Gaspare Cucinella

Background/objectives: Gestational trophoblastic diseases (GTDs) are rare premalignant and malignant conditions characterized by abnormal proliferation of trophoblastic tissue. They are often asymptomatic but may present with vaginal bleeding. GTDs include hydatidiform moles and gestational trophoblastic neoplasms (GTNs). Current research aims to improve diagnostic tools and treatment strategies to reduce cancer risk and improve survival. Increasing attention is being paid to immunotherapy and treatment personalization, with the goal of minimizing long-term side effects and enhancing quality of life. Less toxic therapies are ideal for low-risk patients to reduce drug-related toxicity. Materials and Methods: A narrative review was conducted to analyze studies from the last twenty years on the diagnosis, staging, and treatment of GTDs. Sources included PubMed, Scopus, and Cochrane Library, using keywords such as “trophoblastic disease,” “hydatidiform mole,” and “gestational trophoblastic neoplasia.” Results: In recent years, the clinical management of gestational trophoblastic disease (GTD) has made significant progress through diagnostic, prognostic, and therapeutic innovations. More sensitive imaging techniques and serial monitoring of serum β-hCG now allow early diagnosis of hydatidiform mole and gestational trophoblastic neoplasia (GTN), reducing the risk of complications and metastasis. Conclusions: In the last decade, GTD management has improved significantly, with better diagnostic techniques, standardized staging, and more effective treatments. However, challenges persist, including relapse management, long-term monitoring, and psychological support. Early diagnosis is key, with ultrasound being essential for detecting abnormalities in the first weeks of pregnancy. Staging follows FIGO and WHO criteria, considering hCG levels and metastasis. This review highlights recent advances in diagnostic tools, emerging therapies—including immunotherapy—and the need for personalized, less toxic treatment approaches to improve patient outcomes.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation.

Cold knife hysteroscopic myomectomy (CKHM) is a minimally invasive surgical technique used to remove submucosal fibroids, commonly associated with infertility. Methods: A comprehensive literature search was conducted across databases including PubMed, Scopus, and Google Scholar, focusing on studies published from 2011 to 2024. The aim of this narrative review was to highlight the minimally invasive cold loop resectoscopic approach for the treatment of submucosal fibroids. Results: The review revealed that CKHM is associated with favorable fertility outcomes, with studies reporting increased pregnancy rates; most studies indicated that CKHM did not negatively affect endometrial function. Conclusions: Cold knife hysteroscopic myomectomy is a safe and effective option for women with submucosal fibroids who wish to preserve fertility due its minimal invasiveness and low complication rates.

Background and Objectives: We compared mini-laparoscopic and laparoscopic hysterectomy in terms of surgery duration, postoperative pain, conversion rate, blood loss, postoperative complications (Clavien-Dindo classification), and the length of hospital stay. Materials and Methods: Patients were recruited between 1 January 2017 and 1 January 2024, at the Department of Gynecology, “Villa Sofia-Cervello” Hospital. Indications for hysterectomy included uterine myoma, endometriosis, endometrial hyperplasia, adenomyosis, high-grade cervical dysplasia, early-stage endometrial cancer, and microinvasive cervical cancer. Patients were divided according to treatment into conventional laparoscopic hysterectomy (LH) with all 5 mm ports or the needlescopic approach (minilaparoscopic hysterectomy [MLH]), using 3 mm instruments. Postoperative pain was assessed using the visual analog scale (VAS) at multiple time points (2, 6, 12, and 24 h post-surgery). Results: A total of 308 patients were enrolled, with 153 women in the LH group and 155 in the MLH group. The surgery duration was on average 105.5 min in LH and 98.8 min in MLH (p < 0.0001). The intraoperative blood loss averaged 195.1 mL in LH and 100.3 mL in MLH (p < 0.001). The average length of hospital stay was 4.0 days for women undergoing LH compared to 3.2 days for women undergoing MLH (p < 0.001). Conclusions: This retrospective study demonstrated that MLH is an effective and functional technique for treating various gynecological conditions, with advantages in terms of aesthetic outcomes and reduced perioperative pain and recovery times. The positive results, supported by key parameters such as surgical duration, blood loss, and complications, could serve as a foundation for future studies on larger populations and for improving clinical practices in gynecology.

