Faculty Bibliography

We aim to present two rare cases of ovarian torsion immediately following controlled ovarian hyperstimulation and their prolonged recovery state at an academic fertility center. Patient 1 is a 38-year-old nulligravid woman with a history of prior right oophorectomy and patient 2 is a 37-year-old nulligravid woman with a previous left oophorectomy. The main objective of our paper is to characterize the recovery time after ovarian detorsion surgery. These case reports highlight that ovarian torsion after controlled ovarian hyperstimulation may be associated with prolonged systemic symptoms including increased abdominal pain, persistent low-grade fevers, and mild leukocytosis for several weeks following laparoscopic ovarian de-torsion. A proposed mechanism for this extended inflammatory state could be due to higher levels of luteinizing hormone surge activating Phospholipase C-Protein Kinase C pathway and vascular endothelial growth factors involved in follicular growth and luteinization.

PURPOSE/OBJECTIVE:To determine factors associated with embryo disposition decisions at a large academic fertility center. METHODS:We performed a single-center retrospective cohort study of patients who made final embryo disposition (discard or donation to research) between January 1, 2020, and February 28, 2024, via electronic consent. Demographic and cycle-specific variables were collected via chart review. Chi-square and Mann-Whitney U tests were used for data analysis (p < 0.05). RESULTS:Of 1280 patients, 900 (70.3%) discarded embryos and 380 (29.7%) donated to research. Patients who donated were more likely to have a diagnosis of recurrent pregnancy loss (6.1% vs 2.4%, p < 0.002). Patients who chose to donate had transferred more embryos (2 vs 1, p < 0.033) and had transferred more euploid embryos (44.7% vs 36.6%, p < 0.007). There was no difference in total number, number of euploids, or type of embryo disposed (p = 0.24, p = 0.96, p = 0.34). There was no difference observed among those who communicated with the center (p = 0.81) or those using donor gametes (egg p = 0.34, sperm p = 0.29). An additional analysis compared patients who achieved live birth (n = 902) to those who did not (n = 378), and those who donated were more likely to have achieved live birth (32.0% vs 24.1%, p < 0.005). CONCLUSION(S)/CONCLUSIONS:At final embryo disposition, more patients discarded embryos than donated. Donators were more likely to have recurrent pregnancy loss as their reason for pursuing embryo creation, transfer more embryos across all cycles, and achieve a live birth. Discarders were more likely to have transferred untested or no embryos.

PURPOSE/OBJECTIVE:To evaluate the live birth rate (LBR) following donor frozen embryo transfer (dFET) of preimplantation genetic testing for aneuploidy (PGT-A) versus untested donor embryos, stratified by blastocyst morphologic grade (MG). METHODS:This was a retrospective cohort study of 146 patients undergoing dFET of a single euploid blastocyst from fresh or frozen oocytes using PGT-A compared to age-matched controls (1:1 ratio) who did not use PGT-A. Primary outcome was LBR. LBR was compared among cohorts, with further stratification by (1) high/low MG and (2) fresh/frozen oocyte status. Secondary outcomes included perinatal outcomes. RESULT(S)/RESULTS:Median age in both groups was 44.5 years (p = 0.98). LBR was similar among the two cohorts (PGT-A: 57.5% vs. untested: 50.0%, p = 0.20). There was similar LBR in fresh (PGT-A: 59.2% vs. untested: 50.0%, p = 0.20) and frozen (PGT-A: 47.6% vs. untested: 50.0%, p = 0.85) oocyte subgroups. When stratified by MG, we appreciated similar LBR among high-quality blastocysts (PGT-A-high: 56.5% vs. untested-high: 52.3%, p = 0.49) among the whole cohort, as well as in fresh (fresh-PGT-A-high: 58.3% vs. fresh-untested-high: 52.9%, p = 0.46) and frozen (frozen-PGT-A-high: 44.4% vs. frozen-untested-high: 51.7%, p = 0.59) subgroups. Similarly, we appreciated no difference in LBR among low-quality blastocysts (PGT-A-low: 75.0% vs. untested-low: 31.2%, p = 0.08) among the whole cohort, as well as in the fresh (fresh-PGT-A-low: 80.0% vs. fresh-untested-low: 16.1%, p = 0.08) or frozen (frozen-PGT-A-low: 66.7% vs. frozen-untested-low: 40.0%, p = 0.56) subgroups. Gestational age (37.8 weeks, p = 1.0) and infant birth weight (PGT-A: 3128.0 g vs. untested: 3150.2 g, p = 0.60) were similar. CONCLUSION(S)/CONCLUSIONS:Though limited by the small number of MG blastocysts, overall PGT-A did not improve LBR regardless of blastocyst quality from fresh and previously frozen donor oocytes. CAPSULE/UNASSIGNED:Use of PGT-A did not improve live birth rate regardless of blastocyst quality from both fresh and previously frozen donor oocytes.

