Faculty Bibliography

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.

The objective of this study was to investigate the utility of using serum gonadotropin levels to predict optimal luteinizing hormone (LH) response to gonadotropin releasing hormone agonist (GnRHa) trigger. A retrospective cohort study was performed of all GnRH-antagonist controlled ovarian hyperstimulation (COH) cycles at an academic fertility center from 2017-2020. Cycles that utilized GnRHa alone or in combination with human chorionic gonadotropin (hCG) for trigger were included. Patient and cycle characteristics were collected from the electronic medical record. Optimal LH response was defined as a serum LH ≥ 40 mIU/mL on the morning after trigger. Total sample size was 3865 antagonist COH cycles, of which 91% had an optimal response to GnRHa trigger. Baseline FSH (B-FSH) and earliest in-cycle LH (EIC-LH) were significantly higher in those with optimal response. Multivariable logistic regression affirmed association of optimal response with EIC-LH, total gonadotropin dosage, age, BMI and Asian race. There was no difference in the number of oocytes retrieved (p = 0.14), maturity rate (p = 0.40) or fertilization rates (p = 0.49) based on LH response. There was no difference in LH response based on use of combination vs. GnRHa alone trigger (p = 0.21) or GnRHa trigger dose (p = 0.46). The EIC-LH was more predictive of LH trigger response than B-FSH (p < 0.005).The optimal B-FSH and EIC-LH values to yield an optimal LH response was ≥ 5.5 mIU/mL and ≥ 1.62 mIU/mL, respectively. In an era of personalized medicine, utilizing cycle and patient characteristics, such as early gonadotropin levels, may improve cycle outcomes and provide further individualized care.

Objective: Fragile X (FgX) is a recommended part of carrier screening with pre- and full mutations associated with a spectrum of disease including intellectual disability, tremor ataxia syndrome and premature ovarian insufficiency. Risk of expansion is categorized based on number of CGG repeats.¹ Testing for AGG interruptions can offer further risk assessment in some cases.¹ As these tests become more commonplace, our objective was to determine how often screened patients select PGT-M for FgX.
Material(s) and Method(s): This is a retrospective case series at a single academic fertility center. Electronic medical records were queried to identify patients with a positive carrier screen for FgX from 2008-2022 and those undergoing PGT-M for FgX. Assisted reproductive treatments and outcomes were reviewed. Kruskal Wallis and Chi-square statistical tests were performed (p<0.05 significant).
Result(s): 393 positive FgX reports were identified including 20 prospective oocyte donors. 63% (247/393) had an intermediate (INT) number of CGG repeats (45-54), 34% (133/393) had a premutation (PRE) (55-200 repeats) and 0.8% (3/393) had a full mutation (FUL) (>200 repeats). 61% (238/393) underwent fertility treatment at our center. PRE patients were younger (INT: 36 (17-47) vs PRE: 33 (21-44) vs FUL: 37 (37-39) years (Y), p<0.01). Anti-mullerian hormone levels were similar (INT: 1.9 (0.03-14) vs PRE: 1.5 (0.01-8.7) vs FUL: 3 (0.1-5) ng/mL, p=0.08). Only 37% (49/133) of PRE carriers underwent AGG testing to further risk stratify expansion potential, as did 2% (4/247) of INT. 25% (13/53) had 0 AGGs: 4 declined fertility treatment, 4 cryopreserved oocytes, 5 underwent PGT-M. 12% (49/393) in total underwent PGT-M: 4% INT (2/49), 73% PRE (36/49), 6% FUL (3/49). 27% (13/49) of PGT-M patients underwent AGG testing: 38% (5/13) had 0 AGG, 38% (5/13) had 1 AGG, and 23% (3/13) had 2 AGGs. 8% (4/49) additional patients were offered but declined AGG testing. 18% (9/49) of PGT-M patients had terminated an affected pregnancy prior to PGT-M. 10% (5/49) had documented family members affected or PRE carriers. Patients underwent median 2 retrieval cycles (range 0-5) and 1 embryo transfer cycle (range 0-5). 31% (14/45) of patients with completed treatment did not achieved an autologous euploid unaffected embryo for transfer; two of these patients transferred non-euploid unaffected embryos and 71% (10/14) had AMH <0.8ng/mL. 1 INT and 2 PRE female embryos were also transferred. 46% (13/28) of transfers resulted in a live birth.
