Faculty Bibliography

BACKGROUND: Low functional ovarian reserve (LFOR) has been associated with hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation has been reported to improve aneuploidy rates. We, therefore, assessed whether in infertile women undergoing in vitro fertilization (IVF) androgen concentrations are associated with aneuploidy rates. METHODS: This study was performed in 2 academically affiliated fertility centers in New York City and an academically affiliated steroid chemistry laboratory in Utah. Androgen concentrations were measured in blinded fashion from 84 infertile women (age 40.3 +/- 2.4 years) at New York University (NYU), using a validated LC-MS/MS method, in cryopreserved serum samples of patients who had undergone IVF with concomitant preimplantation genetic screening (PGS), utilizing a 24-chromosome platform. The Center for Human Reproduction (CHR) provided plasma samples of 100 historical controls (ages 38.6+/-5.0 years) undergoing IVF without PGS. Statistical comparisons were made of androgen concentrations, and of associations between androgen concentrations and embryo aneuploidy. RESULTS: Women undergoing IVF + PGS at NYU revealed no association between embryo aneuploidy and androgen concentrations but demonstrated significantly lower androgen concentrations than the 100 control patients from CHR, CONCLUSIONS: Though this study revealed no association between androgen levels and embryo ploidy, the extremely low androgen levels in the NYU study group raise the possibility of a threshold effect below which testosterone no longer affects aneuploidy. Before an androgen effect on embryo ploidy can be completely ruled out, a patient population with more normal androgen levels has to be investigated.

OBJECTIVE: To compare the euploidy outcome in patients that underwent 2 ovarian stimulation cycles with trophectoderm biopsy. DESIGN: Retrospective repeated-measures cohort study. SETTING: University-based fertility center. PATIENT(S): A total of 116 patients, from 2011 through 2013, that underwent 2 ovarian stimulation cycles followed by trophectoderm biopsy with array comparative genomic hybridization. INTERVENTION(S): Days of stimulation, average diameter of the 2 lead follicles on day of trigger, dose of gonadotropins, type of cycle (gonadotropin-releasing hormone [GnRH] antagonist, GnRH-antagonist plus clomiphene citrate [CC], microdose GnRH agonist). MAIN OUTCOME MEASURE(S): Number of euploid embryos. RESULT(S): Patients were analyzed based on whether they had >/=1 euploid embryos in their first cycle vs. none. There was no increase in the number of euploid embryos with more days of stimulation or increases in the dose of gonadotropins in either group. Significantly more euploid embryos were seen in patients who had no euploid embryo(s) in the first cycle (Group 0) that had CC added to a GnRH-antagonist cycle (1.11 more euploid embryos) or were triggered when follicle sizes were 2 mm larger (0.40 euploid embryos), but these increases were not significant compared with a control group. Patients with euploid embryo(s) in the first cycle (Group 1) had significantly more euploid embryos when daily dose was increased by 75-149 international units, but this relationship was not significant compared with a control group with no increase in daily dose. CONCLUSION(S): No specific intervention increased the number of euploid embryos within the same patient any more than simply repeating a similar stimulation cycle. An attempt was made to control for interpatient variability, but individual patients have considerable intercycle variability.

OBJECTIVE: To determine if long-term cryopreservation of human oocytes affects oocyte developmental competence, blastocyst euploidy, or live-birth rates. DESIGN: Retrospective cohort study. SETTING: University-based fertility center. PATIENT(S): A total of 33 patients with cryopreserved oocytes underwent oocyte thaw, blastocyst culture, trophectoderm biopsy, and 24-chromosome preimplantation genetic screening (PGS) with array comparative genomic hybridization between December 2011 and July 2014; subjects were compared with 2:1 age-matched controls with fresh oocytes whose embryos underwent trophectoderm biopsy and PGS during the same period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of fertilization, blastulation, euploidy, implantation, and live birth. RESULT(S): Thirty-three patients (mean age 36.2 +/- 3.8 y) thawed 475 oocytes that had been cryopreserved for a median of 3.5 years. Compared with 66 age-matched controls who underwent in vitro fertilization and PGS with fresh oocytes, embryos derived from cryopreserved oocytes demonstrated compromised blastocyst formation (54.5% vs. 66.2%) despite no impairment in fertilization (72.8% vs. 73.2%). Results showed no difference in the number of euploid blastocysts (1.7 +/- 1.9 vs. 2 +/- 2.5), percentage of euploid blastocysts (44.5% vs. 47.6%), rate of implantation (65% vs. 65%), or rate of live birth and ongoing pregnancy (62.5% vs. 55%) after 24-chromosome PGS with cryopreserved or fresh oocytes. CONCLUSION(S): Embryos derived from cryopreserved oocytes demonstrate impaired blastulation but equivalent rates of euploidy, implantation, and live birth compared with blastocysts derived from fresh oocytes, supporting the safety and efficacy of oocyte cryopreservation.