Pelvic floor dysfunction (PFD) is one of the most significant postoperative consequences in gynecological surgery, leading to impaired bowel function, structural alteration, and reduced quality of life. The conventional technique using fluoroscopic defecography and perineal ultrasonography provides an incomplete assessment of multi-compartment defects and post-surgical changes. Magnetic resonance defecography (MRD) represents a valuable alternative imaging method in the assessment of PFD following gynecological surgery, increasing diagnostic accuracy and enabling personalized treatment planning. MRD achieves high-resolution multi-compartmental assessment of the pelvic floor in dynamic states. Particularly, it is able to detect postoperative complications such as mesh retraction, organ prolapse, and fistula formation, not visible to other modalities. This narrative review discusses the role of MRD in diagnosing PFD and its advantages in detecting functional and anatomical changes following gynecological surgery. This review also examined the ability of MRD to demonstrate surgical changes and its contribution to possible standardization in clinical practice.

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Background/Objectives: The presence of autoimmune thyroiditis was found to be associated with an increased prevalence of sexual dysfunction. Women’s sexual health was not investigated in postpartum disorders of the thyroid gland. The aim of this study was to assess female sexual functioning and depressive symptoms in postpartum thyroiditis. Methods: This study compared four groups of non-lactating women who gave birth within 12 months before the beginning of the study: women with postpartum thyroiditis and overt hypothyroidism (group A), women with postpartum thyroiditis and subclinical hypothyroidism (group B), euthyroid females with postpartum thyroiditis (group C) and healthy euthyroid females without thyroid disease (group D). All patients completed questionnaires assessing female sexual function (FSFI), and the presence and severity of depressive symptoms (BDI-II). Moreover, we assessed thyroid peroxidase and thyroglobulin antibodies, as well as serum levels of thyroid-stimulating hormone (TSH), free thyroid hormones, testosterone, dehydroepiandrosterone sulfate (DHEAS), estradiol and prolactin. Results: The mean total FSFI score was lower in women with overt hypothyroidism (22.74 ± 4.12) than in the remaining groups of women, lower in groups B (25.71 ± 3.84) and C (29.67 ± 4.00) than in group D (32.15 ± 2.98), as well as lower in group B than in group C. Compared to healthy controls, both groups of women with postpartum thyroiditis and thyroid hypofunction had lower scores for all domains, while euthyroid patients with postpartum thyroiditis had lower scores for sexual desire, sexual arousal and lubrication. The total BDI-II score was highest in group A (15.6 ± 3.2) and lowest in group D (7.8 ± 3.2). Serum testosterone and DHEAS levels were lower while serum prolactin levels were higher in women with postpartum thyroiditis than in healthy subjects. The lowest testosterone levels (1.02 ± 0.35 nmol/L) and estradiol levels (190 ± 80 pmol/L) and the highest prolactin concentration (39.9 ± 13.9 ng/mL) were found in group A. Conclusions: The obtained results show that postpartum thyroiditis is complicated by multidimensional impairment of female sexual functioning, which is accompanied by mood deterioration. Severity of sexual dysfunction and depressive symptoms in this clinical entity depends on the degree of thyroid autoimmunity and hypothyroidism. It seems that assessment of sexual functioning and mood should be recommended to all women with postpartum thyroiditis.

