Mature oocyte dysmorphisms may be associated with progesterone levels, mitochondrial DNA content, and vitality in luteal granulosa cells.

PURPOSE: To identify whether follicular environment parameters are associated with mature oocyte quality, embryological and clinical outcomes. METHODS: This retrospective study examined 303 mature oocytes from 51 infertile women undergoing ICSI cycles between May 2018 and June 2021. Exclusion criteria consisted of advanced maternal age (> 36 years old), premature ovarian failure, obesity in women, or use of frozen gametes. Luteal granulosa cells (LGCs) were analyzed for mitochondrial DNA/genomic (g) DNA ratio and vitality. The relationships between hormone levels in the follicular fluid and oocyte features were assessed. Quantitative morphometric measurements of mature oocytes were assessed, and the association of LGC parameters and oocyte features on live birth rate after single embryo transfer was examined. RESULTS: Results indicated an inverse correlation between the mtDNA/gDNA ratio of LGCs and the size of polar body I (PBI). A 4.0% decrease in PBI size was observed with each one-unit increase in the ratio (p = 0.04). Furthermore, a 1% increase in LGC vitality was linked to a 1.3% decrease in fragmented PBI (p = 0.03), and a 1 ng/mL increase in progesterone levels was associated with a 0.1% rise in oocytes with small inclusions (p = 0.015). Associations were drawn among LGC characteristics, perivitelline space (PVS) debris, cytoplasmic inclusions, PBI integrity, and progesterone levels. Certain dysmorphisms in mature oocytes were associated with embryo morphokinetics; however, live birth rates were not associated with follicular parameters and oocyte quality characteristics. CONCLUSION: Follicular markers may be associated with mature oocyte quality features.

Neurophysiology of cognitive behavioural therapy, deep breathing and progressive muscle relaxation used in conjunction with ART treatments: a narrative review.

BACKGROUND: Infertility is defined as the failure to achieve clinical pregnancy after 12 months of regular unprotected intercourse. It could be due to male or female factors, each requiring different treatment options. ART treatment exposes couples to numerous psychological stressors. Therefore, it has been recommended by the ESHRE Psychology and Counselling Guideline Development Group recently that psychosocial support should be offered as a complementary therapy during infertility treatments. In this context, the efficiency of different psychological interventions, such as cognitive behaviour therapy (CBT), deep breathing (DB), and progressive muscle relaxation (PMR), was evaluated in several clinical trials in terms of couples' mental health and pregnancy outcomes. OBJECTIVE AND RATIONALE: The neurophysiology of CBT, DB and PMR, which are used in interventional studies, in both men and women undergoing ART, has not yet been fully elucidated. This review represents a comprehensive report, aiming to collate novel insights into the neurobiological processes and physiological mechanisms that occur during the practice of CBT, DB and PMR. SEARCH METHODS: PubMed, Google Scholar and Cochrane Library were interrogated to conduct this comprehensive literature review. The search was carried out using combinations of MeSH terms and keywords: infertility, assisted reproductive techniques, IVF, ICSI, emotions, psychological stress, cognitive behavioural therapy, mind-body therapies and relaxation. Relevant information related to the mechanism of action of stress management techniques were obtained from original articles and reviews published in English without taking into consideration the time of publication. Moreover, as it was not the major focus of the review, only recent systematic reviews (2015-2019) pinpointing the effects of psychological interventions on infertility treatment outcomes were also retrieved from the above-mentioned databases. OUTCOMES: CBT, DB and PMR may modify the activity of stress-related brain regions such as the prefrontal cortex, amygdala, hypothalamus and hippocampus, as demonstrated by functional MRI and electroencephalogram studies. Furthermore, applying these techniques was associated with mood improvements and a decline in stress biomarkers, and, hypothetically, reducing stress biomarkers attenuates the stress-induced effects on ART outcomes. WIDER IMPLICATIONS: Increasing the knowledge of fertility staff, researchers and physicians regarding the mechanisms of action of these stress management techniques has several advantages. For instance, understanding the underlying neurophysiological pathways would assist practitioners to engage ART couples in the practice of these techniques. Also, it may enhance the quality of the support programmes and psychological research. Accordingly, this will ensure that these interventions reach their full potential and therefore improve clinical outcomes.

Improvement of Human Sperm Vacuolization and DNA Fragmentation Co-Cultured with Adipose-Derived Mesenchymal Stem Cell Secretome: In Vitro Effect.

