Artificial intelligence-powered assisted ranking of sibling embryos to increase first cycle pregnancy rate.

RESEARCH QUESTION: Could EMBRYOLY, an artificial intelligence embryo evaluation tool, assist embryologists to increase first cycle pregnancy rate and reduce cycles to pregnancy for patients? DESIGN: Data from 11,988 embryos were collected via EMBRYOLY from 2666 egg retrievals (2019-2022) across 11 centres in France, Spain and Morocco using three time-lapse systems (TLS). Data from two independent clinics were also examined. EMBRYOLY's transformer-based model was applied to transferred embryos to evaluate ranking performances against pregnancy and birth outcomes. It was applied to cohorts to rank sibling embryos (including non-transferred) according to their likelihood of clinical pregnancy and to compute the agreement with the embryologist's highest ranked embryo. Its effect on time to pregnancy and first cycle pregnancy rate was evaluated on cohorts with multiple single blastocyst transfers, assuming the embryologist would have considered EMBRYOLY's ranking on the embryos favoured for transfer. RESULTS: EMBRYOLY's score correlated significantly with clinical pregnancies and live births for cleavage and blastocyst transfers. This held true for clinical pregnancies from blastocyst transfers in two independent clinics. In cases of multiple single embryo transfers, embryologists achieved a 19.8% first cycle pregnancy rate, which could have been improved to 44.1% with the adjunctive use of EMBRYOLY (McNemar's test: P < 0.001). This could have reduced cycles to clinical pregnancy from 2.01 to 1.66 (Wilcoxon test: P < 0.001). CONCLUSIONS: EMBRYOLY's potential to enhance first cycle pregnancy rates when combined with embryologists' expertise is highlighted. It reduces the number of unsuccessful cycles for patients across TLS and IVF centres.

Aberrant cortex contractions impact mammalian oocyte quality.

The cortex controls cell shape. In mouse oocytes, the cortex thickens in an Arp2/3-complex-dependent manner, ensuring chromosome positioning and segregation. Surprisingly, we identify that mouse oocytes lacking the Arp2/3 complex undergo cortical actin remodeling upon division, followed by cortical contractions that are unprecedented in mammalian oocytes. Using genetics, imaging, and machine learning, we show that these contractions stir the cytoplasm, resulting in impaired organelle organization and activity. Oocyte capacity to avoid polyspermy is impacted, leading to a reduced female fertility. We could diminish contractions and rescue cytoplasmic anomalies. Similar contractions were observed in human oocytes collected as byproducts during IVF (in vitro fertilization) procedures. These contractions correlate with increased cytoplasmic motion, but not with defects in spindle assembly or aneuploidy in mice or humans. Our study highlights a multiscale effect connecting cortical F-actin, contractions, and cytoplasmic organization and affecting oocyte quality, with implications for female fertility.

Discontinuous gradient centrifugation (DGC) decreases the proportion of chromosomally unbalanced spermatozoa in chromosomal rearrangement carriers.

STUDY QUESTION: Can the proportion of unbalanced spermatozoa in chromosomal rearrangement carriers be decreased through the use of discontinuous gradient centrifugation (DGC)? SUMMARY ANSWER: DGC significantly decreases the proportion of genetically unbalanced spermatozoa in chromosomal rearrangement carriers. WHAT IS KNOWN ALREADY: Chromosomal rearrangement carriers present with a certain proportion of unbalanced gametes, which can lead to miscarriages or malformations in the offspring. There is presently no known way to select the balanced spermatozoa and use them for IVF. STUDY DESIGN, SIZE, DURATION: The proportion of unbalanced spermatozoa after DGC was compared with that before DGC in 21 patients with a chromosomal rearrangement. At least 500 spermatozoa were analysed per observation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-one male patients with a chromosomal rearrangement were included in this prospective study. They initially consulted for infertility, recurrent miscarriages or a history of abnormal pregnancy. The samples were split into two, with one part undergoing DGC and the other being immediately fixed. Fluorescence in situ hybridization was performed to establish the chromosome segregation pattern of each spermatozoon. MAIN RESULTS AND THE ROLE OF CHANCE: DGC significantly decreased the proportion of unbalanced spermatozoa in all but 1 of the 21 chromosomal rearrangement carriers (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Although DGC reduces the proportion of unbalanced spermatozoa in ejaculates from patients with chromosome rearrangements this elimination is only partial and some abnormal spermatozoa remain. Means to exclude these spermatozoa to ensure that only balanced ones are used in IVF remain to be discovered. The motility and morphology of the sperm before and after DGC were not measured. WIDER IMPLICATIONS OF THE FINDINGS: Used in IVF or intrauterine insemination, DGC could decrease the chance that a man carrying a chromosomal rearrangement will father an abnormal fetus.

Simultaneous cell by cell study of both DNA fragmentation and chromosomal segregation in spermatozoa from chromosomal rearrangement carriers.

