Advances in Reproductive Health

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Obstetrics and Gynecology".

Deadline for manuscript submissions: 10 November 2026 | Viewed by 4147

Special Issue Editor


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Guest Editor
Department of Surgical Sciences, Obstetrics and Gynecology, Faculty of Medicine and Pharmacy, University of Oradea, 1 University Street, 410087 Oradea, Romania
Interests: childbirth; gynecological ultrasound; obstetric gynecological ultrasonography; colposcopy; gynecological laparoscopic surgery; maternal-fetal medicine; couple infertility treatment and assisted human reproduction

Special Issue Information

Dear Colleagues,

Reproductive health is a rapidly evolving field, shaped by biomedical innovation and demographic change. Declining birth rates, increasing infertility, and the expanding use of assisted reproductive technologies (ARTs) underline its medical and societal importance. Current estimates show that one in six adults worldwide will face infertility during their lifetime, affecting more than 110 million women and 55 million men. In parallel, ART has grown steadily, with about 2.5 million in vitro fertilization (IVF) cycles performed annually, leading to the birth of over 13 million children since 1978.

This Special Issue offers a platform to highlight the latest advances in reproductive health, with a focus on both fundamental science and clinical translation. We invite contributions on reproductive endocrinology, infertility diagnostics and treatment, maternal–fetal medicine, fertility preservation, contraception, and ART innovation. We especially encourage studies exploring embryo culture media, invasive and non-invasive embryo testing, genetic screening in fertility care, the influence of sperm parameters on outcomes, and the role of chronic endometritis in implantation failure. The importance and the use of AI (artificial intelligence) in the field of reproductive medicine also warrants consideration.

By bringing together original research, clinical studies, and critical reviews, this Special Issue aims to foster interdisciplinary dialogue and provide new insights that advance evidence-based practice and improve reproductive outcomes worldwide.

Dr. Anca Huniadi
Guest Editor

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Keywords

  • in vitro fertilization
  • PGT-A
  • non-invasive embryo testing
  • chronic endometritis
  • embryo culture
  • aneuploidy
  • artificial intelligence

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Published Papers (5 papers)

