Revisiting the Ramachandran plot based on statistical analysis of static and dynamic characteristics of protein structures.

Ramachandran plots, which describe protein structures by plotting the dihedral angle pairs of the backbone on a two-dimensional plane, have played an important role in structural biology over the past few decades. However, despite continued discovery of new protein structures to date, the Ramachandran plot is still constructed by only a small number of data points, and further it cannot reflect the steric information of proteins. Here, we investigated the secondary structure of proteins in terms of static and dynamic characteristics. As for static feature, the Ramachandran plot was revisited for the dataset consisting of 9,148 non-redundant high-resolution protein structures released in the protein data bank until April 1, 2022. By calculating amino acid propensities, it was found that the proportion of secondary structures with respect to residue depth is directly related to their hydrophobicity. As for dynamic feature, normal mode analysis (NMA) based on an elastic network model (ENM) was carried out for the dataset using our KOSMOS web server (http://bioengineering.skku.ac.kr/kosmos/). All ENM-based NMA results were stored in the KOSMOS database, allowing researchers to use them in various ways. In this process, it was commonly found that high B-factors appeared at the edge of the alpha helix region, which was elucidated by introducing residue depth. In addition, by investigating the change in dihedral angle, it was possible to quantitatively survey the contribution of structural change of protein on the Ramachandran plot. In conclusion, our statistical analysis of protein characteristics will provide insight into a range of protein structural studies.

The multistep process of vaginal cancer arising from deep infiltrating endometriosis: a case report.

BACKGROUND: Malignant transformation of endometriosis in extraovarian sites remains rare. Furthermore, the process is not definitely understood. CASE PRESENTATION: Herein, we report the case of a 40-year-old premenopausal nulligravida woman who presented with vaginal bleeding and who was finally diagnosed with a vaginal cancer originating from endometriosis and with a synchronous endometrial cancer. A gynecologic examination revealed a multiple polypoid mass on the posterior vaginal fornix. Magnetic Resonance Imaging of the pelvis showed two masses abutting respectively on the anterior uterine wall, and in the rectovaginal septum. The patient underwent a total laparoscopic excision of the rectovaginal mass, radical hysterectomy and low anterior resection of the rectum. The lesions were diagnosed as endometriosis, endometriosis-associated complex hyperplasia and endometrioid cancer. Furthermore, a synchronous endometrioid endometrial cancer was reported. CONCLUSIONS: This case revealed the multistep process of malignant transformation of deep infiltrating endometriosis. The progression was individualized between implantation sites and in the same organ.

Parity: a risk factor for decreased pelvic floor muscle strength and endurance in middle-aged women.

INTRODUCTION AND HYPOTHESIS: The incidence of pelvic floor muscle (PFM) dysfunction increases rapidly with menopause and aging. Despite the raised magnitude and prevalence of pelvic floor disorders in middle-aged women, the risk factors underlying PFM dysfunction still remain to be identified. PFM function can be clinically measured as the maximum strength and endurance using manometry. The aim of this study was to evaluate PFM function in terms of strength and endurance by perineometer and to assess the risk factors that decrease PFM strength and endurance in middle-aged women. METHODS: This was a cross-sectional study. Overall, 125 parous women (age 40-60 years) completed the study. A questionnaire was used to collect information on several demographic and obstetric variables. The Peritron perineometer measured PFM strength and endurance. Multiple linear regression analysis was used to evaluate the effects of sociodemographic variables on PFM function. RESULTS: Both average strength of PFMs and maximum muscle strength significantly reduced as the number of parity increased. Average and maximum strength of PFMs showed a significant difference between women with parities of two and one (ß = -0.435, p < .001; ß = -0.441, p < 0.001, respectively). Both were even more influenced in women with parity of three (ß = -0.503, p < .001; ß = -0.500, p < .001). However, PFM endurance did not decrease with increasing parity number until the parity of two; however, it decreased in women with parity of three (ß = -0.302, p < 0.05). CONCLUSION: Parity appeared to have a dominant influence on weakness of PFM, and strength was more significantly associated with parity than endurance in middle-aged women.

Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer.

