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20 pages, 1471 KB  
Review
Role of Uterine Fluid-Derived Molecules in Embryo Implantation
by Chen Zhou, Xiaoqing Zhu, Lijun Guan, Zhiqian Xu, Xiangbin You, Xiaoxia Li and Youbing Yang
Reprod. Med. 2026, 7(3), 43; https://doi.org/10.3390/reprodmed7030043 - 27 Aug 2026
Abstract
Embryo implantation is a highly selective and hormonally regulated event, critically dependent on endometrial receptivity and the molecular microenvironment of uterine fluid (UF). UF is actively secreted by endometrial glands and epithelial cells and comprises proteins, metabolites, hormones, and extracellular vesicles (EVs) carrying [...] Read more.
Embryo implantation is a highly selective and hormonally regulated event, critically dependent on endometrial receptivity and the molecular microenvironment of uterine fluid (UF). UF is actively secreted by endometrial glands and epithelial cells and comprises proteins, metabolites, hormones, and extracellular vesicles (EVs) carrying miRNAs, lncRNAs, and regulatory proteins. These components coordinate embryo development, trophoblast invasion, angiogenesis, and maternal–fetal immune tolerance. Dysregulation of UF composition is increasingly implicated in reproductive disorders, including recurrent implantation failure, unexplained infertility, endometriosis, adenomyosis, and polycystic ovary syndrome, highlighting its potential as a noninvasive biomarker of endometrial function. Despite advances, challenges remain in standardizing UF sampling, addressing temporal and inter-individual variability, and elucidating upstream regulatory networks. Integrative multi-omics analyses, functional organoid–embryo models, and longitudinal clinical studies are essential to translate UF insights into predictive diagnostics and therapeutic strategies, ultimately improving implantation success and reproductive outcomes. Full article
(This article belongs to the Special Issue Impact of Environmental Factors on Reproductive Health)
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27 pages, 1197 KB  
Article
An LLM and Retrieval Pipeline for Reproductive-Health Misinformation and Stigma
by Sara Behnamian, Zeinab Shahbazi, Fatemeh Fogh, Bita Baghestani, Ameneh Khani and Arash Darzian Rostami
Reprod. Med. 2026, 7(3), 42; https://doi.org/10.3390/reprodmed7030042 - 25 Aug 2026
Abstract
Background/Objectives: Reproductive-health topics such as polycystic ovary syndrome (PCOS), endometriosis, fertility, and menstruation attract both unsupported claims and stigmatizing framing on social media. We present an evidence-grounded pipeline combining large language models (LLMs) with biomedical retrieval, extended with a novel layer that scores [...] Read more.
Background/Objectives: Reproductive-health topics such as polycystic ovary syndrome (PCOS), endometriosis, fertility, and menstruation attract both unsupported claims and stigmatizing framing on social media. We present an evidence-grounded pipeline combining large language models (LLMs) with biomedical retrieval, extended with a novel layer that scores the stigma framing of each claim independently of its truth. Methods: From 991 keyword-sampled English-language Bluesky posts we extracted 937 health claims, grounded each in evidence from PubMed, openFDA, and authoritative clinical guidelines (ACOG, NICE, NHS, WHO), and classified veracity into five categories using only the retrieved evidence. A parallel module scored five stigma dimensions and, separately, empowerment as a counter-stigma indicator. Results: Most claims (75.2%) were non-supported, though a relevance audit shows this largely records evidence that was not retrieved rather than claims shown to be false; the dominant frame was empowerment rather than overt shame. Stigma increased monotonically as claims departed from the evidence. The gradient was modest but robust (Kruskal–Wallis p < 107, ε2 = 0.039; ρ = 0.20), surviving cluster-aware reanalysis of claims nested within posts. Stigma varied sharply by condition, highest for infertility and endometriosis. Conclusions: Non-supported claims and stigmatizing framing co-occur, though this cross-sectional design cannot establish a direction. Single-coder validation was a pilot diagnostic check: stigma scores aligned directionally with human judgment, while five-way veracity agreement was limited. Results describe this keyword-sampled, single-platform corpus, not platform-wide prevalence. Full article
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12 pages, 639 KB  
Article
Embryo Donation as a Clinical Model: Recipient Body Mass Index and Offspring Sex Distribution After Assisted Reproduction
by Robert Czech, Dariusz Wójcik, Tomasz Skweres, Wojciech Śliwiński, Dorota Zamkowska and Przemysław Ciepiela
Reprod. Med. 2026, 7(3), 41; https://doi.org/10.3390/reprodmed7030041 - 21 Aug 2026
Viewed by 149
Abstract
Background/Objectives: Embryo donation/adoption separates the recipient environment from the genetic origin of the embryo and provides a clinical model for studying offspring sex distribution after assisted reproduction. We evaluated whether recipient body mass index (BMI) was associated with sex distribution among live-birth events [...] Read more.