PURPOSE: Balanced chromosomal translocations are found in one out of 500 subjects in the general population. They usually do not carry any phenotypic consequences, except for possible infertility and for the production of unbalanced gametes leading to spontaneous abortions or chromosomal syndromes in the offspring. An association between chromosomal rearrangements and increased apoptosis markers has been demonstrated on a global scale in sperm samples of translocation and inversion carriers. In order to specify which kind of sperm cells is subject to an increased apoptosis process, this present study was aimed to analyse both chromosomal segregation and DNA fragmentation, sperm cell by sperm cell. METHODS: Six patients carrying a chromosomal rearrangement (three reciprocal translocations, two Robertsonian translocations, and one chromosomal pericentric inversion) were included in a retrospective manner. Both DNA fragmentation and chromosomal segregation in spermatozoa were evaluated simultaneously using a modified TUNEL assay associated with FISH. Two thousand spermatozoa were analysed for each patient. RESULTS: We showed a higher proportion of spermatozoa with fragmented DNA among the unbalanced sperm cells, compared to the balanced ones, in all six patients. CONCLUSIONS: These results suggest an increased fragility of unbalanced spermatozoa to exogenous fragmentation factors. The exact mechanisms of those processes remain to be elucidated.

Semen Cryopreservation in Adolescents and Young Adults with Hematologic Diseases: from Bed to Benchside.

Purpose: Infertility in adolescents and young adult (AYA) survivors of malignant disease remains a major long-term adverse effect, but semen collection for fertility preservation in fertility centers is not always feasible and makes AYAs uncomfortable. We evaluated the feasibility of collecting sperm samples on the ward versus in fertility centers. Methods: Consecutive hospitalized AYA-aged male patients in the Hematology AYA unit (Saint-Louis Hospital, France) between August 2010 and June 2016 with hematological disease and indication of semen collection (n = 95) were included in this retrospective study. Semen quality was analyzed according to World Health Organization guidelines and was compared according to semen collection place: on the ward (n = 46) or in fertility center (n = 49). Results: The median age was median age 19.1 years (range: 13.7-33.3; interquartile range: 17.1-22.8) and 85 patients successfully collected semen. Sperm collection failure was ∼11% and was comparable between the two modalities as were main sperm quality characteristics (semen volume, sperm concentration, total sperm count, progressive motility and vitality, sperm morphology, and multiple anomalies index). Oligospermia was significantly higher in the samples obtained in fertility center (47.7%) than on the ward (26.8%), p = 0.047. Average frozen straws were comparable, 12.2 ± 6.4 on the ward versus 11.9 ± 6.3 in fertility center. Conclusion: Semen collection on the ward is feasible and would be particularly interesting for AYA male patients without altering semen quality characteristics.

RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres.

Improving and controlling the capacity of endogenous or grafted adult neural stem cells to repair the nervous system relies on a better knowledge of interactions between immune cells and neural stem cells. Class I major histocompatibility complex (MHC) family members comprise numerous proteins playing either immune or nonimmune function. Among the latter, MHC functions in the central nervous system has started to receive recent interest. Here, our first goal was to investigate the potential relationship between MHC class I molecules and neurogenesis. For the first time, we report the expression of two MHC class I-related members by neural stem/progenitor cells: retinoic acid early induced transcript (RAE)-1 and CD1d. The expression of RAE-1 but not CD1d disappears when differentiation of neurosphere cells is induced. Interestingly, RAE-1 transcripts are expressed in the brain during development, and we demonstrate they persist in one of the main area of adult neurogenesis, the subventricular zone (SVZ). So far, RAE-1 is only known for its immune functions as a ligand of the activating receptor NKG2D expressed by natural killer (NK) cells, natural killer T, Tγδ, and some T CD8 lymphocytes. Here, we do not detect any NKG2D expression in the SVZ either in physiological or in pathological conditions. Interestingly, inhibition of RAE-1 expression in neurosphere cells reduces cell proliferation without alteration of cell viability, which argues for a nonimmune role for RAE-1. These results reveal an unexpected role of RAE-1 in regulating adult SVZ neurogenesis by supporting stem/progenitor cells proliferation.

Is intracouple assisted reproductive technology an option for men with large-headed spermatozoa? A literature review and a decision guide proposal.

Although the presence of spermatozoa with an abnormally large head is rare, it is associated with low fertility or even total infertility. We reviewed the literature on assisted reproductive technology (ART) strategies and outcomes for men with large-headed spermatozoa. We also discuss additional analyses that can usefully characterize sperm defects and help with the choice between intra-couple ART and insemination with donor sperm. Lastly, we propose a classification for cases of large-headed spermatozoa.

La présence de spermatozoïdes macrocéphales est généralement associée à une hypofertilité ou une infertilité. Nous présentons une revue de la littérature concernant les stratégies de prise en charge en aide médicale à la procréation et leurs issues lorsque l'analyse du sperme met en évidence la présence de spermatozoïdes macrocéphales. Nous discutons également les examens complémentaires permettant de mieux caractériser ces anomalies spermatiques et de choisir entre l'aide médicale à la procréation avec ou sans donneur de sperme. Enfin nous proposons ici une classification pour les cas de spermatozoides macrocephales avec pour les 6 types définis une proposition de prise en charge.

Adipokines in human reproduction.

Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age.

Posttesticular sperm maturation, infertility, and hypercholesterolemia.

Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia) affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.