Human oocytes image classification method based on deep neural networks.

BACKGROUND: The effectiveness of in vitro fertilization depends on the assessment and selection of oocytes and embryos with the highest developmental potential. One of the tasks in the ICSI (intracytoplasmic sperm injection) procedure is the classification of oocytes according to the stages of their meiotic maturity. Oocytes classification traditionally is done manually during their observation under the light microscope. The paper is part of the bigger task, the development of the system for optimal oocyte and embryos selection. In the hereby work, we present the method for the automatic classification of oocytes based on their images, that employs DNN algorithms. RESULTS: For the purpose of oocyte class determination, two structures based on deep neural networks were applied. DeepLabV3Plus was responsible for the analysis of oocyte images in order to extract specific regions of oocyte images. Then extracted components were transferred to the network, inspired by the SqueezeNet architecture, for the purpose of oocyte type classification. The structure of this network was refined by a genetic algorithm in order to improve generalization abilities as well as reduce the network's FLOPs thus minimizing inference time. As a result, [Formula: see text] at the level of 0.964 was obtained at the level of the validation set and 0.957 at the level of the test set. Generated neural networks as well as code that allows running the processing pipe were made publicly available. CONCLUSIONS: In this paper, the complete pipeline was proposed that is able to automatically classify human oocytes into three classes MI, MII, and PI based on the oocytes' microscopic image.

Semantic segmentation of human oocyte images using deep neural networks.

BACKGROUND: Infertility is a significant problem of humanity. In vitro fertilisation is one of the most effective and frequently applied ART methods. The effectiveness IVF depends on the assessment and selection of gametes and embryo with the highest developmental potential. The subjective nature of morphological assessment of oocytes and embryos is still one of the main reasons for seeking effective and objective methods for assessing quality in automatic manner. The most promising methods to automatic classification of oocytes and embryos are based on image analysis aided by machine learning techniques. The special attention is paid on deep neural networks that can be used as classifiers solving the problem of automatic assessment of the oocytes/embryos. METHODS: This paper deals with semantic segmentation of human oocyte images using deep neural networks in order to develop new version of the predefined neural networks. Deep semantic oocyte segmentation networks can be seen as medically oriented predefined networks understanding the content of the image. The research presented in the paper is focused on the performance comparison of different types of convolutional neural networks for semantic oocyte segmentation. In the case study, the merits and limitations of the selected deep neural networks are analysed. RESULTS: 71 deep neural models were analysed. The best score was obtained for one of the variants of DeepLab-v3-ResNet-18 model, when the training accuracy (Acc) reached about 85% for training patterns and 79% for validation ones. The weighted intersection over union (wIoU) and global accuracy (gAcc) for test patterns were calculated, as well. The obtained values of these quality measures were 0,897 and 0.93, respectively. CONCLUSION: The obtained results prove that the proposed approach can be applied to create deep neural models for semantic oocyte segmentation with the high accuracy guaranteeing their usage as the predefined networks in other tasks.

The Influence Of Intrauterine Pressure On Embryo Retention In A Catheter After Embryo Transfer.

The retention of the embryo in the transfer catheter after embryo transfer (ET) during in vitro fertilization is a very common phenomenon, encountered by even the most experienced operators, and embryos retained in the transfer catheter or its sleeve require a repeat transfer. The exact mechanism of embryo retention has not been explained. Therefore, the present study aimed to investigate the mechanism of embryo retention in the catheter during embryo transfer by using a transparent uterus model equipped with pressure sensors and a video recorder. The results indicate that pressure changes in the uterine cavity during ET can influence the distribution of the transferred fluid containing the embryo. Under certain conditions, the transferred fluid can flow backward in the catheter, which may lead to retention of the embryo in the catheter.

Pro-inflammatory cytokines associated with clinical severity of dry eye disease of patients with depression.

PURPOSE: The aim of this study was to assess the correlation of inflammatory cytokines levels in tears with severity of dry eye disease in a cohort of patients with depression. MATERIAL AND METHODS: Tear fluid samples were collected from 32 patients with depression treated with antidepressants, and 34 healthy subjects. Cytokines were assessed by ELISA. All the subjects completed the Beck Depression Inventory and performed the ophthalmic examination, including dry eye tests. RESULTS: The tear fluid levels of IL-6, IL-17 and TNF-α in depressive patients were higher than in controls. The clinical severity of dry eye disease correlated significantly with the IL-17 and TNF-α levels. CONCLUSIONS: Our results suggest a crucial role of inflammatory cytokines, especially IL-17 and TNF-α, in the development of severe dry eye disease in patients with depression. Clarification of the role pro-inflammatory cytokines in the pathogenesis of ocular findings in depressive patients may be useful in establishing immunotherapeutic strategies for this disease.