PURPOSE/OBJECTIVE:To investigate the relationship between early serum hCG levels after frozen embryo transfer and fetal anomalies. METHODS:This was a case-control study at a single academic fertility center between 1/2010 and 12/2021, including all patients who underwent euploid frozen embryo transfers resulting in any fetal anomaly confirmed at the time of induced abortion > 10 weeks or any anomaly reported at delivery. Controls included patients with healthy live births matched for age and day/grade of embryo after euploid FET. The primary outcome was fetal anomaly, with comparisons made using serum hCG levels from cycle day 28 to cycle day 35 and percent change between days 28 and 35. RESULTS:Both cycle day 28 serum hCG levels and day 35 serum hCG levels were significantly lower in the anomalous group (day 28: 152 vs 177.5 mIU/mL, p < 0.04; day 35: 3033 vs 3744 mIU/mL, p < 0.05). Patients with anomalous outcomes had a significantly lower hCG to start with 5/78 (6.4%) < 50 mIU/mL, 16/78 (20.5%) 51-100 mIU/mL, and 57/78 (73.1%) > 101 mIU/mL, compared to controls 3/78 (3.8%) < 50 mIU/mL, 8/77 (10.3%) 51-100 mIU/mL, and 66/77 (85.7%) > 101 mIU/mL (p < 0.02). However, the rate of rise between day 28 and day 35 was not statistically different (1758.0% vs 2097.0%, p = 0.23). CONCLUSION/CONCLUSIONS:Patients with anomalous fetal outcomes following frozen embryo transfer had lower early serum hCG levels than controls with healthy live births, highlighting the potential utility of this serum marker to identify high-risk pregnancies in the first trimester and expedite treatment as appropriate for this rare but devastating outcome.

PURPOSE/OBJECTIVE:To assess the impact of sperm source on cumulative live birth rate (CLBR) after oocyte thaw in autologous oocyte cryopreservation (AOC) patients. METHODS:A retrospective cohort study of autologous oocyte thaw patients at an urban academic fertility center from 2006 to 2021. Patients were stratified by sperm source [partner sperm (PS) vs. donor sperm (DS)]. The primary outcome was CLBR per patient. Secondary outcomes were the oocyte survival rate and usable embryo rate. Statistics included Mann-Whitney U, Kruskal-Wallis, Fisher's exact, chi-square, two-sample t-tests, and multiple logistic regression (p < 0.05). RESULTS:A total of 653 patients were included; 455 (69.7%) used PS and 198 (30.3%) used DS. Time from the first AOC to the first thaw did not differ among DS and PS users (56.8 vs. 54.0 months, p = 0.20). PS users were younger at AOC (37.9 vs. 38.5 years, p < 0.001) and thaw (42.3 vs. 43.1 years, p < 0.001). There were equivalent overall CLBRs (39.9% PS vs. 40.6% DS, p = 0.85) and CLBRs in patients < 35 years at AOC (51.2% PS vs. 100% DS, p = 0.18), 35-37 years at AOC (45.9% PS vs. 60.4% DS, p = 0.10), 38-40 years at AOC (35.4% PS vs. 35.2% DS, p = 0.93), 41-42 years at AOC (28.9% PS vs 14.3% DS, p = 0.21), and > 43 years at AOC (12.5% PS vs 16.7% DS, p = 0.83) among PS and DS users. There were no significant differences in the oocyte survival (79% PS vs 80.5% DS, p = 0.08) or the proportion of patients with usable embryos (27.3% vs 27.8%, p = 0.70) between PS and DS groups. CONCLUSIONS:In AOC patients, CLBR, oocyte survival rate, and usable embryo rate did not differ based on sperm source.