BACKGROUND AND OBJECTIVES: Oxidative stress (OS) is known to be an important factor of male infertility. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to have immune-modulatory and anti-oxidant effects through their secretions, hence raising the idea of their potential benefit to improve sperm parameters. This study aims at investigating the effect of AD-MSCs conditioned medium (CM) on human sperm parameters in the presence and absence of H2O2-induced OS. METHODS AND RESULTS: Sperm samples were collected from 30 healthy men and divided into two groups: non-stressed and H2O2-stressed. Isolated AD-MSCs from healthy donors undergoing liposuction were cultured and CM was collected at 24, 48 and 72 h. Both sperm groups were cultured with CM and a time course was performed followed by an evaluation of sperm parameters. The incubation of non-stressed and stressed sperm samples with AD-MSCs-CM for 24 h was found to have the optimum impact on sperm vacuolization, DNA fragmentation and OS levels in comparison to other incubation timings, while preserving motility, viability and morphology of cells. Incubation with CM improved all sperm parameters except morphology in comparison to the non-treated group, with the best effect noted with CM collected at 24 h rather than 48 or 72 h for sperm vacuolization and DNA fragmentation. When compared to fresh semen parameters (T0), samples cultured with CM 24 h showed a significant decrease in sperm vacuolization and DNA fragmentation while keeping other parameters stable. CONCLUSIONS: AD-MSCSs-CM improves sperm quality, and hence can be used in treating infertility and subsequently enhancing IVF outcomes.

What are the effects of vitamin C on sperm functional properties during direct swim-up procedure?

SummaryDirect swim-up procedure is widely used to separate the motile competent spermatozoa from the antioxidant-rich semen. Subsequently, spermatozoa become more vulnerable to reactive oxygen species (ROS) due to their cytological characteristics. The effect of vitamin C, a highly concentrated antioxidant in the semen, on direct swim-up-enriched sperm population is not fully investigated. Therefore, the aim of the present study was to assess the effect of vitamin C on sperm functional properties during direct swim-up procedure. Semen samples were collected from 22 participants. Each semen sample was divided into several aliquots. The first portion was overlaid with sperm medium without ascorbic acid (0 µM AA). The second and third fractions were overlaid with sperm medium supplemented with 300 µM and 600 µM AA; respectively. After 1 h of incubation, basic sperm parameters, intracellular ROS levels, acrosome reaction, chromatin integrity, and glucose uptake were assessed. Swim-up without AA significantly increased the percentage of ROS(+) spermatozoa compared with the raw semen (P<0.01). Interestingly, swim-up with 300 µM AA did not increase the percentage of ROS(+) sperm compared with the raw semen. In parallel, the percentage of sperm with altered chromatin integrity was significantly lower in the 300 µM AA group compared with that in the raw semen (P<0.05). These findings suggest that supplementation of vitamin C to sperm medium could be beneficial for direct swim-up-derived spermatozoa.

Paternal obesity: how bad is it for sperm quality and progeny health?

There is substantial evidence that paternal obesity is associated not only with an increased incidence of infertility, but also with an increased risk of metabolic disturbance in adult offspring. Apparently, several mechanisms may contribute to the sperm quality alterations associated with paternal obesity, such as physiological/hormonal alterations, oxidative stress, and epigenetic alterations. Along these lines, modifications of hormonal profiles namely reduced androgen levels and elevated estrogen levels, were found associated with lower sperm concentration and seminal volume. Additionally, oxidative stress in testis may induce an increase of the percentage of sperm with DNA fragmentation. The latter, relate to other peculiarities such as alteration of the embryonic development, increased risk of miscarriage, and development of chronic morbidity in the offspring, including childhood cancers. Undoubtedly, epigenetic alterations (ie, DNA methylation, chromatin modifications, and small RNA deregulation) of sperm related to paternal obesity and their consequences on the progeny are poorly understood determinants of paternal obesity-induced transmission. In this review, we summarize and discuss the data available in the literature regarding the biological, physiological, and molecular consequences of paternal obesity on male fertility potential and ultimately progeny health.

