Faculty Bibliography

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.

OBJECTIVE:To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis. DATA SOURCES/METHODS:We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate. METHODS OF STUDY SELECTION/METHODS:Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included. TABULATION, INTEGRATION, AND RESULTS/RESULTS:Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88-1.01, P=.10), number of oocytes retrieved (mean difference -0.26, 95% CI -0.68 to 0.15, P=.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI -0.14 to 0.75, P=.18), fertilization rate (OR 0.99, 95% CI 0.87-1.11, P=.83), implantation rate (OR 0.92, 95% CI 0.84-1.00, P=.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86-1.06, P=.40), or live-birth rate (OR 0.95, 95% CI 0.78-1.17, P=.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results. CONCLUSION/CONCLUSIONS:Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies. SYSTEMATIC REVIEW REGISTRATION/BACKGROUND:PROSPERO, CRD42023400023.

The objective of this review is to provide an update on planned oocyte cryopreservation. This fertility preservation method increases reproductive autonomy by allowing women to postpone childbearing whilst maintaining the option of having a biological child. Oocyte cryopreservation is no longer considered experimental, and its use has increased dramatically in recent years as more women delay childbearing for personal, professional and financial reasons. Despite increased usage, most patients who have undergone oocyte cryopreservation have not yet warmed their oocytes. Most women who cryopreserve oocytes wait years to use them, and many never use them. Studies have demonstrated that oocyte cryopreservation results in live birth rates comparable with IVF treatment using fresh oocytes, and does not pose additional safety risks to offspring. Based on current evidence, cryopreserving ≥20 mature oocytes at <38 years of age provides a 70% chance of one live birth. However, larger studies from a variety of geographic locations and centre types are needed to confirm these findings. Additional research is also needed to determine the recommended age for oocyte cryopreservation, recommended number of oocytes to cryopreserve, return and discard/non-use rates, cost-effectiveness, and how best to distribute accurate and up-to-date information to potential patients.

The objective of this study was to describe the opinions and attitudes toward planned oocyte cryopreservation (POC) among Black Obstetrician Gynecologists (BOG) and their experiences in counseling patients of color. A web-based, cross-sectional survey was distributed to BOGs. The survey consisted of questions pertaining to personal family building goals, fertility preservation, education and patient counseling experiences regarding POC. Of the 136 potential participants, the response rate was 50% (n = 68). Sixty-six percent of respondents felt the need to postpone childbearing due to medical training and 19% had already undergone POC or planned to in the future. A majority (70%) felt that all women planning to undergo medical training should consider POC, and a subgroup analysis showed this was more likely to be reported within BOG trainees (p < 0.01). Fifty-seven percent received education on POC and 25% felt "very comfortable" counseling patients on POC. Those age < 35 years were more likely to feel the need to postpone family building due to their medical training (p < 0.01). Generalist attendings who had not undergone POC were significantly more likely to report regret, compared to subspecialists (p < 0.03). Medical careers may have an unfavorable impact on family building, and our results highlight this effect in Black women. A better understanding of the mitigating factors is needed to develop culturally appropriate counseling and educational interventions for Black women and other women of color.

Embryos are diagnosed as mosaic if their chromosomal copy number falls between euploid and aneuploid. The purpose of this study was to investigate the impact of mosaicism on global gene expression. This study included 42 blastocysts that underwent preimplantation genetic testing for aneuploidy (PGT-A) and were donated for IRB approved research. Fourteen blastocysts were diagnosed as mosaic with Next-generation Sequencing (NGS). Three NGS diagnosed euploid embryos, and 25 aneuploid embryos (9 NGS, 14 array Comparative Genomic Hybridization, 2 Single Nucleotide Polymorphism array) were used as comparisons. RNA-sequencing was performed on all of the blastocysts. Differentially expressed genes (DEGs) were calculated using DESeq2/3.5 (R Bioconductor Package) with p < 0.05 considered significantly differentially expressed. Pathway analysis was performed on mosaic embryos using EnrichR with p < 0.05 considered significant. With euploid embryo gene expression used as a control, 12 of 14 mosaic embryos had fewer DEGs compared to aneuploid embryos involving the same chromosome. On principal component analysis (PCA), mosaic embryos mapped separately from aneuploid embryos. Pathways involving cell proliferation, differentiation, and apoptosis were the most disrupted within mosaic embryos. Mosaic embryos have decreased disruption of global gene expression compared to aneuploid embryos. This study was limited by the small sample size, lack of replicate samples for each mosaic abnormality, and use of multiple different PGT-A platforms for the diagnosis of aneuploid embryos.

