Search Results (19)

Sperm DNA fragmentation (SDF) is increasingly regarded as a biomarker of male infertility, but its predictive value for intracytoplasmic sperm injection (ICSI) outcomes remains controversial. This retrospective cohort study analyzed 870 fresh single-blastocyst ICSI cycles performed between January 2023 and December 2024. SDF was measured using the Sperm Chromatin Dispersion test and patients were categorized into low (SDF ≤ 20%, n = 664) and high (SDF > 20%, n = 206) groups. Higher SDF was significantly associated with reduced semen quality, lower fertilization rates, and poorer blastocyst development. In multivariable analysis, each 1% increase in SDF reduced the odds of achieving a fertilization rate > 80% by 1.6% (OR = 0.984, 95% CI: 0.971–0.997, p = 0.015) and decreased the chance of obtaining top-quality blastocysts on day 5 by 2.5% (OR = 0.975, 95% CI: 0.958–0.992, p = 0.004). A trend toward impaired day-3 embryo quality was observed (OR = 0.983, p = 0.068). No significant association was found with clinical pregnancy (OR = 0.989, p = 0.155), while the relationship with miscarriage was borderline (OR = 0.961, p = 0.053). These findings suggest that elevated SDF adversely impacts early embryological outcomes in ICSI, supporting its use as a prognostic tool during ART counseling. Full article

Background and Clinical Significance: Pituitary adenomas, also termed pituitary neuroendocrine tumors, pose a significant risk of hypogonadotropic hypogonadism (HH) after surgical resection, with profound consequences for fertility and sexual function in young patients. Case Presentation: We present the case of a 29-year-old man from rural Japan who developed severe HH and azoospermia following two transsphenoidal resections for a large pituitary adenoma. Despite early engagement with neurosurgery teams, fertility management was delayed by the absence of on-site endocrinology expertise and limited local oncofertility resources. After comprehensive endocrine evaluation and counseling, the patient began combined human chorionic gonadotropin and recombinant follicle-stimulating hormone therapy, resulting in full recovery of sexual function and normalization of semen parameters, ultimately leading to spontaneous conception and the birth of a healthy child. Building on this real-world case, we provide a narrative review of current practical management strategies for HH after pituitary surgery, including the utility of hormone-stimulation tests, Japanese guideline-based subsidy systems, and best-practice approaches to hormonal replacement. Conclusions: This case underscores not only the necessity for early, interdisciplinary collaboration and preoperative counseling but also highlights a rare instance in which a patient with a benign tumor received care that did not address his fertility-related needs, emphasizing that such considerations should be integrated into preoperative counseling even for non-malignant conditions. Strengthening regional oncofertility networks and improving healthcare providers’ awareness of fertility-preservation options remain essential for improving outcomes. Full article

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

Polystyrene microplastics (PS-MPs) released in the environment reportedly affect the reproduction of various organisms, induced oxidative stress and apoptosis, resulting in altered sperm parameters. In this in vitro study, we tested the cytotoxicity and genotoxicity of PS-MPs by exposing human semen samples to PS-MPs levels (105 and 210 μg/mL) for 30–60–90 min. Semen parameters, genome stability, sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) production were analyzed before and after exposure. Moreover, we also evaluated the expression level of spermatozoa-specific expressed genes essential for the fusion with oocyte (DCST1, DCST2, IZUMO1, SPACA6, SOF1, and TMEM95). After PS-MP exposure, semen concentration and morphology did not differ, while sperm vitality and motility decreased in a time-dependent manner. In addition, sperm agglutination was observed in the groups exposed to both PS-MPs concentrations tested. A time- and concentration-dependent reduction in genomic stability, as well as increased SDF and ROS production, was also observed. Moreover, all investigated transcripts were down-regulated after PS-MP exposure. Our results confirm the oxidative stress-mediated genotoxicity and cytotoxicity of PS-MPs on human spermatozoa. The sperm agglutination observed after treatment could be due to the aggregation of PS-MPs already adhered to the sperm membranes, hindering sperm movement and fertilizing capability. Interestingly, the downregulation of genes required for sperm–oocyte fusion, resulting from data on the in vitro experimental system, suggests that PS-MP exposure may have implications for sperm functionality. While these findings highlight potential mechanisms of sperm dysfunction, further investigations using in vivo models are needed to determine their broader biological implications. Possible environmental and working exposure to pollutants should be considered during the counselling for male infertility. Full article