Effective Mobilization of Very Small Embryonic-Like Stem Cells and Hematopoietic Stem/Progenitor Cells but Not Endothelial Progenitor Cells by Follicle-Stimulating Hormone Therapy.

Recently, murine hematopoietic progenitor stem cells (HSCs) and very small embryonic-like stem cells (VSELs) were demonstrated to express receptors for sex hormones including follicle-stimulating hormone (FSH). This raised the question of whether FSH therapy at clinically applied doses can mobilize stem/progenitor cells in humans. Here we assessed frequencies of VSELs (referred to as Lin(-)CD235a(-)CD45(-)CD133(+) cells), HSPCs (referred to as Lin(-)CD235a(-)CD45(+)CD133(+) cells), and endothelial progenitor cells (EPCs, identified as CD34(+)CD144(+), CD34(+)CD133(+), and CD34(+)CD309(+)CD133(+) cells) in fifteen female patients subjected to the FSH therapy. We demonstrated that FSH therapy resulted in statistically significant enhancement in peripheral blood (PB) number of both VSELs and HSPCs. In contrast, the pattern of responses of EPCs delineated by different cell phenotypes was not uniform and we did not observe any significant changes in EPC numbers following hormone therapy. Our data indicate that FSH therapy mobilizes VSELs and HSPCs into peripheral blood that on one hand supports their developmental origin from germ lineage, and on the other hand FSH can become a promising candidate tool for mobilizing HSCs and stem cells with VSEL phenotype in clinical settings.

[Influence of naloxone on uterine contractions in patients with primary dysmenorrhea]. / Wplyw naloksonu na czynnosc skurczowa macicy u pacjentek z pierwotnym zespolem bolesnego miesiaczkowania.

UNLABELLED: Dysmenorrhea is a common condition among women in childbearing age. An increased uterine contractions, resulting among others from increased vasopressin and oxitocin secretion, is considered as a main cause of the primary dysmenorrhea. The endogenous opioids play the important role in the control of oxytocin and vasopressin release from the pituitary gland. Naloxone is a selective opioid receptor antagonis. So far, there is not much data on naloxone effect on uterine contractions. The aim of study was to determine the influence of naloxone on uterine contractions in patients with primary dysmenorrhea. MATERIAL AND METHODS: There were 10 female patients with primary dysmenorrhea included into the study. The uterine contractions had been recorded for 30 minutes before and 2 hours after injection of naloxone at the first day of menstruation. RESULTS: The intrauterine pressure recordings revealed a severe spontaneous uterine contractions, with high frequency and amplitude, at the time of dysmenorrhea. An intravenous administration of naloxone decreased uterine contractile activity and pain intensity. CONCLUSIONS: Naloxone acting on central nervous system decreases the uterus contractions in the patients suffering from dysmenorrhea. Unexplained mechanisms and multiple factors involved in the pathogenesis of primary dysmenorrhea indicates a need for the further studies on this subject.

[Dry eye disease in patients treated with antidepressants]. / Zespól suchego oka u pacjentów leczonych lekami antydepresyjnymi.

PURPOSE: Dry eye disease is defined as a multifactorial disease of tears and ocular surfaces that causes discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. This study aimed to determine dry eye findings in patients with depression. MATERIAL AND METHODS: There were 40 patients with depression aged 18-65 years old. A comprehensive ophthalmic examination, including intraocular pressure and dry eye tests, was performed. RESULTS: Among patients with depression 24 patients (70%) had dry eye syndrome. Compared with patients who did not have dry eye, the patients with dry eye were significantly older than the patients without dry eye (44 years old and 36 years old, respectively). Time in duration of depression in patients with depression and with dry eye lasted over 54 months and time of taking antidepressants was longer than 18 months and was significant, in comparing to the patients without dry eye (36 months and 10 months, respectively). CONCLUSIONS: Dry eye is frequent disease in patients with depression, especially in older patients, who have longer duration of depression, and taking antidepressant medication for a longer period of time. Using of antidepressant may be cosidered as potential cause of dry eye syndrome.

