Couple infertility is a multifactorial condition that involves, among other factors, immunological alterations of the endometrium. CD138+ plasma cells and uterine Natural Killer (NK) cells have been associated with implantation failures and recurrent pregnancy loss, although the literature presents considerable heterogeneity in findings. This narrative review aims to synthesize current evidence on the role of these two immunological biomarkers in the pathophysiology of infertility. According to the current literature, the presence of CD138+ plasma cells was strongly associated with chronic endometritis and adverse reproductive outcomes, with improvement following targeted antibiotic therapy. NK cells, particularly in their hyperactive peripheral form, were elevated in infertile women, although data on uterine NK cells remain controversial. Recent studies suggest a possible interaction between chronic inflammation and NK dysfunction. A combined evaluation of CD138+ and NK cells may represent an integrated diagnostic approach in idiopathic infertility. Prospective studies are needed to standardize cut-off values and validate these markers in clinical practice.
Background/Objectives: Outpatient operative hysteroscopy is a cornerstone in the management of intrauterine pathologies within reproductive medicine. However, procedural pain and anxiety remain key barriers leading to failed procedures and referrals for surgery under general anesthesia. This study aimed to assess whether a comfort-enhanced procedural environment could reduce perceived pain and increase procedural success rates. Methods: Analysis of 970 consecutive patients who underwent outpatient operative hysteroscopy at the Hysteroscopy Unit of “Degli Infermi” Hospital (Biella, Italy): 470 in 2023 under standard conditions, 500 in 2024 with an enhanced setting. Surgical technique, analgesic/sedation policies and operators were unchanged. The primary outcome was referral to the OR for completion of the procedure. Secondary outcomes included patient-reported pain assessed by Visual Analog Scale (VAS) in a consecutive subsample. Differences between years were evaluated with appropriate parametric/non-parametric tests. Results: Implementation of the enhanced environment was associated with a lower OR referral rate in 2023 versus 2024. Post hoc power for this comparison was approximately 60%. Mean VAS scores also decreased in 2024, with post hoc power >99%. No adverse events were recorded. Conclusions: Environmental and interpersonal modifications were associated with meaningful decline in reported pain and OR referrals. Prospective studies incorporating systematic case-mix and validated anxiety measures are warranted to confirm these results.
Background: Outpatient operative hysteroscopy is a minimally invasive procedure widely used for the diagnosis and treatment of intrauterine pathologies, including intrauterine adhesions (IUAs), which significantly affect fertility. Despite its therapeutic potential, the procedure itself may predispose patients to de novo adhesion formation. This review evaluates the effectiveness of anti-adhesion gels, particularly hyaluronic-acid-based formulations, in preventing IUAs and improving reproductive outcomes after outpatient operative hysteroscopy. Materials and Methods: A systematic search was performed in PubMed, CINAHL, Embase, and Web of Science for studies published between January 2020 and May 2025. Inclusion and exclusion criteria were defined using PICO guidelines. Relevant studies were screened and selected by two independent reviewers. Results: Anti-adhesion gels, especially hyaluronic acid and its derivatives, were associated with a lower recurrence of IUAs and improved reproductive outcomes. Combination therapies, such as hyaluronic acid gel with intrauterine devices (IUDs), showed better efficacy than monotherapy. Several studies also reported increased endometrial thickness, higher implantation rates, and improved pregnancy outcomes, although live birth rates remained inconsistent. Conclusions: Hyaluronic-acid-based anti-adhesion gels appear effective in reducing postoperative adhesion formation and enhancing reproductive outcomes in outpatient hysteroscopy. The best results are seen with multimodal preventive strategies. However, heterogeneity across studies highlights the need for standardized, prospective, randomized controlled trials to establish optimal clinical use.
Background/Objectives: Lactoferrin has been studied for its antimicrobial, anti-inflammatory, and immunomodulatory properties. While the presence and role of lactoferrin in breast milk have been relatively well described, its potential as a dietary supplement to prevent inflammatory breast conditions has not been adequately addressed in the literature. Animal models—particularly in bovine mastitis—have also suggested a possible protective role for lactoferrin in mammary inflammation. The aim of this review is to critically evaluate existing evidence on the role of lactoferrin in inflammation and immunity, with a particular focus on its potential preventive role in lactational breast conditions. Methods: A comprehensive literature search was performed across PubMed, Embase, and CINAHL. The search was carried out without any temporal restrictions, and studies published in English or Italian were included. Results: Lactoferrin has well-documented properties and evidence from animal models and studies on other inflammatory conditions supports its potential role in reducing inflammation and preventing infections. There is a clear lack of clinical trials specifically evaluating lactoferrin supplementation in the prevention of lactational mastitis. Most studies have been conducted in non-human models, and there is a need for more human-specific research. Conclusions: future studies should be focused on understanding the role of lactoferrin supplementation, its security and efficacy and also its potential use as a diagnostic marker. It is essential to move beyond theoretical and indirect evidence, and to conduct rigorous clinical research to fully understand its potential role in obstetric care, particularly in the prevention of lactational mastitis.