Background/Objectives: Embryo donation/adoption separates the recipient environment from the genetic origin of the embryo and provides a clinical model for studying offspring sex distribution after assisted reproduction. We evaluated whether recipient body mass index (BMI) was associated with sex distribution among live-birth events after frozen embryo transfer involving embryo donation/adoption. Methods: This retrospective cohort study included frozen embryo transfer cycles involving embryo donation/adoption performed between January 2018 and December 2024 at a tertiary fertility center. All embryos were generated by intracytoplasmic sperm injection, cultured to the day-5 blastocyst stage, transferred singly, and not subjected to preimplantation genetic testing. The analytical cohort comprised 104 independent live-birth transfer events representing 104 unique recipients and 104 unique embryo–donor couples. Recipient BMI was evaluated across quartiles and in an exploratory adjusted logistic regression model including female embryo donor BMI and age, endometrial thickness, serum progesterone concentration, and top-quality embryo status. Results: The cohort included 51 male and 53 female live-birth events. Recipient BMI was higher in female than male live-birth events (25.6 ± 4.3 versus 23.5 ± 4.2 kg/m2; p = 0.007). In a descriptive quartile analysis, male live-birth event proportions were 69.2% in the lowest BMI quartile and 34.6% in the highest quartile, with corresponding female proportions of 30.8% and 65.4% (p for trend = 0.007). In the primary adjusted model, higher recipient BMI was associated with lower odds of a male live-birth event (adjusted OR 0.88 per 1 kg/m2; 95% CI 0.80–0.98; p = 0.017). Conclusions: Recipient BMI was associated with sex distribution among live-birth events after embryo donation/adoption. The observed pattern is compatible with a recipient-side post-fertilization association but does not establish a selection mechanism, causality, or the developmental stage at which the association arose. Full article
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40 pages, 3984 KB  
Review
Estrobolome in the Gut–Vagina Axis: A Microbial Endocrinology Perspective
by Lorenzo Agoni, Canio Martinelli, Massimo Candiani and Francesco De Seta
Reprod. Med. 2026, 7(3), 40; https://doi.org/10.3390/reprodmed7030040 - 10 Aug 2026
Viewed by 439
Abstract
The estrobolome, defined as the collection of gut microbial genes encoding enzymes that metabolize estrogens and, by extension, the taxa that harbor them, has emerged as a central node of the new concept of “microbial endocrinology” within the gut–vagina axis. By regulating enterohepatic [...] Read more.
The estrobolome, defined as the collection of gut microbial genes encoding enzymes that metabolize estrogens and, by extension, the taxa that harbor them, has emerged as a central node of the new concept of “microbial endocrinology” within the gut–vagina axis. By regulating enterohepatic recirculation of conjugated estrogens, the estrobolome may modulate systemic estrogen availability and thereby may influence the estrogen-dependent biology of gynecological organs and tissues, including ovaries, endometrium, and the vaginal mucosa with its Lactobacillus-dominated ecosystem. In this narrative review, we synthesize current evidence on how gut microbial β-glucuronidases, sulfatases, and related enzymes shape circulating estrogen pools and, in turn, gynecological health. We outline the enzymatic and taxonomic architecture of the estrobolome, describe its major ecological determinants, and integrate these with mechanisms of the gut–vagina axis. We then examine how estrobolome function varies across a woman’s lifespan and how these dynamics intersect with vaginal health, dysbiosis, and conditions such as recurrent vaginitis, endometriosis, and polycystic ovary syndrome. We also review emerging strategies that may modulate the estrobolome as a microbial endocrine organ and discuss their potential downstream effects on gynecological health. Finally, we highlight major research gaps, particularly the need for causal, longitudinal, multi-omics studies explicitly linking estrobolome activity, systemic estrogens, and gynecological outcomes. Overall, available data support a mechanistically plausible but incompletely defined role for the estrobolome as a key microbial endocrine player in the gut–vagina axis and point toward microbiome-informed strategies to preserve and restore gynecological health across a woman’s lifespan. Full article
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15 pages, 284 KB  
Article
Association Between Self-Perceived Physical Fitness Assessed Using the International Fitness Scale (IFIS) and Pregnancy-Related Low Back Pain in Physically Active Pregnant Women
by Luz M. Gallo-Galán, José L. Gallo-Vallejo and Juan Mozas-Moreno
Reprod. Med. 2026, 7(3), 39; https://doi.org/10.3390/reprodmed7030039 - 6 Aug 2026
Viewed by 220
Abstract
Background and Objectives: Pregnancy-related low back pain (PLBP) is one of the most frequent musculoskeletal complications during pregnancy and may negatively affect physical function, occupational performance, and quality of life. Although regular physical activity (PA) is recommended during pregnancy, the relationship between self-perceived [...] Read more.