OBJECTIVE: The aim of the present study was to investigate unclassified variants (UVs) in BRCA1 and 2 of Korean patients with ovarian cancer. METHODS: We retrospectively analyzed 138 patients diagnosed with ovarian/fallopian tubal/peritoneal cancer between January 2013 and January 2016, whose BRCA genetic test results and clinical characteristics were available for review. Patient peripheral blood lymphocyte specimens were assessed for BRCA mutations and variations by direct sequencing. Identified UVs were classified according to several algorithms. RESULTS: The results of genetic testing revealed 31 (22.5%, 31/138) pathogenic BRCA mutations (24 BRCA1, 7 BRCA2 mutations). The BRCA1 c.390C>A mutation was observed in 4 patients (12.9%, 4/31). Thirty-four (24.6%, 34/138) BRCA UVs were identified in 33 patients. Of these, the BRCA1 c.4883T>C and BRCA2 c.8187G>T variants were each detected in 4 patients (4/34, 11.8%). According to the used algorithms and cosegregation test, the BRCA1 c.5339T>C and BRCA2 c.8437_8439delGGA variants were both predicted to be likely pathogenic. CONCLUSIONS: The 2 identified likely pathogenic UVs require further verification with clinical evidence. Clarifying the clinical significance of UVs is an increasingly important step for cancer treatment in the current era of precision medicine.

Optimal Dose of Vaginal Misoprostol for Cervical Ripening before Hysteroscopy: A Randomized Double-Blind Study.

STUDY OBJECTIVE: To evaluate the optimal dose of vaginal misoprostol (200 and 400 µg) for cervical priming before operative hysteroscopy. DESIGN: A randomized, controlled, double-blind trial (Canadian Task Force classification I). SETTING: A university hospital. PATIENTS: Sixty-eight patients undergoing operative hysteroscopy. INTERVENTIONS: Patients were randomized to receive a low (200 µg) or high (400 µg) dose of misoprostol administered vaginally 8 hours before operative hysteroscopy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was perioperative dilatation time, and the secondary outcome measurements included the subjective difficulty of cervical dilatation assessed by the surgeon, operative time, self-reported adverse events after vaginal administration and before the start of the operation, and complications during the procedure. A comparison of the 200-µg (n = 34) and 400-µg (n = 34) misoprostol cohorts revealed similarities when comparing time with cervical dilatation, operative difficulty, result, and time. Misoprostol-related adverse events were significantly lower in the 200-µg cohort than the 400-µg cohort (58.8% vs 85.3%, p = .015). Abdominal pain was the most common adverse event and was higher in the 400-µg cohort compared with the 200-µg cohort (73.5% vs 50.0%, p = .046). However, there were no operative delays resulting from adverse events, and all individuals reported the procedure to be tolerable and recovered without medication or treatment. CONCLUSION: Both 200 µg and 400 µg vaginally administered misoprostol are effective for cervical dilatation, and we recommend vaginal administration of 200 µg misoprostol for cervical dilatation 8 hours before operative hysteroscopy because of lower adverse events in the 200-µg group as well as similar efficacy between cohorts.

Sequence variations of the EGR4 gene in Korean men with spermatogenesis impairment.

BACKGROUND: Egr4 is expressed in primary and secondary spermatocytes in adult mouse testes and has a crucial role in regulating germ cell maturation. The functional loss of Egr4 blocks spermatogenesis, significantly reducing the number of spermatozoa that are produced. In this study, we examined whether EGR4 variants are present in Korean men with impaired spermatogenesis. METHODS: A total 170 Korean men with impaired spermatogenesis and 272 normal controls were screened. The coding regions including exon-intron boundaries of EGR4 were sequenced by PCR-direct sequencing method. RESULTS: We identified eight sequence variations in the coding region and 3'-UTR regions of the EGR4 gene. Four were nonsynonymous variants (rs771189047, rs561568849, rs763487015, and rs546250227), three were synonymous variants (rs115948271, rs528939702, and rs7558708), and one variant (rs2229294) was localized in the 3'-UTR. Three nonsynonymous variants [c.65_66InsG (p. Cys23Leufs*37), c.236C > T (p. Pro79Leu), c.1294G > T (p. Val432Leu)] and one synonymous variant [c.1230G > A (p. Thr410)] were not detected in controls. To evaluate the pathogenic effects of nonsynonymous variants, we used seven prediction methods. The c.214C > A (p. Arg72Ser) and c.236C > T (p. Pro79Leu) variants were predicted as "damaging" by SIFT and SNAP2. The c.65_66insG (p. Cys23Leufs*37) variants were predicted as "disease causing" by Mutation Taster, SNPs &GO and SNAP2. The c.867C > G (p. Leu289) variants were predicted as "disease causing" only by Mutation Taster. CONCLUSION: To date, this study is the first to screen the EGR4 gene in relation to male infertility. However, our findings did not clearly explain how nonsynonymous EGR4 variations affect spermatogenesis. Therefore, further studies are required to validate the functional impact of EGR4 variations on spermatogenesis.