[Influence of functional status of ovaries on results of controlled ovarian hyperstimulation]. / Wplyw stanu czynnosciowego jajników na wyniki kontrolowanej hiperstymulacji hormonalnej.

UNLABELLED: The controlled ovarian hyperstimulation is an integral part of infertility treatment. Its main objective is to obtain oocytes with a highest developmental potential. The stimulation protocols involving the gonadotropin-releasing hormone analogues and gonadotropins are considered as the most efficient. Despite many years of use, some aspects of controlled ovarian stimulation has not yet been clarified, especially the role of the functional status of ovaries before hormonal stimulation. The aim of study was to assess the influence of the functional status of ovaries on the results of the controlled ovarian hyperstimulation. MATERIALS AND METHODS: The retrospective study included female patients suffering from infertility The patients were divided into two groups depending on ultrasonographic appearance of ovaries before controlled ovarian hyperstimulation. The patients with small antral follicles < 6 mm in diameter were selected into group I. The patients with five or more antral follicles > or = 8 mm in diameter in each ovary were included into group II. The patients from both groups underwent similar treatment process. The major area of interest was the number, type and quality of oocytes obtained from patients from both groups after ovarian puncture. RESULTS: A retrospective study was conducted on 635 infertile patients (group I 382, group II 253). Altogether, 4055 oocytes were obtained in the group I and 2555 oocytes in the group II. The mean number of MII oocytes in group I was 9,2 and 8,7 in group II; p < 0.05. There were significantly more MI oocytes in group I than II. The mean numbers of immature oocytes were comparable between groups. The athretic and dysmorphic oocytes were more prevalent in group II. CONCLUSIONS: The results of the present study indicates that the functional status of ovaries before controlled ovarian hyperstimulation plays pivotal role for the treatment outcome.

[Etiopathogenesis of dysmenorrhea]. / Etiopatogeneza zespolu bolesnegomiesiaczkowania.

Dysmenorrhea is a common and frequently disabling condition among women of childbearing age. Based on results of large epidemiological studies, it is estimated that over a half of the population of young women suffers from dysmenorrhea. In spite of such a high frequency of this condition, its literature. Pain and lower abdominal cramps are among the most common causes for gynecological referral. Dysmenorrhea is sometimes associated with nausea, vomiting, diarrhea, fatigue, fever, headache, back pain, and dizziness. The exact cause of the disorder is not completely understood. However, there are many known factors that play significant roles in the pathogenesis of dysmenorrhea. The most important are: excessive uterine contractility, disturbances in uterine blood supply, synthesis of prostaglandins and anatomical abnormalities of the female reproductive tract. Primary dysmenorrhea refers to painful menstrual bleedings in the absence of any detectable underlying pathology. Secondary dysmenorrhea represents the clinical situation where menstrual pain can be related to an underlying disease, disorder, or structural abnormality either within or outside the uterus. Unexplained mechanisms and multiple factors involved in the pathogenesis of primary dysmenorrhea indicate a vivid need for further studies on this subject.

Influence of embryo transfer on embryo preimplantation development.

OBJECTIVE: To investigate the impact of injection speeds of the transferred load on embryo development. DESIGN: A laboratory model for in vitro simulation of ET was developed to investigate the impact of varying injection speeds of the transferred load on embryo development. SETTING: Academic research institutes of reproduction biotechnology and private centers of reproductive medicine. ANIMAL(S): Mouse hybrid F(1) females (C57bl/10 J × CBA-H; N = 15) aged 2-3 months. INTERVENTION(S): In vitro exposure of mouse embryos with either the fast ET (ejection speed, >1 m/s) or slow ET (ejection speed, <0.1 m/s) and consecutive culture for 36 hours. MAIN OUTCOME MEASURE(S): Development rate, morphology and apoptotic index of embryos. RESULT(S): The development rate was the slowest in embryos exposed to the fast ET. Morphological changes in response to ET were observed only among embryos exposed to the fast ET. The mean apoptotic index was 17.6% in the group exposed to the fast ET, 5.6% in the group exposed to the slow ET, and 2.58% in the control group. CONCLUSION(S): A reduction of the ejection speed of the transferred load allows avoidance of a developmental delay and diminishes injury of the embryos. Therefore, it is reasonable to suggest transferring the embryos at the lowest possible ejection speed.