PURPOSE/OBJECTIVE:To investigate pregnancy outcomes resulting from transfer of embryos with non-mosaic (NM) segmental aneuploid (SA) results following preimplantation genetic testing for aneuploidy (PGT-A). METHODS:All patients who underwent frozen embryo transfer (FET) of at least one embryo with a NM-SA between March 2021 and April 2024 were retrospectively reviewed. Primary outcomes included live birth rate (LBR) and results of prenatal diagnosis. Embryos with NM-SA results were also compared to those with NM whole chromosome aneuploid (WCA) and mosaic SA results. RESULTS:Out of 25 NM-SA embryos transferred, the LBR was 24%. Prenatal diagnosis by amniocentesis and/or chorionic villus sampling was performed in 3/6 pregnancies, and results were normal. Embryos with duplications produced more live births compared to those with deletions. NM-SA embryos had a significantly higher ongoing pregnancy (OP)/LBR compared to embryos with NM-WCA results and a significantly lower OP/LBR compared to embryos with mosaic SA results; however, when compared to embryos with high-level SA mosaicism > 40%, the OP/LBR was not significantly different. CONCLUSION/CONCLUSIONS:Embryos with NM-SAs can result in euploid live births, albeit at reduced rates compared to those with mosaic SAs. These data can be used to aid in patient counseling about PGT-A results and embryo transfer decisions.

PURPOSE/OBJECTIVE:Our aim was to evaluate if maternal age at transfer following autologous oocyte cryopreservation is associated with live birth rate (LBR). METHODS:We performed a retrospective cohort study of all patients who thawed autologous oocytes and then underwent a single frozen euploid embryo transfer between 2011 and 2021 at a large urban university-affiliated fertility center. Each oocyte thaw patient was matched 2:1 to in vitro fertilization (IVF) patients who underwent single embryo transfer < 1 year after retrieval. Primary outcome was LBR. Secondary outcomes included implantation rates (IR) and spontaneous abortion rates (SABR). RESULTS:A total of 169 oocyte thaw patients were matched to 338 IVF patients. As expected, oocyte thaw patients were older (median age 42.5 vs. 37.6 years, p < 0.001) and waited longer between retrieval and transfer than in vitro fertilization patients (median time 59 vs. 1 month, p < 0.001). In univariate analysis, implantation and LBR differed among oocyte thaw and IVF patients (p < 0.05), but SABR did not (p = 0.57). Transfer outcomes in oocyte thaw patients did not differ based on transfer age group (IR: p = 0.18; SABR: p = 0.12; LBR: p = 0.24). In a multiple logistic regression model, age at transfer was not predictive of live birth when controlling for age at retrieval, embryo morphology, and day of blastulation. CONCLUSIONS:Maternal age at transfer after oocyte cryopreservation is not predictive of LBR; this suggests that "an aging womb" does not impair LBR after oocyte thaw and empowers patients to return for transfer when ready for childbearing.

