Faculty Bibliography

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: 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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Objective: The use of GnRH-a trigger in antagonist controlled ovarian hyperstimulation (COH) cycles has increased due to its enhanced safety profile. However, response, as measured by the serum LH level post trigger, vary considerably^1-6. We investigated the impact of serum LH response to GnRH-a trigger in antagonist COH cycles on oocyte yield, oocyte maturity, blastocyst formation, PGT-A and pregnancy outcomes.
Material(s) and Method(s): This is a retrospective cohort study in a single university-based fertility center of all GnRH-antagonist COH cycles utilizing GnRH-a alone or in combination with 1000u of human chorionic gonadotropin (hCG) for trigger from 2017 to 2020. An optimal response to GnRH-a trigger was defined as LH >= 40 mIU/mL and suboptimal response was defined as LH < 40 mIU/mL on the morning after trigger. Subanalyses with responses of LH >= 15 mIU/mL and LH < 15 mIU/mL were also performed. Primary outcomes included oocyte yield, oocyte maturity rate, blastocyst formation rate, euploidy rate, aneuploidy rate and simple mosaic rate. Secondary outcomes included biochemical pregnancy rate (BPR), spontaneous abortion rate (SABR) and ongoing/pregnancy live birth rate (OP/LBR). Primary and secondary outcomes were also stratified by age, race and BMI. Descriptive statistics (median +/- range for continuous variables), Mann Whitey U and Fisher's Exact tests were performed accordingly with p<0.05 defined as significant.
Result(s): This study included 3,833 retrieval cycles with 1,435 single thawed euploid embryo transfers (STEET) among 2,618 patients. Ten percent (351/3446) of retrieval cycles had suboptimal and 90% (3446/3833) had optimal response to GnRH-a trigger. There was no difference in median oocyte yield (16 vs 17 oocytes per cycle, p=0.92), or oocyte maturity (77% vs 76%, p=0.43), fertilization (76% vs 77%, p=0.48) and blastocyst formation (51% vs 52%, p=0.88) rates by response. There were no significant differences in the rate of euploidy (35% vs 39%, p=0.55), aneuploidy (51% vs 47%, p=0.56) and simple mosaic (11% vs 11%, p=1) between groups. Seven percent (102/1435) of STEETs utilized embryos from a cycle with suboptimal response and 93% (1333/1435) from optimal response to GnRH trigger. There were no significant differences in BPR [19/44 (14%) vs 164/1907 (9%), p=0.2], SABR [11/144 (8%) vs 152/1907 (8%), p=1] and OP/LBR [85/144 (59%) vs 1127/1907 (59%), p=1]. No differences in pregnancy outcomes were found in the subanalyses of LH >= and < 15 mIU/mL and when data were stratified by SART age ranges, race and BMI.
Conclusion(s): A suboptimal response to GnRH-a trigger (LH < 40) is not associated with lower oocyte yield, oocyte maturity rate, blastocyst rate, euploidy rate or worse pregnancy outcomes compared to an optimal response (LH >= 40). Additional studies with larger cohorts are needed to further investigate these findings and with different thresholds of response. Impact Statement: A suboptimal LH response to GnRH-a trigger may not predict poor cycle outcomes. Providers should not hesitate to use GnRH-a trigger, especially in patients with identifiable risk factors for ovarian hyperstimulation syndrome (OHSS)⁷. Support: None.
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Objective: Several patient populations prefer to avoid TV monitoring for comfort or to prevent dysphoria. The purpose of this study is to compare TA and TV ultrasound as a means of determining cycle trigger timing and predicting oocyte maturity based on scans performed during ART cycles in this patient population.
Material(s) and Method(s): This was a retrospective cohort study of 59 patients who underwent >= 1 ART cycle at a single academic center. The study group consisted of patients who preferred TA monitoring based on any of 3 following inclusion criteria: 1) if they were virginal, 2) identified as transgender or 3) had a diagnosis of vaginismus. The control group included patients within this cohort that had no preference for TA imaging and thus underwent exclusive TV imaging. Demographics and variables included age, body mass index (BMI), antral follicle count (AFC) and anti-mullerian hormone (AMH), day 2 estradiol (D2 E2) and follicle-stimulating hormone (FSH) levels, # scans per cycle, # stimulation days per cycle, estimated # follicles and follicle sizes at trigger, # eggs retrieved, and oocyte maturity rate. Primary outcomes were 1) % difference between estimated # follicles at trigger and # oocytes retrieved, 2) # oocytes retrieved, and 3) % maturity. Secondary outcomes included % difference between AFC and # oocytes retrieved. Kolmogorov-Smirnov test was used to determine normality with independent sample t-tests and Mann Whitney U-Tests were used where appropriate with p<0.05 considered significant.
Result(s): 59 patients (n=18 TA; n= 41 TV) were included in the analysis. 27.1% (n=9 TA; 7 TV) were virginal, 50.8% (6 TA; 24 TV) had vaginismus and 37.3% (10 TA; 12 TV) identified as transgender. Some patients met 2 criteria (virginal + vaginismus, transgender + virginal, or transgender + vaginismus). Patients in the TA group were significantly younger than those in the TV group (26.2 TA v 37.8 years TV, p<0.001). Median BMI (22.4 TA v 23.7 kg/m² TV, p=0.26) and AMH (2.9 TA v 2.7 ng/mL TV, p=0.99) were similar. There was no statistical significance in mean AFC (12.8 +/- 9.2 TA, 13.6 +/- 8.2 TV, p=0.18). Patients in both groups had similar median D2 E2 (32.0 TA v 41.1 TV pg/mL, p=0.23) and FSH (5.6 TA v 7.2 mIU/mL TV, p=0.23), # scans per cycle (5 TA v 5 TV, p=0.88), and # stimulation days (11 TA v 11 TV, p=0.74). The TA group had higher mean E2 at trigger (3488.5 +/- 1087.0 TA, 2566.1 +/- 1416.1 pg/mL TV, p<0.002). There was no significant difference between estimated # follicles at trigger and # oocytes retrieved (17.7 +/- 31.4% TA, 6.7 +/- 38.0% TV; p= 0.29). Mean # oocytes (21.3 +/- 10.8 TA, 15.9 +/- 8.8 TV, p= 0.05) and median % mature oocytes (0.89 TA, 0.83 TV; p= 0.12) were also similar. Median % difference between AFC and # oocytes retrieved was not significantly different (0.68 TA, 0.82 TV; p= 0.18).
Conclusion(s): TA and TV imaging do not differ in their ability to predict FP cycle characteristics, oocytes retrieved or oocyte maturity rate. TA imaging may offer an acceptable alternative for patients uncomfortable with TV imaging during FP. Impact Statement: TA monitoring for oocyte cryopreservation does not adversely affect oocyte yield in patients with preference against TV imaging.
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The practice of in vitro fertilization (IVF) has changed tremendously since the birth of the first IVF baby in 1978. With the success of early IVF programs in the U.S. there was a significant rise in twin births nationwide. In the mid-1990's, over 30% of IVF cycles resulted in twin or higher-order multiple-gestation pregnancies. Since that time, not only have we witnessed improvements in laboratory and treatment efficacy, but we have also seen a dramatic impact on pregnancy outcomes, specifically regarding twin pregnancies. As the field evolved and the risks of multi-fetal pregnancies became more salient, by 2019, the rate of twin pregnancies had dropped to below 7% of cycles. This improvement is largely due to technical advancements and revised professional guidance: culturing embryos longer before transfer, improved freezing technology, embryo preimplantation genetic testing, and revised professional guidance regarding the number of embryos to transfer. These developments have led to single embryo transfer (SET) becoming the standard of care in most scenarios. We use national IVF surveillance data of all autologous IVF cycles from 1996 to 2019 in order to illustrate trends in the following improved outcomes: autologous embryo transfer cycles involving blastocyst stage embryos, vitrified embryos, preimplantation genetic testing cycles, total number of embryos being transferred per cycle, and SET usage over time; among deliveries from autologous embryo transfers, we highlight trends in singleton births over time, and proportion of deliveries involving twins, triplets, quadruplets or greater. The significant progress in reducing the rate of multiple-gestation pregnancies with IVF is largely attributed to a series of technical and clinical actions, culminating in an 80% reduction in the incidence of multiple births without a loss in overall treatment effectiveness.