Background and Objectives: Pregnancy-related low back pain (PLBP) is one of the most frequent musculoskeletal complications during pregnancy and may negatively affect physical function, occupational performance, and quality of life. Although regular physical activity (PA) is recommended during pregnancy, the relationship between self-perceived physical fitness (SPPF) and PLBP remains insufficiently explored. The aim of this study was to analyze the association between SPPF assessed using the International Fitness Scale (IFIS) and PLBP in a cohort of physically active pregnant women. Materials and Methods: A secondary analysis of a prospective cohort study including 147 physically active pregnant women was performed. All participants fulfilled the World Health Organization recommendations for PA during pregnancy (≥600 MET·min/week). PA was assessed using the International Physical Activity Questionnaire (IPAQ), whereas SPPF was evaluated using the IFIS. PLBP was assessed using structured questionnaires and the Visual Analog Scale (VAS). Multivariable logistic regression analyses were performed to evaluate independent associations between IFIS scores and PLBP. Results: PLBP was reported by 95 women (64.6%). During pregnancy, women without PLBP showed significantly higher IFIS scores across all evaluated fitness dimensions compared with women with PLBP (all p < 0.05). Women with PLBP additionally exhibited significant reductions in perceived speed/agility and flexibility compared with prepregnancy values. In multivariable analyses, higher global IFIS scores during pregnancy were independently associated with lower odds of PLBP (adjusted OR: 0.30; 95% CI: 0.15–0.60; p < 0.001). No significant associations were observed between IFIS scores and occupational interruption, umbilical artery pH, or instrumental delivery. Conclusions: Lower SPPF assessed using the IFIS was associated with PLBP in physically active pregnant women. Higher IFIS scores during pregnancy were independently associated with lower odds of PLBP, highlighting the potential clinical relevance of SPPF beyond PA volume alone. Given its simplicity, low cost, and ease of administration, the IFIS may constitute a practical tool for the assessment of SPPF during routine prenatal care. However, prospective studies are needed to clarify the temporal relationship between SPPF and PLBP and to determine its potential predictive value. Full article
(This article belongs to the Special Issue Advances in Maternal–Fetal Medicine)
29 pages, 4896 KB  
Article
“It Gave Me the Validation That I Wasn’t Crazy”: The Impact of Diagnosis and Treatment on Endometriosis Patient Journeys in Aotearoa New Zealand
by Katherine Ellis, Alina Meador, Rachael Wood and Jacqueline Donoghue
Reprod. Med. 2026, 7(3), 38; https://doi.org/10.3390/reprodmed7030038 - 4 Aug 2026
Viewed by 737
Abstract
Background: Endometriosis is a condition that is very challenging to diagnose and manage. Objectives: The purpose of this study is to assess the impacts of diagnosis and treatments in the journeys of endometriosis patients in Aotearoa New Zealand. Methods: Two [...] Read more.