Background/Objectives: Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection is the primary treatment, but success rates are unpredictable, causing significant emotional and financial burdens. Traditional clinical and hormonal predictors have shown inconsistent reliability. This review aims to evaluate current and emerging non-invasive preoperative predictors of successful sperm retrieval in men with NOA, highlighting promising biomarkers and their potential clinical applications. Methods: A comprehensive literature review was conducted, examining studies on clinical and hormonal factors, imaging techniques, molecular biology biomarkers, and genetic testing related to TESE outcomes in NOA patients. The potential role of artificial intelligence and machine learning in enhancing predictive models was also explored. Results: Traditional predictors such as patient age, body mass index, infertility duration, testicular volume, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, inhibin B) have limited predictive value for TESE success. Emerging non-invasive biomarkers—including anti-Müllerian hormone levels, inhibin B to anti-Müllerian hormone ratio, specific microRNAs, long non-coding RNAs, circular RNAs, and germ-cell-specific proteins like TEX101—show promise in predicting successful sperm retrieval. Advanced imaging techniques like high-frequency ultrasound and functional magnetic resonance imaging offer potential but require further validation. Integrating molecular biomarkers with artificial intelligence and machine learning algorithms may enhance predictive accuracy. Conclusions: Predicting TESE outcomes in men with NOA remains challenging using conventional clinical and hormonal parameters. Emerging non-invasive biomarkers offer significant potential to improve predictive models but require validation through large-scale studies. Incorporating artificial intelligence and machine learning could further refine predictive accuracy, aiding clinical decision-making and improving patient counseling and treatment strategies in NOA. Full article

As the incidence of colorectal cancer (CRC) increases among younger adults, the need for discussions regarding treatment-related infertility is growing. The negative impacts of gonadotoxic chemotherapy and pelvic radiation are well documented, but the role that surgical intervention for CRC plays in infertility is less clear. Additionally, treatment-related infertility counseling occurs infrequently. This review provides an overview of the connection between abdominal and pelvic surgery on male and female infertility and elucidates the role of surgeons in counseling to alleviate psychological distress in newly diagnosed patients. A review of the literature revealed that pelvic surgery leads to increased adhesion formation, which is known to be associated with female infertility. Furthermore, nerve damage from pelvic surgery has significant implications for ejaculatory issues in males and sexual dysfunction in both males and females, which ultimately impact pregnancy success. Patients have significant distress related to treatment-related infertility, and pre-treatment fertility counseling has been shown to alleviate some of this psychological burden. Nevertheless, many patients do not receive counseling, particularly in surgical clinics, despite surgeons often being the first providers to see newly diagnosed non-metastatic patients. Efforts should be made to enact protocols that ensure fertility conversations are being had with patients in surgical clinics and that patients are being referred to fertility specialists appropriately. This patient-centered approach will lessen the psychological burden placed on patients during a vulnerable time in their lives. Full article

Odad3 gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the Odad3 gene in mice replicates several features of PCD, such as hydrocephalus, defects in left–right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of Odad3 knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the Odad3 gene during gonad development and in adult testes. We showed that Odad3 starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that Odad3 plays a role in spermatozoa formation. Subsequently, we conditionally deleted the Odad3 gene in adult males and demonstrated that even partial ablation of the Odad3 gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in Odad3-deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous Odad3^+/− knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, Odad3^+/− males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of Odad3 and Odad3 gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying Odad3 loss-of-function mutations. Full article

Infertility affects around 20% of couples of reproductive age; however, in some societies, as many as one-third of couples are unable to conceive. Different factors contribute to the decline of male fertility, such us environmental and professional exposure to endocrine disruptors, oxidative stress, and life habits with the risk of de novo epigenetics dysregulation. Since the fantastic development of new “omes and omics” technologies, the contribution of inherited or de novo genomes and epigenome disorders to male infertility have been further elucidated. Many other techniques have become available to andrology laboratories for the investigation of genome and epigenome integrity and the maturation and the competency of spermatozoa. All these new methods of assessment are highlighting the importance of genetics and epigenetics investigation for assisted reproduction pathology and for supporting professionals in counselling patients and proposing different management strategies for male infertility. This aims to improve clinical outcomes while minimizing the risk of genetics or health problems at birth. Full article

Background: Infertility affects about 80 million individuals worldwide and 10–15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. Methods: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. Results: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. Conclusions: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children. Full article

