The Landscape of Telomere Length and Telomerase in Human Embryos at Blastocyst Stage.

The telomere length of human blastocysts exceeds that of oocytes and telomerase activity increases after zygotic activation, peaking at the blastocyst stage. Yet, it is unknown whether aneuploid human embryos at the blastocyst stage exhibit a different profile of telomere length, telomerase gene expression, and telomerase activity compared to euploid embryos. In present study, 154 cryopreserved human blastocysts, donated by consenting patients, were thawed and assayed for telomere length, telomerase gene expression, and telomerase activity using real-time PCR (qPCR) and immunofluorescence (IF) staining. Aneuploid blastocysts showed longer telomeres, higher telomerase reverse transcriptase (TERT) mRNA expression, and lower telomerase activity compared to euploid blastocysts. The TERT protein was found in all tested embryos via IF staining with anti-hTERT antibody, regardless of ploidy status. Moreover, telomere length or telomerase gene expression did not differ in aneuploid blastocysts between chromosomal gain or loss. Our data demonstrate that telomerase is activated and telomeres are maintained in all human blastocyst stage embryos. The robust telomerase gene expression and telomere maintenance, even in aneuploid human blastocysts, may explain why extended in vitro culture alone is insufficient to cull out aneuploid embryos during in vitro fertilization.

Vitrification with Dimethyl Sulfoxide Induces Transcriptomic Alteration of Gene and Transposable Element Expression in Immature Human Oocytes.

Despite substantial advancements in the field of cryobiology, oocyte and embryo cryopreservation still compromise developmental competence. Furthermore, dimethyl sulfoxide (DMSO), one of the most commonly used cryoprotectants, has been found to exert potent effects on the epigenetic landscape of cultured human cells, as well as mouse oocytes and embryos. Little is known about its impact on human oocytes. Additionally, few studies investigate the effects of DMSO on transposable elements (TE), the control of which is essential for the maintenance of genomic instability. The objective of this study was to investigate the impact of vitrification with DMSO-containing cryoprotectant on the transcriptome, including on TEs, of human oocytes. Twenty-four oocytes at the GV stage were donated by four healthy women undergoing elective oocyte cryopreservation. Oocytes were paired such that half from each patient were vitrified with DMSO-containing cryoprotectant (Vitrified Cohort), while the other half were snap frozen in phosphate buffer, unexposed to DMSO (Non-Vitrified Cohort). All oocytes underwent RNA sequencing via a method with high fidelity for single cell analysis, and which allows for the analysis of TE expression through Switching Mechanism at the 5'-end of the RNA Transcript sequencing 2 (SMARTseq2), followed by functional enrichment analysis. Of the 27,837 genes identified by SMARTseq2, 7331 (26.3%) were differentially expressed (p < 0.05). There was a significant dysregulation of genes involved in chromatin and histone modification. Mitochondrial function, as well as the Wnt, insulin, mTOR, HIPPO, and MAPK signaling pathways were also altered. The expression of TEs was positively correlated with the expression of PIWIL2, DNMT3A, and DNMT3B, and negatively correlated with age. These findings suggest that the current standard process of oocyte vitrification, involving DMSO-containing cryoprotectant, induces significant transcriptome changes, including those involving TEs.

Serum Gonadotropin Levels Predict Post-Trigger Luteinizing Hormone Response in Antagonist Controlled Ovarian Hyperstimulation Cycles.

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.

Factors associated with disparate outcomes among Black women undergoing in vitro fertilization.

Objective: To determine if Black women have worse in vitro fertilization (IVF) outcomes than women of other races/ethnicities, and to establish which factors are associated with the IVF outcomes of Black women. Design: Retrospective cohort study. Setting: Not applicable. Patients: All patients undergoing IVF. Interventions: Not applicable. Main Outcome Measures: Spontaneous abortion rate, clinical pregnancy rate, and live birth rate. Results: A total of 71,389 patient cycles were analyzed. Of the 40,545 patients who were included, 6.4% of patients were Black, 62% were White, 7.3% were Hispanic/Latino, and 15% were Asian. After IVF, Black women had significantly more miscarriages than White but not Hispanic or Asian patients (8.0% Black vs. 6.9% White, 7.4% Hispanic, and 7.5% Asian). Clinical pregnancy rates were significantly lower for Black women compared with all other races (45% Black vs. 52% White, 52% Hispanic, and 53% Asian). The odds ratio (OR) of live birth from all cycles were 30% less than that for White women (OR, 1.00 Black vs. 1.43 White) and 22% less than that for Hispanic women (OR, 1.00 Black vs. 1.29 Hispanic). This statistically significant difference in the live birth rate persisted even after adjusting for patient characteristics (OR, 1.00 Black vs. 1.32 White, 1.23 Hispanic, and 1.18 Asian). Conclusions: Black women have worse IVF outcomes than women of all other racial backgrounds undergoing IVF. The factors associated with the disparate outcomes of Black women undergoing IVF outcomes include older age starting IVF, higher body mass index, tubal factor infertility, and diabetes.