Background: Endometriosis is a condition that is very challenging to diagnose and manage. Objectives: The purpose of this study is to assess the impacts of diagnosis and treatments in the journeys of endometriosis patients in Aotearoa New Zealand. Methods: Two online surveys were conducted with cohorts of 616 and 679 endometriosis patients to assess diagnosis and treatments, respectively. Results: In this exploratory study, the diagnosis cohort self-reported a median delay from symptom onset to confirmation of the diagnosis of 10 years, with a median delay from symptom onset to first seeing a doctor (“doctor delay”) of 4 years. Upon receiving their diagnosis, 53.7% indicated the “number one” emotion they felt was relief. In the treatment cohort, the only medical management strategy perceived as “effective” by over 75% of users was hysterectomy (84.3%), despite this not being a cure for endometriosis. Common first-line treatments were viewed poorly for their perceived effectiveness, with over-the-counter pain relief viewed as effective by 25.8% of users, combined oral contraceptive pills by 23.2% of users, progesterone-only pills by 42.8% of users, and intrauterine contraceptive devices by 49.7% of users. Conclusions: Endometriosis is a condition typified by challenges for patients with its delayed diagnosis, resistance to management, and a high prevalence of discouraging experiences in medical care settings. These large-sample cohorts highlight that improvements in the diagnosis and management of endometriosis warrant urgent attention by clinicians and policymakers alike. Full article
(This article belongs to the Special Issue Pathology and Diagnosis of Gynecologic Diseases, 3rd Edition)
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9 pages, 379 KB  
Brief Report
Pilot Evaluation of ddPCR-Based NIPT for Fetal Trisomy Screening in Advanced-Maternal-Age Pregnancies in Mongolia
by Khaliunaa Tuvshinjargal, Gerelsuren Batbayar, Nomuun Oyunbat, Dolgion Damdinbazar, Jamiyan Purevsuren, Oyunsuren Tsendsuren and Gantulga Davaakhuu
Reprod. Med. 2026, 7(3), 37; https://doi.org/10.3390/reprodmed7030037 - 3 Aug 2026
Viewed by 229
Abstract
Background/Objectives: Advanced maternal age (≥35 years) significantly increases the risk of fetal chromosomal abnormalities, particularly trisomies 21, 18, and 13. Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) in maternal plasma has substantially improved the accuracy and safety of prenatal screening. [...] Read more.
Background/Objectives: Advanced maternal age (≥35 years) significantly increases the risk of fetal chromosomal abnormalities, particularly trisomies 21, 18, and 13. Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) in maternal plasma has substantially improved the accuracy and safety of prenatal screening. Methods: We previously developed and clinically validated a multiplex droplet digital PCR (ddPCR)-based NIPT assay for detecting fetal trisomies 21, 18, and 13 in Mongolia. The assay targeted specific loci on chromosomes 21, 18, and 13, using chromosome 1 as an internal reference. A Z-score threshold > 3 indicated high risk, and all positive results were confirmed by invasive karyotyping. Results: In this study, we collected 74 pregnant women of advanced maternal age and samples were successfully analyzed, with high technical performance (mean > 100,000 accepted droplets per reaction and clear signal separation). Ten high-risk pregnancy cases were identified (eight trisomy 21 and two trisomy 18), all of which showed complete concordance with confirmatory karyotyping. Complete concordance with available reference standard results were observed in this limited cohort. No trisomy 13 cases were detected. Conclusions: This ddPCR-based NIPT assay exhibited excellent diagnostic accuracy and reproducibility in a Mongolian cohort of advanced-maternal-age pregnancies. Its technical simplicity, relatively low cost, and minimal infrastructure requirements make it a promising tool for implementation in resource-limited settings. However, the small sample size limits generalizability, and larger multicenter studies are needed to confirm clinical utility across broader populations, including low-risk pregnancies. Full article
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21 pages, 3165 KB  
Review
Antibiotics’ Influence on Fertility: A Narrative Review
by Mihai Nechifor, Cristina Gales, Gabriela Rusu-Zota, Carmen Lacramioara Zamfir and Daniel Costel Gales
Reprod. Med. 2026, 7(3), 36; https://doi.org/10.3390/reprodmed7030036 - 22 Jul 2026
Viewed by 2097
Abstract
The purpose of this review is to highlight the complex influence of antibiotics on human fertility and the need for them not to be underestimated. In creating this review article, data and information from the following international databases were used: PubMed, Scopus and [...] Read more.