Hereditary cancers mostly affect the adolescent and young adult population (AYA) at reproductive age. Mutations in BReast CAncer (BRCA) genes are responsible for the majority of cases of hereditary breast and ovarian cancer. BRCA1 and BRCA2 act as tumor suppressor genes as they are key regulators of DNA repair through homologous recombination. Evidence of the accumulation of DNA double-strand break has been reported in aging oocytes, while BRCA expression decreases, leading to the hypothesis that BRCA mutation may impact fertility. Moreover, patients exposed to anticancer treatments are at higher risk of fertility-related issues, and BRCA mutations could exacerbate the treatment-induced depletion of the ovarian reserve. In this review, we summarized the functions of both genes and reported the current knowledge on the impact of BRCA mutations on ovarian ageing, premature ovarian insufficiency, female fertility preservation strategies and insights about male infertility. Altogether, this review provides relevant up-to-date information on the impact of BRCA1/2 mutations on fertility. Notably, BRCA-mutated patients should be adequately counselled for fertility preservation strategies, considering their higher sensitivity to chemotherapy gonadotoxic effects. Full article

Advanced reproductive technologies are utilized to identify the genetic mutations that lead to spermatogenic impairment, and allow informed genetic counseling to patients to prevent the transmission of genetic defects to offspring. The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Genetic variants that may cause infertility are identified by combining the targeted next-generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Our analysis revealed five distinct affected genes covering seven SNPs based on the targeted NGS panel and WES data: SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150), and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. These findings strongly support the hypothesis that the dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2, and DRC7 mutations are associated with male infertility, specifically azoospermia, and a further examination of this genetic function is required. Full article

Increasing intrauterine insemination (IUI) success rates is essential to improve the quality of care for infertile couples. Additionally, straight referral of couples with less probability of achieving a pregnancy through IUI to more complex methods such as in vitro fertilization is important to reduce costs and the time to pregnancy. The aim of the present study is to prospectively evaluate the threshold values for different parameters related to success in intrauterine insemination in order to provide better reproductive counseling to infertile couples, moreover, to generate an algorithm based on male and female parameters to predict whether the couple is suitable for achieving pregnancy using IUI. For that, one hundred ninety-seven infertile couples undergoing 409 consecutive cycles of intrauterine insemination during a two-year period were included. The first year served as a definition of the parameters and thresholds related to pregnancy achievement, while the second year was used to validate the consistency of these parameters. Subsequently, those parameters that remained consistent throughout two years were included in a generalized estimating equation model (GEE) to determine their significance in predicting pregnancy achievement. Parameters significantly associated with the lack of pregnancy through IUI and included in the GEE were (p < 0.05): (i) male age > 41 years; (ii) ejaculate sperm count < 51.79 x 10⁶ sperm; (iii) swim-up alkaline Comet > 59%; (iv) female body mass index > 45 kg/m²; (v) duration of infertility (>84 months), and (vi) basal LH levels > 27.28 mUI/mL. The application of these limits could provide a pregnancy prognosis to couples before undergoing intrauterine insemination, therefore avoiding it in couples with low chances of success. The retrospective application of these parameters to the same cohort of patients would have increased the pregnancy rate by up to 30%. Full article

Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017–June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5–10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40–72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic–lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory. Full article

According to current estimates, infertility affects one in four couples trying to conceive. Primary or secondary infertility can be due either to both partners or only to the man or the woman. Up to 15% of infertility cases in men can be attributed to genetic factors that can lead to irreversible partial or complete spermatogenic arrest. The increased use of assisted reproductive technology (ART) has provided not only insights into the causes of male infertility but also afforded a diagnostic tool to detect and manage this condition among couples. Genes control a variety of physiological attributes, such as the hypothalamic–pituitary–gonadal axis, development, and germ cell differentiation. In the era of ART, it is important to understand the genetic basis of infertility so as to provide the most tailored therapy and counseling to couples. Genetic factors involved in male infertility can be chromosome abnormalities or single-gene disorders, mitochondrial DNA (mtDNA) mutations, Y-chromosome deletions, multifactorial disorders, imprinting disorders, or endocrine disorders of genetic origin. In this review, we discuss the role of mitochondria and the mitochondrial genome as an indicator of sperm quality and fertility. Full article

Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was indicated as second-line treatment or in the case of male factor. The combined approach of surgery followed by ART proved to offer higher chances of pregnancy in infertile women with endometriosis. However, it was highlighted how pelvic surgery for endometriosis, especially in cases of ovarian endometriomas, could cause iatrogenic damage due to ovarian reserve loss, adhesion formation (scarring), and ischemic damage. Furthermore, in the last few years, the trend to delay the first childbirth, recent technological advances in ultrasound diagnosis, and technological progress in clinical and laboratory aspects of ART have certainly influenced the approach to infertility and endometriosis with, ART assuming a more relevant role. Management of endometriosis should take into account that the disease is chronic and involves the reproductive system. Consequently, treatment and counselling should aim to preserve the chances of pregnancy for the patient, even if it is not associated with infertility. This review will analyse the evolution of the management of infertility associated with endometriosis and propose an algorithm for treatment decision-making based on the most recent acquisitions. Full article