IVF protocol efficacy in women with expected suboptimal response depending on ovary stimulation mode.

INVESTIGATION OBJECTIVE: IVF protocol efficacy estimation in women with expected suboptimal response depending on ovary stimulation mode. MATERIALS AND TECHNIQUE: A randomized controlled study embracing results of 51 IVF cycle in women with ovary suboptimal response. The suboptimal response prognostic analysis was performed basing on ≤9 oocyte cumulus complexes obtained in previous IVF programs, the presence of no less than 5-9 antral follicles in both oocytes and amount of anti-Mullerian Hormone ≥0,8 ng/mL. In Group I (n = 25), the stimulation was performed by recombinant corifollitropin alfa combined with highly purified urinary gonadotropin, while in Group II (n = 26) it was made by means of recombinant follitropin/lutropin alfa within the protocol of applying gonadotropin-releasing hormone antagonists. RESULTS: The total gonadotropin dose in Group II patients was authentically lower compared to Group I (p˂,01). No statistical difference between the two studied groups was detected concerning the number of obtained oocytes, 2pn zygote, good-quality transferred embryos and clinical pregnancy rate (p>.05). Embryo cryopreservation was performed only for group-II patients. CONCLUSION: Corifollitropin alfa administration combined with highly purified menotropin in IVF cycles for suboptimal responders is quite effective, however, this strategy has no preference over other stimulation modes. The strategy of using recombinant follitropin/lutropin alfa can be promotive to IVF outcomes for suboptimal responders by means of embryo banking. ClinicalTrials.gov Identifier: NCT03177538.

Interactions of NK Cells and Trophoblast Cells. Methodological Aspects.

NK cells present in different organs differ by their functional characteristics, in particular, proliferative activity. For studying tissue-resident NK cells, tissue-specific microenvironment should be reproduced. In case of decidual NK cells, this microenvironment is created by trophoblast cells. We developed a method for evaluation of proliferative activity of peripheral blood NK cells in the presence of trophoblast cells. Proliferative activity of peripheral blood NK cells was evaluated by the expression of protein Ki-67 after culturing with JEG-3 trophoblast cells. This method allows evaluating the functional state of NK cells in microenvironment specific for the decidua.

Immunohistochemical criteria for endometrial receptivity in I/II stage endometriosis IVF-treated patients.

Abstracts Background: Implantation failure of in vitro fertilization (IVF) cycles is recognized as one of key problems in contemporary reproductive medicine. Implantation itself is a multifactorial process and one can hardly expect to find a single criterion for the endometrium receptivity. Endometrium biopsy still remains the most applicable technique to diagnose abnormalities causing decrease or complete loss of endometrial receptivity. MATERIALS AND METHODS: We have studied 95 endometrial biopsy samples from 45 patient with I/II stage endometriosis and 40 controls from October 2014 to December 2015. Immunohistochemical analysis of key biological molecules participating in implant window formation (LIF, ER, PR, integrin, TGF-ß1 and VEGF) was done to assess their predicting value for endometrial receptivity troubles. RESULTS: The discriminant analysis demonstrated that highest information capacity was characteristic for LIF expression percent area, integrin αVß3 both percent area and optic density in endometrial stroma and glands and finally TGFß1 and VEGF-А percent area expression in endometrial stroma. The model test done on a checking group showed 89.1% correct discrimination. Cross-checking in a teaching group showed a bit lower but still high correct answer percentage (88.8%). A decision-making classification tree was worked out. CONCLUSION: The produced model is sufficient for predicting IVF treatment failure and allows producing reasonable treatment tactics as well as encourages IVF treatment effectiveness improvement in patients with endometriosis.

Ectopic pregnancy following in vitro fertilization: meta-analysis and single-center experience during 6 years.