KEY WORDS/BACKGROUND:postpartum hemorrhage, thromboelastography, coagulopathy, fibrinogen, massive transfusion. OBJECTIVE:Thromboelastography, a point-of-care test that measures blood's dynamic viscoelastic properties, is routinely used to guide resuscitation in surgical specialties with high hemorrhage risk. Patients with ongoing postpartum hemorrhage often develop coagulopathy and hypofibrinogenemia. Timely assessment of fibrinogen is crucial because cryoprecipitate for repletion requires thawing prior to administration. Thromboelastography may provide rapid assessment of coagulopathy in ongoing hemorrhage but this has not been thoroughly studied. Our objective was to determine if thromboelastography accurately reflects coagulopathy in ongoing postpartum hemorrhage when compared to standard assays. STUDY DESIGN/METHODS:This was a retrospective cohort study of people with ongoing postpartum hemorrhage (quantified blood loss >1000 mL), from 1/1/16-12/31/19. Thromboelastography variables and standard coagulation parameters were compared in patients who had both assays drawn simultaneously. As a secondary analysis, patients who had thromboelastography were compared to those who did not. Mann-Whitney, Fisher's Exact, Kruskal-Wallis, Spearman's Rho, and logistic regression tests were used for analysis. Significance was set at p < 0.05. RESULTS:A total of 680 patients were included. 69 had thromboelastography and coagulation parameters drawn simultaneously and were included in the primary analysis. The remainder were included in the secondary analysis. Thromboelastography variables and coagulation assays correlated significantly - prolonged R with increased PTT (rho 0.25, p=0.04), prolonged K and decreased alpha angle with decreased fibrinogen (rho -0.61, p<0.001; rho 0.24, p<0.001), and decreased maximum amplitude with decreased platelets (rho 0.62, p<0.001). Those who had thromboelastographic assays had higher blood loss and need for interventions to manage hemorrhage than those who did not. CONCLUSION/CONCLUSIONS:Thromboelastography correlated significantly with standard laboratory assays in ongoing postpartum hemorrhage, including for patients with hypofibrinogenemia Given the point-of-care nature and rapid turnaround time, thromboelastography should be considered for timely hemorrhage evaluation and directed resuscitation of coagulopathy.

PURPOSE/OBJECTIVE:To explore whether letrozole improved outcomes in subsequent controlled ovarian hyperstimulation (COH) cycles. METHODS:This was a retrospective repeated measures cohort study examining COH cycles. Patients were included if they underwent two cycles for unexplained infertility, male factor infertility, or planned oocyte/embryo cryopreservation. The first cycles for all patients implemented a non-letrozole, conventional gonadotropin protocol. Second cycles for the study group included letrozole (2.5-7.5 mg for 5 days) with no medication change to second cycles amongst controls. Our primary objective was to compare oocyte yield. Cohorts were then subdivided by pursuit of oocyte (OC) or embryo (IVF) cryopreservation. Secondary outcome amongst the OC subgroup was oocyte maturation index (metaphase II (MII)/total oocytes). Secondary outcomes amongst the IVF subgroup were normal fertilization rate (2-pronuclear zygotes (2PN)/oocytes exposed to sperm), blastocyst formation rate (blastocysts/2PNs), and embryo ploidy (%euploid and aneuploid). RESULTS:Fifty-four cycles (n = 27) were included in letrozole and 108 cycles (n = 54) were included in control. Oocyte yield was higher in second cycles (p < 0.008) in the letrozole group but similar in second cycles (p = 0.26) amongst controls. Addition of letrozole did not impact MII index (p = 0.90); however, MII index improved in second cycles amongst controls (p < 0.001). Both groups had similar rates of normal fertilization (letrozole: p = 0.52; control: p = 0.61), blast formation (letrozole: p = 0.61; control: p = 0.84), euploid (letrozole: p = 0.29; control: p = 0.47), and aneuploid embryos (letrozole: p = 0.17; control: p = 0.78) between cycles. CONCLUSIONS:Despite improved oocyte yield, letrozole did not yield any difference in oocyte maturation or embryo outcomes.