Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial.

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%.

Cushing's Disease May Have Higher Incidence than Previously Thought: A Nationwide Study in Iceland 2010-2019.

Introduction: In 2011, we reported the overall incidence of Cushing's disease (CD) in Iceland from 1955 through 2009 to be 1.5 cases per million per year with highest incidence in the last decade of the study, a higher incidence then earlier reported. We now present a follow-up study reporting the epidemiology of the disease in Iceland during the 10-year period from 2010 to 2019.

Correlations between a deep learning-based algorithm for embryo evaluation with cleavage-stage cell numbers and fragmentation.

Research Question: Do cell numbers and degree of fragmentation in cleavage-stage embryos, assessed manually, correlate with evaluations made by deep learning algorithm model iDAScore v2.0?

Design: Retrospective observational study (n = 5040 embryos; 1786 treatments) conducted at two Swedish assisted reproductive technology centres between 2016 and 2021. Fresh single embryo transfer was carried out on days 2 or 3 after fertilization.

A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer.

Study Question: Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone?

Summary Answer: The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone.

What Is Known Already: Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection.

[Obesity isn't always obesity: Cushing's disease - case report].

Woman in her thirties presented to the emergency room with a two-week history of worsening headache and diplopia. For eight years she had suffered from progressive weight gain, diabetes and hypertension that didn't improve with lifestyle modification. A lumbar puncture demonstrated increased intracranial pressure and MRI a pituitary adenoma.

Comprehensive analysis of soluble RNAs in human embryo culture media and blastocoel fluid.

Purpose: miRNAs have been suggested as biomarkers of embryo viability; however, findings from preliminary studies are divergent. Furthermore, the presence of other types of small RNA molecules remains to be investigated. The purpose of this study was to perform a comprehensive analysis of small non-coding RNA levels in spent and unconditioned embryo culture media, along with miRNA levels in blastocoelic fluid samples from human embryos.

Transplanting embryonic stem cells onto damaged human corneal endothelium.

Aim: To investigate whether human embryonic stem cells (hESCs) could be made to attach, grow and differentiate on a human Descemet's membrane (DM).

Methods: Spontaneously differentiated hESCs were transferred onto a human corneal button with the endothelial layer removed using ocular sticks. The cells were cultured on a DM for up to 15 d.

Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions?

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT.

Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

Objective: To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media.

Design: Randomized, double-blinded sibling trial.

Setting: Independent in vitro fertilization (IVF) clinics.

Choosing the best embryo by time lapse versus standard morphology.

Within the past few years the morphological evaluation of in vitro fertilized embryos has been extended to include continuous surveillance, enabled by the introduction of time-lapse incubators developed specifically for IVF treatment. As a result time-lapse monitoring has been implemented in many clinics worldwide. The proposed benefits compared with culture in a standard incubator and fixed time-point evaluation are uninterrupted culture, a flexible workflow in the laboratory, and improved embryo selection.

Epidemiology of Primary Immunodeficiency in Iceland.

Purpose: Primary immunodeficiencies (PID) are rare heterogeneous diseases. Little is known about the prevalence of PID in Iceland and no national registry exists. The aim of the study was to describe the epidemiology of PID in Iceland.

No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis.

Study Question: What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)?

Summary Answer: The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone.

What Is Known Already: Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer.

Prediction of live birth in frozen-thawed single blastocyst transfer cycles by pre-freeze and post-thaw morphology.

Study Question: What pre-freeze and post-thaw morphological parameters can be used to predict live birth outcomes after frozen-thawed blastocyst transfer cycles?

Summary Answer: Pre-freeze blastocoele expansion and trophectoderm (TE) grade and post-thaw degree of re-expansion are the most significant predictors of live birth in frozen-thawed blastocyst transfer cycles.

What Is Known Already: Currently, blastocoele re-expansion after thawing is used to indicate blastocyst cryosurvival and reproductive potential. The predictive roles of other pre-freeze and post-thaw morphological parameters are neglected.

Transplantation of human embryonic stem cells onto a partially wounded human cornea in vitro.

Purpose: The aim of this study was to investigate whether cells originating from human embryonic stem cells (hESCs) could be successfully transplanted onto a partially wounded human cornea. A second aim was to study the ability of the transplanted cells to differentiate into corneal epithelial-like cells.

Methods: Spontaneously, differentiated hESCs were transplanted onto a human corneal button (without limbus) with the epithelial layer partially removed.

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial.

Background: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers.

Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer.

Background: In order to select the best blastocyst for transfer, in humans, three morphological parameters have routinely been used, i.e. degree of blastocoele expansion and appearance of both the trophectoderm (TE) and the inner cell mass (ICM).

Cross-validation and predictive value of near-infrared spectroscopy algorithms for day-5 blastocyst transfer.

Near-infrared (NIR) spectroscopic metabolomic profiling of spent embryo-culture media has been used to calculate a viability score for individual embryos. These scores have been found to correlate to the reproductive potential of cleavage-stage embryos. In this study, 137 spent blastocyst media samples were collected after single-embryo transfer and analysed by NIR spectroscopy to generate an algorithm and calculate viability scores.

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome.

Purpose: Assessment of embryo viability is a key component of in vitro fertilization (IVF) and currently relies largely on embryo morphology and cleavage rate. In this study, we used receiver operating characteristic (ROC) analysis to compare the Viability Score (generated by metabolomic profiling of spent embryo culture media using near infrared (NIR) spectroscopy) to morphologic grading for predicting pregnancy in women undergoing single embryo transfer (SET) on day 5.

Methods: A total of 198 spent embryo culture media samples were collected in four IVF centers located in the USA, Europe and Australia.

Obstetric outcomes after transfer of vitrified blastocysts.

Background: It has been claimed that the risks to the child resulting from vitrification as compared with the slow-freezing technique, may be higher owing to the high concentrations of potentially toxic cryoprotectants. We therefore retrospectively compared the obstetric and neonatal outcomes in a cohort of children born after transfer of vitrified blastocysts, fresh blastocysts and slow-frozen early cleavage stage embryos.

Methods: All children born after transfer of vitrified blastocysts (n = 106), fresh blastocysts (n = 207) and slow-frozen early cleavage stage embryos (n = 206) during the period January 2006 to May 2008 at Fertility Center Scandinavia were included.

Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication.

Background: In a randomized controlled study aiming to test the effectiveness of preimplantation genetic screening (PGS) in women of advanced maternal age, embryos diagnosed as chromosomally abnormal and those with no diagnosis were fixed for reanalysis. The aim of this study was to determine how well the chromosomal constitution of one biopsied blastomere reflects the status of the entire embryo.

Methods: One hundred and seventy-three embryos diagnosed as chromosomally abnormal, 22 with no PGS result and four degenerated embryos originally diagnosed as normal were fixed and reanalysed by fluorescence in situ hybridization.