Correlation of self-reported racial background to euploidy status and live birth rates in assisted reproductive technology cycles.

PURPOSE: To determine whether the embryonic euploidy rate and live birth outcomes following single, euploid embryo transfer (SEET) differ among women of self-reported racial and ethnic backgrounds. METHODS: This retrospective cohort study included all infertile patients of different self-reported racial backgrounds who underwent In vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) and an autologous single euploid embryo transfer (SEET) from December 2015 to December 2019 at a single private and academic assisted reproduction technology center. Primary outcome measures included ploidy rates among different racial groups. Secondary outcomes included clinical pregnancy, clinical pregnancy loss, and live birth rates. RESULTS: Five thousand five hundred sixty-two patients who underwent an IVF cycle with ICSI-PGT-A were included. A total of 24,491 blastocysts were analyzed. White participants had on average more euploid embryos and higher euploidy rates when compared to their counterparts (p ≤ 0.0001). However, after controlling for confounding factors, there was no association between race and the odds of having  a higher euploidy rate (aOR 1.31; 95% CI 0.63-2.17, p = 0.42). A total of 4949 patients underwent SEET. Pregnancy outcomes did not differ among patients of varying self-reported races. CONCLUSIONS: Euploidy rates and pregnancy outcomes were comparable among patients of different racial backgrounds who underwent a SEET.

Determinant of Prenatal Diagnostic Testing among Women with Increased Risk of Fetal Aneuploidy and Genetic Disorders.

OBJECTIVE: This study aimed to assess factors that influence patients' decisions in accepting prenatal diagnostic testing following genetic counseling for increased risk of fetal aneuploidy. METHODS: This is a retrospective cohort study of women at increased risk of fetal aneuploidy and genetic disorders who had genetic counseling from January 2012 to December 2016 at a single academic center. Demographics, indications for genetic counseling, and rates of diagnostic testing were collected and compared between those who accepted diagnostic testing and those who chose cell free DNA. The variables were analyzed using Chi-square, Fisher's exact test, and multiple logistic regression. RESULT: Of the 2,373 pregnant women who underwent genetic counseling for increased risk of fetal aneuploidy and genetic disorders during the study period, 321 women had diagnostic testing (13.5%). Women at 35 years and older accepted diagnostic testing more than women younger than 35 years (20.7 vs. 11.5%, p < 0.001). Asian women accepted diagnostic testing at 27.7% more than white, non-Hispanic Black, and Hispanic women at 18.0, 12.1, and 11.7%, respectively, p = 0.002. Number of indications for genetic counseling influenced the likelihood of accepting diagnostic testing. Women with one indication had 11.5% acceptance of diagnostic testing, and with two and three indications, it was 17.0 and 29.2%, respectively. The commonest indication for diagnostic testing was cystic hygroma (risk ratio [RR] = 7.5, 95% confidence interval [CI]: 3.12-8.76 p < 0.001). The relative risk of diagnostic testing for fetuses with shortened long bones, femur and humerus, thickened nuchal fold, echogenic bowel, single umbilical artery, and increased nuchal translucency were 4.0, 3.3, 3.1, 2.7, and 2.7, respectively. Abnormal serum analyte alone was associated with less acceptance of diagnostic testing (RR = 0.8, 95% CI: 0.7-0.96, p = 0.017). CONCLUSION: Age, race, ethnicity, and cumulative number of indications for genetic counseling influenced acceptance of diagnostic testing in at-risk women of fetal aneuploidy and genetic disorders. KEY POINTS: · Genetic counseling.. · Fetal aneuploidy.. · Genetic disorders.. · Prenatal diagnostic testing. Prenatal diagnostic testing in women with increased risk of fetal aneuploidy and genetic disorders..

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.

We are here for you: infertility clinic communication during the first wave of the COVID-19 pandemic.