Objective/UNASSIGNED:To describe a unique case of primary ovarian insufficiency and review the systemic barriers in place that hinder reproductive autonomy for Black women who require third-party reproduction. Design/UNASSIGNED:Case report and review of the literature. Setting/UNASSIGNED:Safety-net hospital in an urban community. Patients/UNASSIGNED:A 36-year-old Black woman, gravida 0, with primary ovarian insufficiency who desires future fertility but is restricted by systemic barriers. Interventions/UNASSIGNED:Chromosome analysis. Main Outcome Measures/UNASSIGNED:Not applicable. Results/UNASSIGNED:Balanced reciprocal translocation between chromosomes 1 and 13: 46,XX,t(1;13)(q25;q14.1). Conclusions/UNASSIGNED:The field of assisted reproductive technology has evolved at an exponential rate, yet it unfortunately benefits some and not all. It is imperative that when we advocate for full spectrum infertility care, that this encompasses everyone. As we continue to further study and develop assisted reproductive technology, we must not forget to consider the factors leading to racial and socioeconomic disparities in reproductive care access, utilization, and outcomes.

PURPOSE/OBJECTIVE:To determine whether sociodemographic differences exist among female patients accessing fertility services post-cancer diagnosis in a representative sample of the United States population. METHODS:All women ages 15-45 with a history of cancer who responded to the National Survey for Family Growth (NSFG) from 2011 to 2017 were included. The population was then stratified into 2 groups, defined as those who did and did not seek infertility services. The demographic characteristics of age, legal marital status, education, race, religion, insurance status, access to healthcare, and self-perceived health were compared between the two groups. The primary outcome measure was the utilization of fertility services. The complex sample analysis using the provided sample weights required by the NSFG survey design was used. RESULTS:Five hundred forty-five women reported a history of cancer and were included in this study. Forty-three (7.89%) pursued fertility services after their cancer diagnosis. Using the NSFG sample weights, this equates to a population of 161,500.7 female cancer survivors in the USA who did utilize fertility services and 1,811,955.3 women who did not. Using multivariable analysis, household income, marital status, and race were significantly associated with women utilizing fertility services following a cancer diagnosis. CONCLUSIONS:In this nationally representative cohort of reproductive age women diagnosed with cancer, there are marital, socioeconomic, and racial differences between those who utilized fertility services and those who did not. This difference did not appear to be due to insurance coverage, access to healthcare, or perceived health status.

