Chromosomal rearrangements in males : meiotic chromosome segregation and reproduction

Les translocations chromosomiques et les autres types de réarrangements peuvent, bien qu'associées à un phénotype normal, mener à la transmission d'un contenu génétique déséquilibré à la descendance. Il n'est pas possible de distinguer les chromosomes équilibrés des déséquilibrés, ce qui empêche toute sélection dans le cadre d'une fécondation in vitro (FIV). Nous avons ainsi mené une série de projets de recherche dont le but a été de mettre en évidence des caractéristiques spécifiques de ces spermatozoïdes déséquilibrés, afin de pouvoir les distinguer au cours d'une FIV. Nous avons montré que les spermatozoïdes déséquilibrés présentaient des taux de fragmentation de l'ADN plus élevés, étaient moins denses, et avaient un volume nucléaire supérieur. Ces constatations ont mené au développement d'une procédure de sélection des spermatozoïdes équilibrés chez les porteurs de réarrangements chromosomiques. En utilisant le hypo-osmotic swelling test (HOST), nous avons montré qu'une morphologie flagellaire spécifique était associée à un contenu chromosomique équilibré. Nous proposons d'utiliser cette procédure de sélection dans le cadre d'une ICSI, afin d'améliorer le pronostic reproductif chez les couples concernés. Nous proposons également d'évaluer la proportion de spermatozoïdes déséquilibrés chez chaque patient porteur de réarrangement chromosomique. En effet, bien que ce taux varie d'un patient à l'autre, il est stable dans le temps pour un patient donné. Il est de plus un élément déterminant dans le choix d'une des options de prise en charge : reproduction naturelle, insémination artificielle avec test de migration survie (TMS), ICSI avec sélection par HOST, et diagnostic préimplantatoire (DPI).Chromosomal translocations and other balanced rearrangements, although usually associated with a normal phenotype, can lead to the transmission of an abnormal unbalanced genetic content to the offspring. Balanced and unbalanced spermatozoa are indistinguishable, making it impossible to select them prior to in vitro fertilization. We conducted a series of research projects aimed at evidencing specific characterics for unbalanced spermatozoa, in a way to ultimately distinguish them from balanced ones during in vitro fertilization. We showed that unbalanced spermatozoa had higher DNA fragmentation rates, were less dense, and that their nuclear volume was higher. This led to developing a selection procedure for balanced spermatozoa in rearrangement carriers. Using the hypo-osmotic swelling test (HOST), we showed that a specific flagellar morphology was associated with balanced chromosomal status. We suggest using this procedure prior to ICSI in order to improve the reproductive prognosis in those patients. We also suggest evaluating the proportion of unbalanced spermatozoa in every patient with a chromosomal rearrangement. Although this proportion varies among patients, it is stable over time for a given patient. We believe this is a decisive element in choosing between the different available options : natural conception, artificial insemination with discontinuous gradient centrifugation, ICSI with HOST-based selection, and pre-implantation genetic diagnosis (PGD)

Etude conjointe de la ségrégation chromosomique et de l apoptose spermatique chez des patients porteurs de translocations chromosomiques

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Kiri Aignan Noel Julien'ile

Forth-Rouen,Alexandre de, prantsuse diplomaat, parunJulien, Aignan Noel, 1799-1873, prantsuse orientalistTeatab, et on kätte saanud adressaadi kirj

Selecting the most competent sperm for assisted reproductive technologies

International audienceThis paper discusses the variety of effective sperm selection techniques that have been developed for use in assisted reproductive technologies. Available methods for isolating the competent sperm in an ejaculate are outlined, as well as techniques for selecting single sperm for use in intracytoplasmic sperm injection procedures. Case-specific methods for selecting the most competent sperm are discussed, with reference to the potential causes of male factor infertility and guidance for the embryologist based on the issues present for each couple seeking treatment

