A Review of Recent Studies on the Effects of SARS-CoV-2 Infection and SARS-CoV-2 Vaccines on Male Reproductive Health.

According to world statistics, men are more susceptible to the coronavirus disease 2019 (COVID-19) than are women. Considering the interconnection between infections and male infertility, investigation of the potential impact of COVID-19 on men's reproductive health is now a particularly relevant topic. Published data indicate decreased sperm quality and orchitis development in patients with COVID-19, including reduced sperm count, decreased sperm motility, and elevated DNA fragmentation index. Although mass vaccination against COVID-19 is currently being carried out worldwide using available authorized vaccines, the effect of these vaccines on men's reproductive health has not yet been investigated. There is currently no evidence that SARS-CoV-2 can be transmitted in semen, but available data suggest that it can infect spermatogonia, spermatids, Leydig cells, and Sertoli cells. Therefore, SARS-CoV-2 orchitis and reduced male fertility may be long-term complications of COVID-19, which requires further investigation. Currently, there is also no evidence that vaccines against SARS-CoV-2 have any pathological effects on spermatogenesis or male reproductive health. Thus, further studies are needed to determine the effects of COVID-19 and COVID-19 vaccines on men's reproductive health, which will help to optimize the management and rehabilitation of these patients. This review aims to discuss recent studies on the impact of the COVID-19 and COVID-19 vaccines on men's reproductive health. The article addresses various issues such as the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on testosterone biosynthesis, semen parameters, testicular tissue, and epididymis.

Gene Expression Signature of Endometrial Samples from Women with and without Endometriosis.

STUDY OBJECTIVE: To develop a prototype of a complex gene expression biomarker for the diagnosis of endometriosis on the basis of differences between the molecular signatures of the endometrium from women with and without endometriosis. DESIGN: Prospective observational cohort study. Evidence obtained from a well-designed, controlled trial without randomization. SETTING: Department of reproductive medicine and surgery, A.I. Evdokimov Moscow State University of Medicine and Dentistry. PATIENTS: A total of 33 women (aged 32-38 years) were included in this study. Patients with and without endometriosis were divided into 2 separate groups. The group composed of patients with endometriosis included 19 living patients with endometriosis who underwent laparoscopic excision of endometriosis. The control group included 6 living patients who underwent laparoscopic excision of incompetent uterine scar after cesarean section, with both surgically and histologically confirmed absence of endometriosis and adenomyosis. An additional control/verification group included various previously RNA-sequencing-profiled tissue samples (endocervix, ovarian surface epithelium) of 8 randomly selected healthy female cadaveric donors aged 32 to 38 years. The exclusion criteria for all patients were hormone therapy and any intrauterine device use for more than 1 year preceding surgery, as well as absence of other diseases of the uterus, fallopian tubes, and ovaries. INTERVENTIONS: Laparoscopic excision of endometriotic foci and hysteroscopy with endometrial sampling were performed. The cadaveric tissue samples included endocervix and ovarian surface epithelium. Endometrial sampling was obtained from the women in the control group. RNA sequencing was performed using Illumina HiSeq 3000 equipment (Illumina, Inc., San Diego, CA) for single-end sequencing. Unique bioinformatics algorithms were developed and validated using experimental and public gene expression datasets. MEASUREMENTS AND MAIN RESULTS: We generated a characteristic signature of 5 genes downregulated in the endometrium and endometriotic tissue of the patients with endometriosis, selected after comparison with the endometrium of the women without endometriosis. This gene signature showed a capacity for nearly perfect separation of all 52 analyzed tissue samples of the patients with endometriosis (endometrial as well as endometriotic samples) from the 14 tissue samples of both living and cadaveric donors without endometriosis (area under the curve = 0.982, Matthews correlation coefficient = 0.832). CONCLUSION: The gene signature of the endometrium identified in this study may potentially serve as a nonsurgical diagnostic method for endometriosis detection. Our data also suggest that the statistical method of 5-fold cross-validation of differential gene expression analysis can be used to generate robust gene signatures using real-world clinical data.

Direct Mass Spectrometry Differentiation of Ectopic and Eutopic Endometrium in Patients with Endometriosis.

