In vitro fertilization (IVF) has the potential to give babies to millions more people globally, yet it continues to be underutilized. We established a globally applicable and locally adaptable IVF prognostics report and framework to support patient-provider counseling and enable validated, data-driven treatment decisions. This study investigates the IVF utilization rates associated with the usage of machine learning, center-specific (MLCS) prognostic reports (the Univfy report) in provider-patient pre-treatment and IVF counseling.
View Article and Find Full Text PDFThe uterine myometrium expands and maintains contractile quiescence before parturition. While the steroid hormone progesterone blocks labor, the role of progesterone signaling in myometrial expansion remains elusive. This study investigated the myometrial functions of the progesterone receptor, PGR.
View Article and Find Full Text PDFObjective: To evaluate the feasibility of generating a center-specific embryo morphokinetic algorithm by time-lapse microscopy to predict clinical pregnancy rates.
Design: A retrospective cohort analysis.
Setting: Academic fertility clinic in a tertiary hospital setting.
Background: Financial hardship among adolescents and young adults (AYA) with cancer who receive gonadotoxic treatments may be exacerbated by the use of fertility services. This study examined whether AYA women with cancer who used fertility preservation had increased financial hardship.
Methods: AYA women with cancer in North Carolina and California completed a survey in 2018-2019.
Objective: To investigate if patients with polycystic ovary syndrome (PCOS) have altered embryo morphokinetics when compared with controls.
Design: Retrospective cohort analysis.
Setting: Single academic fertility clinic in a tertiary hospital setting.
Proc Natl Acad Sci U S A
March 2021
Uterine contractile dysfunction leads to pregnancy complications such as preterm birth and labor dystocia. In humans, it is hypothesized that progesterone receptor isoform PGR-B promotes a relaxed state of the myometrium, and PGR-A facilitates uterine contraction. This hypothesis was tested in vivo using transgenic mouse models that overexpress PGR-A or PGR-B in smooth muscle cells.
View Article and Find Full Text PDFJ Pediatr Endocrinol Metab
March 2021
Objective: To characterize the age of ovarian failure in Turner Syndrome (TS) patients by karyotype.
Methods: Retrospective cohort study of individuals with TS at an academic university hospital. Subjects were seen in TS Clinic at UNC Hospital between 2014 and 2018.
Purpose: Controversy exists around the use of epididymal sperm for in vitro fertilization and intracytoplasmic sperm injection for couples with obstructive azoospermia, and the ability to reliably predict fertility outcomes with surgically extracted epididymal sperm remains limited. To provide additional clinical context, we sought to compare in vitro fertilization/intracytoplasmic sperm injection outcomes of epididymal sperm from couples with obstructive azoospermia to outcomes of couples using normal, ejaculated sperm.
Materials And Methods: We performed a case-control analysis of 40 couples who underwent office based epididymal sperm retrieval for obstructive azoospermia followed by in vitro fertilization/intracytoplasmic sperm injection compared with a control group of 38 female, age matched couples with no evidence of female factor infertility who underwent in vitro fertilization/intracytoplasmic sperm injection with normal, ejaculated sperm.
Using a Rosa26 gene targeting strategy in mouse embryonic stem cells, we have generated a new transgenic mouse (Pgr-B ), which is designed to conditionally express the epitope-tagged mouse progesterone receptor-B (PGR-B) isoform when crossed with a specific cre driver mouse. To functionally validate this transgenic mouse, we crossed the Pgr-B mouse with the MMTV-CREA transgenic mouse to create the MMTV-CREA/Pgr-B bigenic (termed PR-B:OE to denote PGR-B overexpressor). As expected, transgene-derived PGR-B protein was specifically targeted to the virgin mammary gland epithelium.