Background: To evaluate whether the ongoing coronavirus disease 2019 (COVID-19) pandemic has had an impact on assisted reproductive technology (ART) outcomes and assess the possible role of geographic differences in the pandemic's trajectory on these outcomes. Methods: Multi-center retrospective cohort study involving patients who underwent oocyte cryopreservation, in vitro fertilization (IVF), embryo cryopreservation, or frozen euploid embryo transfer in 2019 and 2020 at two academic fertility centers located in regionally distinct areas of the US with high coronavirus infection rates. Patients were screened for infectious symptoms, exposure to sick contacts, and fevers, and tested with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing within 5 days of oocyte retrieval. The primary outcomes were the number of oocytes retrieved, embryos fertilized, blastocyst or euploid embryos produced in oocyte retrieval and IVF cycles, and rates of embryo implantation, biochemical pregnancy or no pregnancy following frozen embryo transfer (FET). Results: We found no consistent significant differences in the number of oocytes retrieved, embryos fertilized, blastocysts or euploid embryos produced at either institution over the study period. Furthermore, we did not detect any differences in FET outcomes, including rates of embryo implantation, biochemical pregnancy, or no pregnancy, at either institution during the study time period. Conclusions: There were no significant differences in ART outcomes in patients who received fertility treatment during the pandemic at our centers. Patients and providers can be reassured that with proper testing, sanitizing, and distancing measures, treatments can continue safely during the pandemic without compromising outcomes.