PURPOSE: To study how SART-member fertility clinics communicated via clinic websites during the first wave of the COVID-19 pandemic following publication of ASRM COVID-19 Task Force recommendations. METHODS: SART-member fertility clinic websites were systematically surveyed for the presence of an REI-specific COVID-19 message (REI-CM) and analyzed for their adherence to ASRM guidance. RESULTS: Of the 381 active clinic websites, 249 (65.3%) had REI-specific COVID messaging. The presence of REI-CM was more common in private than in academic practices (73% vs 38%, p < 0.001) and with increasing practice volume: 38% of clinics with < 200 annual cycles vs 91% of clinics with > 1000 cycles (p < 0.001). Adherence to ASRM guidance was more common in academic than in private practices (54% vs 31%, p = 0.02). Additionally, 9% of REI-CM (n = 23) announced continued treatment regardless of a patient's clinical urgency. This messaging was more common in groups doing > 1000 cycles a year (18%, p = 0.009). Clinics treating all-comers were less likely to cite ASRM than other clinics (41% vs 62%, p = 0.045). However, 75% (n = 14) cited COVID-19 guidance from WHO, CDC, and state and local governments. CONCLUSIONS: Clinic response to ASRM recommendations during the first wave of COVID-19 pandemic was heterogeneous. Although academic practices were more likely to follow ASRM guidance, there was a lower extent of patient-facing messaging among academic practices than private clinics. In event of further escalations of this and future pandemics, clinics can learn from experiences to provide clear messaging to patients.

Exposure of human fallopian tube epithelium to elevated testosterone results in alteration of cilia gene expression and beating.

STUDY QUESTION: How does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)? SUMMARY ANSWER: Elevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating. WHAT IS KNOWN ALREADY: The presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating. Women with polycystic ovarian syndrome (PCOS) may have twice the serum level of testosterone than ovulatory women. To date, the effect of elevated androgens on the function of the human fallopian tube is not well-understood. We chose to examine the impact of elevated testosterone on hFTE. STUDY DESIGN, SIZE, DURATION: A prospective basic science study of human fallopian tube specimens from reproductive-aged women undergoing benign gynecologic surgery was performed. Fallopian tube removal at a large US academic center was collected and provided to us to continue with epithelium isolation and culturing. A total of 12 patients were analyzed in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fallopian tube epithelium was isolated and exposed to two different conditions: normal with low testosterone concentration of 0.8 nM and PCOS-like, with high testosterone concentration of 2 nM. The study was conducted in both static and dynamic conditions in microfluidic devices for a total of 14 days, after which the tissue was collected for processing including RNA extraction, quantitative PCR and immunohistochemistry. After the first 7 days of each experiment, a sample of tissue from each condition was imaged to quantify cilia beating frequency. MAIN RESULTS AND THE ROLE OF CHANCE: hFTE exposed to the 2 nM testosterone displayed slower cilia beating, inhibited estrogen signaling and decreased expression of the ciliary marker FOXJ1 when compared to stimulation with 0.8 nM testosterone. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The in vivo response to elevated testosterone may differ from in vitro studies. RNA amount was limited from tissue cultured in the microfluidic devices as compared to static culture. WIDER IMPLICATIONS OF THE FINDINGS: Understanding elevated testosterone in tubal function may explain an additional contribution to subfertility in women with PCOS and other hyper-androgen disorders, aside from oligo-ovulation. Furthermore, this adds to the body of literature of fallopian tube function using a microfluidic device. STUDY FUNDING/COMPETING INTEREST(S): NIH grants: UH3 ES029073 and R01 CA240301. There are no competing interests.

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling.