View Article and Find Full Text PDFInfertility and early embryo miscarriage is linked to inadequate endometrial decidualization. Although transcriptional reprogramming is known to drive decidualization in response to progesterone, the key signaling effectors that directly mediate this hormone response are not fully known. This knowledge gap is clinically significant because identifying the early signals that directly mediate progesterone-driven decidualization will address some of the current limitations in diagnosing and therapeutically treating patients at most risk for early pregnancy loss.
View Article and Find Full Text PDFHigh-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.
View Article and Find Full Text PDFThis short technical report describes the generation and characterization of a bioluminescence reporter mouse that is engineered to detect and longitudinally monitor the expression of doxycycline-induced constitutively active β-catenin. The new responder transgenic mouse contains the TetO-ΔN89β-CatTMILA transgene, which consists of the tet-operator followed by a bicistronic sequence encoding a stabilized form of active β-catenin (ΔN89β-catenin), an internal ribosome entry site, and the firefly luciferase gene. To confirm that the transgene operates as designed, TetO-ΔN89β-CatTMILA transgenic mouse lines were crossed with an effector mouse that harbors the mouse mammary tumor virus-reverse tetracycline transactivator (MMTV-rtTA) transgene (termed MTB hereon), which primarily targets rtTA expression to the mammary epithelium.
View Article and Find Full Text PDFUltrasonography 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.
View Article and Find Full Text PDFJ Adolesc Young Adult Oncol
June 2017
Purpose: Adolescents and young adults (AYAs) receiving cancer treatments that may impair fertility should receive counseling about risk of infertility and options for fertility preservation (FP) before treatment and/or during survivorship. Our objective was to define the AYA patient population referred to an on-site fertility consultation service within a comprehensive cancer center and determine factors associated with patients proceeding with FP treatment.
Methods: We conducted a retrospective chart review of AYA women who completed a consultation at the MD Anderson Fertility Preservation and Family Building Service during the first year of service.
Progesterone, via the progesterone receptor (PGR), is essential for endometrial stromal cell decidualization, a cellular transformation event in which stromal fibroblasts differentiate into decidual cells. Uterine decidualization supports embryo implantation and placentation as well as subsequent events, which together ensure a successful pregnancy. Accordingly, impaired decidualization results not only in implantation failure or early fetal miscarriage, but also may lead to potential adverse outcomes in all three pregnancy trimesters.
View Article and Find Full Text PDFObjective: Integrin α11β1 is a collagen receptor specific to fibroblasts that regulates myofibroblast differentiation. We sought to determine whether α11β1 is expressed in myometrium and fibroids and whether tissue expression varies.
Design: Comparison of α11 in human myometrium and fibroids using Western blot and RNA in situ hybridization.
Objective: To serve as a pilot feasibility study for a randomized study of excision versus ablation in the treatment of endometriosis by (1) estimating the magnitude of change in symptoms after excision only at multiple referral centers and (2) determining the proportion of women willing to participate in a randomized trial.
Methods: We performed a multicenter prospective study of women undergoing excision for endometriosis (Canadian Task Force class II-3) at Duke University Center for Endometriosis Research & Treatment (currently the Saint Louis University Center for Endometriosis), Center for Endometriosis Care, Northshore University Health System, Memorial University (Canada), and Florida Hospital. The study comprised 100 female patients, aged 18 to 55 years, with endometriosis-suspected pelvic pain.
Background: Progesterone is produced by the corpus luteum until completion of the luteal-placental shift at approximately 6-10 weeks following last menstruation. Studies have shown that first trimester progesterone levels are predictive of pregnancy viability, and some authors support a level of 5 ng/mL as an absolute threshold to indicate viability.
Case: A 47-year-old woman with recurrent pregnancy loss was noted to have a very low first trimester progesterone level (1.
Am J Physiol Regul Integr Comp Physiol
September 2008
The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at embryonic day (E)13.5-14.
View Article and Find Full Text PDFHere we report that epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3. Transgenic mice with keratinocytes expressing a constitutively active Stat3 (K5.Stat3C mice) develop a skin phenotype either spontaneously, or in response to wounding, that closely resembles psoriasis.
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