Disparities in fertility knowledge among women from low and high resource settings presenting for fertility care in two United States metropolitan centers.

BACKGROUND: Few studies have examined health literacy and fertility knowledge among women from low income, socio-culturally diverse communities presenting for fertility care in the United States. Our study sought to examine demographic predictors of fertility-related knowledge among infertile women from low and high-resource communities in two major metropolitan centers in the United States. METHODS: Fertility Knowledge Assessments were administered to women presenting for fertility care at county medical centers serving low-resource, largely immigrant patients and to women from largely affluent populations presenting to comprehensive fertility centers in two cities. The influence of demographic predictors on fertility knowledge was examined through regression analysis. RESULTS: A total of 143 women were included in our analysis. In the county hospital/low resource clinic (LR, n = 70), the mean age was 32.8 ± 6.1 years vs 35.0 ± 5.0 years in the fee-for-service/high resource clinic (HR, n = 73). Among the LR patients, 74% were immigrants, 71% had an annual income <$25,000 and 52% had completed high school. Among HR patients, 36% were immigrants, 60% had an annual income >$100,000, and 95% had some college or above. On average, women from HR settings scored 3.0 points higher on the Fertility Knowledge Assessment than their LR counterparts (p < 0.001). Upon multivariate analysis, education level remained the sole independent factor associated with fertility knowledge assessment score (p < 0.001). Stratifying by resource level revealed that income was highly associated with fertility knowledge (p < 0.01) among high resource individuals even when adjusting for education level. CONCLUSIONS: Women from low resource, largely immigrant communities, seeking fertility care have greater disparities in fertility knowledge and lower health literacy compared to women from high resource clinical settings. Further studies are needed to understand these barriers and to develop targeted inventions to lower disparities and improve care for these vulnerable populations.

Preovulatory exposure to a protein-restricted diet disrupts amino acid kinetics and alters mitochondrial structure and function in the rat oocyte and is partially rescued by folic acid.

BACKGROUND: Detrimental exposures during pregnancy have been implicated in programming offspring to develop permanent changes in physiology and metabolism, increasing the risk for developing diseases in adulthood such as hypertension, diabetes, heart disease and obesity. This study investigated the effects of protein restriction on the metabolism of amino acids within the oocyte, liver, and whole organism in a rat model as well as effects on mitochondrial ultrastructure and function in the cumulus oocyte complex. METHODS: Wistar outbred female rats 8-11 weeks of age (n = 24) were assigned to three isocaloric dietary groups, including control (C), low protein (LP) and low protein supplemented with folate (LPF). Animals were superovulated and 48 h later underwent central catheterization. Isotopic tracers of 1-13C-5C2H3-methionine, 2H2-cysteine, U-13C3-cysteine and U-13C3-serine were administered by a 4 h prime-constant rate infusion. After sacrifice, oocytes were denuded of cumulus cells and liver specimens were obtained. RESULTS: Oocytes demonstrated reduced serine flux in LP vs. LPF (p < 0.05), reduced cysteine flux in LP and LPF vs. C (p < 0.05), and a trend toward reduced transsulfuration in LP vs. C and LPF. Folic acid supplementation reversed observed effects on serine flux and transsulfuration. Preovulatory protein restriction increased whole-body methionine transmethylation, methionine transsulfuration and the flux of serine in LP and LPF vs. C (p = 0.003, p = 0.002, p = 0.005). The concentration of glutathione was increased in erythrocytes and liver in LP and LPF vs. C (p = 0.003 and p = 0.0003). Oocyte mitochondrial ultrastructure in LP and LPF had increased proportions of abnormal mitochondria vs. C (p < 0.01 and p < 0.05). Cumulus cell mitochondrial ultrastructure in LP and LPF groups had increased proportions of abnormal mitochondria vs. C (p < 0.001 and p < 0.05). Preovulatory protein restriction altered oocyte expression of Drp1, Opa-1, Mfn1/2, Parl and Ndufb6 (p < 0.05) and Hk2 (p < 0.01), which are genes involved in mitochondrial fission (division) and fusion, mitochondrial apoptotic mechanisms, respiratory electron transport and glucose metabolism. CONCLUSIONS: Preovulatory protein restriction resulted in altered amino acid metabolism, abnormal cumulus oocyte complex mitochondrial ultrastructure and differential oocyte expression of genes related to mitochondrial biogenesis.

A Novel Use of Three-dimensional High-frequency Ultrasonography for Early Pregnancy Characterization in the Mouse.

