Mammographic breast density in infertile and parous women

BACKGROUND: Mammographic breast density is a useful marker for breast cancer risk, as breast density is considered one of the strongest breast cancer risk factors. The study objective was to evaluate and compare mammographic breast density in infertile and parous women, as infertility may be associated with high breast density and cancer occurrence. METHODS: This study evaluated mammographic breast density using two different systems, BIRADS and Boyd. A selected patient population of 151 women with primary infertility (case group) was compared to 154 parous women who had at least one previous pregnancy (control group). Both groups were premenopausal women aged ≥ 35. RESULTS: Evaluation of mammographic features showed that 66.9% of case group patients and 53.9% of control group patients were classified BIRADS-3/BIRADS-4; p < 0.05. Adjusted Odds ratio for the case group in the categories BIRADS-3/BIRADS-4 was 1.78 (95% CI: 1.10-2.89). Using the Boyd classification system, 53.6% of case group patients and 31.8% of control group patients were classified E/F; p < 0.05. Adjusted Odds ratio for case group patients in Boyd categories E/F was 2.05 (95 % CI: 1.07-3.93). CONCLUSIONS: Both systems yielded a higher percentage of increased breast density in the case group. Boyd and BIRADS classification systems indicate to what extend breast cancer lesions may be missed on mammography due to masking by dense tissue. Therefore, patients with a high BIRADS or Boyd score should undergo further investigation

A Markov-model simulation of IVF programs for PCOS patients indicates that coupling myo-Inositol with rFSH is cost-effective for the Italian Health System

Accumulating evidence suggests that oral supplementation with myo-Inositol (myo-Ins) is able to reduce the amount of gonadotropins and days of controlled ovarian hyperstimulation (COS) necessary to achieve adequate oocyte maturation in assisted reproduction technology (ART) protocols, particularly in women affected by polycystic ovary syndrome (PCOS). We used computational calculations based on simulation modellings. We simulated in vitro fertilization (IVF) procedures-with or without intracytoplasmic sperm injection (ICSI)-with 100,000 virtual patients, accounting for all the stages of the entire IVF procedure. A Monte Carlo technique was used to account for data uncertainty and to generate the outcome distribution at each stage. We considered virtual patients with PCOS undergoing IVF cycles to achieve pregnancy. Computational data were retrieved from clinical experience and published data. We investigated three parameters related to ART protocols: cost of single procedure; efficacy to achieve ongoing pregnancy at 12 gestational weeks; overall cost per single pregnancy. The administration of oral myo-Ins during COH protocols, compared to the standard COH with recombinant Follicle Stimulating Hormone (rFSH) only, may be considered a potential strategy to reduce costs of ART for the Italian Health System

Ultrastructural and morphometric evaluation of aged cumulus-oocyte-complexes

Maternal age is one of the most significant factors influencing oocyte quality (1). 35 years of age seems to be a watershed in reproductive potential. The aim of this study was to reveal the amount and distribution of specific ultrastructural organelles in human mature cumulus-oocyte-complexes belonging to women of different ages (&lt;35 years old; ≥35 years old/ reproductive aging) and to evaluate their different response during 24 hours prolonged culture (defined as in vitro aging) (1). The samples were studied by light and transmission electron microscopy; a morphometric analysis of TEM data was performed (2). In all aged samples, the amount of mitochondria- smooth endoplasmic reticulum aggregates, cortical granules and microvilli decreased (p&lt;0,05), while the amount of mitochondria-vesicle complexes increased up (p&lt;0,05). Occasional vacuoles were found in oocytes from older women after in vitro aging. A significant (p&lt;0,05) increase of zona pellucida thickness was linked to the donor age but not to in vitro aging. A re-compaction of cumulus cells was seen in in vitro aged samples. Morphometric data strongly confirmed our preliminary results (3) revealing that: i) reproductive aging and in vitro aging share specific ultrastructural features ii) In vitro aging can be consider a model for reproductive aging iii) young oocytes seem to be less sensitive to in vitro aging than older ones. The above results may represent a reliable background for further multidisciplinary studies regarding aged oocytes and may be also useful in clinical settings