OBJECTIVE: To determine whether an association exists between body mass index (BMI) and embryo ploidy in patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy and 24-chromosome preimplantation genetic screening (PGS). DESIGN: Retrospective cohort study. SETTING: University-based fertility center. PATIENT(S): 279 women aged 20-45 years with documented height and weight from the day of oocyte retrieval who underwent 24-chromosome PGS between 2010 and 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes: number and percentage of euploid embryos. RESULT(S): Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n = 11), normal weight (18.5-24.9, n = 196), overweight (25-29.9, n = 50), and obese (>/=30, n = 22). Groups were similar by age (mean +/- standard error of the mean: 37.5 +/- 1.2 to 39.2 +/- 0.9), ovarian reserve, and IVF cycle parameters. There was no difference in the number or percentage of euploid embryos by BMI category (<18.5: 27.6% +/- 8.5; 18.5-24.9: 34.5% +/- 2.2; 25-29.9: 32.1% +/- 4.3; >/=30: 30.9% +/- 7.3). Age was inversely related to euploidy, but adjusted multivariate regression models failed to demonstrate a statistically significant relationship between BMI and euploidy in underweight (adjusted odds ratio [AOR] 0.44; 95% confidence interval [CI], 0.09-2.10), overweight (AOR 0.90; 95% CI, 0.43-2.00), or obese (AOR 0.74; 95% CI, 0.25-2.20) patients compared with the normal-weight reference group. CONCLUSION(S): No statistically significant relationship was identified between BMI and euploidy in an otherwise homogenous cohort of patients undergoing IVF with PGS, suggesting that the negative impact of overweight and obesity on IVF and reproductive outcomes may not be related to aneuploidy.

PURPOSE: In Vitro Fertilization is an effective treatment for infertility; however, it has relatively low success in women of advanced maternal age (>37) who have a high risk of producing aneuploid embryos, resulting in implantation failure, a higher rate of miscarriage or birth of a child with chromosome abnormalities. The purpose of this study was to compare the implantation, miscarriage and live birth rates with and without preimplantation genetic screening (PGS) of embryos from patients aged 40 through 43 years. METHODS: This is a retrospective cohort study, comparing embryos screened for ploidy using trophectoderm biopsy and array comparative genomic hybridization to embryos that were not screened. We compared pregnancy outcomes for traditional fresh IVF cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period between 1/1/2011 and 12/31/2012. RESULTS: The implantation rate of euploid embryos transferred in FET cycles (50.9 %) was significantly greater than for unscreened embryos transferred in either fresh (23.8 %) or FET (25.4 %) cycles. The incidence of live birth per transferred embryo for PGS-FET (45.5 %) was significantly greater than for No PGS fresh (15.8 %) or No PGS FET (19.0 %) cycles. The incidences of live birth per implanted sac for PGS FET cycles (89.3 %), No PGS fresh cycles (66.7 %) and No PGS FET cycles (75.0 %) were not significantly different. CONCLUSIONS: The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.

PURPOSE: To determine if day of embryo transfer (ET) affects gestational age (GA) and/or birth weight (BW) at a single university fertility center that primarily performs day 5/6 ET. METHODS: Retrospective cohort study of 2392 singleton live births resulting from IVF/ICSI at a single large university fertility center from 2003 to 2012. Patients were stratified by day 3 or day 5/6 ET. Outcome variables included patient age, gravidity, prior miscarriages, prior assisted reproduction technology cycles, number of embryos transferred, number of single ET, infertility diagnosis, neonatal sex, GA at birth, and BW. Subanalyses were performed on subgroups of preterm infants. A comparison was made between the study data and the Society of Assisted Reproductive Technologies (SART) published data. RESULTS: There was no difference in GA at birth (39 +/- 2.1 weeks for day 3 ET, 39 +/- 1.9 weeks for day 5/6 ET) or BW between ET groups (3308 +/- 568 g for day 3 ET, 3268 +/- 543 g for day 5/6 ET). There was also no difference in the number of preterm deliveries (8.5 % for day 3 ET vs. 10.8 % for day 5/6 ET). The day 5/6 ET study data had significantly fewer pre-term deliveries than the SART day 5/6 ET data. CONCLUSION: In contrast to published SART data, GA and BW were not influenced by day of ET. Data may be more uniform at a single institution. Day 5/6 ET continues to offer improved pregnancy rates without compromising birth outcomes.