Adaptive data-driven models to best predict the likelihood of live birth as the IVF cycle moves on and for each embryo transfer.

PURPOSE: To dynamically assess the evolution of live birth predictive factors' impact throughout the in vitro fertilization (IVF) process, for each fresh and subsequent frozen embryo transfers. METHODS: In this multicentric study, data from 13,574 fresh IVF cycles and 6,770 subsequent frozen embryo transfers were retrospectively analyzed. Fifty-seven descriptive parameters were included and split into four categories: (1) demographic (couple's baseline characteristics), (2) ovarian stimulation, (3) laboratory data, and (4) embryo transfer (fresh and frozen). All these parameters were used to develop four successive predictive models with the outcome being a live birth event. RESULTS: Eight parameters were predictive of live birth in the first step after the first consultation, 9 in the second step after the stimulation, 11 in the third step with laboratory data, and 13 in the 4th step at the transfer stage. The predictive performance of the models increased at each step. Certain parameters remained predictive in all 4 models while others were predictive only in the first models and no longer in the subsequent ones when including new parameters. Moreover, some parameters were predictive in fresh transfers but not in frozen transfers. CONCLUSION: This work evaluates the chances of live birth for each embryo transfer individually and not the cumulative outcome after multiple IVF attempts. The different predictive models allow to determine which parameters should be taken into account or not at each step of an IVF cycle, and especially at the time of each embryo transfer, fresh or frozen.

Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa.

Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses.

Seminal cell-free DNA and sperm characteristic's: An added biomarker for male infertility investigation.

Cell-free DNA (Cf-DNA) fragments may constitute an easy-to-measure molecular tool for guiding the choice of care provided to infertile couples who benefit assisted reproductive technology (ART) programmes. Data on Cf-DNA levels in the seminal plasma of men with sperm alterations are scarce. The objective of the present study was to quantify the presence of Cf-DNA in semen by using a quantitative real-time PCR. We compared men with abnormal sperm characteristics (n = 21) with normospermic controls (n = 21). The PCR assay evidenced significantly higher mean Cf-DNA levels in patients with sperm abnormalities than in controls (2.09 versus 1.18 µg/ml, respectively; p = .0003). The Cf-DNA levels were notably higher in men with azoospermia (3.65 µg/ml, versus 1.34 µg/ml in matched controls; p = .03) and men with teratozoospermia (1.80 µg/ml, versus 1.29 µg/ml in matched controls; p = .008). Our data report a significant association between elevated Cf-DNA levels and sperm abnormalities. These results may open up new diagnostic and prognostic perspectives in male infertility.

Cannabis consumption might exert deleterious effects on sperm nuclear quality in infertile men.

RESEARCH QUESTION: Can cannabis consumption alter sperm nuclear integrity in infertile men? DESIGN: A retrospective cross-sectional study conducted between July 2003 and December 2013, which included 54 men who consulted for male-factor infertility. Twenty-seven infertile men who were regular cannabis users were matched to 27 infertile men who were cannabis non-users. To complement the conventional semen parameter and plasma hormone level assessments, sperm nuclear alterations were explored using fluorescence in-situ hybridization to assess numerical chromosomal abnormalities, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling to investigate DNA fragmentation, aniline blue staining to examine chromatin condensation and a motile sperm organelle morphology examination to detect vacuoles in sperm heads. RESULTS: The rates of sperm aneuploidy (P = 0.0044), diploidy (P = 0.037), total chromosome abnormalities (P = 0.0027) and DNA fragmentation (P = 0.027) were significantly higher in cannabis users than in non-cannabis users. CONCLUSIONS: Cannabis consumption might have deleterious effects on sperm nuclear quality in infertile men by increasing numerical chromosome abnormalities and DNA fragmentation. Cannabis consumption induces these detrimental effects on the progression of spermatogenesis from meiotic stages to spermiogenesis and potentially on post-testicular sperm maturation in infertile men. Any potential findings, however, need to be validated with larger sample size, and our data are only exploratory findings.

[Fertility preservation]. / Préservation de la fertilité.

Fertility preservation. The treatment used to treat cancer or other non-cancer diseases have improved the prognosis of these pathologies. However, these treatments (chemotherapy, radiotherapy or even surgery) have a toxicity on the ovary or on the testicle with consequently a decrease or an arrest of the production of mature oocyte or spermatozoa. Fertility preservation uses freezing procedures of gametes (oocytes, spermatozoa), embryos or germinal tissues (ovary or testicle) in order to restore the fertility of cured patients. The French national sperm banking network (CECOS) is a national network of assisted reproductive technology centers that manage, in a coordinated manner, all of these fertility preservation techniques.

Préservation de la fertilité. Les traitements des cancers, voire de certaines maladies non tumorales ont amélioré le pronostic de ces pathologies. Cependant, ces traitements (chimiothérapie, radiothérapie, voire chirurgie) ont une toxicité sur l'ovaire ou le testicule avec pour conséquence une diminution ou un arrêt de la production d'ovocytes matures ou de spermatozoïdes. La préservation de la fertilité utilise des techniques de congélation des gamètes (ovocytes, spermatozoïdes), des embryons ou des tissus germinaux (ovaire ou testicule) afin de restaurer la fertilité des patients guéris. La Fédération des centres d'étude et de conservation des oeufs et du sperme humains (CECOS) constitue un réseau national de centres d'assistance médicale à la procréation mettant en oeuvre de manière coordonnée l'ensemble de ces techniques de préservation de la fertilité.