Primary ovarian insufficiency: a glimpse into the racial and socioeconomic disparities found within third-party reproduction.

Objective: 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: Case report and review of the literature. Setting: Safety-net hospital in an urban community. Patients: A 36-year-old Black woman, gravida 0, with primary ovarian insufficiency who desires future fertility but is restricted by systemic barriers. Interventions: Chromosome analysis. Main Outcome Measures: Not applicable. Results: Balanced reciprocal translocation between chromosomes 1 and 13: 46,XX,t(1;13)(q25;q14.1). Conclusions: 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.

Planned Oocyte Cryopreservation and the Black Obstetrician Gynecologist: Utilization and Perspectives.

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.

Changing the Narrative, Starting With Us.

Infertility can affect anyone, including Black women who, contrary to popular belief, are most likely to suffer from infertility, less likely to seek fertility care, and more likely to delay or completely forgo fertility treatment (Chin et al Paediatr Perinat Epidemiol 29(5):416-25, 5). These trends are likely fueled by deep-rooted stigma generated from a multitude of origins. Some black women may feel uncomfortable discussing their experience with infertility due to the pervasive stereotype that Black women are hyper-fertile (Ceballo et al Psychol Women Q 39(4):497-511, 20). This stereotype also has important implications within the medical field, in which provider implicit bias may affect referrals and treatment plans, further contributing to stratified reproduction (Chapman et al J Gen Intern Med 28(11):1504-10, 15, FitzGerald and Hurst BMC Med Ethics 18(1):19, 16). It is time for the medical community to shift our focus to what we can change, starting with how we perceive the narrative. In order to effect change, providers should first become and remain aware of racial/ethnic disparities within reproduction. We can make a concerted effort to effectively counsel Black women about their fertility and future childbearing goals, as well as strive to debunk false racial/ethnic fertility stereotypes with medical evidence. We should actively work to understand our biases, where they stem from, and how to resolve them. We must aim to always provide respectful, equitable, and consistent care, especially when deciding how to counsel someone regarding fertility preservation and infertility treatment options. In sum, we can approach solving this complicated racial-ethnic gap in health equity by taking small intentional and parallel steps, starting now.

Investigation of racial disparities in semen parameters among white, black, and Asian men.

BACKGROUND: Male factor infertility is the primary cause of infertility in 20% of couples. Primary evaluation of male factor infertility includes a semen analysis (SA). The World Health Organization (WHO) criteria are widely used to interpret SA. However, the current normative values seen in WHO criteria have led to research showing racial disparities in prevalence of abnormal SA. OBJECTIVE: To assess the relationship between different self-reported racial groups and rates of abnormal SA. MATERIALS & METHODS: We conducted a retrospective cohort study at a single large tertiary care facility. All men who underwent a SA for evaluation of suspected male infertility, unexplained infertility, intrauterine insemination, and in vitro fertilization between January 1, 2017 and December 31, 2019, were considered for inclusion in the study. Exclusion criteria were unreported race or ethnicity, SA for fertility preservation only, history of varicocele or testicular surgery, chromosomal abnormalities, congenital bilateral absence of vas deferens, prior testosterone use, or prior exposure to chemotherapy and/or radiation. Samples obtained via testicular sperm extraction or post-ejaculatory urine collection, or those analyzed ≥1 h from ejaculation, were also excluded. RESULTS: 872 SAs were identified, of which 615 met inclusion criteria, yielding 384 normal and 231 abnormal results. Only race (p < 0.0001) and age (p = 0.002) were statistically significant. Black men had the highest rate of abnormal SA (54%) and were significantly more likely to have lower semen volume, sperm concentration, total sperm count, percent motile sperm, and total motile sperm (p < 0.05). In a logistic regression model, controlling for age and using White Non-Hispanic as the referent group, only Blacks had lower odds for a normal SA (OR = 0.41, 95% CI 0.28, 0.60). DISCUSSION AND CONCLUSIONS: Black men are more likely to have an abnormal SA based on the 2010 WHO criteria. Black men seeking infertility treatment should be educated on the incidence of abnormal SA and actively seek infertility evaluation.

