Birutė Žilaitienė

Background/Objectives: To evaluate the diagnostic yield of phenotype-guided cytogenetic and targeted molecular genetic testing in patients referred for infertility and reproductive disorders within a tertiary medical genetics referral pathway. Methods: This retrospective study included 900 consecutive patients (473 males, 427 females) referred to a tertiary medical genetics center between January 2020 and December 2024. Conventional karyotyping was performed in all patients. Additional targeted molecular tests were applied based on clinical indication: Y chromosome microdeletion analysis in azoospermia or oligospermia, CFTR sequencing in suspected congenital bilateral absence of the vas deferens, and F2/F5 genotyping in recurrent pregnancy loss (RPL). Diagnostic yield was analyzed in a predefined subgroup of 566 patients with RPL, unexplained infertility, azoospermia, or oligospermia; remaining referrals were included in descriptive cytogenetic analyses only. Results: Chromosomal abnormalities were identified in 3.22% (29/900) of the total cohort and in 5.12% (29/566) of the diagnostic-yield cohort. Targeted testing yields were 3.75% (6/160) for Y chromosome microdeletions, 9.38% (3/32) for CFTR variants, and 3.31% (4/121) for F2/F5 variants. Diagnostic yield varied markedly by phenotype, being highest in azoospermia (33.3%), followed by oligospermia (6.6%), RPL (5.3%), and unexplained infertility (3.1%). In unexplained infertility, all chromosomal abnormalities were detected in female patients. Conclusions: In a tertiary referral setting, phenotype-guided genetic testing provides the greatest diagnostic value in well-defined infertility phenotypes, particularly azoospermia. Lower yields in other referral groups support a targeted, indication-based approach to genetic evaluation and highlight the need for advanced genomic strategies in persistently unexplained cases.

Background/Objectives: Erectile dysfunction (ED) is a common sexual disorder in men, frequently linked to endothelial dysfunction affecting penile vasculature. Accumulating evidence suggests that vitamin D (VD) status may influence endothelial function and, consequently, erectile function. VD deficiency has also been associated with cardiovascular risk factors, which are well-known contributors to ED. Methods: A systematic review following PRISMA guidelines was conducted, analyzing studies from PubMed and Cochrane databases published between 2010 and 2025. Randomized controlled trials, observational studies, and pilot clinical trials examining the relationship between VD levels and ED in the general male population were included. Results: Out of 1335 identified articles, 10 studies met inclusion criteria, encompassing over 13,000 men. Observational studies consistently showed that men with moderate-to-severe or arteriogenic ED had significantly lower serum VD levels and poorer erectile function scores compared to those with mild ED. VD deficiency was independently associated with higher ED prevalence, irrespective of lifestyle, cardiovascular risk, or sex hormone levels. Although several observational studies suggested a potential optimal vitamin D threshold, definitive recommendations cannot be established due to the heterogeneity of available evidence and conflicting findings from randomized controlled trials. The latter demonstrated inconsistent effects of vitamin D supplementation on erectile dysfunction outcomes, with the largest trial reporting no significant reduction in disease prevalence. These findings underscore the critical need for rigorously designed trials targeting populations with severe VD deficiency and arteriogenic ED. Conclusions: This systematic review highlights an association between vitamin D status and erectile dysfunction, particularly in men with moderate-to-severe or arteriogenic ED. However, most of the evidence is derived from low-certainty observational studies. While observational data suggest potential benefits of adequate VD levels for sexual health, well-designed randomized controlled trials are essential to delineate causal relationships and potential for therapeutic efficacy.

Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women with thyroid disorders and examined its associations with thyroid function, age, menopausal status, and body mass index (BMI). Methods: A population-based survey was conducted in Kaunas, Lithuania, within the WHO MONICA framework. A random sample of 1569 women aged 25–69 years was included in the final analysis after applying the exclusion criteria. Anthropometric measurements were taken using standardized procedures, and the BMI was calculated. Sexual function was assessed using the 19-item Female Sexual Function Index (FSFI). Thyroid structure was evaluated by a team of trained physicians using ultrasound, while thyroid function was assessed via serum analysis (ELISA-based assays for TSH, fT4, and anti-TPO antibodies). Results: Of the 1569 women analyzed, 64.1% had sexual dysfunction (SD) (FSFI ≤ 26.55). Age and BMI showed significant negative correlations with all FSFI domains, with the strongest associations for arousal, lubrication, and total FSFI score (p < 0.01). SD was more prevalent among postmenopausal (43.6%) women than in premenopausal women (22.6%, p < 0.001) and increased with a higher BMI (p < 0.001). HT was found in 28.3% of participants. Compared with the reference group, women with HT were older, had higher BMI, higher TSH levels, and more hypothyroidism (p < 0.001). SD was more common in the HT group (71.7% vs. 64.2%, p < 0.001), with significantly lower lubrication and higher pain scores. In the multivariate analysis, only goiter remained an independent predictor of SD (p = 0.04). Conclusions: In conclusion, women with HT were older; had a higher BMI; and more frequently experienced SD, particularly reduced lubrication and increased pain, compared with the reference group. Although several thyroid conditions were associated with sexual dysfunction, only goiter remained an independent predictor after adjusting for age and BMI.

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of 1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment.