% in the 2BT group). CONCLUSION(S): Women who are <40 years of age undergoing nondonor fresh IVF cycles can electively choose to transfer a single blastocyst for the purpose of significantly reducing their risk of multiples without compromising their PR

OBJECTIVE: To compare rates of implantation, pregnancy, miscarriage, multiple gestation, and selective reduction between patients undergoing day 5 (d5) and day 3 (d3) ETs. DESIGN: Retrospective cohort study. SETTING: University-based IVF center. PATIENT(S): The first d5 ET cycle of patients 42 years of age from 2003 to 2006 was compared with a historical control of first cycle d3 ET patients 42 years of age from 1996 to 1999 who would have met current d5 ET criteria. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of implantation, clinical pregnancy, miscarriage, live birth, high order multiple pregnancy (HOMP), and selective reduction. RESULT(S): D5 ET patients had higher implantation rates (39% vs. 30%), with no difference in the no-transfer rate. D5 ET patients had lower rates of HOMP (2.5% vs. 11%) and HOMP delivery (0.7% vs. 3.5%), multiple pregnancy (27% vs. 33%), multiple delivery (19% vs. 26%), and twin delivery (18% vs. 23%). There were fewer selective reductions of HOMP with d5 ET (1.7% vs. 3.8%). CONCLUSION(S): Extended culture improves embryo selection through increased implantation, facilitating fewer embryos per transfer, which lowers multiple gestation rates and the need for HOMP reduction

OBJECTIVE: To explore the use of oocyte cryopreservation as a fertility-conserving option. Cancer treatments administered during the reproductive and adolescent years can result in sterility. Previous fertility preservation efforts focused on embryo rather than oocyte storage because the latter was deemed inefficient. Recently, several large reports of healthy births resulting from the transfer of embryos derived from frozen/thawed oocytes have been published. We sought to establish an oocyte cryopreservation program at our center. DESIGN: Twenty-three oocyte cryopreservation cycles were performed. Collected oocytes were cryopreserved by either the slow or the vitrification method. Approximately 1-4 months later, a programmed cycle of thawing/warming, fertilization with intracytoplasmic sperm injection, and ET was performed; cycle and pregnancy outcomes were assessed. SETTING: University-based fertility center. PATIENT(S): Twenty-two infertile women. INTERVENTION(S): Oocyte cryopreservation. MAIN OUTCOME MEASURE(S): Oocyte survival, embryo development, pregnancy outcomes. RESULT(S): Oocyte survival, 2-pronuclei fertilization, and blastocyst formation rates were 92%, 79%, and 43%, respectively. Fourteen women became pregnant; one miscarried; 10 have delivered 13 viable infants, and three pregnancies are ongoing for an ongoing/delivered pregnancy rate of 57%. This result was not statistically different from cycles performed consecutively in age-matched controls using fresh, nonfrozen autologous or donor oocytes during a similar time period. CONCLUSION(S): Oocyte cryopreservation appears to be a viable option for fertility preservation in some centers

OBJECTIVE: To determine whether there is a difference in pregnancy outcomes between women undergoing a shared versus exclusive donor oocyte cycle. DESIGN: Retrospective analysis. SETTING: University IVF center. PATIENT(S): Women undergoing either a shared (n=656 cycles), exclusive (n=225 cycles), or shared converted to exclusive (n=22 cycles) donor oocyte cycle from January 2000-December 2005. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of eggs retrieved, eggs fertilized, embryos transferred, embryos cryopreserved, clinical pregnancy rates (PR), live birth rates, spontaneous abortion rates. RESULT(S): Pregnancy outcomes in 656 shared cycles were compared with 225 exclusive cycles and 22 shared converted to exclusive donor oocyte cycles. Overall, there was no difference in the clinical PR among the three groups; however, the exclusive group did have a significantly greater number of embryos cryopreserved and this event occurred more frequently in such a cycle. CONCLUSION(S): Women undergoing a donor oocyte IVF cycle can choose to share the donor's oocytes with another recipient without compromising their PR; however, the probability of cryopreservation in such a shared donor oocyte cycle is significantly reduced. Therefore, the recipient must weigh the financial burden of an exclusive cycle with the desires for cryopreservation in an IVF cycle

Background: Early detection programs combined with improved treatment protocols have allowed cancer patients (CP) to live substantially longer lives. Therefore, quality-of-life issues, such as fertility preservation (FP), have become increasingly important. Previously, time constraints and poor success limited the effectiveness of such procedures. However, recent advancements in oocyte cryopreservation (OC) technology have made this a viable option. OC not only eliminates the need for donor gametes but also the ethical, personal and religious constraints associated with embryo freezing. The novelty of OC has limited its universality; only recently have oncologists begun to refer CP for OC with even fewer yet returning to use these oocytes. To ensure feasibility, we compared OC outcomes of CP to all women without cancer who have completed oocyte thaw (n=32). Methods: CP referred for FP underwent extensive counseling in compliance with the ASRM (2009); those electing OC were included. Ovarian stimulation was achieved with injectable gonadotropins. OC was performed using slow cooling and vitrification methods. Results: 50 CP completed an OC cycle (baseline ovarian reserve testing was normal for all CP); 6 had 1 child already. Malignant diagnoses included 22 gyn, 12 breast, 8 hematologic, 2 GI, 2 CNS and 4 other; 7/9 pts >= age 38 had breast cancer. FP treatment was completed on average in 12 +/-0.3 days. Outcome data are shown in the Table. Conclusions: OC is a novel and potentially successful FP option offering desired reproductive choice. With a dedicated team, OC can be performed expeditiously and successfully, minimizing interference with cancer treatment. As future parenthood greatly impacts quality-of-life, OC should be an integral component of FP counseling in young cancer patients. (Table presented)