De plus en plus de données tendent à montrer que l'obésité paternelle a non seulement des effets néfastes sur la santé métabolique et reproductive de l'individu mais également sur celle de sa descendance. Les mécanismes mis en jeu dans ce processus incluraient des altérations physiologiques et hormonales des fonctions reproductives de l'homme obèse ainsi que des altérations épigénétiques au niveau du génome spermatique. Les modifications hormonales associées à l'obésité et qui se caractérisent principalement par une réduction du taux d'androgènes et une augmentation du niveau d'estrogène induiraient une altération des paramètres spermatiques, une diminution de la concentration ou de la numération totale en spermatozoïde et du volume séminal. Le stress oxydatif dans le testicule induirait une augmentation de la fragmentation de l'ADN spermatique et pourrait rendre compte de l'augmentation des risques de fausses-couches, des problèmes de développement embryonnaire ainsi que de l'augmentation des risques de mortalité chez la descendance, problèmes fréquemment rencontrés lorsque le père est. obèse. Les modifications épigénétiques (altérations des profils de méthylation de l'ADN, de la structure de la chromatine ou/et des profils d'expression des ARN spermatiques) induites par l'obésité sont, quant à elles, loin d'être comprises, même si elles sont, surement, les vecteurs clés de la transmission épigénétique paternelle des maladies métaboliques. L'objet de cette revue est. de résumer puis de discuter les différentes études expérimentales et épidémiologiques publiés à ce jour sur les conséquences physiologiques et moléculaire de l'obésité paternelle sur la santé de l'individu et sur celle de sa descendance.

The risk of neuro-orthopaedic malformations following in-vitro fertilization.

The purpose of this study was to assess the risk of neuro-orthopaedic malformations after in-vitro fertilization. We compared the prevalence of neuro-orthopaedic malformations in two groups of pregnancies conceived either naturally or by in-vitro fertilization, and used multivariate analysis to study the impact of each variable. The results showed a prevalence of 0.89% neuro-orthopaedic malformations in the in-vitro fertilization cohort and 0.32% in the natural conception cohort. The three times greater risk of malformations in the in-vitro fertilization cohort was reduced after adjustment to other variables. We concluded that the increased risk of neuro-orthopaedic malformations after in-vitro fertilization is not due to the technique itself but rather to factors associated with it.

Malignant female adnexal tumor of probable wolffian origin relapsing after pregnancy.

BACKGROUND: Female adnexal tumors of probable wolffian origin (FATWO) represent a rare gynecologic tumor and display in the majority of cases a benign behavior. CASE: A 27-year-old woman underwent a laparotomy for a left adnexal mass. Pathologic examination showed a FATWO. Three years later, 1 month after a vaginal delivery, a recurrence of the disease was observed. Immunohistochemistry revealed the presence of progesterone receptors that may explain recurrence after pregnancy. CONCLUSION: In light of this case, hormone dependency of FATWO may be suggested.

[Long follow-up of breast cancer revealed by clustered microcalcifications without palpable mass]. / Suivi à long terme des cancers du sein révélés par microcalcifications sans tumeur palpable.

OBJECTIVES: In the past two decades, nonpalpable breast cancer incidence has greatly increased by routine screening mammography. Microcalcifications are the most frequent radiological feature. METHODS: Between 1964 and 1994, 789 breast cancers revealed by clustered microcalcifications without palpable mass were treated at Institut Curie. Patients who had a past history of breast cancer or a contralateral cancer were eliminated like those with lobular carcinoma in situ. The definitive treatment was decided on the margins of the initial excision and the presence of microcalcifications on postoperative mammograms. RESULTS: Mean follow-up of the patients was 77 months (9-358). The treatment was conservative in 49.5% and radical in 50.5%. Histologically, 43.5% of the lesions were intraductal carcinoma, 25.5% were microinvasive and 31% were infiltrating cancers. Five and ten years overall survival were 98% and 92.5% respectively, 50% of the patients died from their breast cancer. This survival was identical for intraductal, microinvasive and invasive carcinomas without lymph node metastasis, but was less favorable in patients with node metastasis. There were no survival differences for the two treatment modalities, although local recurrences were more frequent in the conservative one. The 5-year recurrence rate was 3.5% for intraductal subtype, 4.4% for microinvasive and 6% for invasive cancers. The difference was not statistically significant. CONCLUSION: Under the impact of mammographic screening, sizable proportions of breast cancer patients are being seen in a totally nonpalpable state with either a very small invasive, microinvasive or intraductal breast cancer. These lesions have an excellent prognosis, and can benefit from less aggressive treatments. In the case of diffuse microcalcifications, where a radical treatment is indicated, skin sparing mastectomy can be easily done followed by immediate reconstructive surgery.