BACKGROUND: Ectopic pregnancy (EP) has been reported to occur in 1.4-5.4% of all clinical pregnancies resulting from in vitro fertilization (IVF) and embryo transfer (ET). Data on factors associated with abnormal embryo implantation following assisted conception are limited. MATERIALS AND METHODS: A systematic review and meta-analysis was performed to determine whether there is an association between the day (cleavage-stage, D3, versus blastocyst, D5) or the type (fresh versus frozen/thawed) of ET and EP rate. Risk factors for EP were evaluated in a retrospective study of 1194 women, who achieved pregnancy at our IVF unit between 2010 and 2016. RESULTS: Sixteen papers were considered for the meta-analysis. EP rate did not differ between D3 and D5 fresh ET groups (RR = 0.99, 95%CI: 0.76-1.30) and was higher after fresh versus frozen ET (RR = 1.56, 95%CI: 1.25-1.95). At our clinic, 21 (1.76%) pregnancies were documented as ectopic. The risk of EP was associated with tubal pathology (OR = 3.37, 95%CI: 1.39-8.2), previous appendectomy and past chlamydial infection. CONCLUSIONS: Present meta-analysis suggests that EP rate is similar following fresh blastocyst and cleavage ETs, but is significantly reduced after frozen compared with fresh ET. Our own findings demonstrate that tubal pathology has the major impact on EP occurrence following assisted conception.

Maternal insulin-like growth factors and insulin-like growth factor-binding proteins for macrosomia prediction in diabetic and nondiabetic pregnancy: A prospective study.

OBJECTIVE: Attributable to the insulin-like growth factor (IGF) axis involvement in fetal growth regulation, possible contribution of the maternal IGF axis to antenatal fetal macrosomia diagnosis is a subject of particular interest in diabetic pregnancy. METHODS: A total of 130 women were prospectively enrolled in a longitudinal single-center cohort study. The four study groups were: type 1 diabetes (n = 40), type 2 diabetes (n = 35), gestational diabetes (n = 40), and control (n = 15). IGF-1 and IGF-2 and insulin-like growth factor-binding protein (IGFBP) 1, 3, 6, and 7 serum levels were analyzed in 11- to 14-week and 30- to 34-week samples with a specific immunoassay. RESULTS: In mothers of large-for-gestational-age neonates (90th percentile), higher (median test) first-trimester IGF-1 (P = 0.007) and lower IGFBP-1 (P = 0.035) were observed. The IGF-1/IGFBP-1 ratio was positively associated with neonatal weight (r = 0.434, P < 0.001). Receiver operating characteristic analysis revealed an association between large for gestational age and the first-trimester IGF-1 (area under the curve [AUC] = 0.747, P < 0.001), IGFBP-1 (AUC = 0.334, P = 0.011), and IGF-1/IGFBP-1 ratio (AUC = 0.750, P < 0.001). IGF-1/IGFBP-1 ratio had better performance for prediction of birth weight over 4000 g (AUC = 0.822, P < 0.001). CONCLUSION: The authors detected different first-trimester IGF-1 and IGF-1/IGFBP-1 thresholds applicable for either supposition or rejection of macrosomia diagnosis. Further investigation is needed to determine how the maternal IGF axis can contribute to fetal macrosomia prediction.

Corrigendum: Violent Behavior During Psychiatric Inpatient Treatment in a German Prison Hospital.

[This corrects the article DOI: 10.3389/fpsyt.2019.00762.].

Violent Behavior During Psychiatric Inpatient Treatment in a German Prison Hospital.

Violent behavior in correctional facilities is common and differs substantially in type, target, implication, and trigger. Research on frequency and characteristics of violent behavior in correctional facilities and psychiatric hospitals is limited. Results from recent research suggest that comorbidity of severe mental disorder, personality disorder, and diagnosis of substance abuse is related to a higher risk of violent behavior. In the Berlin prison hospital, a database was created to collect data from all violent incidences (n=210) between 1997 and 2006 and between 2010 and 2016. In a retrospective, case-control study, we analyzed specific socioeconomic data and psychiatric diagnosis and compared the group of prisoners with violent behavior with randomly selected prisoners of the same department without violent behavior (n = 210). Diagnosis of schizophrenia, non-German nationality, no use of an interpreter, no children, and no previous sentence remained significantly associated with the dependent variable violent behavior. There were no significant differences regarding age and legal statuses. Practical implications for clinical work are discussed.