Selecting the most competent sperm for assisted reproductive technologies

International audienceThis paper discusses the variety of effective sperm selection techniques that have been developed for use in assisted reproductive technologies. Available methods for isolating the competent sperm in an ejaculate are outlined, as well as techniques for selecting single sperm for use in intracytoplasmic sperm injection procedures. Case-specific methods for selecting the most competent sperm are discussed, with reference to the potential causes of male factor infertility and guidance for the embryologist based on the issues present for each couple seeking treatment

Selecting the most competent sperm for assisted reproductive technologies

International audienceThis paper discusses the variety of effective sperm selection techniques that have been developed for use in assisted reproductive technologies. Available methods for isolating the competent sperm in an ejaculate are outlined, as well as techniques for selecting single sperm for use in intracytoplasmic sperm injection procedures. Case-specific methods for selecting the most competent sperm are discussed, with reference to the potential causes of male factor infertility and guidance for the embryologist based on the issues present for each couple seeking treatment

First Birth after Sperm Selection through Discontinuous Gradient Centrifugation and Artificial Insemination from a Chromosomal Translocation Carrier

Introduction. Balanced chromosomal carriers, though usually healthy, are confronted with recurrent spontaneous abortions and malformations in the offspring. Those are related to the transmission of an abnormal, chromosomally unbalanced genotype. We evidenced that the proportion of unbalanced spermatozoa can be significantly decreased through a sperm preparation process called discontinuous gradient centrifugation (DGC). We therefore started offering intrauterine inseminations with this procedure to couples with a male translocation carriers. Case Presentation. We report the case of a 37-year-old man carrying a t(3;10)(q25;p13) reciprocal translocation. He and his partner had had trouble conceiving for ten years and had four spontaneous abortions. DGC in this patient decreased the proportion of unbalanced spermatozoa from 63.6% to 52.3%. They were therefore offered intrauterine insemination with DGC, which eventually led to the birth of a healthy female child carrying the paternal translocation. Conclusion. We showed that translocation carriers could be offered intrauterine inseminations with DGC. Before this, the only two options were natural conception with prenatal diagnosis and termination of chromosomally unbalanced fetuses or preimplantation genetic diagnosis, which is a much heavier and costly procedure. We are currently offering this option through a multicentric program in France, and this is the first birth originating from it

Polysomnographic parameters in long-COVID chronic insomnia patients

While COVID-19 is predominantly considered to be an acute self-remitting disease, it has been pointed out that a variety of symptoms can linger for several months, a phenomenon identified as long-COVID. Insomnia is particularly prevalent in long-COVID. In the present study, we aimed at confirming and characterising insomnia in long-COVID patients through polysomnography and to identify whether its parameters differ from patients with chronic insomnia and no long-COVID history

Chromosomal segregation analysis and HOST-based sperm selection in a complex reciprocal translocation carrier

International audienceIntroduction: Complex chromosomal rearrangements (CCRs) involve two or more chromosomes and at least three breakpoints. Due to their complexity, they are associated with a high number of unbalanced gametes, whose fertilization is often incompatible with viable fetal development. Preimplantation genetic diagnosis (PGD) is usually offered to those patients and typically shows modest results considering the high number of unbalanced embryos. We previously showed that a sperm selection process using the hypo-osmotic swelling test (HOST) allows for an 83% reduction in the proportion of unbalanced spermatozoa (US) in male rearrangements carriers. This is the first report of the use of this procedure in a CCR carrier.Case description: We report on the case of a 36-year-old male t(4;7;14)(q12;p21;q11.2) carrier who presented to our center for infertility. Sperm fluorescent in situ hybridization showed an 88% proportion of unbalanced spermatozoa. After hypo-osmotic incubation and selection of spermatozoa with a specific flagellar conformation, the proportion of unbalanced spermatozoa dropped to 15%.Discussion: In the present case, we show that it is possible to select chromosomally balanced prior to in vitro fertilization in male CCR carriers. This technique has the potential of increasing the proportion of euploid embryos and therefore the chances of healthy pregnancy and birth