Faculty Bibliography

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

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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Introduction: Uterine rupture is a rare but catastrophic complication with significant perinatal morbidity and mortality. The initial signs and symptoms can be non-specific, thus delaying definitive, life saving interventions. The purpose of this study was to identify maternal and/ or fetal "alarm criteria" in patients at risk for uterine rupture whole undergoing TOLAC.
Method(s): A retrospective chart review was conducted of patients undergoing TOLAC, from March 2013 through December 2017. Inclusion criteria: patients aged 18-54 years, with 1 or 2 previous Cesarean sections (C/S), with singleton, vertex, >/= 34 weeks gestations. Exclusion criteria: patients with fetal demise, preterm gestation, contraindications to vaginal birth.
Result(s): There were 30,000 deliveries during the study period. Of these, 12,900 (43%) underwent TOLAC and 2486 of these patients had 2 prior C/S. Uterine rupture at delivery was confirmed in 193 (1.5%) women, with 172 (88.8%) being identified at C/S and 21 (11.1%) at vaginal delivery. Anterior or side wall ruptures occurred in 136 (70.4%) patients. Of these, 86 (63%) were located in the previous uterine scar. Category II or III fetal heart tracings occurring within the last hour of the diagnosis of rupture and/ or delivery, were noted in 164 (85.2%) patients. Abdominal pain, rated by the patients as "moderate/severe" in spite of previously adequate epidural analgesia, occurred in 185 (96%) patients. Intrapartum vaginal bleeding (>/=75 cc), occurred in 78 (40.7%) and loss of station of the presenting part in 57 (29.6%) patients. Loss of adequate uterine contraction pattern occurred in 57 (29.6%) patients.
Conclusion(s): The most frequent indicator of uterine rupture was moderate/ severe pain in spite of previously adequate analgesia versus FHR abnormalities, which are noted in the literature as being the most frequent and reliable indicator. We suggest that pain in this clinical setting is THE alarm criterion which should initiate interventions to mitigate adverse outcomes in these patients

Two of the many milestone developments in the field of assisted reproduction have been oocyte donation and preimplantation genetic testing for aneuploidy (PGT-A). Because it has been demonstrated that even young women produce a meaningful proportion of aneuploid embryos, screening out such abnormalities could potentially increase the efficacy of donor egg (DE) cycles. In this retrospective cohort study, we investigated the effect of PGT-A on DE cycle outcomes, including implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate. We used fresh and frozen donor cycles not using PGT-A as comparison groups; all cases involved single embryo transfer. Data analysis revealed that PGT-A did not improve pregnancy outcome metrics in DE cycles, although there was a trend toward decreasing the SABR. There was a significant increase in IR with fresh cycles outperforming all frozen cycles. Overall, these results suggest that the benefits of performing PGT-A on embryos derived from young DEs may be limited and that there is an effect of the freezing process on pregnancy outcomes. These findings may provide useful insights into the science and practice of PGT-A across all of its applications.

Unveiling the transcriptome of human blastocysts can provide a wealth of important information regarding early embryonic ontology. Comparing the mRNA production of embryos with normal and abnormal karyotypes allows for a deeper understanding of the protein pathways leading to viability and aberrant fetal development. In addition, identifying transcripts specific for normal or abnormal chromosome copy number could aid in the search for secreted substances that could be used to non-invasively identify embryos best suited for IVF embryo transfer. Using RNA-seq, we characterized the transcriptome of 71 normally developing human blastocysts that were karyotypically normal vs. trisomic or monosomic. Every monosomy and trisomy of the autosomal and sex chromosomes were evaluated, mostly in duplicate. We first mapped the transcriptome of three normal embryos and found that a common core of more than 3,000 genes is expressed in all embryos. These genes represent pathways related to actively dividing cells, such as ribosome biogenesis and function, spliceosome, oxidative phosphorylation, cell cycle and metabolic pathways. We then compared transcriptome profiles of aneuploid embryos to those of normal embryos. We observed that non-viable embryos had a large number of dysregulated genes, some showing a hundred-fold difference in expression. On the contrary, sex chromosome abnormalities, XO and XXX displayed transcriptomes more closely mimicking those embryos with 23 normal chromosome pairs. Intriguingly, we identified a set of commonly deregulated genes in the majority of both trisomies and monosomies. This is the first paper demonstrating a comprehensive transcriptome delineation of karyotypic abnormalities found in the human pre-implantation embryo. We believe that this information will contribute to the development of new pre-implantation genetic screening methods as well as a better understanding of the underlying developmental abnormalities of abnormal embryos, fetuses and children.