Immune Responses of Healthy Pregnant Women following an Elective Cesarean Section: Effects of Anesthetic Procedures.

A weakened immune system and more inflammatory cytokines being released are possible effects of the surgical stress that a cesarean section induces. This kind of reaction, in addition to the altered reaction to catecholamines, has the potential to significantly affect the immune system of the mother and the patients' general postoperative course. This prospective study compared the plasma levels of catecholamines and cytokines in healthy pregnant patients having cesarean sections under spinal anesthesia versus general anesthesia. A total of 30 pregnant women undergoing elective cesarean sections were divided into two groups: 15 who received general anesthesia (GA) and 15 who received spinal anesthesia (SA). Blood samples were collected from all subjects before anesthesia induction (pre-OP), 6 h postoperatively (6 h post-OP), and 12 h (12 h post-OP), to measure levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-8, IL-4, IL-10, norepinephrine (NE), and epinephrine (EPI). When we compared the two groups, we discovered that only IL-6 and IL-4 had significantly higher levels pre-OP, whereas all studied cytokines exhibited an increase in the GA versus SA group at 6 and 12 h post-OP. In the case of catecholamines, we discovered that serum levels are positively related with pro-inflammatory or anti-inflammatory cytokines, depending on the time of day and type of anesthetic drugs. Compared to SA, GA has a more consistent effect on the inflammatory response and catecholamine levels. The findings of this study confirm that the type of anesthesia can alter postoperative immunomodulation to various degrees via changes in cytokine and catecholamine production. SA could be a preferable choice for cesarean section because it is an anesthetic method that reduces perioperative stress and allows for less opioid administration, impacting cytokine production with proper immunomodulation.

A Prospective Study on the Progression, Recurrence, and Regression of Cervical Lesions: Assessing Various Screening Approaches.

(1) Background: The prediction of cervical lesion evolution is a challenge for clinicians. This prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors in the prediction of progression, regression, or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions who underwent follow-up in a private clinic. We calculated the predictive performance of individual tests (cervical cytology, HPV genotyping, CINtecPlus results, and clinical risk factors) or their combination in the prediction of cervical lesion progression, regression, and persistence; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model comprising a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least three clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesion regression or persistence was modest when using individual or combined tests; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Clinical Characteristics and Local Histopathological Modulators of Endometriosis and Its Progression.

Endometriosis (E) and adenomyosis (A) are associated with a wide spectrum of symptoms and may present various histopathological transformations, such as the presence of hyperplasia, atypia, and malignant transformation occurring under the influence of local inflammatory, vascular and hormonal factors and by the alteration of tumor suppressor proteins and the inhibition of cell apoptosis, with an increased degree of lesion proliferation. MATERIAL AND METHODS: This retrospective study included 243 patients from whom tissue with E/A or normal control uterine tissue was harvested and stained by histochemical and classical immunohistochemical staining. We assessed the symptomatology of the patients, the structure of the ectopic epithelium and the presence of neovascularization, hormone receptors, inflammatory cells and oncoproteins involved in lesion development. Atypical areas were analyzed using multiple immunolabeling techniques. RESULTS: The cytokeratin (CK) CK7+/CK20- expression profile was present in E foci and differentiated them from digestive metastases. The neovascularization marker cluster of differentiation (CD) 34+ was increased, especially in areas with malignant transformation of E or A foci. T:CD3+ lymphocytes, B:CD20+ lymphocytes, CD68+ macrophages and tryptase+ mast cells were abundant, especially in cases associated with malignant transformation, being markers of the proinflammatory microenvironment. In addition, we found a significantly increased cell division index (Ki67+), with transformation and inactivation of tumor suppressor genes p53, B-cell lymphoma 2 (BCL-2) and Phosphatase and tensin homolog (PTEN) in areas with E/A-transformed malignancy. CONCLUSIONS: Proinflammatory/vascular/hormonal changes trigger E/A progression and the onset of cellular atypia and malignant transformation, exacerbating symptoms, especially local pain and vaginal bleeding. These triggers may represent future therapeutic targets.