Sexual function and stress level of male partners of infertile couples during the fertile period.

OBJECTIVES: To evaluate the sexual function and stress level during timed intercourse (TI) of male partners of infertile couples. PATIENTS AND METHODS: The study included 236 male partners of couples with >1 year of infertility who sought medical care or an evaluation of couple infertility. Besides infertility evaluation, all men were asked to complete the five-item version of the International Index of Erectile Function (IIEF-5) for evaluation of sexual function, and stresses related to infertility and TI were measured using 10-division visual analogue scales (VAS). RESULTS: Stress levels for sexual function were higher during fertile than non-fertile periods in109 of the 236 (46.2%) male partners, with 122 (51.7%) reporting no difference in stress during fertile and non-fertile periods. The mean (sd) VAS score of sexual relationship stress was significantly higher during fertile than non-fertile periods, at 3.4 (2.6) vs 2.1 (2.2) (P < 0.001). Of the 236 men, 21 (8.9%) reported more than mild-to-moderate erectile dysfunction (ED; IIEF-5 score ≤16) and 99 (42%) reported mild ED (IIEF-5 score 17-21). CONCLUSION: Male partners of infertile couples experience significantly higher TI-related stresses during the fertile period compared with the non-fertile period. Sexual dysfunction is also common in male partners of infertile couples. Medical personnel dealing with infertile couples should be aware of these potential problems in male partners and provide appropriate counselling.

An analysis of Y-chromosome microdeletion in infertile Korean men with severe oligozoospermia or azoospermia.

PURPOSE: Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. MATERIALS AND METHODS: A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. RESULTS: In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p<0.001), higher luteinizing hormone level (9.7±4.6 IU/L vs. 6.0±2.2 IU/L, p<0.001), and lower testis volume (10.6±4.8 mL vs. 13.3±3.8 mL, p<0.001) were observed in azoospermia patients compared to severe oligozoospermia patients. CONCLUSIONS: Y-chromosome microdeletion is a common genetic cause of male infertility. Therefore, Y-chromosome microdeletion test is recommended for the accurate diagnosis of men with azoospermia or severe oligozoospermia. Appropriate genetic counseling is mandatory before the use of assisted reproduction technique in men with Y-chromosome microdeletion.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.

OBJECTIVE: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). METHODS: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. RESULTS: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. CONCLUSION: The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02139267.

Effect of male age on reproductive function: A comparison of young and middle-aged men.

PURPOSE: There have been concerns regarding potential effects of older paternal age on male reproductive function. However, currently available data on this topic are insufficient and controversy exists. We analyzed semen characteristics and reproductive hormones in young men and middle-aged men to investigate the effect of age on male reproductive function. MATERIALS AND METHODS: This study examined healthy males of reproductive age who visited a single infertility center from January 2016 to July 2021. The young group consisted of men who were less than 35 years-old, and the middle-age group consisted of men who were more than 45 years-old. RESULTS: The two groups had no significant differences in sperm concentration ([89.9±59.4]×106/mL vs. [104.4±82.1]×106/mL, p=0.108) or sperm morphology (normal forms: 3.6%±1.5% vs. 3.4%±1.6%, p=0.131). However, the middle-age group had a smaller semen volume (3.2±1.5 mL vs. 2.5±1.4 mL, p<0.001), lower sperm motility (42.3%±9.8% vs. 31.2%±12.4%, p<0.001), lower progressive sperm motility (39.2%±10.3% vs. 28.4%±12.6%, p<0.001), and a higher serum follicle-stimulating hormone level. CONCLUSIONS: Our results suggest that advanced male age might have a negative effect on fertility potential, as in women. This finding has important clinical implications because more couples are choosing to have children when they are older. Further studies on this issue, especially those that examine reproductive outcome, are warranted.

