Machine learning tool for predicting mature oocyte yield and trigger day from start of stimulation: towards personalized treatment.

Research Question: Can machine learning tools predict the number of metaphase II (MII) oocytes and trigger day at the start of the ovarian stimulation cycle?

Design: A multicentre, retrospective study including 56,490 ovarian stimulation cycles (primary dataset) was carried out between 2020 and 2022 for analysis and feature selection. Of these, 13,090 were used to develop machine learning models for trigger day and the number of MII prediction, and another 5103 ovarian stimulation cycles (clinical validation dataset) from 2023 for clinical validation. Machine learning algorithms using deep learning were developed using optimal features from the primary dataset based on correlation.

Embryo long-term storage does not affect assisted reproductive technologies outcome: analysis of 58,001 vitrified blastocysts over 11 years.

Background: Recently, the potential detrimental effect that the duration of storage time may have on vitrified samples has raised some concerns, especially when some studies found an association between cryostorage length and decreased clinical results.

Objective: This study aimed to evaluate the effects of the storage time length of day-5 vitrified blastocysts in 2 study groups: freeze-all cycles and nonelective frozen embryo transfers.

Study Design: This was a retrospective study that included 58,001 vitrified/warmed day-5 blastocysts from 2 different populations, according to the reason for frozen embryo transfer.

Deciphering a shared transcriptomic regulation and the relative contribution of each regulator type through endometrial gene expression signatures.

Backgorund: While various endometrial biomarkers have been characterized at the transcriptomic and functional level, there is generally a poor overlap among studies, making it unclear to what extent their upstream regulators (e.g., ovarian hormones, transcription factors (TFs) and microRNAs (miRNAs)) realistically contribute to menstrual cycle progression and function.

Medroxyprogesterone acetate: an alternative to GnRH-antagonist in oocyte vitrification for social fertility preservation and preimplantation genetic testing for aneuploidy.

Research Question: Can medroxyprogesterone acetate (MPA) be used as a pituitary suppressor instead of a gonadotrophin releasing hormone (GnRH) antagonist during ovarian stimulation in elective fertility preservation and preimplantation genetic testing for aneuploidy (PGT-A) cycles?

Design: A multicentre, retrospective, observational, cohort study conducted in 11 IVIRMA centres affiliated to private universities. Of a total of 1652 cycles of social fertility preservation, 267 patients were stimulated using a progestin-primed ovarian stimulation protocol (PPOS), and 1385 patients received a GnRH antagonist. In the PGT-A cycles, 5661 treatments were analysed: 635 patients received MPA and 5026 patients received GnRH antagonist.

Clinical validation of an automatic classification algorithm applied on cleavage stage embryos: analysis for blastulation, euploidy, implantation, and live-birth potential.

Study Question: Is a commercially available embryo assessment algorithm for early embryo evaluation based on the automatic annotation of morphokinetic timings a useful tool for embryo selection in IVF cycles?

Summary Answer: The classification provided by the algorithm was shown to be significantly predictive, especially when combined with conventional morphological evaluation, for development to blastocyst, implantation, and live birth, but not for euploidy.

What Is Known Already: The gold standard for embryo selection is still morphological evaluation conducted by embryologists. Since the introduction of time-lapse technology to embryo culture, many algorithms for embryo selection have been developed based on embryo morphokinetics, providing complementary information to morphological evaluation.

COVID-19 mRNA vaccines have no effect on endometrial receptivity after euploid embryo transfer.

Research Question: Does the COVID-19 vaccination affect endometrial receptivity after single euploid embryo transfer, measured by sustained implantation rate?

Design: A retrospective cohort study analysing two groups of single euploid embryo transfers using own oocytes: one historical cohort of 3272 transfers 1 year before the pandemic; and one comprising 890 transfers in women previously vaccinated with mRNA vaccines against severe acute respiratory syndrome coronavirus 2. The main outcomes were clinical pregnancy rate (CPR) and sustained implantation rate (SIR) per embryo transfer. These outcomes were compared between non-vaccinated and vaccinated women, and women who had received one and two doses.

The higher the score, the better the clinical outcome: retrospective evaluation of automatic embryo grading as a support tool for embryo selection in IVF laboratories.

Study Question: Is the automatic embryo grading function of specific time-lapse systems clinically useful as a decision support tool for IVF laboratories?

Summary Answer: Blastocyst grading according to the automatic scoring system is directly associated with the likelihood of implantation and live birth, at least in treatments without preimplantation genetic testing for aneuploidy (PGT-A).

What Is Known Already: Several embryo selection algorithms have been described since the introduction of time-lapse technology in IVF laboratories, but no one algorithm has yet been sufficiently consolidated for universal use. Multicentric models based on automated grading systems offer promise for standardization of embryo selection.

Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure.

Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10-25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs.

Elevated serum progesterone does not impact euploidy rates in PGT-A patients.

Purpose: Some women undergoing stimulated cycles have elevated serum progesterone (P) on the day of ovulation trigger, but its effect on embryo quality is unclear. We analyze embryo quality among patients with high and low serum P undergoing preimplantation genetic testing for aneuploidy (PGT-A).

Methods: This retrospective study included 1597 patients divided into two groups by serum P values: < 1.

Oocyte vitrification for fertility preservation for both medical and nonmedical reasons.