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Research

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13 pages, 575 KB  
Article
Relationship Between Sperm DNA Fragmentation and Composite Morphological Indices: A Multivariable Analysis
by Veliscu Andreea Carp, Liana Ștefan, Petronela Naghi, Diana Mocuța, Cristina Aur, Liliana Sachelarie and Mircea Sandor
Medicina 2026, 62(4), 679; https://doi.org/10.3390/medicina62040679 - 2 Apr 2026
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Abstract
Background and Objectives: Although conventional semen analysis remains central in male infertility evaluation, the biological relationship between sperm morphology and genomic integrity remains incompletely defined. Sperm DNA fragmentation (SDF) has emerged as a clinically relevant marker of genomic instability; however, its relationship [...] Read more.
Background and Objectives: Although conventional semen analysis remains central in male infertility evaluation, the biological relationship between sperm morphology and genomic integrity remains incompletely defined. Sperm DNA fragmentation (SDF) has emerged as a clinically relevant marker of genomic instability; however, its relationship with composite morphological indices of spermatogenic dysfunction remains debated. This study aimed to evaluate the relationship between sperm DNA fragmentation assessed in the post-swim-up fraction and composite sperm morphological indices derived from raw semen, using a multivariable analytical framework that accounts for conventional semen parameters. Materials and Methods: This observational study included 183 semen samples from men undergoing fertility evaluation. SDF was assessed using a sperm chromatin dispersion (SCD)-based assay in the post-swim-up fraction. Sperm morphology was evaluated in raw semen according to World Health Organization criteria, and composite morphological indices, namely the Teratozoospermia Index (TZI), Sperm Deformity Index (SDI), and Multiple Anomalies Index (MAI), were calculated. Associations were examined using Spearman correlation and multivariable linear regression models adjusted for sperm concentration and progressive motility. Exploratory distributional analyses were performed across clinically defined SDF categories. Results: Bivariate analyses demonstrated weak, non-significant positive correlations between SDF and all composite morphological indices. None of the morphological indices independently predicted SDF after adjustment for sperm concentration and progressive motility in multivariable regression models. In contrast, sperm concentration showed a consistent inverse association with SDF. Distributional analyses revealed substantial overlap between morphological severity and SDF categories, indicating heterogeneity in the co-occurrence of structural abnormalities and DNA fragmentation at the individual sample level. Conclusions: Composite sperm morphological indices were not independently associated with sperm DNA fragmentation after adjusting for quantitative semen parameters in the present analytical framework. These findings suggest that structural abnormalities and genomic instability may capture complementary aspects of male infertility rather than representing interchangeable markers. SDF assessment may therefore provide complementary diagnostic information beyond morphology-based evaluation, particularly in assisted reproductive contexts. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
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17 pages, 361 KB  
Article
Divergent Associations of the VEGF (–2578C/A) Polymorphism with Imaging-Based Severity and Symptom Profile of Adenomyosis in Infertile Women: An Exploratory Analysis
by Mihai Surcel, Mihaela Iancu, Ioana Cristina Rotar, Iulian Goidescu, Adelina Staicu, Georgiana Nemeti, Dan Boitor-Borza, Roxana Liana Lucaciu, Adriana Corina Hangan, Daniel Mureșan and Lucia Maria Procopciuc
Medicina 2026, 62(3), 571; https://doi.org/10.3390/medicina62030571 - 19 Mar 2026
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Abstract
Background and Objectives: Adenomyosis is increasingly being recognized as a heterogeneous uterine disorder with variable clinical expressions. Current ultrasound-based classifications do not consistently align structural severity with symptom burden. Given its role in angiogenesis, inflammation, and endometrial remodeling, vascular endothelial growth factor [...] Read more.
Background and Objectives: Adenomyosis is increasingly being recognized as a heterogeneous uterine disorder with variable clinical expressions. Current ultrasound-based classifications do not consistently align structural severity with symptom burden. Given its role in angiogenesis, inflammation, and endometrial remodeling, vascular endothelial growth factor (VEGF) signaling may influence both morphological features and clinical manifestations. This study evaluated the association between three VEGF polymorphisms (−2578C/A, −634G/C, −936C/T) and adenomyosis presence, ultrasound-based severity, and symptoms in infertile women undergoing in vitro fertilization (IVF). Materials and Methods: In this prospective cohort study, 85 infertile women were assessed for adenomyosis using MUSA criteria and Exacoustos grading. VEGF genotyping was performed by PCR-RFLP. Clinical data included menstrual bleeding status scores and dysmenorrhea intensity. Results: Under a dominant model, the variant genotypes (AA+CA) of the VEGF–2578C/A polymorphism −2578 A showed increased odds of adenomyosis versus CC (adjusted OR = 4.00, 95% CI: 1.48–10.84; p = 0.0037). The A allele frequency was higher in women with adenomyosis (57.14% vs. 33%), which was consistent with increased susceptibility (OR = 2.71, 95% CI: 1.44–5.09; p = 0.003). The AA + CA genotypes were more frequent with higher ultrasound-based severity (p = 0.0029; 50% vs. 72% vs. 100% across increasing severity strata); however, among women with adenomyosis, AA + CA carriers had lower odds of clinically relevant dysmenorrhea (adjusted OR = 0.18, 95% CI: 0.06–0.55; p = 0.0017), which remained significant after correction for multiple testing (adjusted p = 0.0051). No significant associations were identified for −936C/T or −634G/C across adenomyosis presence, ultrasound-based severity, number of sonographic features, dysmenorrhea, or heavy menstrual bleeding (all p > 0.05). Conclusions: These preliminary findings suggest divergent associations of VEGF −2578C/A with structural severity versus symptom expression, supporting a partial dissociation between ultrasound-defined severity and clinical phenotype in adenomyosis. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
13 pages, 458 KB  
Article