Conclusion(s): PGT-M is most commonly used for PRE carriers and with a history of prior affected pregnancy or family member, with varied use of AGG testing. Patients with low ovarian reserve are less likely to achieve an autologous live birth of an unaffected embryo from PGT-M. Impact Statement: FgX premutation carriers do not have uniform uptake of AGG testing or PGT-M and require individualized counseling due to differences in risk assessment and varied assisted reproductive technology outcomes. Support: None REFERENCES:: 1. Monaghan KG, Lyon E, Spector EB; American College of Medical Genetics and Genomics. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013 Jul;15(7):575-86.
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Objective: Though the ability of an AMH result to predict ovarian reserve is debated[1], patient interest in their own fertility is growing. Our objective was to understand the social media content surrounding the search term: AMH level.
Material(s) and Method(s): This is a retrospective cohort study of the use of term "AMH level" on Google Trends (GO) and #AMHlevel/ #AMHlevels on Instagram (IG) from 1/1/2019 to 12/31/2021. On IG, all single user posts in the "most recent" search function were included. Posts were characterized by author type (fertility clinic/ FC, influencer, provider, patient/parent), content, and tone (positive, negative, neutral). Likes per post and total account followers were quantified to calculate percent of likes (PL) and assess activity. Chi square and ANOVA was used with p-value < 0.05 considered significant.
Result(s): On IG, the term "#AMHlevel" was mentioned in 196 posts and #AMHlevels in 161 posts. Hashtag use increased over time, with amounts of 59 (16.5%), 121 (33.9%) and 177 (49.6%) respectively by year (Table 1). Mean number of likes, followers and PL was 93.7 +/- 558.3, 2953.3 +/- 12762.1 and 4.7 +/- 6.3 respectively. PL was not associated with author type (p-value=0.487). Positive and negative posts received a higher PL compared to neutral (6.8 v 6.4 v 3.8, p=0.00). Mean PL also varied by content (Celebrity Story 10.0 +/- 16.6, Patient Story 6.2 +/- 6.2, Personal Story 5.6 +/- 5.8, Support 4.5 +/- 3.0, Literature 1.4 +/- 1.4 p-value = 0.012) On GO, "AMH level" was most searched in May - August 2021 and least in April 2019 and 2020. Within the USA, it was most utilized in New York, California, Texas, and Florida in descending order. Overall use has remained consistent over time (m=0.009).
Conclusion(s): Use of #AMHlevel/s on Instagram, especially by FCs, has grown. Activity on influencer and celebrity posts has also grown. Comparatively, searches of "AMH Level" on GO has remained mostly unchanged, possibly showing a shift away from search engines and towards social media for information. Impact Statement: This is the first study to characterize the use of search terms related to AMH levels on social media. As access and attention to AMH levels rises, it is important to understand where patients are receiving their information. [Formula presented] REFERENCES:: 1. Moolhuijsen LM, Visser JA. Anti-Mullerian hormone and ovarian reserve: update on assessing ovarian function. The Journal of Clinical Endocrinology & Metabolism. 2020 Nov 1;105(11):3361-73.
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Objective: Data regarding the chance of more than one LB from oocyte cryopreservation (OC) is lacking. We reviewed outcomes from patients (pts) with >=1 LB from thawed autologous oocytes (AOs) to examine: 1) how many have inventory (AOs or resultant euploid/untested/no result embryos), and 2) embryo transfer (ET) outcomes after 1^st LB.
Material(s) and Method(s): We reviewed all pts who thawed AOs at our center in 2006-2021 and had >=1 resultant LB. Pts were excluded if OC was performed for a medical reason, as research, due to lack of sperm or a natural disaster, with embryo banking or for gestational carrier use.