To treat or not to treat: perceptions of the initial American Society for Reproductive Medicine COVID-19 recommendations among women's health providers.

PURPOSE: The objective of this study was to evaluate the perception of the initial ASRM COVID-19 recommendations for infertility treatment held by women's health providers within varying subspecialties, as well as their attitudes toward pregnancy and fertility during this time. METHODS: An electronic survey was sent to all women's healthcare providers, including physicians, mid-level providers and nurses, in all subspecialties of obstetrics and gynaecology (Ob/Gyn) at a large tertiary care university-affiliated hospital. RESULTS: Of the 278 eligible providers, the survey response rate was 45% (n = 127). Participants represented 8 Ob/Gyn subspecialties and all professional levels. Participants age 18-30 years were significantly more likely to feel that women should have access to infertility treatment despite the burden level of COVID-19 in respective community/states (p = 0.0058). Participants within the subspecialties of general Ob/Gyn, maternal foetal medicine and gynecologic oncology were significantly more likely to disagree that all women should refrain from planned conception during the COVID-19 pandemic, in comparison to those in urogynecology and reproductive endocrinology and infertility (p = 0.0003). CONCLUSIONS: Considering the immediate and unknown long-term impact of the COVID-19 pandemic on fertility care delivery, a better understanding of perceptions regarding infertility management during this time is important. Our study shows overall support for the initial ASRM recommendations, representing a wide spectrum of women's health providers.

Infertility and assisted reproductive technology outcomes in Afro-Caribbean women.

OBJECTIVE: To assess the causes of infertility and artificial reproductive technology (ART) outcomes in women of African descent living in the Caribbean and Bermuda. DESIGN: Cross-sectional study composed of a questionnaire administered to providers who care for women undergoing ART in the Caribbean and Bermuda. MATERIAL AND METHODS: A questionnaire from the Deerfield Institute was adapted to meet the aims of our study with their permission. Eight infertility clinics in the Caribbean and Bermuda were identified. The primary physician at each site was contacted via email and invited to participate in the study. Questionnaires were completed via interview or electronically. Responses were collected in a REDCap database for statistical analysis. RESULTS: There were five respondents from Barbados, Bermuda (× 2), Puerto Rico, and the Bahamas. The most commonly reported etiologies of infertility among Afro-Caribbean patients were female-male factor and uterine factor. In vitro fertilization (IVF) combined with intracytoplasmic sperm injection (ICSI) is performed more often than conventional IVF. The cumulative live birth rates (LBR) after ART for those ages ≤ 34, 35-37, 38-42, and > 42 were 52%, 40%, 22%, and 12%, respectively. The cumulative live birth rate was 31.5% for total patients. The factors reported to be most important in hindering patients from cycling were coping emotionally with poor ovarian response and cost. The biggest restraints to infertility care were costs and a lack of local IVF centers on all islands. CONCLUSION: Afro-Caribbean women receiving infertility care in the Caribbean may have better ART outcomes compared to African-American women in the United States (US).

Infertility knowledge and treatment beliefs among African American women in an urban community.

BACKGROUND: To assess infertility knowledge and treatment beliefs among African American women in an urban community in Atlanta, Georgia. METHODS: This was a cross sectional study at a safety net hospital. A convenience sample of a total of 158 women receiving outpatient obstetrical or gynecologic care from March-April 2017 were recruited. Infertility knowledge and treatment beliefs were assessed using a previously applied and field-tested survey from the International Fertility Decision Making Study. RESULTS: The mean infertility knowledge score was 38.15% for total subjects. Those with a higher level of education (p < 0.0001) and those with paid employment (p = 0.01) had a significantly higher level of infertility knowledge. Those who had a history of infertility therapy were significantly more likely to agree with negative treatment beliefs (p = 0.01). There was no significant difference in infertility knowledge or treatment beliefs based on age, sexuality, parity or being pregnant at the time of survey completion. CONCLUSIONS: African American women in our urban clinic setting seem to have a limited level of knowledge pertaining to infertility. Further research is needed to understand how differences in knowledge and beliefs translate into infertility care decision-making and future childbearing.