Fallopian tube epithelium (FTE) plays a critical role in reproduction and can be the site where High Grade Serous Ovarian Carcinoma (HGSOC) originates. Tumorigenic oviductal cells, which are the murine equivalent of human fallopian tube secretory epithelial cells (FTSEC), enhance testosterone secretion by the ovary when co-cultured with the ovary, suggesting that testosterone is part of the signaling axis between the ovary and FTSEC. Furthermore, testosterone promotes proliferation of oviductal cells. Oral contraceptives, tubal ligation, and salpingectomy, which are all protective against developing ovarian cancer, also decrease circulating levels of androgen. In the current study, we investigated the effect of increased testosterone on FTE and found that testosterone upregulates wingless-type MMTV integration family, member 4 (WNT4) and induces migration and invasion of immortalized human fallopian tube cells. We profiled primary human fallopian tissues grown in the microfluidic system SOLO-microfluidic platform -(MFP) by RNA sequencing and found that p53 and its downstream target genes, such as paired box gene 2 (PAX2), cyclin-dependent kinase inhibitor 1A (CDK1A or p21), and cluster of differentiation 82 (CD82 or KAI1) were downregulated in response to testosterone treatment. A microfluidic platform, the PREDICT-Multi Organ System (PREDICT-MOS) was engineered to support insert technology that allowed for the study of cancer cell migration and invasion through Matrigel. Using this system, we found that testosterone enhanced FTE migration and invasion, which was reversed by the androgen receptor (AR) antagonist, bicalutamide. Testosterone also enhanced FTSEC adhesion to the ovarian stroma using murine ovaries. Overall, these results indicate that primary human fallopian tube tissue and immortalized FTSEC respond to testosterone to shift expression of genes that regulate invasion, while leveraging a new strategy to study migration in the presence of dynamic fluid flow.

Racial and Ethnic Variation in Genetic Susceptibility: Are Disparities in Infertility Prevalence and Outcomes more than Black and White?

Race, as a social construct without a clear genetic underpinning, is frequently referenced in medicine as predictor of multiple diseases including that of infertility. The authors will discuss how systematic racism can have downstream consequences ranging from overt physician bias to use of medical algorithms that may potentiate the same disparities they attempt to narrow. Then, the authors explore the utility and pragmatic use of genetic ancestry to estimate disease prevalence, instead of racial categories. Finally, the authors explore how health inequities, rooted in systematic racism, can influence disease heritability effectively advocating for research to disentangle the contributions of racism to genetic susceptibility in infertility.

See one, do one, teach one: Reimagining reproductive endocrinology and infertility training programs to expand access to care.

Objective: To provide a review of the current literature surrounding barriers to reproductive medicine and present examples of how resident and fellow education can be used to overcome these barriers. Design: A review of the relevant literature addressing barriers to reproductive medicine, resident and fellow education, and related materials was completed. Setting: Academic medical institutions. Patients: None. Interventions: None. Main Outcome Measures: Health disparities and barriers in access to care. Results: Of barriers in access to care, 3 were reviewed in detail: cost of health care, racial inequities, and marginalization of immigrant communities. The suggested strategies to mitigate these barriers include the following: reducing racial inequities through improved diversity within reproductive medicine and through antiracism training, developing opportunities for trainees to engage in advocacy, strengthening reproductive endocrinology and infertility clinical exposure and educational curricula in training programs, inclusion of residents and fellows in clinical care, and improving the accessibility of fertility care through implementing approaches to optimize the management of infertility in challenging, resource-constrained settings. Conclusions: Infertility is one of the most prevalent reproductive health diseases, yet profound disparities and inequities in access to care exist today in the United States. Lower-income, minority, and immigrant communities are among those most marginalized. Improved access to care begins with broadened obstetrics and gynecology and reproductive endocrinology and infertility trainee education, which acknowledges the barriers these communities face and provides strategies to help overcome these obstacles to care.

Provision of infertility care for the underserved in reproductive endocrinology and infertility practices associated with obstetrics and gynecology residency training programs in the United States.