Result(s): 191 pts had >=1 LB (median # OC cycles 1, median age at 1^st OC 37 years (y), median # cryopreserved AOs 18, median # AOs thawed before 1^st LB 15). After LB, 61% of pts (n=117) had inventory and 39% (n=74) did not; see table. Among pts with inventory, 12% (n=14) discarded or donated, 3% (n=4) transported out and 10% (n=12) consumed all inventory as of 1/2022. 22% of pts with inventory (n=26) had >=1 ET after LB. Among these pts, 21 thawed embryos (median # thawed 1, range 1-2), 4 thawed AOs (median # thawed 11, range 5-40) and 1 thawed both AOs + embryos (15 AOs + 4 embryos). Median time from the ET that led to 1^st LB and next ET was 26 months (range 15-57) and median age at next ET was 44y (range 37-53). This ET resulted in: implantation rate of 63% (19/30), spontaneous abortion rate of 16% (3/19) and ongoing pregnancy (OP) + LB rate of 58% (15/26); 1 pregnancy was terminated for monozygotic twins. Among pts who had a LB from this ET, 66% (10/15) had remaining inventory and 33% (5/15) did not. Among pts who did not have a LB from this ET, 45% (5/11) had remaining inventory and 54% (6/11) did not; 5 of these unsuccessful pts returned for another ET and 2 had a LB. In total, 16 pts had 2 ETs result in OP/LB and 1 pt had 3 ETs result in LB. 10 more pts had >=2 children from a single ET (9 twins, 1 triplet); thus, we report 27 pts with >=2 children from OC. Among pts with >=2 children, median # OC cycles was 1 (range 1-8), median age at 1^st OC was 37y (range 34-41), median # cryopreserved AOs was 20 (range 5-102) and median # thawed AOs was 19 (range 5-58).
Conclusion(s): Most pts (61%) had inventory after their 1^st LB from OC, and most pts (65%) who returned for ET after LB achieved another OP/LB. Further research must explore pts' thoughts regarding OC inventory after LB and its associated storage fees. Impact Statement: OC can help pts achieve their ideal family size, even if >1 child. [Formula presented] Support: None.
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Objective: Planned OC is increasing; yet, there is a lack of thaw data to provide an accurate estimate of CLBR.¹ We reviewed our AO thaws to determine CLBR by age and #AOs.
Material(s) and Method(s): We reviewed AO thaws at our academic center from 2004-2021. Inclusion criteria: 1) >=1 live birth (LB)/ongoing pregnancy (OP) >12 weeks, or 2) all AOs + embryos from OC consumed. Exclusion criteria: 1) OC for a medical reason, as research, due to lack of sperm or a natural disaster, combined with embryos or for gestational carrier use, or 2) AOs/embryos from OC transported out before a LB. Primary outcome was CLBR (LB + OP). Patients (pts) were stratified by age and #AOs or metaphase II oocytes (M2s) thawed. If pts had >=1 OC cycle, we calculated a weighted age: [SIGMA (#AOs thawed x age at OC)] / [#AOs thawed]. Statistics included multiple logistic regression (MLR), Fischer's exact test, and chi-squared test (p<0.05 significant).
Result(s): 548 pts (median age at OC 38y, range 28-45y; 151 weighted ages used) underwent 767 OC (location: 90% our center, 9% elsewhere, 2% both; method: 77% vitrification, 4% slow cooling, 19% both), 604 thaw and 465 transfer cycles. 40% (n=218) of pts had >=1 LB/OP, resulting in 221 babies + 30 OPs. See table for CLBRs. In pts of all ages and <38y, CLBR increased as #AO/M2s thawed increased from 0-10 to 11-20 to >20 (p<0.03). In pts 38-39y, CLBR was lower if 0-10 vs. 11-20 or >20 AOs were thawed (p<0.01), but was similar if 11-20 vs. >20 AOs (p=0.34) or M2s (p=0.13) were thawed. In pts >=40y, CLBR did not differ based on #AOs (p=0.81) or M2s thawed (p=0.17). For pts with any # or >20 AO/M2s thawed, CLBR was higher in pts <38y and 38-39y vs. pts >=40y (p<0.04). In a MLR model adjusting for effect of age on #AOs, age and age-independent #AOs were predictive of LB.
Conclusion(s): CLBR increases as more AO/M2s are thawed. OC at <38y has a CLBR of ~50%, a reasonable rate in younger pts at an ideal age for OC. Impact Statement: Pts who freeze >20 AOs at <38y can expect >=70% CLBR based on actual outcomes. This is the largest report to date of AO thaw outcomes from a single U.S. center. [Formula presented] REFERENCES:: 1 Practice Committee of the American Society for Reproductive Medicine. Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline. Fertil Steril. 2021 Jul;116(1):36-47.
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Objective: To evaluate differences in oocyte cryopreservation (OC) in BRCA 1/2 patients with and without cancer diagnoses compared to controls who underwent elective cryopreservation.