STUDY OBJECTIVE: To introduce a method for the rapid assessment of endometriotic tissues using direct mass spectrometry (MS)-based lipidomics. DESIGN: A prospective observational cohort study (Canadian Task Force classification II2). SETTING: Department of Operative Gynecology of the Research Centre for Obstetrics, Gynecology and Perinatology. PATIENTS: Fifty patients with ovarian cysts and peritoneal endometriosis who underwent laparoscopic surgery between 2014 and 2016. INTERVENTION: Differences in mass spectrometric profiles of ectopic endometria (endometriosis) and eutopic endometria were analyzed for each patient in combination with morphohistologic evaluation. The lipidomic approach was applied using a direct high-resolution MS method. MEASUREMENTS AND MAIN RESULTS: Of 148 metabolites, 15 showed significant differences between endometriotic tissue and a healthy endometrium of the same patient, considered as a control in this study. The main lipids prevalent in endometriotic tissues were phosphoethanolamine (PE O-20:0), sphingomyelin (SM 34:1), diglycerides (DG 44:9), phosphatidylcholines (PC 32:1, PC O-36:3, PC 38:7, PC 38:6, PC 40:8, PC 40:7, PC 40:6, PC 40:9, and PC O-42:1), and triglycerides (TG 41:2, TG 49:4, and TG 52:3). Using partial least squares discriminant analysis models, MS showed that the lipidomic profile of endometriotic tissue (peritoneal endometriosis and ovarian endometriomas) was clearly separated from the eutopic endometrium, indicating tissue-type differentiation. CONCLUSION: Our results suggest that direct MS may play an important role for endometriotic tissue identification. Such an approach has potential usefulness for real-time tissue determination and differentiation during surgical treatment. Lipids of 3 important classes, sphingolipids, phospholipids, and the fatty acids (di- and triglycerides), were identified. Validation is required to determine whether these lipids can be used to discriminate between patients with endometriosis and those with other gynecologic diseases.

The 10 "Cardinal Sins" in the Clinical Diagnosis and Treatment of Endometriosis: A Bayesian Approach.

Evidence-based data for endometriosis management are limited. Experiments are excluded without adequate animal models. Data are limited to symptomatic women and occasional observations. Hormonal medical therapy cannot be blinded if recognised by the patient. Randomised controlled trials are not realistic for surgery, since endometriosis is a variable disease with low numbers. Each diagnosis and treatment is an experiment with an outcome, and experience is the means by which Bayesian updating, according to the past, takes place. If the experiences of many are similar, this holds more value than an opinion. The combined experience of a group of endometriosis surgeons was used to discuss problems in managing endometriosis. Considering endometriosis as several genetically/epigenetically different diseases is important for medical therapy. Imaging cannot exclude endometriosis, and diagnostic accuracy is limited for superficial lesions, deep lesions, and cystic corpora lutea. Surgery should not be avoided for emotional reasons. Shifting infertility treatment to IVF without considering fertility surgery is questionable. The concept of complete excision should be reconsidered. Surgeons should introduce quality control, and teaching should move to explain why this occurs. The perception of information has a personal bias. These are the major problems involved in managing endometriosis, as identified by the combined experience of the authors, who are endometriosis surgeons.

COVID-19-associated inhibition of energy accumulation pathways in human semen samples.

OBJECTIVE: To investigate transcriptional alterations in human semen samples associated with COVID-19 infection. DESIGN: Retrospective observational cohort study. SETTING: City hospital. PATIENTS: Ten patients who had recovered from mild COVID-19 infection. Eight of these patients had different sperm abnormalities that were diagnosed before infection. The control group consisted of 5 healthy donors without known abnormalities and no history of COVID-19 infection. INTERVENTIONS: We used RNA sequencing to determine gene expression profiles in all studied biosamples. Original standard bioinformatic instruments were used to analyze activation of intracellular molecular pathways. MAIN OUTCOME MEASURES: Routine semen analysis, gene expression levels, and molecular pathway activation levels in semen samples. RESULTS: We found statistically significant inhibition of genes associated with energy production pathways in the mitochondria, including genes involved in the electron transfer chain and genes involved in toll-like receptor signaling. All protein-coding genes encoded by the mitochondrial genome were significantly down-regulated in semen samples collected from patients after recovery from COVID-19. CONCLUSIONS: Our results may provide a molecular basis for the previously observed phenomenon of decreased sperm motility associated with COVID-19 infection. Moreover, the data will be beneficial for the optimization of preconception care for men who have recently recovered from COVID-19 infection.

Risk of mesh extrusion and other mesh-related complications after laparoscopic sacral colpopexy with or without concurrent laparoscopic-assisted vaginal hysterectomy: experience of 402 patients.