Involvement of the heparanase procoagulant domain in bleeding and wound healing.

Essentials Heparanase forms a complex with tissue factor and enhances the generation of factor Xa. The present study was aimed to identify the procoagulant domain of heparanase. Procoagulant peptides significantly shortened bleeding time and enhanced wound healing. Tissue factor pathway inhibitor (TFPI)-2 derived peptides inhibited the procoagulant peptides. SUMMARY: Background Heparanase, which is known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of activated factor X (FXa). Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase, and attenuated inflammation, tumor growth, and vascularization. Aims To identify the procoagulant domain in the heparanase molecule, and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis. Methods Twenty-four potential peptides derived from heparanase were generated, and their effect was studied in an assay of FXa generation. Peptides 14 and 16, which showed the best procoagulant effect, were studied in a bleeding mouse model and in a wound-healing mouse model. Results Peptides 14 and 16 increased FXa levels by two-fold to three-fold, and, at high levels, caused consumption coagulopathy. The TFPI-2-derived peptides explored in our previous study were found to inhibit the procoagulant effect induced by peptides 14 and 16. In the bleeding model, time to clot formation was shortened by 50% when peptide 14 or peptide 16 was topically applied or injected subcutaneously. In the wound-healing model, the wound became more vascular, and its size was reduced to one-fifth as compared with controls, upon 1 week of exposure to peptide 14 or peptide 16 applied topically or injected subcutaneously. Conclusions The putative heparanase procoagulant domain was identified. Peptides derived from this domain significantly shortened bleeding time and enhanced wound healing.

[Methodological approaches to quantitative immunohistochemical evaluation of expression of breast apoptosis and proliferation markers].

Apoptosis and proliferative markers were studied in fibroadenoma and fibrocystic breast lesions. A quantitative immunohistochemical test for these factors using computer system of microscopic images is presented. It provides the advantages for interpretation of immunohistochemical reactions by design of expression standards for different pathologies in the breast.

Obstructive sleep apnea and acute myocardial infarction: clinical implications of the association.

It is not known whether patients with acute myocardial infarction (MI) with coexistent obstructive sleep apnea (OSA) have a poor clinical course during the acute phase of MI. Therefore, we investigated the impact of OSA on in-hospital morbidity and mortality during an acute MI. Patients admitted to the intensive cardiac unit (ICU) with acute MI underwent Holter monitoring and night pulse oximetry (SpO2). During the first complete day at the ICU, both recordings (ECG and SpO2) were matched in time to determine association between cardiac arrhythmias and hypoxemia episodes. We identified and compared 55 heavy snorers with daytime sleepiness who showed more than 10 episodes of desaturation per hour on pulse oximetry (OSA group), and 196 nonOSA patients. There was an increase in the incidence of premature ventricular contraction (PVC, p < 0.05) and couplets PVC (p < 0.05) in OSA patients; the proportion of those arrhythmias increased in parallel with desaturation episodes in the OSA group. There were no differences between OSA and nonOSA groups for major MI complications (38.2% vs 34.2%, p > 0.05), ICU/hospital stay (3.6 +/- 1.2 vs 2.7 +/- 0.9 days, p > 0.05), or mortality within 30 days (14.5% vs 12.2%, p > 0.05). In conclusion, despite the greater incidence of some types of cardiac arrhythmias during an acute MI in OSA, these patients have the same clinical course in hospital and mortality rate as nonOSA patients.

Risk factors associated with candidaemia in the neonatal intensive care unit: a case-control study.