Growing evidence of successful outcomes achieved with the oocyte vitrification technique has greatly contributed to its application in the field of fertility preservation (FP). The population that can benefit from FP includes women at a risk of losing their ovarian function because of either iatrogenic causes or natural depletion of their ovarian reserve. Therefore, oncological patients and healthy women who wish to delay motherhood for various reasons-elective FP-are currently being offered this option.

Differential sperm proteomic profiles according to pregnancy achievement in intracytoplasmic sperm injection cycles: a pilot study.

Purpose: To describe the proteomic profiles in semen samples and define the differences in sperm proteomic profiles among samples that ultimately achieved pregnancy (P) via intracytoplasmic sperm injection (ICSI) in an oocyte donation program and those that were unsuccessful (NP).

Methods: Prospective, analytical, observational nested case and control study evaluating the proteomic profile of spermatozoa from patients' ejaculates where pregnancies were (group pregnant (P), n= 4) or were not (group non-pregnant (NP), n=4) achieved after ICSI in an oocyte donation program aiming to standardize female factor. Proteins were separated and analyzed by means of SWATH-MS) and compared between P/NP groups to identify sperm biomarkers of fertility/infertility.

Prediction of embryo survival and live birth rates after cryotransfers of vitrified blastocysts.

Research Question: Which pre-vitrification parameters are the most predictive of survival and live birth in vitrified-warmed blastocyst transfer cycles?

Design: A retrospective study including 11,936 warmed blastocysts. Pre-vitrification morphological parameters analysed for blastocysts included day of vitrification; blastocyst expansion degree; trophoectoderm grade (A, B and C); and inner cell mass grade (A, B and C). Univariate and multivariate generalized estimating equations models were used to analyse survival, clinical pregnancy and live birth rate.

Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis.

Research Question: How does the number of oocytes used affect the cumulative live birth rate (CLBR) in endometriosis patients who had their oocytes vitrified for fertility preservation?

Design: Retrospective observational study including data from 485 women with endometriosis who underwent fertility preservation from January 2007 to July 2018. Survival curves and Kaplan-Meier plots were used to analyse the CLBR according to the number of vitrified oocytes used. Endometriosis curves were compared with plots developed using elective fertility preservation (EFP) patients as control group.

Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone.

Study Question: Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced?

Summary Answer: Serum P levels <8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles.

What Is Known Already: We previously found that serum P levels <9.

Novel and conventional embryo parameters as input data for artificial neural networks: an artificial intelligence model applied for prediction of the implantation potential.

Objective: To describe novel embryo features capable of predicting implantation potential as input data for an artificial neural network (ANN) model.

Design: Retrospective cohort study.

Setting: University-affiliated private IVF center.

The influence of oxygen concentration during embryo culture on obstetric and neonatal outcomes: a secondary analysis of a randomized controlled trial.

Study Question: Does oxygen concentration during 3-day embryo culture affect obstetric and neonatal outcomes?

Summary Answer: Oxygen concentration during 3-day embryo culture does not seem to affect the obstetric and neonatal outcomes measured.

What Is Known Already: Atmospheric oxygen appears to be harmful during extended embryo culture. Embryo culture conditions might therefore be a potential risk factor for subsequent fetal development and the health of future children.

Oocyte vitrification for fertility preservation in women with endometriosis: an observational study.

Objective: To describe the outcome of fertility preservation (FP) using vitrified oocytes in patients with endometriosis and to determine the impact of ovarian surgery.

Design: Retrospective observational study.

Setting: University-affiliated private in vitro fertilization (IVF) center.

Cervical pregnancy in assisted reproduction: an analysis of risk factors in 91,067 ongoing pregnancies.

Research Question: What is the frequency of cervical pregnancy in women undergoing assisted reproductive technologies (ART) and what are the risk factors?

Design: Case-control study of women undergoing assisted reproductive technology (ART) at 25 private assisted reproduction clinics run by the same group in Spain. Two control groups (tubal ectopic pregnancies and intrauterine pregnancies) were established. The main outcome measure was frequency of cervical pregnancy.

Time of morulation and trophectoderm quality are predictors of a live birth after euploid blastocyst transfer: a multicenter study.

Objective: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET).

Design: Observational cohort study conducted in two phases: training and validation.

Setting: Private in vitro fertilization centers.

Reproductive outcomes after hysteroscopic metroplasty for women with dysmorphic uterus and recurrent implantation failure.

Background: The aim of this study was to assess the reproductive outcomes of women with recurrent implantation failure (RIF) after hysteroscopic metroplasty for dysmorphic uteri.

Methods: This retrospective observational study included 190 women with a diagnosis of RIF. These patients were eligible for hysteroscopic metroplasty for dysmorphic uteri, including T-shaped uteri, between January 2008 and September 2015 at the Instituto Valenciano de Infertilidad (IVI) in Valencia, Spain.

A new system of sperm cryopreservation: evaluation of survival, motility, DNA oxidation, and mitochondrial activity.

Background: Sperm vitrification (V) is a method for cryopreservation, without the use of conventional cryoprotectants, by plunging the sperm suspension directly into liquid nitrogen (LN25).

Objective: This study aimed to compare the new system of V with conventional freezing (CF) protocol using fresh spermatozoa as reference (C).

Material And Methods: Prospective cohort study.