The purpose of this review is to highlight the complex influence of antibiotics on human fertility and the need for them not to be underestimated. In creating this review article, data and information from the following international databases were used: PubMed, Scopus and Clarivate Analytics. Only full text articles were used. Antibacterial antibiotics are a group of drugs essential in fighting infections, having multiple mechanisms of action at the level of the bacterial cell; but at the same time they also act on human cells. One of the important actions of antibiotics is on fertility. There are both experimental and clinical data showing the influence of some antibiotics on fertility. There are both positive and negative influences of these drugs on fertility. Some of the most important actions with a positive impact on fertility are: therapy of pelvic infections in women, treatment of endometritis, reduction in post-abortion infections, treatment of infections of the male genital tract—infections that reduce fertility. The most important negative implications of some antibiotics are the direct effects of reducing the production of gametes, decreasing the activity or quality of the gametes, reducing the synthesis of sexual hormones and negative influences on the evolution of pregnancy, including spontaneous abortion in some cases. Other negative influences are produced by the direct action of some antibiotics on the embryo. Some antibiotics such as azithromycin and nitrofurantoin increase the risk of miscarriage. Although only a limited number of antibiotics are known to have an influence on fertility, this influence should not be underestimated in clinical practice. Full article
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21 pages, 2985 KB  
Article
Body Mass Index and Ovarian Follicular Response in Assisted Reproductive Technology: A Cross-Sectional Analysis
by Michelle Estefanía Canchig-Aguilar, Washington David Guevara-Castillo, José Isaac Zablah, José Augusto Durán-Chávez, Nelly Andrade Mejía, Lupe Carolina Espinoza, Lilian Sosa and Raynier Zambrano-Villacres
Reprod. Med. 2026, 7(3), 35; https://doi.org/10.3390/reprodmed7030035 - 21 Jul 2026
Viewed by 654
Abstract
Background: Excess adiposity has been associated with endocrine and metabolic alterations that may affect ovarian physiology and outcomes in assisted reproductive technology (ART). Objectives: The purpose of this study was to evaluate whether body mass index (BMI) was independently associated with [...] Read more.
Background: Excess adiposity has been associated with endocrine and metabolic alterations that may affect ovarian physiology and outcomes in assisted reproductive technology (ART). Objectives: The purpose of this study was to evaluate whether body mass index (BMI) was independently associated with ovarian follicular response in women undergoing assisted reproductive procedures. Methods: A cross-sectional study was conducted including 259 women aged 18 to 43 years. Analyses included nutritional status, diet quality, and follicular response. Associations were analyzed using chi-square and Kruskal–Wallis tests and negative binomial regression adjusted for age and indication. Results: Mean age was 32.8 ± 6.3 years, and mean BMI was 24.7 ± 3.2 kg/m2. Diet quality was not associated with follicle number or morphological quality. Overall, 47.5% of participants had normal weight, 42.9% were overweight, and 6.9% had class I obesity. Follicular yield differed across BMI categories in unadjusted analyses (p = 0.017), but BMI was not independently associated with follicle count after adjustment (IRR = 1.010; 95% CI: 0.983–1.036; p = 0.488). Age remained the only independent predictor, with each additional year associated with a 5.9% reduction in expected follicle count (IRR = 0.941; 95% CI: 0.920–0.963; p < 0.001). Conclusions: BMI was not independently associated with follicular yield after adjustment, whereas age remained the principal determinant of ovarian response. These findings should be confirmed in prospective studies incorporating ovarian reserve markers and stimulation-related variables. Full article
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14 pages, 537 KB  
Review
Glucagon-like Peptide-1 Receptor Agonists and Endometrial Cancer: Potential Future in Fertility-Sparing Treatment
by Sonia Kotanidou, Roxani Dampali, Omer Devaja, Stephen Attard-Montalto, Michelle Godfrey, Andreas John Papadopoulos, Angelos Daniilidis, Nikolaos Nikolettos and Konstantinos Nikolettos
Reprod. Med. 2026, 7(3), 34; https://doi.org/10.3390/reprodmed7030034 - 18 Jul 2026
Viewed by 466
Abstract
Background: Endometrial cancer (EC) is one of the most prevalent cancers in women globally, which has recently gained attention as an increase has been noted among premenopausal women. Improving fertility-sparing treatments is crucial to assist women in completing their family planning. Methods [...] Read more.
Background: Endometrial cancer (EC) is one of the most prevalent cancers in women globally, which has recently gained attention as an increase has been noted among premenopausal women. Improving fertility-sparing treatments is crucial to assist women in completing their family planning. Methods: This study aims to explore the current evidence on the mechanisms of action and correlation between Glucagon-like Peptide-1 (GLP-1) and its agonists with EC, as well as the potential application in the conservative therapy for early-stage EC. A narrative review of the worldwide literature was conducted according to Scale for the Assessment of Narrative Review Articles (SANRA) principles, intending to analyze the correlation of GLP-1 receptor agonists (GLP-1RAs) with EC and their precise effect in the fertility-sparing treatment in women with atypical endometrial hyperplasia (AEH) or early-stage EC. Results: Preclinical studies indicate that GLP-1 receptor (GLP-1R) expression on healthy and malignant endometrial tissues of models regulates apoptosis via the AMPK-mTOR pathway. Observational and early clinical studies conclude that their role in the improvement of metabolic and hormonal imbalance increases the risk for the development of EC, as well as anti-tumour and anti-inflammatory effects. Conclusions: GLP-1RAs represent a potentially promising addition to the conservative management of AEH and early-stage EC in premenopausal women; however, further extensive clinical trials are required to ensure their safety and efficacy in future treatment algorithms and preconception exposure. Full article
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11 pages, 3738 KB  
Case Report
Lipschutz Ulcer—A Case Report with a Narrative Literature Review
by Doroteya Georgieva, Yavor Kornovski, Stanislav Slavchev, Yonka Ivanova, Angel Yordanov and Stoyan Kostov
Reprod. Med. 2026, 7(3), 33; https://doi.org/10.3390/reprodmed7030033 - 17 Jul 2026
Viewed by 476
Abstract
Background/Objectives: Lipschutz ulcers were first described in 1912 by the Austrian dermatologist Benjamin Lipschutz. The onset presents with flu-like symptoms with consecutive development of painful vulvar ulcers. The term is currently used to describe painful genital lesions associated with an immunological reaction to [...] Read more.