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

OBJECTIVE: POC is underutilized by Black women and persons of color1 . We sought to describe the opinions and attitudes toward POC among BOGs and their experiences in counseling patients of color. MATERIALS AND METHODS: An anonymous survey was distributed to BOGs via separate listservs belonging to a BOG organization and a historically Black college/university in April 2021. The survey included 30 demographic and qualitative questions pertaining to personal family building goals, fertility preservation, and patient counseling experiences. Analyses included descriptive statistics and chi square test to compare answers across demographic, professional and subspecialty groups using SPSS (v25) with p<0.05 considered significant.
RESULT(S): Of the 136 potential participants, the response rate was 49% (n=67). The majority of respondents were female (93%) and heterosexual (93%). The mean age was 34.2 years. Attendings (ATT), fellows (FEL) and residents (RES) represented 47%, 17% and 36% of respondents, respectively. Fifty-four percent of ATTs were generalists. Subspecialties represented by ATTs and FELs included Maternal Fetal Medicine (24%), Minimally Invasive Gynecology (2%), Reproductive Endocrinology and Infertility (14%), and Urogynecology (8%). Sixty-six percent of subjects did not currently have children and 20% did not want children. Sixty-eight percent felt the need to postpone family building due to medical training, most commonly citing career plans (88%) and financial concerns (60%). Of the 41% who had tried to conceive in the past, 9% required fertility treatment. Nineteen percent had already undergone POC or planned to in the future. Most (70%) felt that all women planning to undergo residency +/- fellowship training should consider POC. Fifty-six percent reported receiving some form of education on POC and 22% felt ''very comfortable'' counseling patients on POC. Fifty-six percent had recommended POC to patients in the past. When asked to exclude cost, the most common reported personal barriers for POC were time (31%) and fear/stigma (22%) and the most common barriers for their patients of color were knowledge (41%) and fear/stigma (25%). Those <35 years were more likely to not have a child (p <0.01) and more likely to feel the need to postpone family building due to their medical training (p<0.01). RES and FELs were more likely to agree that all women planning medical training should consider POC (p<0.03). Generalist ATTs who had not undergone POC trended toward having more regret compared to subspecialists (p=0.05).
CONCLUSION(S): Medical careers can have an unfavorable impact on family building and our results highlight this effect in Black women and persons of color. Most BOGs think trainees may benefit from POC. Improved education and access to POC could support personalized reproductive planning. IMPACT STATEMENT: Considering the underutilization of POC among Black women1 and the increase in infertility among female physicians2 , a better understanding of the mitigating factors is important in order to develop culturally appropriate counseling and educational interventions for women of color

OBJECTIVE: LBR models used in patient counseling often fail to account for oocyte cryopreservation and donation. Our aim was to evaluate the effect of oocyte cryopreservation and donation on predicted LBRs in STEETs. MATERIALS AND METHODS: All STEETs from 2014-2019 at a large academic center were identified. STEETs were excluded if embryos were CP before the blastocyst stage, embryos underwent >1 biopsy or >1 cryopreservation, blastocyst day or Gardner grade was unknown, age at oocyte cryopreservation or birth outcome was unknown, or reciprocal IVF or gestational carrier was used. The primary outcome was LBR. Statistical analyses included stepwise multiple logistic regressions. Significant parameters were chosen using the Akaike Information Criterion (AIC).
RESULT(S): 3421 STEET cycles were included; the female gametes used for embryo creation included 2951 fresh autologous oocytes (86.3%), 193 CP autologous oocytes (5.6%), 258 fresh donor oocytes (7.5%) and 19 CP donor oocytes (0.6%). See table for actual LBRs for select blastocyst days and Gardner grades. The following AIC regression equation was obtained: ln(OR [live birth / no live birth]) = +0.017 x age at CP (years) -0.027 x age at transfer (years) -0.36 x blastocyst day (coded as day 5 = 0, day 6 = 1, day 7 = 2) -0.39 x blastocyst stage (coded as: not filling zona = 0, filling zona or expanding = 1, hatched = 2) -0.44 x inner cell mass (ICM) grade (coded as A = 0, B = 1, C = 2) -0.62 x trophectoderm (TE) grade (coded as a = 0, beta = 1, c = 2) +2.45. Inclusion of a random variable for neither CP oocytes nor donor oocytes resulted in an e-fold improvement of the likelihood (did not meet the AIC criterion).
CONCLUSION(S): As previously established, blastocyst day and Gardner grade are predictors of LBR in STEET cycles. When adjusting for age at cryopreservation, age at transfer, blastocyst day and stage, and ICM and TE grades, cycles with CP or donor oocytes had no impact on the fit of the regression. Thus, embryos of equal blastocyst day and Gardner grade have similar LBRs when comparing fresh autologous, CP and donor oocytes. IMPACT STATEMENT: To the best of our knowledge, this is the first model that predicts LBRs in STEETs while accounting for whether oocytes were cryopreserved or donated. Our model suggests STEET LBRs are similar regardless of whether the female gamete is a fresh autologous oocyte, a cryopreserved oocyte or a donor oocyte