Objective: To survey practice patterns designed to increase access to infertility care and evaluate the exposure of obstetrics and gynecology residents to infertility care for the underserved. Design: Cross-sectional. Setting: Reproductive endocrinology and infertility (REI) practices associated with Accreditation Council for Graduate Medical Education-accredited obstetrics and gynecology residency training programs. Patients: None. Interventions: Questionnaire survey. Main Outcome Measures: Presence of clinical programs designed to improve access to REI care, resident involvement in such programs, and perceived barriers to expanding access to care. Results: Clinical initiatives to expand access included discounted infertility services (38%, n = 30), utilization of a low-cost in vitro fertilization (IVF) program (28%, n = 22), and utilization of a resident- and/or fellow-staffed clinic to provide infertility care (39%, n = 31). The most commonly discounted infertility services were IVF (73%, n = 22), clinical consultation (70%, n = 21), and intrauterine insemination (53%, n = 16). The provision of discounted prices was correlated with the increasing practice size (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.23-4.24) and number of assisted reproductive technology cycles performed annually (OR, 3.65; 95% CI, 1.48-9.02). Academic REI practices (OR, 3.6; 95% CI, 0.98-13.25) were more likely to have a low-cost IVF program. Less than half of obstetrics and gynecology residency programs (39%, n = 31) had an associated REI clinic in which obstetrics and gynecology residents provide direct infertility care to the medically underserved. Frequency and services offered in trainee clinics varied. Multiple barriers to expanding access to care were reported. Conclusions: Reproductive endocrinology and infertility practices associated with obstetrics and gynecology residency programs utilize a diverse range of approaches to provide infertility care to the underserved in the backdrop of considerable challenges and barriers, but significant gaps persist.

The Evolving Role of Natural Compounds in the Medical Treatment of Uterine Fibroids.

Uterine fibroids (UFs) remain a significant health issue for many women, with a disproportionate impact on women of color, likely due to both genetic and environmental factors. The prevalence of UFs is estimated to be approximately 70% depending on population. UF-derived clinical symptoms include pelvic pain, excessive uterine bleeding, gastrointestinal and voiding problems, as well as impaired fertility. Nowadays numerous methods of UF treatment are available-from conservative treatment to invasive surgeries. Selecting an appropriate treatment option should be individualized and adjusted to the patient's expectations as much as possible. So far, the mainstay of treatment is surgery, but their negative impact of future fertility is clear. On the other hand, emerging new pharmaceutical options have significant adverse effects like liver function impairment, hot flashes, bone density loss, endometrial changes, and inability to attempt conception during treatment. Several natural compounds are found to help treat UFs and relieve their symptoms. In this review we summarize all the current available data about natural compounds that may be beneficial for patients with UFs, especially those who want to preserve their future fertility or have treatment while actively pursuing conception. Vitamin D, epigallocatechin gallate, berberine, curcumin, and others are being used as alternative UF treatments. Moreover, we propose the concept of using combined therapies of natural compounds on their own or combined with hormonal agents to manage UFs. There is a strong need for more human clinical trials involving these compounds before promoting widespread usage.

Preterm Delivery and Low Birth Weight Among Neonates Conceived With Intracytoplasmic Sperm Injection Compared With Conventional In Vitro Fertilization.

OBJECTIVE: To examine the prevalence of prematurity and low birth weight (LBW) among singletons conceived with intracytoplasmic sperm injection (ICSI) compared with those conceived with conventional in vitro fertilization (IVF). METHODS: Using the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System, we conducted a retrospective cohort study of women undergoing a first, fresh autologous ICSI or conventional IVF cycle from 2004 to 2013. Singleton live births were included in the analysis. Primary outcomes were preterm delivery and LBW. Secondary outcomes were very preterm delivery, preterm LBW, term LBW, and very LBW. Logistic regression models and propensity score matching were used to compare perinatal outcomes between ICSI and IVF cycles. Subset analyses were performed after stratification by sperm source, male factor infertility, and female prognosis. RESULTS: Of the 90,401 cycles included in the analysis, ICSI was used in 60,719 (67.2%) and conventional IVF was used in 29,682 (32.8%). After propensity score matching and covariate adjustment, the two groups had similar odds of preterm delivery (adjusted odds ratio [OR] 1.02, 95% CI 0.89-1.18) and LBW (adjusted OR 0.92, 95% CI 0.78-1.10). Using the matched data set, subset analyses demonstrated no significant association between the method of fertilization and the examined perinatal outcomes. CONCLUSION: Rates of preterm delivery and LBW were similar between pregnancies conceived with ICSI and conventional IVF after propensity score matching and stratifying by baseline patient characteristics. Previously reported differences in these outcomes were likely secondary to patients' inherent risk factors rather than the fertilization procedure itself.