Faculty Bibliography

BACKGROUND: Preimplantation genetic screening (PGS) affords couples the knowledge of embryo ploidy status prior to embryo transfer (ET). Many patients arrive at donor egg (DE) after multiple failed autologous in vitro fertilization (IVF) cycles, of which many may be due to aneuploidy. Our goal was to assess if knowledge of ploidy status decreases disposition time to DE and, ultimately, live birth (LB). OBJECTIVE: To determine if patient knowledge of embryo ploidy status through use of PGS using array comparative genomic hybridization (aCGH) changes disposition time DE enrollment at a large university-based fertility center. MATERIALSAND METHODS: Patients who enrolled in the DE program between 2011 and 2014 at the NYU Fertility Center that had a prior in vitro fertilization (IVF) cycle were identified. The number of IVF egg retrievals (ER) and ET with and without PGS performed before enrolling in DE were collected. The primary outcome was time in months from initial consultation visit to first DE transfer and to live birth. If the patient had a prior LB, the consultation visit was the first visit after the LB to discuss continued childbearing. Unpaired t-tests and chi-square were used for analysis with p< 0.05 defined as significance. RESULTS: A total of 110 patients had both IVF and DE cycles at NYUFC. There were 9 patients that underwent day 3 embryo biopsy and PGS with aCGH and 19 patients that had previously undergone trophectoderm biopsy and PGS with aCGH. Of these patients that did PGS, only 7/28 (25%) made at least one euploid embryo. Use of PGS did not decrease the number of IVF cycles, disposition time to DE, or time to DE LB. Prior parity and pregnancy rates were similar in both groups. CONCLUSIONS: One might expect that knowledge of embryo aneuploidy would affect disposition time to DE. This small retrospective cohort study shows no difference in disposition time to DE. However, given that trophectoderm biopsy with aCGH is a relatively new technology, it may be too early to assess the true impact on knowledge of ploidy status on disposition to DE (Figure Presented)

PURPOSE: Preimplantation genetic screening (PGS) and diagnosis (PGD) with euploid embryo transfer is associated with improved implantation and live birth rates as compared to routine in vitro fertilization. However, misdiagnosis of the embryo is a potential risk. The purpose of this study was to investigate the clinical discrepant diagnosis rate associated with transfer of trophectoderm-biopsied blastocysts deemed to be euploid via array comparative genomic hybridization (aCGH). METHODS: This is a retrospective cohort study including cycles utilizing PGS or PGD with trophectoderm biopsy, aCGH, and euploid embryo transfer at a large university-based fertility center with known birth outcomes from November 2010 through July 2014 (n = 520). RESULTS: There were 520 embryo transfers of 579 euploid embryos as designated by aCGH. Five discrepant diagnoses were identified. Error rate per embryo transfer cycle was 1.0 %, 0.9 % per embryo transferred, and 1.5 % per pregnancy with a sac. The live birth (LB) error rate was 0.7 % (both sex chromosome errors), and the spontaneous abortion (SAB) error rate was 17.6 % (3/17 products of conception tested, but could range from 3/42 to 7/42). No single gene disorders were mistakenly selected for in any known cases. CONCLUSIONS: Although aCGH has been shown to be a highly sensitive method of comprehensive chromosome screening, several possible sources of error still exist. While the overall error rate is low, these findings have implications for counseling couples that are contemplating PGS and PGD with aCGH.

This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.

OBJECTIVE: To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN: Decision-tree mathematical model with sensitivity analyses. SETTING: Not applicable. PATIENT(S): A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cost per live birth. RESULT(S): Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from $55,060 to $39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to $61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S): In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

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.