Longitudinal 8-Epi-Prostaglandin F2-Alpha and Angiogenic Profile Mediator Evaluation during Pregnancy in Women with Suspected or Confirmed Pre-eclampsia.

Background: In this exploratory study, we aimed to evaluate the dynamics of angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), soluble Endoglin (sEng), and sFlt-1/PlGF, PlGF/sFlt-1, and sEng/PlGF ratios] and oxidative stress [8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and 8-epi-PGF2α/PlGF ratio] mediator levels in women with suspected or confirmed pre-eclampsia (PE) at least two times during pregnancy. We also wanted to identify the possible correlations between 8-epi-PGF2α and angiogenic mediator levels at the time of inclusion of pregnant women. Methods: We included 40 pregnant women with suspected or confirmed PE, with a mean age of 29 years (range between 18 and 41 years) and gestational age between 18 and 28 weeks at inclusion in this study. The Enzyme-Linked Immunosorbent Assay (ELISA) method to measure the levels of serum angiogenic and oxidative stress mediators was used. Results: The evaluation of baseline sFlt-1/PlGF ratios using a cut-off of 38 suggested that 25 pregnant women had a sFlt-1/PlGF ratio of >38 (sFlt-1/PlGF ratio of >38 group) and 15 had a sFlt-1/PlGF ratio of ≤38 (sFlt-1/PlGF ratio of ≤38 group). The increases in sFlt-1/PlGF ratio in the sFlt-1/PlGF ratio of >38 group were caused by both an increase in sFlt-1 (2.04-fold) and a decrease in PlGF levels (2.55-fold). The 8-epi-PGF2α median levels were higher in the sFlt-1/PlGF ratio of >38 group (1.62-fold). During follow-up after pregnancy, we observed that the mean values of sFlt-1 and sEng and the median values of 8-epi-PGF2α and sFlt-1/PlGF, sEng/PlGF, and 8-epi-PGF2α/PlGF ratios increased directly proportional to gestational age for each measurement time until delivery in both groups. For five women who had a sFlt-1/PlGF ratio ≤38 at inclusion, sFlt-1/PlGF ratio was observed to increase to >38 later in pregnancy. We observed that, in the sFlt-1/PlGF ratio >38 group, baseline 8-epi-PGF2α levels better correlated with angiogenic mediator levels. Conclusions: Our study shows that 33.33% of pregnant women evaluated for suspected or confirmed PE with a sFlt-1/PlGF ratio of ≤38 displayed a rise in sFlt-1/PlGF ratio in subsequent weeks. In addition, together with angiogenic mediators, 8-epi-PGF2 α can be utilized as an independent predictor factor to help clinicians identify or predict which pregnant women will develop PE.

Association between Serum 8-Iso-Prostaglandin F2α as an Oxidative Stress Marker and Immunological Markers in a Cohort of Preeclampsia Patients.

BACKGROUND: We aimed to analyze the presence and clinical use of serum 8-iso-prostaglandin F2-alpha (8-iso-PGF2α) as an oxidative stress marker and some inflammatory status biomarkers (tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-10, high-sensitivity C-reactive protein (hs-CRP), and pentraxin-3 (PTX3)) for patients with preeclampsia (PE). METHODS: Sixty pregnant women, including thirty diagnosed with PE and thirty who were healthy (NP), were included in this study. For the assessment of serum levels of biomarkers, we used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. RESULTS: Our preliminary study showed that the expression level of serum 8-iso-PGF2α in the PE group was higher than in the PE after delivery (PE-AD) group (742.00 vs. 324.00 pg/mL, p < 0.0001). Groups of preeclamptic patients (PE + PE-AD) expressed significantly elevated levels for all of the assessed inflammatory mediators as compared to NP. Significant strong positive correlations with 8-iso-PGF2α levels were found for systolic blood pressure (SBP), and TNF-α (Spearman's rho = 0.622, p-value = 0.020 and rho = 0.645, p-value = 0.002, respectively). Our study demonstrates that 8-iso-PGF2α and PTX3 have the greatest diagnostic value for pregnant women with PE. CONCLUSIONS: 8-iso-PGF2α and PTX3 can be used as independent predictor factors, along with already-known cytokines, that could represent a prophylactic way to help clinicians identify or predict which pregnant women will develop PE.