Azoospermic Men with a History of Cryptorchidism Treated by Orchiopexy Have Favorable Outcomes after Testicular Sperm Extraction: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis investigated the sperm retrieval rate (SRR) and pregnancy rate after testicular sperm extraction in men with azoospermia and those with a history of cryptorchidism treated by orchiopexy. MATERIALS AND METHODS: The SRR and clinical pregnancy rate were investigated. We performed a sub-analysis that included factors such as bilaterality, age, and idiopathic non-obstructive azoospermia (iNOA). The analysis comprised 13 studies from January 1995 to July 2021. The data sources were PubMed/MEDLINE, Embase, and the Cochrane Library included "cryptorchidism", "orchidopexy", "azoospermia", and "testicular sperm extraction". RESULTS: The overall mean SRR was 63.3% (95% confidence interval [CI], 57.6%-68.6%; I²=62.4%), and the overall mean clinical pregnancy rate was 30.1% (95% CI, 22.6%-38.8%; I²=69.9%). The meta-analysis comparing the SRR, there was no significant difference between patients with a history of bilateral and unilateral orchiopexy (relative risk [RR]=1.02; 95% CI, 0.89-1.16; p=0.79). Orchiopexy performed under the age of 10 years showed significantly increased SRR compared to the age of over 10 years (RR=1.25; 95% CI, 1.06-1.47; p=0.008). Azoospermic men with a history of cryptorchidism treated by orchiopexy had significantly higher SRR than iNOA (RR=1.90; 95% CI, 1.40-2.58; p<0.0001). CONCLUSIONS: Men with azoospermia and a history of cryptorchidism treated by orchiopexy had significantly higher SRR than those with iNOA after testicular sperm extraction. Furthermore, patients who underwent orchiopexy before the age of ten years had significantly higher SRR than patients operated at an older than the age of ten years.

Semen quality and sperm DNA fragmentation in cancer patients undergoing sperm cryopreservation.

PURPOSE: We compared semen quality and sperm DNA fragmentation in cancer patients who underwent sperm banking and controls who underwent sperm cryopreservation for assisted reproductive technology (ART). MATERIALS AND METHODS: A total of 132 men, 65 cancer patients and 67 controls, were prospectively enrolled and performed sperm cryopreservation for fertility preservation from May 2019 to February 2021. Sperm quality was determined by measuring semen volume, sperm concentration, sperm motility, and sperm DNA fragmentation index (DFI). Sperm quality and sperm DFI were compared in cancer patients and controls. RESULTS: The major cancers of the 65 cancer patients were leukemia (26.2%), testicular cancer (23.1%), and lymphoma (20.0%). Sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls. Sperm DFI was significantly higher in cancer patients than in controls (24.32%±15.69% vs. 19.11%±11.63%; p=0.033). After excluding 8 cancer patients who received chemotherapy before sperm banking, sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls, but there was no significant difference in sperm DFI for cancer patients and controls (23.14%±12.79% vs. 19.11%±11.63%; p=0.069). CONCLUSIONS: Sperm quality was lower in cancer patients than in controls. There was no difference in the sperm DFI of cancer patients prior to chemotherapy and men presenting for sperm cryopreservation for ART. We recommend that all men who are planning cancer therapy should be offered sperm banking prior to gonadotoxic chemotherapy as a standard of fertility preservation.

The relationship between interleukin-6, tumor necrosis factor-α, and fatigue in terminally ill cancer patients.

Although many cancer patients receiving palliative care experience distressing levels of fatigue, no well-designed studies have investigated contributing factors in Korean patients. We conducted a cross-sectional study using the Brief Fatigue Inventory-K (BFI-K) to measure fatigue while assessing a variety of possible correlates. Ninety patients with incurable cancer in the terminal stage (median survival: 27 days) participated in a structured interview and questionnaire related to their medical conditions and underwent blood sampling for laboratory data and cytokines, including interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Body mass index, dyspnea, the Eastern Cooperative Oncology Group performance status, and levels of albumin, blood urea nitrogen (BUN), total bilirubin, and C-reactive protein were significantly associated with fatigue. However, levels of the two proinflammatory cytokines, IL-6 and TNF-α, were not significantly correlated with the BFI-K score. In stepwise multiple linear regression, fatigue was related to elevated BUN (ß = 0.376, p = 0.002), severe pain intensity (ß = 0.349, p = 0.004), and impaired performance status (ß = 0.268, p = 0.027), but not related to levels of inflammatory cytokines. In conclusion, the diagnostic work-up and therapeutic plan for patients with cancer-related fatigue should include an evaluation of laboratory parameters, pain severity, and physical performance.

Clinical performance assessment of five human papillomavirus DNA tests using liquid-based cytology samples.