[Influence of the anti-inflammatory, anti-bacterial and anti-oxidative treatment combined with the dietary supplementation on sperm parameters]. / Wplyw skojarzonego leczenia przeciwzapalnego, przeciwbakteryjnego i antyoksydacyjnego oraz suplementacji zywieniowej mwzczyzn na jakosc nasienia.

UNLABELLED: The severe oligospermia and lukocytospermia is diagnosed among 25-40% of the infertile patients despite the absence of any clinical manifestation of the inflammatory process. The white blood cells are the main source of the free oxidative radicals, which can injure the cell membranes and the sperm DNA integrity influencing the reproductive potential of the male gametes. The aim of study was to assess the influence of the anti-inflammatory anti-bacterial and anti-oxidative treatment combined with the dietary supplementation on sperm parameters in the patients with severe oligospermia and lukocytospermia. MATERIALS AND METHODS: 100 patients with a severe oligospermia and leukocytospermia were qualified into the study. The anti-inflammatory anti-bacterial and anti-oxidative treatment combined with dietary supplementation was applied for 90 days. The sperm analysis was performed before and after the treatment. RESULTS: The mean volume of sperm samples and spermatozoa concentration were comparable before and after treatment. The leukocyte concentration was significantly lower after the therapy. There were significantly more spermatozoa in the fast and slow forward movement, less spermatozoa without movements and comparable concentration in spermatozoa in slow undirected movement after applied treatment. CONCLUSIONS: The present study demonstrated that the anti-inflammatory, anti-bacterial and anti-oxidative treatment combined with dietary supplementation in the patients with severe oligospermia and lukocytospermia improves the sperm movement parameters and reduces the inflammatory response. Therefore, it might be beneficial to patient suffering from the infertility.

[Thrombosis in the course of ovarian hyperstimulation syndrome]. / Zespól Hiperstymulacyjny Powiklany Zakrzepica.

A 28-year-old woman sought medical advice in the gynecology department because of infertility. Based on the results of the infertility workup, it was decided to apply in vitro fertilization treatment in her case. On the 12th day after embryo transfer, the patient was admitted to hospital because of nausea, vomiting, abdominal distention, and difficulties in breathing. The diagnosis was early pregnancy and the ovarian hyperstimulation syndrome (OHSS). After conservative treatment, the OHSS symptoms disappeared, and she was discharged in a good condition. However, nine days later the patient was readmitted due to a dull pain in her left shoulder, radiating onto the neck and left arm. Ultrasound examination revealed a thrombotic clot at the junction of the left external jugular vein and subclavian vein. Treatment with low-molecular-weight heparin was initiated. After 21 days of medication, the patient's symptoms resolved and, further, her pregnancy continued without complications. Although thromboembolic events are not frequently encountered in the course of OHSS, prophylactic anticoagulant therapy should be considered in all such patients.

Fluid dynamics during embryo transfer.

OBJECTIVE: To study fluid dynamics during ET. DESIGN: Computational fluid dynamics were applied to calculate fluid velocity changes, dynamic pressure differences, and shear stress in the transferred load for the following injection speeds: 0.1, 1, 6, 12, and 20 m/sec. SETTING: Academic research institute of mechanical engineering and reproduction biotechnology and private centers of reproductive medicine. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fluid velocity, dynamic pressure, and shear stress during injection of the transferred load. RESULT(S): An increase of injection speed for the transferred load increased the shear stress, dynamic pressure, and velocity differences acting on the embryo. The narrowing of the catheter lumen diameter by 20% amplified the transferred fluid velocity by 78%. An embryo positioned in proximity to the catheter's wall was exposed to considerably higher shear stress, dynamic pressure, and velocity difference than an embryo in the center of the catheter's lumen. CONCLUSION(S): The transfer of an embryo should be conducted gently and with minimal injection speed. Any narrowing of the catheter lumen should be eliminated. Preferably the embryo should be kept far from the catheter's wall during injection of the transferred load.

Pressure induced nucleus DNA fragmentation.