Material(s) and Method(s): This was a single-center retrospective cohort study of BRCA mutation carriers who presented for fertility preservation. A data query was performed to identify all patients who were referred to our academic center from 2006-2022 to discuss fertility preservation in the setting of known BRCA 1/2-carrier status with or without cancer diagnosis. BRCA 1/2 carriers without cancer (Group A), with cancer (Group B) and controls (Group C) were included in the study. Patient demographic information, gynecologic history, antral follicle count (AFC) and cycle characteristics were reviewed. The control group consisted of 308 patients who underwent elective OC in 2021, with a 1:10 ratio of study to control group. Primary outcomes included 1) median number of oocytes retrieved, 2) oocyte maturity rate and 3) rate of M1 or GV oocytes amongst BRCA 1/2 carriers who underwent oocyte cryopreservation compared to the control group. Secondary outcomes included 1) mean anti-mullerian hormone levels (AMH), 2) median number of stimulation days and 3) cumulative dose of exogenous FSH and hMG administered during stimulation. Data was analyzed using Kruskal-Wallis analysis and Mann Whitney U-tests. A P-value of < 0.05 was considered statistically significant.
Result(s): Of 242 BRCA 1/2 carriers who were referred to our center for fertility consultation, 103 underwent ART cycles, of which 38 completed at least 1 OC cycle (21 BRCA1, 17 BRCA2), with a total of 49 OC cycles within the study group. 7 BRCA 1/2 carriers had breast cancer at time of OC (2 BRCA1, 5 BRCA2). There was no significant difference between median numbers of oocytes retrieved amongst groups (A: 18, B: 20, C: 16, p = 0.93). Oocyte maturity also did not vary significantly between groups (A: 74.4 +/- 13.5%, B: 57.3 +/- 24.8%, C: 73.4 +/- 18.1%; p=0.3). BRCA 1/2 carriers without cancer had a higher rate of M1 oocytes compared to cancer and control groups (A: 8.9 +/- 10.4%, B: 4.5 +/- 4.8%, C: 4.7 +/- 8.9%; p=0.02). Furthermore, BRCA1/2 carriers with and without cancer had a significantly higher percent of GV oocytes (A: 8.6 +/- 11.6%, B: 10.8 +/- 11.4%, C: 0.02 +/- 0.48%; p=0.001) compared to controls. Mean AMH was significantly lower in BRCA 1/2 patients with cancer compared to those without and controls (A: 3.8 +/- 2.4, B: 1.5 +/- 1.9, C: 3.2 +/- 2.6 ng/mL; p=0.04). There was no significant difference in median number of stimulation days and cumulative dose of exogenous FSH or hMG between groups.
Conclusion(s): BRCA1/2 carrier status does not compromise stimulation cycle characteristics or oocyte maturity rates. Although BRCA1/2 carriers with and without cancer at time of cycle had higher rates of M1 and GV oocytes per OC cycle, they had similar maturity rates overall compared to controls. Impact Statement: BRCA1/2 carriers should be encouraged to pursue fertility preservation if they are interested. BRCA status and/or active breast cancer diagnosis do not negatively impact cycle characteristics or oocyte maturity potential.
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Objective: Infertility affects >100 million people worldwide; improving FC access is essential, especially for low socioeconomic and minority groups. In NYC's public hospital system, patients (pts) are referred to a fellow-led reproductive endocrinology and infertility (REI) clinic that provides consults, work-ups and ultrasound-monitored controlled ovarian hyperstimulation and ovulation induction (OI). REI referrals (REF) are in high demand limiting appointment (appt) availability¹ with new pts waiting >5 months. We developed a QIP to identify pts for OI counseling and initiation in GYN clinic.
Material(s) and Method(s): REI fellows screened all REFs, and scheduled eligible pts in GYN. QIP criteria: age <38 years (y); anti-Mullerian hormone (AMH) >2ng/mL; normal prolactin, thyroid function and hemoglobin A1C; no known reproductive issues/comorbidities requiring high risk obstetrics; <3 prior OI cycles. Eligible pts received early follicular letrozole 2.5mg for 5 days (d) in GYN and were then followed in REI's OI program. Non-eligible pts were scheduled in REI. To assess effectiveness, we retrospectively compared all REF outcomes from PRE-(3/1/21-5/31/21) to POST-(9/1/21-11/30/21) QIP as of 2/14/22. A transition period (6/1/21-8/31/21) was excluded. Primary outcome was time from REF to scheduled appt. Secondary outcomes included time from REF to OI prescription/cycle start. Statistics included Mann-Whitney, Chi-square, Fischer's exact and Two-sample t tests (p<0.05 significant).