The incidence of candidaemia is steadily increasing in neonatal intensive care units (NICUs). Several neonatal risk factors for candidaemia have been identified, however, the number of cases in controlled studies is small and knowledge concerning maternal and perinatal risk factors is limited. The present study attempted to identify modifiable, independent maternal, perinatal and neonatal risk factors for candidaemia using a retrospective case-control study in the NICU of a tertiary-care paediatric medical centre. The study group consisted of 56 neonates admitted to the NICU between 1996 and 2000 who acquired candidaemia. The control group comprised the first infant admitted immediately after each study infant matched for gestational age (+/-10 days) and birthweight (+/-200 g). Potential maternal, perinatal and neonatal risk factors were compared between the groups using statistical methods and analysed by univariate and multivariate stepwise logistic regression models. The independent risk factors found to be significantly associated with increased risk of candidaemia were duration of ventilation and presence of bacteraemia before candidaemia. Maternal steroids had a significant protective effect. The positive predictive value using these three parameters was 78.38%. Maximizing in-utero steroid treatment in high-risk pregnancies, minimizing the days of mechanical ventilation and investment of efforts in prevention of bacteraemia may help to reduce the incidence of candidaemia in the NICU.

[Changes in the biochemical parameters of lymphocyte functional activity in simian adenovirus SA7(C8)-induced carcinogenesis]. / Izmenenie nekotorykh biokhimicheskikh parametrov funktsional'noi aktivnosti limfotsitov pri kantserogeneze, indutsirovannom adenovirusom SA7(C8) obez'ian.

A functional defect of lymphocytes in hamsters with tumours during carcinogenesis induced by monkey adenovirus SA7(C8) was found and estimated by means of the blast transformation reaction. An increased activity of transport ATPases, the disturbance of cyclic nucleotide levels (cAMP, cGMP) and a decrease in both basal and Con A-activated calcium transportation were observed simultaneously with changes in the activation of immunocompetent cells under Con A influence.

[A tumor-associated antigen of cervical cancer]. / Opukholeassotsiirovannyi antigen raka sheiki matki.

The tumour-associated antigen was identified with the aid of antisera obtained from rabbits immunized with 3 M KCl extract of pool human cervical carcinoma cells. The antigen was found in 92.5% specimens of human cervical squamous cell carcinoma, in 4.7% specimens of other localization of the tumours. The antigen was absent from sets of normal human tissues. The tumour-associated antigen was not identical with CEA, alpha-fetoprotein, SP1, EPA and lactoferrin and it was localized in cytoplasm of cervical carcinoma cells.

Primary squamous cell carcinoma of the pilonidal area.

Two patients with primary squamous cell carcinoma of the pilonidal area are presented. No chronic infection or any other lesion predisposing to malignant transformation was present in either patient. Physicians and surgeons should be aware of the possibility of skin cancer appearing in this area in elderly patients. Biopsy of the lesion, leading to an early diagnosis, may prompt surgical treatment. Complete excision of the lesion is a prerequisite for cure.

The role of weightlessness in the genetic damage from preflight gamma-irradiation of organisms in experiments aboard the Salyut 6 orbital station.

The effect of weightlessness on chromosomal aberration frequency in preflight irradiated Crepis capillaris seeds, on the viability, fertility and mutation frequency in Arabidopsis thaliana, and on the frequency of nondisjunction and loss of X chromosomes in pre-flight irradiated Drosophila melanogaster gametes was studied aboard the Salyut 6 orbital station. The following effects were observed: a flight-time dependent amplification of the effects of preflight gamma-irradiation in A. thaliana with respect to all the parameters studied; unequal effects in seeds and seedlings Crepis capillaris; and a significant increase in the frequency of nondisjunction and loss of chromosomes during meiosis in Drosophila females. These observations are discussed in terms of the data of ground-based model experiments and flight experiments with a different time of exposure of objects to weightlessness. An attempt is made to elucidate the role of weightlessness in the modification of ionizing radiation effects.