PURPOSE: The present study was designed to investigate the impact of pressure on nuclear DNA integrity in viable cells of mouse blastocysts. METHODS: The blastocysts of hybrid F1 females [(C57Bl/10 J × CBA-H);N = 15] aged 2-3 months were exposed into the pressure impulse lasting ~0.021 s and characterized by a positive pressure peak of ~76 mmHg. The nuclear DNA fragmentation index of mouse blastocysts was assessed by TUNEL assay within 60 s after exposure to pressure impulse. RESULTS: The mean nuclear DNA fragmentation index was significantly higher in the experimental group (83%) than in the control group (19.7%); p < 0.001. CONCLUSION(S): A low magnitude pressure impulse can induce nuclear DNA fragmentation in mouse blastocysts. The compression and decompression forces appearing during pressure fluctuations are responsible for the observed DNA shearing.

Influence of embryo transfer on blastocyst viability.

OBJECTIVE: To investigate the impact of injection speeds of the transferred load on embryo viability. DESIGN: Laboratory model for in vitro simulation of embryo transfer (ET). SETTING: Academic research institutes of reproduction biotechnology and private centers of reproductive medicine. ANIMAL(S): Mouse hybrid F1 females, C57bl/10J × CBA-H (N = 15), aged 2 to 3 months. INTERVENTION(S): In vitro exposure of mouse blastocysts to either fast ET with an ejection speed of the transferred load of >1 m/s or slow ET with an ejection speed of <0.1 m/s. MAIN OUTCOME MEASURE(S): Morphologic changes and apoptotic index of blastocysts. RESULT(S): Morphologic changes in response to ET were most prevalent in blastocysts exposed to fast ET. The mean apoptotic index was 52% in the group exposed to fast ET, 25% in the group exposed to slow ET, and 12.8% in control group. CONCLUSION(S): Fast ejection of the transferred load can trigger both morphologic changes and apoptosis in mouse blastocysts. A reduction of the ejection speed of the transferred load minimizes injury to the embryos. Therefore, embryos should be transferred at the lowest possible speed.

Pressure changes during embryo transfer.

OBJECTIVE: To investigate the pressure changes in the transferred load during mock ET. DESIGN: Experimental setup. SETTING: Academic Research Institute of Mechanical Engineering and private centers of reproductive medicine. PATIENTS(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Laboratory simulations of ET into a rigid transparent uterine model equipped with a pressure sensor. RESULT(S): Injection of a transferring load during mock ET could increase pressure locally up to 155 mm Hg in <0.1 seconds. The recorded pressure increase slope reached values as high as 72,000 mmHg/s, and the pressure decrease slope reached 144,000 mmHg/s. The pressure buildup in the transferred liquid was proportional to the ejection speed of the transferred load. CONCLUSION(S): ET can cause rapid pressure fluctuations in the transferred liquid. Therefore, it is advisable to transfer the embryo gently with minimum ejection speed, to avoid exposing the embryo to the steep pressure gradient.

Macular pigmentary changes as a sequelae of retinal hemorrhages in premature infants with retinopathy of prematurity.

PURPOSE: We assess the incidence of macular changes in ROP patients with retinal hemorrhages. PATIENTS AND METHODS: The premature group consisted of 360 children born 32 weeks gestation and/or with weight below 1,500 g. We used the RetCam-120 Digital Retinal Camera to document retinal changes. RESULTS: Of the 360 premature infants 241 (67%) had no ROP, and 119 (33%) had ROP. Of the preterm infants with ROP retinal hemorrhages were found in 46 (38%) children. Of the newborns with ROP and with retinal hemorrhages, macular pigmentary changes were found in 3 (6%) patients. Of these 3 patients, the first had pre-threshold ROP, the second threshold ROP and had underwent diode laser photocoagulation, and the third patient had stage 2 ROP. In the patients with pre-threshold and threshold ROP retinal hemorrhages appeared 6 weeks after birth and macular pigmentary changes were found 6 months after birth. In the patient with stage 2 ROP hemorrhages appeared 7-8 weeks after birth and macular pigmentary changes were detected 12 months after birth. CONCLUSIONS: Although macular hemorrhages almost always resorb without complications, our study allows the assumption that retinal hemorrhages may cause macular pigmentary changes in the macula, and thus may lead to deprivation amblyopia. Our results may suggest that the presence of the macular pigmentary changes may be related to the hemorrhage and not to the specific therapy or to the disease.

[Endometrial carcinoma during the IVF program]. / Ca endometrii w trakcie przygotowania do programu IVF.

The paper presents a case of abnormal endometrium proliferation detected during routine examinations before the final stage of the in vitro fertilization and embryo transfer program (IVF-ET). Diagnostic excochleation of the uterus histopathologically revealed Ca endometrium.