In vitro fertilization is typically associated with high failure rates per transfer, leading to an acute need for the identification of embryos with high developmental potential. Current methods are tailored to specific times after fertilization, often require expert inspection, and have low predictive power. Automatic methods are challenged by ambiguous labels, clinical heterogeneity, and the inability to utilize multiple developmental points. In this work, we propose a novel method that trains a classifier conditioned on the time since fertilization. This classifier is then integrated over time and its output is used to assign soft labels to pairs of samples. The classifier obtained by training on these soft labels presents a significant improvement in accuracy, even as early as 30 h post-fertilization. By integrating the classification scores, the predictive power is further improved. Our results are superior to previously reported methods, including the commercial KIDScore-D3 system, and a group of eight senior professionals, in classifying multiple groups of favorable embryos into groups defined as less favorable based on implantation outcomes, expert decisions based on developmental trajectories, and/or genetic tests.

PURPOSE/OBJECTIVE:Whether differences in stimulation parameters alter the number and proportion of MII oocytes retrieved. METHODS:Records of 2546 patients were examined, looking at age, day 2/3 follicle-stimulating hormone (FSH) and estradiol (E2) levels, total dose of gonadotropins administered (including FSH and human menopausal gonadotropin [hMG]), fraction of hMG administered, number of days of treatment with gonadotropins, and the dose of gonadotropins administered per day. We segregated the patients into 3 different classes depending on the trigger method used and 2 groups based on egg freeze vs. ICSI. Multiple regression methods were used to examine associations between stimulation parameters and the total number of eggs, number of immature oocytes (Poisson regression), and the fraction of retrieved oocytes that were immature (Logistic regression). RESULTS:After adjustments for different triggers and egg freeze versus ICSI, both the #immature oocytes and the immature fraction of oocytes were associated with the total gonadotropin dose (inversely) and the gonadotropin dose/day (positively). Other parameters were associated with the number of immature oocytes but were also associated with the number of oocytes retrieved. CONCLUSIONS:Stimulations using less total gonadotropin and more gonadotropin per day were associated with more immaturity. The type of trigger method used for final maturation was associated with immaturity but was believed to be predominantly due to trigger assignment to patients based on response. The association between use of ICSI and less immaturity was believed to be due to additional time for maturation in the ICSI group.

OBJECTIVE: COVID-19 has affected nearly every facet of modern life, and has left many wondering what implications, if any, the virus has on reproductive health. Increased levels of psychological stress, concern for viral contamination in embryology labs, and reports of decreased male fertility following COVID infection, have also been thought to contribute negatively to ART outcomes.We sought to determine whether the pandemic resulted in any differences in IVF/OOF outcomes. MATERIALS AND METHODS: Patients who tested negative for COVID-19 and underwent GnRH-antagonist IVF and OOF cycles from January 2020 through December 2020 at NYU Fertility Center, a period marked by the COVID-19 pandemic, were separated by month of treatment and compared with patients from the corresponding month in the prior year. In patients with multiple cycles over this time period, only the first cycle was used. Patient age, AMH, #oocytes retrieved, #oocytes matured, #fertilized, #blastocysts, and #euploid embryos were compared using Student's T-test.
RESULT(S): 2,467 patients were compared. While the number of cycles were remarkably decreased over March and April of 2020 (59 and 25 respectively), the total number of cycles were very similar for the entire year (1,239 in 2019; 1,228 in 2020). There were no consistently significant differences in age, AMH, #oocytes retrieved, #oocytes matured, #blastocysts formed, or #euploid embryos formed, between the two years.
CONCLUSION(S): Despite initial concerns, and prior research suggesting otherwise, we did not detect any consistent quantitative or qualitative differences in retrieval outcomes amongst COVID negative patients receiving care during the pandemic. IMPACT STATEMENT: These results can reassure patients and their providers that IVF/OOF cycles can be continued safely during the pandemic without compromising outcomes