Background/Objectives: Lipschutz ulcers were first described in 1912 by the Austrian dermatologist Benjamin Lipschutz. The onset presents with flu-like symptoms with consecutive development of painful vulvar ulcers. The term is currently used to describe painful genital lesions associated with an immunological reaction to an extragenital source of infection, usually viral or bacterial infections or certain vaccines. This disease affects predominantly adolescent non-sexually active females and is usually self-limiting. Methods: We searched PubMed, Research Gate and Google Scholar using the keywords “Lipschutz ulcer”, “Ulcus vulvae acutum Lipschutz”, “Acute genital ulcer”, and “Reactive non-sexually related acute genital ulcers”. A total of 24 articles in English between the years 2000 and 2025 were selected in order to mark the latest advancements towards diagnostic and treatment plans. Only 19 provided thorough information about the treatment and follow-up of the patients, encompassing a total of 69 girls and women. Results: This review synthesizes the most common etiological factors for Lipschutz ulcers and explores the mechanism behind their development. Different treatment approaches were also investigated. Based on our findings, we propose a diagnostic and treatment algorithm depending on the patient’s general condition and severity of the ulcers. We reported a 12-year-old girl’s case, diagnosed and treated at our department. Despite our efforts, conservative therapy proved inefficient. Surgery was performed. Conclusions: Lipschutz’s ulcer is a diagnosis often overlooked. Therefore, further research is needed to address the best treatment strategies. Surgery should be reserved only for patients who show no improvement with conservative treatment. Full article
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8 pages, 540 KB  
Article
Comparison of Chromosomal Abnormalities in Blastocysts Generated by TESE-Derived and Ejaculated Sperm with High DNA Fragmentation
by Noura Khalid Alfhead, Sameerah Yasain Shaheen, Murid Javed and Hamad Alsufyan
Reprod. Med. 2026, 7(3), 32; https://doi.org/10.3390/reprodmed7030032 - 13 Jul 2026
Viewed by 447
Abstract
Objective: High sperm DNA fragmentation (SDF) results in fewer euploid embryos. Although sperm retrieved by testicular sperm extraction (TESE) has low SDF compared to the ejaculated sperm, there is little data comparing the prevalence of chromosomal abnormalities in the resulting embryos. The [...] Read more.
