Infertility is a condition defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person’s capacity to reproduce either as an individual or with their partner. The authors have set out to succinctly investigate, explore, and assess infertility treatments, harnessing the potential of stem cells to effectively and safely treat infertility; in addition, this paper will present the legal and regulatory complexities at the heart of stem cell research, with an overview of the legislative state of affairs in six major European countries. For couples who cannot benefit from assisted reproductive technologies (ART) to treat their infertility, stem-cells-based approaches have been shown to be a highly promising approach. Nonetheless, lingering ethical and immunological uncertainties require more conclusive findings and data before such treatment avenues can become mainstream and be applied on a large scale. The isolation of human embryonic stem cells (ESCs) is ethically controversial, since their collection involves the destruction of human embryonic tissue. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. The effort to untangle the complex web of ethical and legal issues associated with such therapeutic approaches will have to rely on evidence-based, broadly shared standards, guidelines, and best practices to make sure that the procreative rights of patients can be effectively reconciled with the core values at the heart of medical ethics.

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.

Endometriosis is a chronic inflammatory disease that affects about 10% of women, and it is characterized by the presence of endometrial tissue outside the uterine cavity. Associated symptoms are dyspareunia, chronic pelvic pain, and infertility. The diagnosis of endometriosis can be challenging due to various clinical and imaging presentations. Laparoscopy is the gold standard for the diagnosis, but it is an invasive procedure. The literature has increasingly promoted a switch to less invasive imaging techniques, such as ultrasound and magnetic resonance imaging (MRI). The latter, also in relation to the latest technological advances, allows a comprehensive and accurate assessment of the pelvis and it can also identify sites of endometriosis that escape laparoscopic evaluation. Furthermore, MRI has been found to be more accurate than other imaging techniques in relation to its improved sensitivity and specificity in identifying disease sites, also due to the role of new emerging sequences. This article aims to review the current role of advanced MRI applications in the assessment of endometriosis.

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.

Absolute uterine factor infertility (AUFI) is a form of infertility whereby conception and/or maintenance of pregnancy is impossible as a result of uterine absence or its completed dysfunction. It affects 1/500 women of reproductive age while the incidence is about 8% of infertile couples. Uterus transplantation (UTx) has been gaining ground as a viable option to enable women with AUFI to have biological children and as an alternative to surrogacy, a highly controversial practice still banned in many countries. The authors have set out to strike a reasonable balance between UTx benefits and the still numerous risks, whether clinical or ethical, associated with such an innovative form of transplant, which is not life-saving, requires immunosuppression throughout pregnancy and the organ to be removed right after childbirth. While still far from achieving mainstream status, considerable strides have been made in UTx outcomes, with many live births already recorded. Procedures from living donor are reportedly more effective in terms of success rates. Organ tissue engineering has been explored and developed with promising results. UTx entails various risks and ethical quandaries which have to do with reproductive autonomy and rights. New human attempts and clinical trials of UTx should be performed to further optimize the procedure in relation to safety and effectiveness. Techniques such as tissue engineering could lead in the medium-long term to a wholly bioengineered uterus to be used for transplantation, relying on scaffolds from decellularized organs or tissues that can be recellularized by several types of autologous somatic/stem cells. Such advances hold promise in terms of solving UTx-related complications and organ supply difficulties.

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.