Result(s): PRE (n=121) and POST (n=102) REFs had similar median ages [36 (interquartile range (IQR): 32-39) PRE vs 35y (IQR: 31-40) POST, p=0.73], ethnic/racial identity [56.2% (68/121) PRE vs 53.9% (55/102) POST Hispanic (p=0.79); 34.7% (42/121) PRE vs 30.4% (31/102) POST Black (p=0.59)], and rates of no prior FC [88.4% (107/121) PRE vs 93.1% (95/102) POST, p=0.15]. QIP identified pts for GYN who were younger [median age 29 (IQR: 27-33) vs 38y (IQR: 33-41), p<0.01], had higher AMHs [median 3.065 (IQR: 2.315-4.883) vs 1.230 ng/mL (IQR: 0.513-3.630), p<0.01], and had fewer comorbidities [100% (19/19) vs 72.5% (50/69), p<0.01] compared to REI. After QIP implementation, median time from REF to scheduled appt decreased from PRE 151 (IQR: 125-173) to POST 98d (IQR: 73-137) (p<0.01). For pts seen in clinic thus far, median time from REF to OI prescription decreased from 150 (IQR: 122-173) to 82d (IQR: 63-119) (p<0.01) and to 1st follicle check from 202 (IQR: 159-221) to 107d (IQR: 98-115) (p<0.04). In the POST cohort, 86.3% (88/102) of REFs had visits scheduled, with 21.6% (19/88) in GYN and 78.4% (69/88) in REI. OI was started at initial visit for 61.5% (8/13) of GYN pts vs 25.8% (8/31) of REI pts (p<0.04). 38.5% (5/13) of GYN pts met criteria for QIP, but were pending >1 blood test, while 51.6% (16/31) of REI pts were pending further work-up.
Conclusion(s): Our QIP expedited FC for all pts by reducing the time from REF to scheduled fertility appt by 35% (median of 53d) and to OI prescription/cycle start by nearly 45% (medians of 68d/95d). Impact Statement: Similar OI pathways could improve access to FC for underserved populations in broader practice settings. REFERENCES: 1 Blakemore JK, Maxwell SM, Hodes-Wertz B, Goldman KN. Access to infertility care in a low-resource setting: bridging the gap through resident and fellow education in a New York City public hospital. J Assist Reprod Genet. 2020 Jul;37(7):1545-1552.
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Objective: Patients with 5 or fewer follicles during IVF face a difficult choice: should they cancel the cycle or proceed to retrieval? Limited data exist to guide this decision. This study evaluates LBRs for retrievals with <=5 follicles at trigger.
Material(s) and Method(s): This retrospective cohort study from an academic fertility center reviewed all IVF cycles yielding <=10 oocytes from 2016-2020. Cycles were included if <=5 follicles measuring >=14 mm were verified at trigger. The primary outcome was rate of ongoing pregnancy or live birth per retrieval (LBR) after fresh or frozen transfer. Secondary outcomes were number of oocytes, mature oocytes (M2s), 2 pronuclear zygotes (2PNs), blastocysts for transfer or biopsy and euploid blastocysts (if preimplantation genetic testing for aneuploidy (PGT) was used). Statistics included Chi-squared, Fisher's exact and Kruskal Wallis tests (p<0.05 significant).
Result(s): 1502 cycles (900 with PGT) from 972 patients were included. Median age was 40 years (y) (range: 26-48). See table for outcomes. Mean oocytes, M2s, 2PNs, blastocysts and euploids differed by follicle number (FN) (p<0.001). Across all ages, there were differences in LBR associated with FN (p<0.001). For patients <35y, LBR did not differ by FN. In the 35-37y group, LBR with 2, 3 or 4 follicles was lower than LBR with 5 (p<0.01). In the 38-40y group, LBR with 3 follicles was lower than LBR with 4 or 5 (p<0.02). In the 41-42y group, LBR with 2 or 3 follicles was lower than LBR with 5 (p<0.02). In the >42y group, LBR with 4 follicles was lower than LBR with 5 (p<0.03). There were no other differences in LBR by FN.
Conclusion(s): We provide clear, specific outcomes for patients with <=5 follicles at trigger. As expected, LBR is higher with more follicles. Our data can guide patients with <=5 follicles as they weigh the emotional, physical and financial costs of retrieval. Impact Statement: Our results can help patients with 5 or fewer follicles decide whether to cancel or proceed to retrieval. Patients with <=3 follicles can be counseled that LBR is likely less than 20% if 35-40 years old and likely 5% or less if 41 years or older. [Formula presented]
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