Objective: High sperm DNA fragmentation (SDF) results in fewer euploid embryos. Although sperm retrieved by testicular sperm extraction (TESE) has low SDF compared to the ejaculated sperm, there is little data comparing the prevalence of chromosomal abnormalities in the resulting embryos. The objective of this study was to compare rates of chromosomal abnormalities in blastocysts from sperm obtained either by TESE or ejaculate with high SDF. Methods: The blastocysts were generated by ICSI in both groups. The preimplantation genetic testing for aneuploidy (PGT-A) was performed by next-generation sequencing (NGS). This study utilized 2242 blastocysts from 400 couples; 200 couples in each group. The TESE-retrieved sperm and ejaculated sperm with high SDF had 1037 and 1205 blastocysts, respectively. The sperm DNA fragmentation was determined by the Halosperm G2 assay. The rates of euploid, aneuploid and mosaic embryos were compared by multivariate logistic regression and mixed-effects models that accounted for female age and ovarian reserve. Results: The TESE-derived sperm group had a significantly higher percentage of euploid blastocysts (67.8%) as compared to those derived from ejaculated sperm with high SDF (48.2%, p = 0.003). The multivariate logistic regression indicated that the sperm origin (TESE/ejaculate) was an independent predictor of euploid blastocysts [OR = 1.85; 95% CI = 1.05–3.26; p = 0.034]. The probability of having euploid blastocysts decreased by 6% for every 1% increase in the SDF. The increased age of the female was a major negative predictor [OR = 0.92 per year; 95% CI = 0.88–96; p = 0.001]. Conclusions: The TESE-derived sperm group had significantly higher euploid blastocysts as compared to the ejaculated sperm with high SDF group. Full article
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14 pages, 637 KB  
Article
Multicenter Post-Marketing Surveillance of Follitropin Alfa and Lutropin Alfa in Korean Patients with Severe Luteinizing Hormone Deficiency: Safety and Descriptive Real-World Outcomes
by Young-Je Kang, Chung-Hoon Kim, Aera Han, Dongho Suh, Kwang Moon Yang, Hee-Sun Lee, Chang Young Hur, Chan Park, Bum-Chae Choi, Miranda Hickey, Hyun-Sun Kong, Sungjin Ahn and Beom Jun Seo
Reprod. Med. 2026, 7(3), 31; https://doi.org/10.3390/reprodmed7030031 - 6 Jul 2026
Viewed by 526
Abstract
Purpose: This post-marketing surveillance study evaluated the real-world safety and descriptive outcomes of a fixed 2:1 recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) combination among Korean women undergoing assisted reproductive technology with severe LH and FSH deficiency (baseline endogenous [...] Read more.
Purpose: This post-marketing surveillance study evaluated the real-world safety and descriptive outcomes of a fixed 2:1 recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) combination among Korean women undergoing assisted reproductive technology with severe LH and FSH deficiency (baseline endogenous serum LH < 1.2 IU/L). Methods: A prospective, multicenter, observational study was conducted across 24 Korean fertility centers between August 2011 and May 2018. Safety outcomes included adverse events (AEs), adverse drug reactions (ADRs), and ovarian hyperstimulation syndrome (OHSS). Descriptive outcomes included endpoint-specific evaluable sets for follicular response and ultrasound-confirmed clinical pregnancy. Analyses were performed in safety (n = 600), follicular-response evaluable (n = 537), and pregnancy-evaluable (n = 486) sets. Results: Among patients in the safety set (mean age, 34.6 years), AEs occurred in 2.7% (16/600; 95% confidence interval [CI], 1.6–4.3), ADRs in 2.2% (13/600; 95% CI, 1.3–3.7), and OHSS in 1.3% (8/600; 95% CI, 0.7–2.6), including one severe case. In the follicular-response evaluable set, follicular response (≥1 follicle ≥17 mm) occurred in 99.3% (533/537; 95% CI, 98.1–99.7). In the pregnancy-evaluable set, clinical pregnancy occurred in 42.0% (204/486; 95% CI, 37.7–46.4), biochemical-only pregnancies in 3.1% (15/486; 95% CI, 1.9–5.0), and total pregnancies (clinical + biochemical-only, reported descriptively) in 45.1% (219/486; 95% CI, 40.7–49.5). Conclusions: In this historically constrained post-marketing surveillance cohort, the fixed 2:1 r-hFSH and r-hLH combination showed a favorable post-marketing safety profile and provided descriptive outcome information within endpoint-specific evaluable sets in women meeting the severe LH-deficiency criterion. Full article
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25 pages, 810 KB  
Review
Chronic Epididymitis and Orchitis: Pathophysiology, Diagnosis and Management in the Context of Male Infertility
by Simone Tammaro, Ugo Amicuzi, Michele Musone, Andrea Rubinacci, Paola Coppola, Dario Di Lieto, Luigi Napolitano, Marco Stizzo, Michelangelo Olivetta, Matteo Ferro, Antonio Madonna, Mariano Coppola, Stefano Chianese, Marco Magliocchetti, Giacomo Puca, Silvestro Imperatore, Pasquale Reccia, Francesco Paolo Calace, Marco Grillo, Dante Di Domenico, Sabin Octavian Tataru, Luigi De Luca, Celeste Manfredi, Davide Arcaniolo, Marco De Sio, Ciro Imbimbo, Felice Crocetto, Dario Del Biondo and Biagio Baroneadd Show full author list remove Hide full author list
Reprod. Med. 2026, 7(3), 30; https://doi.org/10.3390/reprodmed7030030 - 27 Jun 2026
Viewed by 3868
Abstract
Chronic epididymitis and orchitis represent significant yet frequently under-recognized contributors to male infertility, particularly among men of reproductive age. These conditions arise from persistent inflammatory or immunological processes affecting the epididymis and testis, leading to impaired spermatogenesis, altered sperm maturation and possible obstruction [...] Read more.