Curative factors in the psychoanalyses of Holocaust survivors' offspring before and during the Gulf War.

In this paper, I have attempted to explore the curative effect of insight and relational factors in the analyses of Holocaust survivors' offspring before and during the Gulf War. A particular characteristic of children of survivors is their tendency to recreate their parents' experiences in their own life through concretization. An important analytic goal is to help these patients become aware of the unconscious meaning embedded in their acting out through increased insight, so they will be able to extricate themselves from the need to concretize and verbalize instead. The impact of the Gulf War on the children of Holocaust survivors was particularly strong. These patients reacted to the existential threat with feelings of impotence and terror, perceiving it as a repetition of the past. Thus, strengthening the ego forces became the focus of treatment during the war period, and this was facilitated by relational factors. Only near the end of the war was it possible to begin working through the regressive transferences evoked by the traumatic situation through increased insight, or to attempt to disentangle the present from the past through interpretation.

Love and the heritage of the past.

In this paper, the author explores the difficulties in developing the capacity to fall and remain in love, as shown in a case study of a Holocaust survivor's daughter whose mother lived through the Holocaust as a child. These difficulties arose from the inability of the daughter to go through the mourning processes necessary for the separation from her bereaved mother, as well as from the daughter's fixation on the mother's interminable, unresolved mourning. The daughter exploited her relationships with the love objects in her life to play the role of the victim/persecutor. She thus enacted the drama of facing death and being rescued through flight or promiscuity, elements which were dominant in her fantasies relating to her mother's past. The working through of the transference relationship helped her become aware of the unconscious meaning embedded in her actions and eventually lessened her need to live her mother's past in her own life.

Termination and the problem of analytic goals: patient and analyst, different perspectives.

The author of this paper explores the different perspectives through which patient and analyst view termination and the problem of analytic goals. These differences become clear through a case study, in which the patient offered resistance to many of the treatment goals, which did not fit her life goals and, at the same time, threatened her defences and her precarious well-being. In order to achieve the main treatment goal, that of maturity and growth (which in analysis was expressed through sub-goals like separation from her mother, understanding of her symptoms, acceptance of her feminine identity, acceptance of limitations of age and the terminability of life), the patient and the analyst had to confront an intense psychic pain connected to what they perceived as irretrievable losses. The fear of growth and growing old affected both partners of the analytic couple and had an impact on the extent to which analytic goals were met. The author explores the satisfactory aspects of termination, as well as what the analyst viewed as the incomplete results of analysis, when analysis was terminated and ten years later.

From acting out to words and meaning.

This paper presents an explanation and illustration of the behavioural phenomenon of concretization through acting out. The phenomenon refers to the realization of fantasies and psychic conflicts pertaining to the traumatic past of Holocaust survivor parents, which might have been transmitted to the next generation narratively or beyond words. I have illustrated this phenomenon by material taken from the first stages of the analysis of a young man who shot and wounded his father during the latter's attempt to save him from suicide. The analytic experience facilitated the stabilization of ego boundaries and the emergence of a more secure sense of self.

A journey to pain.

This paper explored the restoration of the capacity to feel pain and guilt as a result of the emotional experience in analysis. This was illustrated by the first part of an analysis of a woman who lost her four-month-old baby in a car accident. Analysis revealed in this case a fragmented self unable to deal with unbearable feelings of pain and guilt which threatened to annihilate it. She connected the accident to a series of events which appeared to her to be the realization of her aggressive wishes towards primary objects throughout her life. The perception of the impairment and loss of loved objects as due to her destructiveness led to the inability to differentiate self from object, the impairment in the work of mourning, and aggression turned against the self. The analyst's survival of the destructive attack without retaliation enabled the differentiation, a better adaptation to reality and the restoration of the capacity to feel pain and guilt.