Background/Objectives: Infertility is a multifactorial condition influenced by various factors, including dysbiosis and alterations in the genital tract microbiome. Recent studies emphasize the microbiome’s significant role in influencing a woman’s fertility potential, thereby affecting the chances of spontaneous conception and the outcomes of assisted reproductive treatments. Understanding the microbial characteristics and unique features of a healthy genital microbiome, as well as how changes in its composition can impact fertility, would allow for a more comprehensive and personalized approach to managing assisted reproductive treatments. The microbiome also influences pregnancy outcomes, and restoring its balance has been shown to improve fertility in infertile couples. The human microbiome plays a key role in maintaining the body’s overall health. Disruptions in microbiome balance among women of reproductive age can contribute to a range of pregnancy-related complications, with notable consequences for both maternal and fetal well-being. Emerging research has highlighted a connection between the reproductive tract microbiome and outcomes of assisted reproductive technologies (ART), suggesting that re-establishing a healthy microbial environment may enhance fertility in couples facing infertility. Methods: We conducted a search on PubMed using the keywords “microbiome”, “infertility”, and “ART” over the past 10 years. This article aims to provide an updated overview of the role of the microbiome in female reproductive health, with a focus on its implications for fertility treatment. Results: The microbiome has a significant role in influencing women’s fertility. Conclusions: Understanding the microbiome’s impact on fertility and pregnancy outcomes may lead to more effective and personalized approaches in fertility treatments, improving the chances of successful conception and pregnancy.

Background/Objectives: Male infertility is a complex, multifactorial condition influenced by infectious, inflammatory, and autoimmune components. Immunological factors, though implicated in reproduction, remain poorly understood. This study aims to deepen the understanding of infections, inflammation, and autoimmune factors in male infertility, with a focus on immune-related disorders affecting the testes and epididymis—immunologically privileged but vulnerable sites. These factors can impair sperm quality through oxidative stress (ROS) and antisperm antibodies (ASA), further compromising fertility. Methods: A narrative review was conducted by analyzing scientific literature from the past 10 years conducted on PubMed using keywords such as “male infertility”, “autoimmunity”, and “inflammatory disease”. Studies focusing on testicular and epididymal disorders, immunological impacts, and therapeutic approaches were included. Results: Our research highlights that conditions like epididymitis, vasectomy, testicular trauma, and previous surgeries can trigger inflammatory responses, leading to ASA formation and oxidative stress. ASA, particularly sperm-immobilizing antibodies, inhibits sperm motility and migration in the female reproductive tract. Infections caused by sexually transmitted bacteria or urinary pathogens frequently induce epididymo-orchitis, a primary contributor to male infertility. While standardized methodologies for ASA testing remain elusive, assisted reproductive treatments such as intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and intrauterine insemination (IUI) show promise in overcoming immune-mediated infertility. Conclusions: This review underscores the critical role of infection, inflammation, and autoimmune responses in male infertility. It highlights the necessity of improving diagnostic methods, understanding immune-pathological mechanisms, and addressing medicolegal issues associated with male infertility. This knowledge could pave the way for innovative therapies, ultimately enhancing fertility outcomes, and mitigating the societal and legal repercussions of infertility.

Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate diagnosis and classification of endometrial hyperplasia are crucial. Since the treatment for atypical endometrial hyperplasia is the same as that for early-stage endometrial cancer (i.e., total hysterectomy and bilateral salpingo-oophorectomy), researchers have questioned whether sentinel lymph node mapping could also have a prognostic role in atypical endometrial hyperplasia. Methods: A literature search was conducted in PubMed and Scopus from 2014 to 2025. Of the 65 papers found, 31 relevant articles were selected based on inclusion criteria, focusing on sentinel lymph node staging in patients with atypical endometrial hyperplasia. This review aims to assess whether sentinel lymph node mapping can be routinely used for prognostic and therapeutic purposes in clinical practice. Results: Sentinel lymph node biopsy represents a promising diagnostic technique for patients with atypical endometrial hyperplasia, reducing the need for invasive procedures and postoperative risks. However, its application requires advanced surgical skills and access to specific technologies, raising ethical and financial concerns, while future studies could improve patient selection and the reliability of the procedure through technological innovations. Conclusions: Sentinel lymph node biopsy is a safe and effective method for staging early-stage endometrial cancer and atypical hyperplasia, with low metastasis rates, but future research should focus on identifying patients who would benefit most from this procedure, considering its costs and required expertise.