Faculty Bibliography

Objective: To determine the incidence of euploidy in Blastocysts derived from 0PN and 1PN compared with 2PN embryos.
Design(s): Single center retrospective review of PGT-A cases over a 4 year period (2015-2018) where a biopsy and ploidy determination was performed on blastocysts (blasts) derived from zygotes where pronuclei (PNs) were either not evident (0 PN) or only 1 pronucleus (1 PN) was evident at the time of fertilization check.
Material(s) and Method(s): At NYULMC fertilization checks are conducted ~18 hours post insemination or ICSI. The number of PN in each egg is recorded and zygotes are cultured individually. Cases where <=50% of the mature eggs exhibit 2PN are routinely rechecked later on Day 1. In cases for PGT-A, all viable inseminated eggs excluding those with >=3 PN remain in culture to Day 6/7. Good quality blastocysts with a distinct Inner cell mass and cohesive trophectoderm are considered for PGT-A regardless of whether they were 0PN, 1PN or 2PN at fertilization check. PGT-A results are shown in Table 1 along with PGT-A sex of blasts derived from each group.
Result(s): [Figure presented]
Conclusion(s): Prior to utilization of PGT-A and/or timelapse zygotes not exhibiting 2PN at fertilization check were routinely discarded. However, it is now obvious that a percentage of these, albeit small, are fertilized normally and are euploid. Though they account for only a small percentage these may be the only euploid blasts available. Implantation rates and LB rates following transfer of these blasts are similar to those for 2PN blastocysts. Of interest, ratios of XX:XY blasts derived from 1PN and 0PN zygotes were ~2:1 while those from 2PN zygotes were ~1:1. It should be noted that NGS cannot detect pure haploidy (23, XO) or triploidy (69, XXX thereby possibly misdiagnosing these as euploid although our IR and LB results indicate otherwise.
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Objective: To determine the incidence of euploidy and implantation and delivery of Blastocysts derived from 0PN and 1PN compared with 2PN embryos.
Design(s): Single center retrospective review of PGT-A cases over a 4 year period (2015-2018) where a biopsy and ploidy determination was performed on blastocysts (blasts) derived from zygotes where pronuclei (PNs) were either not evident (0 PN) or only 1 pronucleus (1 PN) was evident at the time of fertilization check.
Material(s) and Method(s): At our center fertilization checks are routinely conducted ~18 hours post insemination or ICSI. The number of PN in each egg is recorded and zygotes cultured individually. Cases where < 50% of the mature eggs exhibit 2PN are routinely rechecked later on Day 1 and omitted from this study if additional PNs seen. In cases for PGT-A, all viable inseminated eggs excluding those with > 3 PN remain in culture to Day 6/7. Good quality blastocysts with a distinct Inner cell mass and cohesive trophectoderm are considered for PGT-A regardless of whether they were 0PN, 1PN or 2PN at fertilization check. PGT-A results are shown in Table 1 along with PGT-A sex of blasts derived from each group.
Result(s): [Figure presented]
Conclusion(s): Prior to utilization of PGT-A and/or timelapse zygotes not exhibiting 2PN at fertilization check were routinely discarded. However, it is now obvious that a percentage of these, albeit small, are fertilized normally and are euploid. Though they account for only a small percentage these may be the only euploid blasts available. Implantation rates and LB rates following transfer of these blasts are similar to those for 2PN blastocysts. Of interest, ratios of XX:XY blasts derived from 1PN and 0PN zygotes were skewed towards female while those from 2PN zygotes were ~1:1. It should be noted that NGS cannot detect pure haploidy (23, X) or triploidy (69, XXX) thereby possibly misdiagnosing these as euploid although our IR and LB results indicate otherwise. Support: None References: None
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Objective: Current data suggests that use of oral antibiotics and corticosteroids (AC) prior to embryo transfer (ET) does not improve ET outcomes. We hypothesized that patients with a history of chronic endometritis (CE) may be an exception to this finding. The objective was to investigate the utility of AC prior to single thawed euploid embryo transfer (STEET) in patients with CE.
Design(s): Retrospective cohort study.
Material(s) and Method(s): Patients who underwent STEET at an academic medical center from 1/2000 to 4/2019 were identified. Cycles prior to 1/2018 received 100 mg doxycycline bid and methylprednisolone 16 mg daily (Pre) prior to ET, and cycles performed after this date did not (Post). Cycles were evaluated for performance of endometrial biopsy (EMB) for CE, with CE defined as presence of plasma cell marker CD-138 (not by hematoxylin and eosin stain alone). Patients positive for CE were treated with 2-3 weeks antibiotics prior to ET cycle start. Outcomes were recorded as not pregnant (NP), biochemical pregnancy (BP), ectopic (E), or intrauterine pregnancy (IUP). Rates of IUP were compared to NP+E and BP. Chi-squared test was used for analysis (p<0.05).