Effects of simulated microgravity In vitro on human metaphase II oocytes: an electron microscopy-based study

The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the high costs and lack of repeatability of the experiments. For these reasons, the use of microgravity simulators for studying, at the cellular level, the effects, such as those, obtained during/after a spatial trip, are developed to confirm that these models can be used in the study of body responses under conditions different from those found in a unitary Gravity environment (1 g). In view of this, this study aimed to investigate in vitro the effects of simulated microgravity on the ultrastructural features of human metaphase II oocytes using a Random Positioning Machine (RPM). We demonstrated for the first time, by Transmission Electron Microscopy analysis, that microgravity might compromise oocyte quality by affecting not only the localization of mitochondria and cortical granules due to a possible alteration of the cytoskeleton but also the function of mitochondria and endoplasmic reticulum since in RPM oocytes we observed a switch in the morphology of smooth endoplasmic reticulum (SER) and associated mitochondria from mitochondria-SER aggregates to mitochondria–vesicle complexes. We concluded that microgravity might negatively affect oocyte quality by interfering in vitro with the normal sequence of morphodynamic events essential for acquiring and maintaining a proper competence to fertilization in human oocyte

Morphological aspects of human aged oocytes: an in vivo and in vitro ultrastructural study

Maternal age significantly affects the outcome of ART by lowering oocyte quality and competence. However, the morphological ultrastructure features of aged human oocytes have been not extensively studied and understood. In this study we analyzed oocytes donated by women &lt;35 (-35) and ? 35 (+35) years old, enrolled in an IVF program, after informed consent.  MII oocytes,  fixed at time of pick up  (in vivo) or after 24 hours culture (in vitro) were evaluated by light and transmission electron microscopy. IN VIVO samples of both -35 and  +35 showed a spherical oocyte surrounded by regular ZP and expanded cumulus, and an ooplasm rich in organelles provided with a homogenous matrix. Oocyte mitochondria-SER aggregates (M-SER), that were numerous in -35, appeared significantly reduced in number/size and partially replaced by mitochondria-vesicle complexes (MVC) in +35. Cortical granules, normally represented in -35, appeared abnormally distributed in +35. Ooplasm microvilli significantly decreased in density and shortened in +35. IN VITRO samples showed several changes. All samples showed a compact cumulus with occasional cumulus cell-oocyte contacts. The inner ZP showed an increased density in +35. Small sized M-SER were occasionally detected in -35 and were almost absent in +35. MVC were present in both -35 and +35,  increased up in number and often showed abnormal vesicles in +35. All samples showed numerous lysosomal structures and reduction of cortical granules. Ooplasm microvilli significantly decreased in density and shortened in +35. This study demonstrated several significant ultrastructural changes occurring in fresh oocytes (in vivo) from older patients and in all 24 hours in vitro cultured oocytes. The altered ultrastructure observed in  in vitro cultured oocytes resembles in vivo aging-related changes and it is significantly more evident in oocytes from older patients. The changes described in the present study may be considered  as ultrastructural markers of oocyte aging

The Epstein–Barr virus nuclear antigen-1 promotes telomere dysfunction via induction of oxidative stress

The Epstein–Barr virus (EBV) nuclear antigen (EBNA)-1 promotes the accumulation of chromosomal aberrations in malignant B cells by inducing oxidative stress. Here we report that this phenotype is associated with telomere dysfunction. Stable or conditional expression of EBNA1 induced telomere abnormalities including loss or gain of telomere signals, telomere fusion and heterogeneous length of telomeres. This was accompanied by the accumulation of extrachromosomal telomeres, telomere dysfunction-induced foci (TIFs) containing phosphorylated histone H2AX and the DNA damage response protein 53BP1, telomere-associated promyelocytic leukemia nuclear bodies (APBs), telomeric-sister chromatid exchanges and displacement of the shelterin protein TRF2. The induction of TIFs and APBs was inhibited by treatment with scavengers of reactive oxygen species (ROS) that also promoted the relocalization of TRF2 at telomeres. These findings highlight a novel mechanism by which EBNA1 may promote malignant transformation and tumor progression