Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study.

PURPOSE: The introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events. METHODS: The present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use. RESULTS: Embryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score. CONCLUSION: The developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.

Ruptured ectopic pregnancy as complete hydatidiform mole: Case report and review of the literature.

Usually, a hydatidiform mole (HM) develops inside the uterus. The occurrence of HM in ruptured tubal pregnancy is exceptional. Cases reported in the literature are scarce. In this article, a case of haemoperitoneum secondary to a ruptured fallopian tube by a complete mole is reported. A 50-year-old gravida 2, para 1 was admitted to the emergency department for acute abdominal pain. After the clinical examination, an abdominal sonography and CT scan were done, revealing the presence of an adnexal left mass associated with an important haemoperitoneum. A urine pregnancy test was done and was positive, indicating an immediate laparoscopic exploration. The laparoscopy revealed a haemoperitoneum secondary to a ruptured tubal mass. The pathological exam concluded a complete hydatidiform mole (CHM) invading the wall of the fallopian tube. Any acute abdominal pain in a potentially pregnant woman imposes first the routine realization of a pregnancy test. The occurrence of CHM in a ruptured fallopian tube is particularly rare and has exceptionally been diagnosed before the laparoscopic exploration.

Targeting Both Autophagy and Immunotherapy in Breast Cancer Treatment.

As clinical efforts towards breast-conserving therapy and prolonging survival of those with metastatic breast cancer increase, innovative approaches with the use of biologics are on the rise. Two areas of current focus are cancer immunotherapy and autophagy, both of which have been well-studied independently but have recently been shown to have intertwining roles in cancer. An increased understanding of their interactions could provide new insights that result in novel diagnostic, prognostic, and therapeutic strategies. In this breast cancer-focused review, we explore the interactions between autophagy and two clinically relevant immune checkpoint pathways; the programmed cell death-1 receptor with its ligand (PD-L1)/PD-1 and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)/CD80 and CD86 (B7-1 and B7-2). Furthermore, we discuss emerging preclinical and clinical data supporting targeting both immunotherapy and autophagy pathway manipulation as a promising approach in the treatment of breast cancer.

Male Age and Progressive Sperm Motility Are Critical Factors Affecting Embryological and Clinical Outcomes in Oocyte Donor ICSI Cycles.

This retrospective cohort study aimed to explore whether paternal age and semen quality parameters affect the embryological and clinical outcomes of ICSI with oocyte donation. A total of 339 oocyte donation (OD)-ICSI cycles were categorized into four groups according to the semen parameter profiles of the male counterparts: normozoospermia (NS, n = 184), oligozoospermia (OS, n = 41), asthenozoospermia (AS, n = 50), and oligoasthenozoospermia (OAS, n = 64). The effect of age, total sperm count, and progressive motility was separately analyzed for reproductive outcomes and compared between the study groups: fertilization, blastulation, and top-quality embryo rate, biochemical and clinical pregnancy, live birth, and miscarriage. A negative correlation between male age and fertilization rate was observed (rs = - 0.23, p < 0.0001), while male age was a significant factor for biochemical pregnancy (p = 0.0002), clinical pregnancy (p = 0.0017), and live birth (p = 0.0038). Reduced total sperm count and lowered progressive motility led to poorer fertilization rates (rs = 0.19 and 0.35, respectively, p < 0.0001) and affected embryo quality (rs = 0.13, p = 0.02, and rs = 0.22, p < 0.0001, respectively). OD-ICSI cycles with asthenozoospermia had significantly lowered success rates in biochemical pregnancy, clinical pregnancy, and live birth (p < 0.05). Our study demonstrated that both advanced male age and reduced progressive motility of spermatozoa exert a significant negative influence on the outcome of assisted reproduction, even in controlled procedures with gamete selection and optimization such as in OD-ICSI. Improvement in treatment strategies and male fertility evaluation requires incorporation of such evidence to obtain better prognosis towards personalized management.

Alterations of the 70 kDa heat shock protein (HSP70) and sequestosome-1 (p62) in women with breast cancer.

Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. Production of the 70 kDa heat shock protein (HSP70) is up-regulated to protect proteins from degradation. Sequestosome-1 (p62) binds to altered proteins and the p62-protein complex is degraded by autophagy. P62 is also a regulator of intracellular kinase activity and cell differentiation. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSP70 and a decrease in intracellular p62. In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSP70 and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSP70 levels were 79.3 ng/ml in PBMCs from women with a malignant lesion as opposed to 44.2 ng/ml in controls (p = 0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (p < 0.001). Mean p62 levels were lowest in women with invasive carcinoma and a positive lymph node biopsy when compared to those with in-situ carcinoma or absence of lymphadenopathy, respectively. Intracellular HSP70 and p62 levels in PBMCs differ between women with a malignant or benign breast lesion. These measurements may be of value in the preoperative triage of women with a breast mass.

Encapsulated Papillary Carcinoma: A Case Report and Review of the Literature.