Chronic epididymitis and orchitis represent significant yet frequently under-recognized contributors to male infertility, particularly among men of reproductive age. These conditions arise from persistent inflammatory or immunological processes affecting the epididymis and testis, leading to impaired spermatogenesis, altered sperm maturation and possible obstruction of the male reproductive tract. Infectious aetiologies, especially those linked to sexually transmitted pathogens and uropathogens, remain predominant; however, non-infectious mechanisms, including autoimmune activation, post-vasectomy changes and idiopathic inflammation, also play critical roles. The persistent inflammatory milieu induces cytokine release, oxidative stress and structural tissue remodelling, ultimately compromising the functional and immune-privileged microenvironment necessary for optimal sperm production and transport. Diagnostic evaluation requires a multimodal approach incorporating clinical examination, microbiological testing, semen analysis and scrotal ultrasonography, with advanced imaging and molecular assays reserved for complex or equivocal cases. Management is individualized and may involve antimicrobial therapy, anti-inflammatory treatment, immunomodulation or microsurgical intervention in cases of ductal obstruction. Assisted reproductive technologies provide additional options when natural conception is not feasible. Despite increased recognition of their impact, chronic epididymitis and orchitis remain insufficiently studied, with gaps in standardized definitions, biomarker validation and long-term outcome data. This review provides a focused synthesis and phenotype-driven clinical framework for chronic epididymitis and orchitis through a fertility-preservation lens, bridging urological and andrological perspectives and integrating evidence on subclinical inflammation, contemporary diagnostic biomarkers and a staged therapeutic pathway. Full article
(This article belongs to the Special Issue Update in Reproductive Surgery)
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Article
Hormonal Profiles and Y Chromosome AZF Microdeletions in Moroccan Azoospermic Men: A Molecular and Endocrine Study
by Manal Abouelouafa, Brahim El Houate, Adnane Hakem, Modou Mamoune Mbaye, Mariame Kabbour, Anas Mbarki, Hicham El Ossmani and Youssef Bakri
Reprod. Med. 2026, 7(3), 29; https://doi.org/10.3390/reprodmed7030029 - 25 Jun 2026
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Abstract
Background/Objectives: Y chromosome microdeletions in the azoospermia factor (AZF) regions are a major genetic cause of severe male infertility, yet their relationship with hormonal profiles in azoospermic men remains unclear. This study aimed to investigate AZF microdeletions and associated hormonal parameters in [...] Read more.
Background/Objectives: Y chromosome microdeletions in the azoospermia factor (AZF) regions are a major genetic cause of severe male infertility, yet their relationship with hormonal profiles in azoospermic men remains unclear. This study aimed to investigate AZF microdeletions and associated hormonal parameters in azoospermic patients. Methods: Azoospermic patients were screened for AZFa, AZFb, and AZFc microdeletions using multiplex real-time PCR targeting sequence-tagged site (STS) markers (sY84, sY127, and sY254). Patients were categorized into AZF-negative and AZF-positive groups, with the latter further stratified according to their deletion subtype. Serum follicle-stimulating hormone (FSH), testosterone, and inhibin B levels were measured. Hormonal parameters were compared between groups using the Mann–Whitney U test, and a logistic regression analysis was performed to evaluate associations between hormonal variables and AZF deletion status. Results: AZF microdeletions were detected in 18.7% (17/91) of patients. Patients without AZF deletions showed a median FSH level of 17.40 (7.12–31.27) IU/L. In contrast, AZFc deletion carriers exhibited an intermediate median FSH level of 21.10 (16.11–26.10) IU/L and lower median inhibin B concentrations (25.50 [25.25–26.00] pg/mL) compared with AZF-negative patients (56.00 [33.50–106.50] pg/mL). Median testosterone levels in AZFc patients (3.61 [2.87–4.35] ng/mL) remained within the expected physiological range. However, no statistically significant differences were observed between the AZF subgroups for age (p = 0.262), FSH (p = 0.506), testosterone (p = 0.615), or inhibin B (p = 0.524). The logistic regression analysis also showed no significant association between hormonal parameters and AZF deletion status. Conclusions: Hormonal parameters alone are insufficient to predict the presence of AZF microdeletions in azoospermic men. These findings highlight the importance of routine genetic screening for accurate diagnosis, clinical management, and reproductive counseling in male infertility. Full article
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