Conservative treatment of borderline ovarian tumors: a retrospective study.

Borderline ovarian tumors (BOTs) are a group of tumors with histological aspects and intermediate biological evolution between benign and malignant tumors, characterized by epithelial proliferation, lack of stromal invasion and nuclear atypia. BOTs account for approximately 10-15% of epithelial ovarian carcinomas. The interest in fertility preservation is very important as most BOTs are diagnosed in patients less than 40 years of age. Since borderline tumors occur in young, fertile women, the therapeutic approach depends on both staging and the need to preserve ovarian function and fertility. Treatment of BOT is primarily surgical, but recently fertility-preserving surgery has become more important. If infertility persists, ovarian induction or in vitro fertilization (IVF) may be suggested in selected cases.

A Retrospective Narrative Mini-Review Regarding the Seminal Microbiota in Infertile Male.

Background: Infertility is a global burden that affects both sexes with the male component remaining as an explored yet crucial research field that might offer novel evidence. Material and Methods: The present narrative mini-review aims to summarize all existing literature regarding the composition of the seminal microflora in infertile men. We performed searches in PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect between 2018 and 2022 using a combination of keywords. Results: A total of n = 33 studies met the eligibility criteria and were further considered. From this, n = 14 were conducted on human patients, n = 3 on zebrafish (Danio rerio), n = 5 on rats, and n = 11 on mice. In twenty-five out of thirty-three papers, the authors sequenced the 16S rRNA; situations occurred where researchers focused on standard laboratory protocols. Lactobacillus and Bifidobacterium are widely recognized as putative beneficial lactic bacteria. These two entities are capable of restoring the host's eubiosis to some extent, blocking pathogens' proliferation and endotoxins, and even alleviating specific patterns encountered in disease(s) (e.g., obesity, type 1 diabetes) due to prolonged exposure to toxicants in adults or from a developmental stage. Over the years, distinct approaches have been perfected, such as the transfer of feces between two species or conventional rudimentary products with proven efficiency. Conclusions: The seminal microflora is decisive and able to modulate psychological and physiological responses. Each individual possesses a personalized microbial profile further shaped by exogenous factors, regardless of sex and species.

Impact of COVID-19 on fertility and assisted reproductive technology (ART): a systematic review.

The appearance of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major obstacle for the performing of current medical activities throughout the world. COVID-19 has affected humanity in many ways, thus causing a great medical, social, economic, and political instability. The aim of this study was to make an analysis of the scientific data obtained by so far to highlight the impact that COVID-19 has had on fertility and assisted reproductive technology (ART). Infection with SARS-CoV-2 alters the normal immune response by local and systemic damage to tissues and organs. After the virus enters the body, the first lesions are produced in the respiratory tract. Extrapulmonary lesions specific to COVID-19 include acute renal lesions/acute kidney damage, hepatocellular lesions, neurological diseases, myocardial dysfunction and arrhythmia, gastrointestinal diseases but also genital impairment. The possible impairment of the male reproductive system is because angiotensin-converting enzyme 2 (ACE2) receptors are in an increased number in the testes, seminiferous duct cells, spermatogonia, Leydig cells and Sertoli cells. Many published studies to date have pointed out that COVID-19 could also affect female fertility and disrupt the functions of the female reproductive system. The theory that this virus can also be transmitted sexually and can cause infertility or testicular damage is supported by the fact that the virus can be isolated in the semen of COVID-19 patients but only during the disease. Choosing the best method of treating infertility during the COVID-19 pandemic is multifactorial, but the risk of infection and compliance with specific ART hygiene protocols must always be considered. Currently, there is no scientific basis regarding the fact that the COVID-19 vaccination would influence fertility.

Morphological and ultrasound findings in multiple pregnancy placentation.