Papillary neoplasms are a distinct assemblage of breast lesions whose main characteristic is the presence of fibrovascular cores which are surrounded by epithelial cells. Papillary lesions are of heterogenous nature, with similar clinical behavior and histomorphologic characteristics. Their biological patterns, however, can be quite different. According to the World Health Organization (WHO) (2019), breast tumors have been recently classified into five subdivisions of papillary neoplasms. They are namely: intraductal papilloma, papillary ductal carcinoma in situ, encapsulated papillary carcinoma (EPC), solid-papillary carcinoma and invasive papillary carcinoma. Despite the papillary architecture being easily recognized, histological variations are diagnostically challenging. The presence or absence of myoepithelial cells in the papillary cores can distinguish the malignant from the benign lesions respectively. EPC is a rare, histologically unique carcinoma type whose main characteristic is a thick fibrous capsule at the periphery and a prolific cell structure with fibrovascular stalk support. A characteristic feature is the absence of myoepithelial cells at the surrounding thick fibrous capsule. Usually, EPC maintains a slowly developing tumor despite the absence of myoepithelial cells. An EPC case presents diagnostic difficulties since it bears close resemblance to malignant and benign papillary breast lesions. Upon a clinical and radiological evaluation, EPC commonly appears as a benign lump. In mammography, the tumor is frequently found in a retroareolar position as a well-defined mass. On the other hand, in an ultrasound, the tumor will appear as a cystic lesion characterized by solid components. The clinical picture of EPC is usually an asymptomatic benign mass which at times can be felt through auto-palpation or screening mammography. A bloody nipple discharge is regarded as a common symptom. We report a case of an EPC of a 81-year-old woman who presented with a mass in the left breast.

Evaluation of lysophosphatidic acid in vaginal fluid as a biomarker for ovarian cancer: A pilot study.

There remains a need to differentiate between women with a benign or a malignant adnexal mass prior to surgery. As part of an ongoing evaluation of vaginal fluid compounds as potential tumor biomarkers we evaluated whether vaginal lysophosphatidic acid (LPA) predicted the subsequent diagnosis of a malignant adnexal mass. In this prospective pilot study vaginal fluid was obtained from 100 post-menopausal women referred for evaluation of a suspicious adnexal mass and tested for LPA by ELISA. Clinical data and serum CA125 results were obtained only after completion of all laboratory testing. Twenty eight of the women were subsequently diagnosed with an ovarian malignancy, four had a borderline tumor and 68 had a benign diagnosis. Among women with a malignant ovarian mass, 11 (39.3%) had an endometrioid adenocarcinoma +/- Clear cell tumor components, 6 (21.4%) had a high grade serous carcinoma, 3 (10.7%) had a mucinous tumor, 2 each (7.1%) had a malignant mixed mesodermal or a granulosa tumor and 1 each (3.6%) had a Clear cell tumor, a mixed cell tumor, leimyosarcoma or metastatic adrenal tumor. Compared to the median vaginal LPA level in women with benign lesions (1.5 µM), LPA was significantly elevated only in women with endometrioid ovarian cancer (7.9 µM) (p = 0.0137). Of the 6 endometrioid tumors in which values for both plasma CA125 and vaginal LPA were available 5 were positive only for LPA while one was only CA125 positive. Detection of LPA in vaginal secretions may be of value for the noninvasive diagnosis of endometrioid ovarian malignancies in post-menopausal women.

Correction to: A Novel Quantitative Method for the Detection of Lipofuscin, the Main By-Product of Cellular Senescence, in Fluids.

In Chapter 12, figure 1 was published with truncated texts within. This figure has now been replaced with a revised figure with the updated text.

A Novel Quantitative Method for the Detection of Lipofuscin, the Main By-Product of Cellular Senescence, in Fluids.

Lipofuscin accumulation is a hallmark of senescence. This nondegradable material aggregates in the cytoplasm of stressed or damaged cells due to metabolic imbalance associated with aging and age-related diseases. Indications of a soluble state of lipofuscin have also been provided, rendering the perspective of monitoring such processes via lipofuscin quantification in liquids intriguing. Therefore, the development of an accurate and reliable method is of paramount importance. Currently available assays are characterized by inherent pitfalls which demote their credibility. We herein describe a simple, highly specific and sensitive protocol for measuring lipofuscin levels in any type of liquid. The current method represents an evolution of a previously described assay, developed for in vitro and in vivo senescent cell recognition that exploits a newly synthesized Sudan Black-B analog (GL13). Analysis of human clinical samples with the modified protocol provided strong evidence of its usefulness for the exposure and surveillance of age-related conditions.

Chlamydia trachomatis: the Persistent Pathogen.

Chlamydia trachomatis is an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. C. trachomatis has evolved successful mechanisms to avoid destruction by autophagy and the host immune system and persist within host epithelial cells. The intracellular form of this organism, the reticulate body, can enter into a persistent nonreplicative but viable state under unfavorable conditions. The infectious form of the organism, the elementary body, is again generated when the immune attack subsides. In its persistent form, C. trachomatis ceases to produce its major structural and membrane components, but synthesis of its 60-kDa heat shock protein (hsp60) is greatly upregulated and released from the cell. The immune response to hsp60, perhaps exacerbated by repeated cycles of productive infection and persistence, may promote damage to fallopian tube epithelial cells, scar formation, and tubal occlusion. The chlamydial and human hsp60 proteins are very similar, and hsp60 is one of the first proteins produced by newly formed embryos. Thus, the development of immunity to epitopes in the chlamydial hsp60 that are also present in the corresponding human hsp60 may increase susceptibility to pregnancy failure in infected women. Delineation of host factors that increase the likelihood that C. trachomatis will avoid immune destruction and survive within host epithelial cells and utilization of this knowledge to design individualized preventative and treatment protocols are needed to more effectively combat infections by this persistent pathogen.