STUDY OBJECTIVE: To estimate the incidence of mesh-related complications including mesh erosion/extrusion rates in patients undergoing laparoscopic sacral colpopexy, with or without concurrent hysterectomy, using macroporous soft polypropylene mesh. DESIGN: Historical cohort study (Canadian Task Force classification II-2). SETTING: Private urogynecology clinic. PATIENTS: A total of 446 consecutive patients with uterovaginal or vaginal vault prolapse underwent laparoscopic sacral colpopexy with use of macroporous soft polypropylene mesh from January 2003 through January 2007. In all, 402 consecutive patients met enrollment criteria. Two groups of patients were identified: (1) those receiving concurrent hysterectomy (n = 130); and (2) those with a history of hysterectomy (n = 272). INTERVENTIONS: Patients were treated with laparoscopic sacral colpopexy with use of macroporous soft polypropylene mesh in conjunction with other laparoscopic and/or vaginal procedures. MEASUREMENTS AND MAIN RESULTS: Data were collected in the form of chart reviews and patient questionnaires. Comparisons were made between groups 1 and 2. Patient demographics, history, mesh erosion/extrusion rates, and mesh-related complications were analyzed. Length of follow-up was 1 to 54 months with a median follow-up time of 12 months. No statistically significant differences existed between 2 groups in rates of mesh erosion/extrusion or other mesh-related complications. Overall vaginal mesh erosion/extrusion rate was 1.2% (95% CI 0.5%-2.7%) with an associated mesh revision rate of 1.2% (95% CI 0.5%-2.7%). Patients with concurrent hysterectomy had an erosion/extrusion rate of 2.3% (3/130) as compared with 0.7% (2/272) in patients with a history of hysterectomy, p = .18. No cases of mesh erosion through organs and tissues other than vaginal mucosa were observed. Cuff abscess occurred in 1 patient with concurrent hysterectomy, with an overall infection rate of 0.3% (95% CI 0.01%-1.2%). One more patient developed an inflammatory reaction to the mesh. Excision of exposed mesh was performed in all 5 patients with mesh extrusion. Vaginal approach to excision was uniformly used. Laparoscopic removal of the entire mesh took place in 4 patients with persistent pelvic pain, in 1 patient with cuff abscess, and in one patient with a questionable mesh reaction. An estimated 975 to 17 000 patients were required in each group to achieve power to detect a statistically significant difference in rate of mesh-related complications in this study. CONCLUSION: Risk of mesh extrusion or other mesh-related complications after laparoscopic sacral colpopexy using soft macroporous Y-shaped polypropylene mesh is about 1% in our study. No significant increase in risk of mesh-related complications was observed in patients receiving concurrent hysterectomy when compared with patients who had a previous hysterectomy. The sample size of almost 2000 patients was needed to detect a statistically significant difference in rate of mesh-extrusion in this study.

Comparative analysis of 5-mm trocars: dilating tip versus non-shielded bladed.

STUDY OBJECTIVE: To examine whether there are statistically significant differences in multiple variables evaluated at different times in the course of surgery and postoperative period when using 5-mm dilating-tip trocars (DTTs) and 5-mm non-shielded-bladed trocars (NSBTs) at randomly selected right or left lateral entry sites on the same patient. DESIGN: Randomized, single-blinded, controlled trial (Canadian Task Force classification I). SETTING: Center for Women's Care and Reproductive Surgery (CWCRS), Atlanta, Georgia. PATIENTS: Ninety-four women, median age 45, undergoing laparoscopic surgery at CWCRS for benign gynecologic conditions were randomly assigned to placement of a DTT to the right or left laparoscopic entry site. The NSBT was placed on the contralateral side of the same patient. INTERVENTION: Each patient had 2 lateral trocars placed, 1 of which was a DTT and the other of which was an NSBT. MEASUREMENTS AND MAIN RESULTS: Comparisons between the sites accessed with the DTT and the NSBT were made by the surgeons at the time of surgery and at the 2-week follow-up, by nurses at 1 and 4 hours after surgery, and by patients at the 2-week follow-up. The nurses and the patients were blinded as to the side of each trocar placement. A visual analog score of 1 to 5 was used for the assessment of 17 studied variables. Questionnaires were standardized and explained to examiners. Wilcoxon's signed-rank test was used for the analysis of time-specific data collected by the same examiner (evaluation by the nurses at 1 and 4 hours after surgery). Friedman's test was applied for analysis of the remaining data. Statistically significant differences were established in ease of placement (chi(2) = 4.691, p = .030) and displacement rate (chi(2) = 7.264, p = .007), in which the NSBT obtained the better results. No statistically significant differences were found in bleeding at the time of placement or removal of the trocars, hematoma/bruising formation, pain, or cosmetic results as assessed by surgeons, nurses, and patients at corresponding stages of intra- and postoperative care. CONCLUSIONS: When used for lateral laparoscopic access in gynecologic surgery, NSBTs were easier to place and had a smaller rate of displacement than DTTs. Despite substantial differences in the design of the trocars, no statistically significant differences in bleeding risk, hematoma/bruising formation, pain, or cosmetic results were established. Individual goals of the surgery and conditions specific to each patient appear to be the best criteria for selection of 1 or the other trocar.