High-frequency ultrasonography (HFUS) is a common method to non-invasively monitor the real-time development of the human fetus in utero. The mouse is routinely used as an in vivo model to study embryo implantation and pregnancy progression. Unfortunately, such murine studies require pregnancy interruption to enable follow-up phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction of HFUS imaging data for early detection and characterization of murine embryo implantation sites and their individual developmental progression in utero. Combining HFUS imaging with 3-D reconstruction and modeling, we were able to accurately quantify embryo implantation site number as well as monitor developmental progression in pregnant C57BL6J/129S mice from 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. with the use of a transducer. Measurements included: number, location, and volume of implantation sites as well as inter-implantation site spacing; embryo viability was assessed by cardiac activity monitoring. In the immediate post-implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in both mesh and solid overlay format enabled visual representation of the developing pregnancies within each uterine horn. As genetically engineered mice continue to be used to characterize female reproductive phenotypes derived from uterine dysfunction, this method offers a new approach to detect, quantify, and characterize early implantation events in vivo. This novel use of 3-D HFUS imaging demonstrates the ability to successfully detect, visualize, and characterize embryo-implantation sites during early murine pregnancy in a non-invasive manner. The technology offers a significant improvement over current methods, which rely on the interruption of pregnancies for gross tissue and histopathologic characterization. Here we use a video and text format to describe how to successfully perform ultrasounds of early murine pregnancy to generate reliable and reproducible data with reconstruction of the uterine form in mesh and solid 3-D images.

Implantation failure of endometrial origin: it is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium.

Repeated implantation failure (RIF) is an intriguing, massive failure of reproductive treatment in otherwise healthy women leading to the introduction of empirical adjuvant interventions that are costly, inefficient, and frustrating for our patients. In this article, we will try to convince the readers that RIF is neither a stigma nor a mysterious pathology but rather our failure to diagnose and properly synchronize the euploid blastocyst with the patient's personalized window of implantation.

Introduction: Endometrial function: facts, urban legends, and an eye to the future.

The embryo alone, though very important, is not sufficient to explain successful or failed implantation. Human embryonic implantation is less efficient than in nonmenstruating species. The main difference lies in the decidual control of early implantation events and the subsequent course of pregnancy versus embryo control in nonmenstruating species. In this article, we introduce the facts behind the low efficiency of this crucial process, address urban legends routinely considered without high clinical quality evidence, and provide a vision of how the endometrial field will develop in the near future.

Three-Dimensional High-Frequency Ultrasonography for Early Detection and Characterization of Embryo Implantation Site Development in the Mouse.

Ultrasonography is a powerful tool to non-invasively monitor in real time the development of the human fetus in utero. Although genetically engineered mice have served as valuable in vivo models to study both embryo implantation and pregnancy progression, such studies usually require sacrifice of parous mice for subsequent phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction in silico of high-frequency ultrasound (HFUS) imaging data for early detection and characterization of murine embryo implantation sites and their development in utero. With HFUS imaging followed by 3-D reconstruction, we were able to precisely quantify embryo implantation site number and embryonic developmental progression in pregnant C57BL6J/129S mice from as early as 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. using a VisualSonics Vevo 2100 (MS550S) transducer. In addition to measurements of implantation site number, location, volume and spacing, embryo viability via cardiac activity monitoring was also achieved. A total of 12 dams were imaged with HFUS with approximately 100 embryos examined per embryonic day. For the post-implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in mesh or solid overlay format enabled visual representation in silico of implantation site location, number, spacing distances, and site volume within each uterine horn. Therefore, this short technical report describes the feasibility of using 3-D HFUS imaging for early detection and analysis of post-implantation events in the pregnant mouse with the ability to longitudinally monitor the development of these early pregnancy events in a non-invasive manner. As genetically engineered mice continue to be used to characterize female reproductive phenotypes, we believe this reliable and non-invasive method to detect, quantify, and characterize early implantation events will prove to be an invaluable investigative tool for the study of female infertility and subfertility phenotypes based on a defective uterus.

Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis.

OBJECTIVE: To analyze the transcriptomic profile of endometrial gene alterations during the window of implantation in infertile obese patients. DESIGN: Multicenter, prospective, case-control study. SETTING: Three academic medical centers for reproductive medicine. PATIENT(S): Infertile patients, stratified into body mass index (BMI) categories according to the World Health Organization guidelines, were included in the study. INTERVENTION(S): Endometrial samples were obtained from women undergoing standardized estrogen and P replacement cycles after 5 days of vaginal P supplementation. MAIN OUTCOME MEASURE(S): To identify endometrial gene expression alterations that occur during the window of implantation in infertile obese patients as compared with infertile normal-weight controls using a microarray analysis. RESULT(S): XCL1, XCL2, HMHA1, S100A1, KLRC1, COTL1, COL16A1, KRT7, and MFAP5 are significantly dysregulated during the window of implantation in the receptive endometrium of obese patients. COL16A1, COTL1, HMHA1, KRCL1, XCL1, and XCL2 were down-regulated and KRT7, MFAP5, and S100A1 were up-regulated in the endometrium of obese patients. These genes are mainly involved in chemokine, cytokine, and immune system activity and in the structural extracellular matrix and protein-binding molecular functions. CONCLUSION(S): Obesity is associated with significant endometrial transcriptomic differences as compared with non-obese subjects. Altered endometrial gene expression in obese patients may contribute to the lower implantation rates and increased miscarriage rates seen in obese infertile patients. CLINICAL TRIAL REGISTRATION NUMBER: NCT02205866.