Result(s): 2774 STEET cycles were included. There were 1870 Pre and 904 Post. 462 cycles had an EMB for CE performed. Of these, 238 were positive for CE and 224 were negative. Rates of IUP versus NP, BP, and E combined were not significantly different between all Pre (n=1247, 67%) and all Post (n=628, 68%) with X²(2, N=2765) =2.24 P>.05. Similarly, rates of IUP were not significantly different in patients who had not had an EMB (Untested), or in patients who were tested for CE and found to be negative. In patients with a history of CE there was a small but significant increase in IUP in Post (n=61, 54%) compared to Pre (n=46, 37%) X²(2, N=238) =9.31 P<0.05.
Conclusion(s): Overall, treatment with AC was not associated with higher IUP rates. The use of AC did not improve outcomes in patients with a history of CE, and unexpectedly resulted in lower IUP rates. [Figure presented]
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Objective: An FSH boost on trigger-day may improve outcomes in fresh transfers by enhancing folliculogenesis and endometrial receptivity. As more patients are freezing all of their embryos, the endometrial effect is less of a concern, but folliculogenesis remains relevant. Recent reports^1,2 conflict over the clinical effects of an FSH boost. We therefore examined the effect of an FSH boost on oocyte retrieval, quality, and development, specifically in patients undergoing PGT-A.
Design(s): Retrospective cohort.
Material(s) and Method(s): Patients undergoing GnRH-antagonist IVF cycles from 1/2015 through 12/2018, were separated into two groups for comparison: those receiving only trigger injections on trigger day (NB), and those also receiving an FSH boost (B). Demographics, days of gonadotropin, #oocytes retrieved, #mature, #blastocysts, and #euploid embryos, were compared (Student's t-test or X²).
Result(s): Both groups were stratified into SART registry age groups. Initial comparisons between the groups, without matching for trigger day estradiol levels (E2Trig), revealed a selection bias. B patients had weaker responses, with lower estradiol levels and fewer eggs. In order to examine the effect of B in each age group, we created NB comparison groups with E2Trig values indistinguishable from the B's. This was done by randomly selecting NB patients from the same age group and E2Trig stratum as B. 1394 patients were included in this matched comparison. 697 received B, and 697 did not. B patients had significantly more days of gonadotropin administration (~1 day) than NB patients. There were no consistent differences for #oocytes retrieved, #mature, fertilization rate, #blastocysts, or #euploid embryos (see table). Overall, costs associated with B amounted to $276,923, or close to $400 per patient. [Figure presented]
Conclusion(s): No benefit of B was found for #oocytes retrieved, #mature, fertilization rates, #blastocysts, or #euploid embryos. There are significant cost savings associated with NB. References: 1. Lamb JD, Shen S, McCulloch C, Jalalian L, Cedars MI, Rosen MP. Follicle-stimulating hormone administered at the time of human chorionic gonadotropin trigger improves oocyte developmental competence in in vitro fertilization cycles: a randomized, double-blind, placebo-controlled trial. Fertility and sterility. 2011 Apr;95(5):1655-60. 2. Juneau CR, Morin SJ, Franasiak JM, Landis JN, Molinaro TA, Scott RT. A follicle-stimulating hormone boost administered at the time of human chorionic gonadotropin trigger does not affect IVF cycle outcomes. Fertility and sterility. 2016;106(3):e189-e90.
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OBJECTIVE: An FSH boost on trigger-day may improve outcomes in fresh transfers by enhancing folliculogenesis and endometrial receptivity. As more patients are freezing all of their embryos, the endometrial effect is less of a concern, but folliculogenesis remains relevant. Recent reports1,2 conflict over the clinical effects of an FSH boost. We therefore examined the effect of an FSH boost on oocyte retrieval, quality, and development, specifically in patients undergoing PGT-A. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Patients undergoing GnRH-antagonist IVF cycles from 1/2015 through 12/2018, were separated into two groups for comparison: those receiving only trigger injections on trigger day (NB), and those also receiving an FSH boost (B). Demographics, days of gonadotropin, #oocytes retrieved, #mature, #blastocysts, and #euploid embryos, were compared (Student's t-test or X2).
RESULT(S): Both groups were stratified into SART registry age groups . Initial comparisons between the groups, without matching for trigger day estradiol levels (E2Trig), revealed a selection bias. B patients had weaker responses, with lower estradiol levels and fewer eggs. In order to examine the effect of B in each age group, we created NB comparison groups with E2Trig values indistinguishable from the B's. This was done by randomly selecting NB patients from the same age group and E2Trig stratum as B. 1394 patients were included in this matched comparison. 697 received B, and 697 did not. B patients had significantly more days of gonadotropin administration (~1 day) than NB patients. There were no consistent differences for #oocytes retrieved, #mature, fertilization rate, #blastocysts, or #euploid embryos (see table). Overall, costs associated with B amounted to $276,923, or close to $400 per patient.
CONCLUSION(S): No benefit of B was found for #oocytes retrieved, #mature, fertilization rates, #blastocysts, or #euploid embryos. There are significant cost savings associated with NB