AIM: To evaluate the performance of five HPV tests (Hybrid Capture 2, Linear Array [LA], DNA chip, type-specific polymerase chain reaction [PCR], and sequencing) in detecting high-risk (HR) HPV DNA and high-grade cervical intraepithelial neoplasia (CIN) and cancer. MATERIAL AND METHODS: A total of 137 women with abnormal cytologies were prospectively enrolled. The diagnostic accuracy of five HPV DNA tests in detecting high-grade CIN and cancer was assessed, and the concordance among HPV genotyping tests was evaluated. All specimens were obtained from cervical swab samples preserved in residual PreservCyt solution that were originally collected for ThinPrep Pap test. RESULTS: The sensitivities of all five HPV tests did not differ significantly among the five HPV tests. The overall concordance level was excellent between LA and sequencing (98.2%, Kappa = 0.9) and was substantial between DNA chip and sequencing (96.4%, Kappa = 0.8). The concordance levels for detecting vaccine-type (HPV 16 and 18) of LA in comparison with DNA chip, type-specific PCR, and sequencing were substantial (Kappa = 0.67, 0.64, and 0.65, respectively). The sensitivities for all five HPV tests were >90% for the detection of CIN2 or higher. No statistically significant differences in sensitivity occurred between any of the tests. CONCLUSION: All five HPV tests showed reliable results in detecting HR HPVs, high-grade CIN, and cancer. Both LA and DNA chip tests may be useful in identifying HR HPV, especially when multiple genotypes are present.

The Association Between the Number of Retrieved Pelvic Lymph Nodes and Ipsilateral Lower Limb Lymphedema in Patients With Gynecologic Cancer.

PURPOSE: While the risk of lower limb lymphedema (LLE) after radical surgery for gynecologic malignancies is multifactorial, the limited assessment of lymph nodes (LNs), such as sentinel LN biopsy, has been incorporated into a standard procedure. We assessed the relationship between the number of LNs retrieved from the hemipelvis and the incidence of ipsilateral LLE (iLLE). METHODS: This retrospective study included 103 women with gynecologic cancer who had LNs removed with minimally invasive surgery between January 2014 and December 2018. For early detection of LLE, the patients were followed up by a lymphedema specialist who complied with the International Society of Lymphedema criteria. Potential risk factors for LLE were collected, and the risk factors were further investigated according to the number of LNs removed in a side-specific manner. RESULTS: LLE was diagnosed in 32 (31.1%) patients, and most of them were diagnosed with unilateral (n = 22) LLE rather than bilateral (n = 10). The number of pelvic LNs removed (p = 0.018), no lymphatic mapping (p = 0.034), and radiation (p = 0.020) were associated with the development of one or both LLEs. A side-specific analysis revealed that the incidence of iLLE increased significantly when four or more LNs were removed from the hemipelvis compared with three or fewer LNs (22.9% vs. 8.3%, p = 0.048). CONCLUSIONS: The number of pelvic LNs retrieved was associated with the incidence of LLE in patients with early gynecologic cancer. We identified the cutoff number per hemipelvis through side-specific analysis that could minimize the risk of iLLE. Further studies are needed to validate our results.

Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers.

PURPOSE: This study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status. MATERIALS AND METHODS: We conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated. RESULTS: Among 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129-8.144; p=0.028). CONCLUSION: The frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type.

Primary hepatoid adenocarcinoma of the endometrium with a high alphafetoprotein level.

Primary hepatoid adenocarcinoma of the endometrium is a rare tumour that is similar to hepatocellular carcinoma histologically. Here, a patient with primary hepatoid carcinoma of the endometrium with a high alphafetoprotein (AFP) level (90,508 ng/mL) is presented in a 75-year-old woman. The pelvic computed tomography and magnetic resonance imaging suggested a submucosal leiomyoma with degeneration or endometrial hyperplasia. However, the endometrial biopsy revealed a primary hepatoid carcinoma of the endometrium. The patient underwent a staging laparotomy including a total abdominal hysterectomy, bilateral salpingo-oophorectomy and lymph node sampling with pelvic cytology. The AFP level can be highly elevated in hepatoid carcinoma of the endometrium.

Update on genetic screening and treatment for infertile men with genetic disorders in the era of assisted reproductive technology.

A genetic etiology of male infertility is identified in fewer than 25% of infertile men, while 30% of infertile men lack a clear etiology, resulting in a diagnosis of idiopathic male infertility. Advances in reproductive genetics have provided insights into the mechanisms of male infertility, and a characterization of the genetic basis of male infertility may have broad implications for understanding the causes of infertility and determining the prognosis, optimal treatment, and management of couples. In a substantial proportion of patients with azoospermia, known genetic factors contribute to male infertility. Additionally, the number of identified genetic anomalies in other etiologies of male infertility is growing through advances in whole-genome amplification and next-generation sequencing. In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic diseases, and discuss the treatment of couples with genetic infertility by microdissection-testicular sperm extraction, personalized hormone therapy, and in vitro fertilization with pre-implantation genetic testing.