Background: Objectives - 1) Establish a prospective registry with long-term follow-up of female cancer patients (CP) who presented for initial consultation for FP; 2) Introduce the FACT-B QOL survey for novel use in a FP population. Methods: All consenting female CP completed the registry survey/FACT-B and agreed to yearly follow-up. Results: From 3/2008 to 1/2010, 22 CP enrolled in the registry, 2 declined, and 1 was lost to follow-up. Cancer diagnoses included 6 cervical, 4 breast, 3 endometrial, 2 ovarian, 2 Hodgkin's, 1 childhood neuroblastoma + renal cell carcinoma, 1 Ewing's sarcoma, 1 thymic carcinoma, 1 AML, 1 papillary mesothelioma. The average age at enrollment was 33.1+/-5 (range 23 - 44) y. Sixteen patients sought FP with oocyte (OC) and/or embryo cryopreservation (EC), and 5 underwent in vitro fertilization (IVF). 15/22 were referred from their medical or surgical oncologists. Thirteen patients sought treatment prior to cancer surgery and/or chemo and began FP treatment an average of 12 (range 1 - 22) days from initial consult. Twenty patients completed 30 cycles; 14 used OC and/or EC, 5 IVF and 1 oocyte donation (OD), of which 7 patients underwent embryo transfers resulting in 1 delivery, 1 ongoing (in 8^th month) and 1 miscarried pregnancy. One year follow-up is ongoing. By survery, most patients (12/22) felt having a child was most important in their life (scale 1 - 7; mean 6.1), and 14/22 were most concerned with the impact of their cancer treatment on fertility (mean 6.1). IVF and OD were the most and least preferred treatments, respectively. Recognizing the limited data on the long-term risks for FP patients, most (14/22) were unsure regarding the risk they would undertake to pursue fertility treatment. Most patients reported high baseline QOL scores across all categories of physical, social, emotional, and functional well being. Conclusions: Fertility after cancer remains a significant issue, yet most patients are unsure of their risk tolerance. We introduce the FACT-B QOL survey for novel use in a FP population and aim to determine the long-term safety, effectiveness, and QOL impact of FP treatment in female CP

In an 8-year review of ectopic pregnancy (EP) rates in donor egg recipients and standard patients undergoing in vitro fertilization-embryo transfer (IVF-ET) at a large university-based program, we report an EP rate of 0.6% in donor egg recipients and 0.9% in standard IVF patients, a difference that is not statistically significant. Donor egg recipients were found to have a significantly lower incidence of tubal disease compared with standard IVF patients; however, tubal disease was not found to be an independent risk factor for EP in our practice, perhaps owing to aggressive management of tubal disease

Cancer patients produce similar numbers of oocytes after ovarian hyperstimulation compared with age-matched infertile controls, suggesting that malignancy does not adversely affect ovarian response

OBJECTIVE: Since many frequent, fatal, and incurable diseases do not have an appropriate disease model and with attainable embryos being scarce, with IRB approval we attempted to generate novel disease-specific human embryonic stem (hES) cells with new protocols for more efficient derivation, maintenance, and differentiation. DESIGN: Experimental. MATERIALS AND METHODS: Zona-free human blastocysts (n=14) previously assessed by preimplantation genetic diagnosis (PGD) for genetic conditions were transferred onto feeder cells and cultured in DMEM-based media. Pieces of the colonies (n=4) were frozen by liquid nitrogen vitrification with cryoprotectants propylene glycol, DMSO, and acetamide and subsequently thawed. Differentiation of hES cells was achieved by colony overgrowth or embryoid body formation. Embryonic and control cells were subjected to marker gene and protein analysis for pluripotency and differentiation by reverse transcription PCR and immunofluorescence, respectively. RESULTS: Colonies (n=10; 71.4% of transferred blastocysts) could be established and maintained which showed the typical morphological features of hES cells such as compact colony formation. Colonies were derived from affected embryos (one each of cystic fibrosis, trisomy X, 18, 21, 22, and Tay-Sachs disease), from embryos tested inconclusively (one of cystic fibrosis and three of Tay-Sachs disease), and from three normal control embryos. Marker gene and protein expression as well as growth pattern analysis suggest that the colony cells retain their undifferentiated state in culture as well as after vitrification and thawing and that they can be differentiated into a variety of cell types, including the tissues most affected by the conditions. CONCLUSIONS: These newly established protocols for the derivation, maintenance, and differentiation of novel disease-specific hES cell lines should enable the efficient generation of new disease models. This will provide new tools to study diseases as well as to develop new therapeutic approaches