Improving IVF Utilization with Patient-Centric Artificial Intelligence-Machine Learning (AI/ML): A Retrospective Multicenter Experience.

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.

Empathetic application of machine learning may address appropriate utilization of ART.

The value of artificial intelligence to benefit infertile patients is a subject of debate. This paper presents the experience of one aspect of artificial intelligence, machine learning, coupled with patient empathy to improve utilization of assisted reproductive technology (ART), which is an important aspect of care that is under-recognized. Although ART provides very effective options for infertile patients to build families, patients often discontinue ART when further treatment is likely to be beneficial and most of these patients do not achieve pregnancy without medical aid.

Antimüllerian hormone levels and antral follicle count as prognostic indicators in a personalized prediction model of live birth.

Objective: To compare antimüllerian hormone (AMH) and antral follicle count (AFC) separately and in combination with clinical characteristics for the prediction of live birth after controlled ovarian stimulation.

Design: Retrospective development and temporal external validation of prediction model.

Setting: Outpatient IVF clinic.

Personalized prediction of first-cycle in vitro fertilization success.

Objective: To test whether the probability of having a live birth (LB) with the first IVF cycle (C1) can be predicted and personalized for patients in diverse environments.

Design: Retrospective validation of multicenter prediction model.

Setting: Three university-affiliated outpatient IVF clinics located in different countries.

The chromatin remodeling factor Chd1l is required in the preimplantation embryo.

During preimplantation development, the embryo must establish totipotency and enact the earliest differentiation choices, processes that involve extensive chromatin modification. To identify novel developmental regulators, we screened for genes that are preferentially transcribed in the pluripotent inner cell mass (ICM) of the mouse blastocyst. Genes that encode chromatin remodeling factors were prominently represented in the ICM, including Chd1l, a member of the Snf2 gene family.

An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.

Landmark events occur in a coordinated manner during pre-implantation development of the mammalian embryo, yet the regulatory network that orchestrates these events remains largely unknown. Here, we present the first systematic investigation of the network in pre-implantation mouse embryos using morpholino-mediated gene knockdowns of key embryonic stem cell (ESC) factors followed by detailed transcriptome analysis of pooled embryos, single embryos, and individual blastomeres. We delineated the regulons of Oct4, Sall4, and Nanog and identified a set of metabolism- and transport-related genes that were controlled by these transcription factors in embryos but not in ESCs.

Predicting personalized multiple birth risks after in vitro fertilization-double embryo transfer.

Objective: To report and evaluate the performance and utility of an approach to predicting IVF-double embryo transfer (DET) multiple birth risks that is evidence-based, clinic-specific, and considers each patient's clinical profile.

Design: Retrospective prediction modeling.

Setting: An outpatient university-affiliated IVF clinic.

Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) are promising candidate cell sources for regenerative medicine. However, despite the common ability of hiPSCs and hESCs to differentiate into all 3 germ layers, their functional equivalence at the single cell level remains to be demonstrated. Moreover, single cell heterogeneity amongst stem cell populations may underlie important cell fate decisions.

Deep phenotyping to predict live birth outcomes in in vitro fertilization.

Nearly 75% of in vitro fertilization (IVF) treatments do not result in live births and patients are largely guided by a generalized age-based prognostic stratification. We sought to provide personalized and validated prognosis by using available clinical and embryo data from prior, failed treatments to predict live birth probabilities in the subsequent treatment. We generated a boosted tree model, IVFBT, by training it with IVF outcomes data from 1,676 first cycles (C1s) from 2003-2006, followed by external validation with 634 cycles from 2007-2008, respectively.

Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo.

Divisions of polarised blastomeres that allocate polar cells to outer and apolar cells to inner positions initiate the first cell fate decision in the mouse embryo. Subsequently, outer cells differentiate into trophectoderm while inner cells retain pluripotency to become inner cell mass (ICM) of the blastocyst. Elimination of zygotic expression of trophectoderm-specific transcription factor Cdx2 leads to defects in the maintenance of the blastocyst cavity, suggesting that it participates only in the late stage of trophectoderm formation.

Gene expression profiles of human inner cell mass cells and embryonic stem cells.

Human embryonic stem cell (hESC) lines are derived from the inner cell mass (ICM) of preimplantation human blastocysts obtained on days 5-6 following fertilization. Based on their derivation, they were once thought to be the equivalent of the ICM. Recently, however, studies in mice reported the derivation of mouse embryonic stem cell lines from the epiblast; these epiblast lines bear significant resemblance to human embryonic stem cell lines in terms of culture, differentiation potential and gene expression.

In vitro embryo culture in defined, sub-microliter volumes.

The high attrition rate of in vitro human embryo culture presents a major obstacle in the treatment of clinical infertility by in vitro fertilization (IVF). Physical and genetic requirements are not well understood for human or mouse preimplantation embryo development. Group culture is an established requirement for optimal embryo development in the mouse model.

A novel and critical role for Oct4 as a regulator of the maternal-embryonic transition.

Background: Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.

Methodology/principal Findings: Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage.

Defining human embryo phenotypes by cohort-specific prognostic factors.

Background: Hundreds of thousands of human embryos are cultured yearly at in vitro fertilization (IVF) centers worldwide, yet the vast majority fail to develop in culture or following transfer to the uterus. However, human embryo phenotypes have not been formally defined, and current criteria for embryo transfer largely focus on characteristics of individual embryos. We hypothesized that embryo cohort-specific variables describing sibling embryos as a group may predict developmental competence as measured by IVF cycle outcomes and serve to define human embryo phenotypes.

A transgenic mouse model for high content, cell cycle phenotype screening in live primary cells.

High content cell-based genetic and small molecule library screens are powerful strategies in drug discovery and investigations of disease mechanisms. We report that primary cells derived from a transgenic mouse model expressing a fluorescence mitosis biosensor provide unambiguous phenotype readouts without the need for transfection or immunocytochemistry. Phenotype profiles of cell cycle disruption and of apoptosis are easily detectable at a single time point selected from time-lapse live fluorescence microscopy.

Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus.

Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell proliferation and local immunosuppression.