The incidence of multiple pregnancy has significantly increased over the past decades, reaching different statistics to double, triple, or even overcome these numerical orders globally. Zygosity and chorionicity are the key elements in the multiple pregnancy but the placentation issue should be correlated primarily with zygosity, unlike chorionicity that should be correlated with the outcome and complications of multifetal gestation. Multiple pregnancy is by itself a special maternal-fetal condition, and the monochorionic one, moreover, due to specific complications. These aspects make early assessment of chorionicity and amnionicity a priority. Ultrasound is essential in pregnancy but pathological placental examination after delivery is complementary, in order to have a complete overview of potential mechanisms and pathogenesis affecting twin gestation. In this review, we highlight both ultrasound aspects specific to multifetal placentation, complemented by macro and microscopic morphological aspects, which underpin the obstetric imaging.

Delayed interval delivery in twin pregnancy - case reports.

The implementation of assisted reproduction has increased the incidence of multiple pregnancies. Prenatal death of one fetus in the second trimester of twin pregnancy confronts the obstetrician with a difficult problem with regard to the management of pregnancy. The scarcity of the condition and the absence of the large-scale studies make it difficult to advise the parents on the prognosis and optimal management. The unavoidable birth or death of one premature neonate has led to the aim of delayed interval delivery for the other twin. We present in this report two cases of twin pregnancies with delayed-interval delivery and favorable outcomes for the surviving twins. The twin pregnancies conceived by in vitro fertilization (IVF) in HitMed Medical Center, Craiova, Romania. In the first case, one fetus dismiss in utero at 20 weeks of gestation. The second fetus was successfully delivered by Caesarean section, at 36 weeks. In the second case, the first fetus was delivered at 22 weeks. To save the surviving fetus, ligation of the umbilical cord at the cervical level was performed. The second fetus was delivered at 31 weeks by Caesarean section, in good conditions. We describe our management of the cases and the deliveries and the neonatal outcomes. In multiple gestation, prolongation of pregnancy after preterm dismiss in utero or even after delivery of one fetus is feasible in a closely monitored environment.

Pregnancy resulting from IMSI after testicular biopsy in a patient with obstructive azoospermia.

In this article, we report a case of pregnancy obtained in an infertile couple diagnosed with severe male factor infertility. The couple attended for fertility examination reporting a history of 10 years of infertility. The cause of infertility was obstructive azoospermia. The treatment consists of in vitro fertilization (IVF). The ovarian stimulation of female patient was done with antagonist protocol and after ovarian puncture was obtained nine oocytes. The urologist performed testicular sperm extraction (TESE). There were selected nine sperm cells by intra-cytoplasmic morphologically selected sperm injection (IMSI). For this purpose, we used an inverted microscope with high magnification equipped with ×60 air objectives with modulation contrast illumination. After intracytoplasmic sperm injection (ICSI) of sperm into the oocytes there were obtained six normal embryos from which three embryos were transferred into the uterus. A singleton pregnancy was achieved which was completed with birth of a healthy baby in time. This successful outcome shows that use of IMSI and ICSI procedures are really useful in selection of best spermatozoa obtained by TESE in treatment of obstructive azoospermia.

Borderline Brenner tumors associated with ovarian cyst - case presentation.

Borderline Brenner tumors represent quite a rare entity of ovarian tumors (about 2%) that develop from the surface ovarian epithelium. They are formed from papillary structures made of fibrovascular conjunctive axes covered by a transition epithelium, similar to the urinary bladder epithelium. According to the WHO classification, Brenner tumors present the following forms: benign, borderline and malignant. The benign ones are the most frequent, representing about 95%, the borderline represent about 5%, and the malignant ones less than 1%. We present the case of a 64-year patient who was diagnosed with right ovary cyst. The histopathological examination highlighted the presence of a borderline Brenner tumor at the same time with the cystic lesion, on the same ovary. The surgical treatment led to a complete cure of the patient, so that the yearly ultrasound reexamination did not trace the presence of any tumoral relapse.

Diagnosis problems in a case of ovarian tumor - case presentation.

Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.