Sperm DNA Fragmentation Is Associated with Impaired Directional Motility and Kinematic Efficiency: A CASA-Based Study
by Ioana Cristina Rotar, Richard Buda, Adelin Marcu, Petronela Naghi, Liliana Sachelarie, David Călin Buzlea, Anca Huniadi and Mircea Ioan Sandor
Medicina 2026, 62(2), 376; https://doi.org/10.3390/medicina62020376 - 13 Feb 2026
Viewed by 684
Abstract
Background and Objectives: Sperm DNA fragmentation (SDF) has emerged as an important marker of male reproductive potential; however, its relationship with sperm kinematic performance remains incompletely understood. While conventional semen analysis primarily evaluates sperm concentration and motility, computer-assisted semen analysis (CASA) enables [...] Read more.
Background and Objectives: Sperm DNA fragmentation (SDF) has emerged as an important marker of male reproductive potential; however, its relationship with sperm kinematic performance remains incompletely understood. While conventional semen analysis primarily evaluates sperm concentration and motility, computer-assisted semen analysis (CASA) enables a more detailed assessment of sperm motility parameters, including velocity, path length, and directionality. Materials and Methods: This observational study included 183 semen samples, stratified by SDF levels into control (1–15%), mild (15.01–25%), moderate (25.01–50%), and severe (>50%) fragmentation groups. Sperm kinematic parameters were assessed using CASA, including curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), straightness (STR), and wobble (WOB). Group comparisons were performed using ANOVA or Kruskal–Wallis tests, correlation analyses were conducted using Spearman’s rank coefficient, and multivariable linear regression models were applied to evaluate the independent effect of SDF after adjustment for sperm concentration and progressive motility. Results: Parameters reflecting directional motility and movement efficiency differed significantly across increasing SDF categories. VSL, LIN, STR, and WOB showed a progressive decline with higher levels of DNA fragmentation, whereas VCL and VAP did not demonstrate a proportional decrease across groups. Correlation analysis revealed significant negative associations between SDF and VSL (ρ = −0.367, p < 0.001), VAP (ρ = −0.323, p < 0.001), and VCL (ρ = −0.202, p = 0.006), while correlations with LIN, STR, and WOB were negative but not statistically significant. Multivariable regression analysis confirmed SDF as an independent negative predictor of VSL and VAP after adjustment for conventional semen parameters, whereas the association with VCL was no longer significant. Conclusions: Increased sperm DNA fragmentation is associated with impaired sperm motility efficiency and directionality, rather than a uniform reduction in motility. These findings highlight the functional relevance of sperm DNA integrity in shaping sperm kinematic performance and support the complementary use of SDF assessment and CASA parameters in evaluating male fertility. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
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13 pages, 297 KB  
Article
Follicular Klotho in the Ovarian Microenvironment: Exploring Its Role in IVF Outcome Prediction
by Mehmet Alican Sapmaz, Sait Erbey, Murat Polat, Selin Yıldız, İnci Kahyaoğlu, Ömer Osman Eroğlu, Emine Utlu Özen and Ayfer Bakır
Medicina 2026, 62(1), 139; https://doi.org/10.3390/medicina62010139 - 9 Jan 2026
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Abstract
Background and Objectives: Klotho (KL) is a multifunctional protein involved in reproductive physiology; however, its precise role in ovarian reserve and in vitro fertilization (IVF) outcomes remains unclear. This study aimed to evaluate the relationship between follicular fluid KL levels, ovarian reserve markers, [...] Read more.
Background and Objectives: Klotho (KL) is a multifunctional protein involved in reproductive physiology; however, its precise role in ovarian reserve and in vitro fertilization (IVF) outcomes remains unclear. This study aimed to evaluate the relationship between follicular fluid KL levels, ovarian reserve markers, and key IVF success parameters. Materials and Methods: This prospective study included a total of 150 women undergoing IVF, of whom 82 had diminished ovarian reserve (DOR) and 68 had normal ovarian reserve (NOR). All participants underwent controlled ovarian stimulation using a standard antagonist protocol. During oocyte pick-up (OPU), the first aspirated follicular fluid sample was collected, processed, and analyzed for KL concentrations using a Human Klotho ELISA kit. Hormonal profiles, ovarian reserve markers, and IVF outcomes were compared between groups. Results: Follicular fluid KL levels were significantly lower in the DOR group compared with the NOR group (117.07 ± 28.88 pg/mL vs. 266.13 ± 58.29 pg/mL; p < 0.001). Anti-Müllerian hormone (AMH) levels were reduced, whereas follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were significantly higher in the DOR group (all p < 0.001). Implantation and clinical pregnancy rates were also significantly lower in the DOR group compared with the NOR group (p < 0.001 and p = 0.003, respectively). KL levels showed a strong positive correlation with the number of fertilized oocytes in both groups (DOR: r = 0.690; NOR: r = 0.552). Each one-unit increase in KL was associated with a 3.7% increase in implantation probability and a 3.2% increase in clinical pregnancy probability in the DOR group, and with corresponding increases of 4.4% and 1.2% in the NOR group (all p < 0.05). Conclusions: This study demonstrates significant associations between follicular fluid KL levels and fertilization, implantation, and clinical pregnancy outcomes. These associations appear to be more pronounced than those observed with traditional ovarian reserve markers such as AMH and antral follicle count. Reduced KL levels are associated with fewer fertilized oocytes, whereas higher KL concentrations correspond to increased implantation and clinical pregnancy probabilities. Nevertheless, similar to other non-invasive biomarkers, current evidence is insufficient to support routine clinical use of KL. Large-scale, well-designed, multicenter studies are therefore required to validate its clinical relevance and to determine whether KL can serve as a reliable and practical predictor of IVF success. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)

Review

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13 pages, 1044 KB  
Review
The Role of Ophthalmic Artery Doppler in Predicting Preeclampsia: A Review of the Literature
by Nicoleta Gana, Ancuța Năstac, Livia Mihaela Apostol, Iulia Huluță, Corina Gica, Gheorghe Peltecu and Nicolae Gica
Medicina 2026, 62(1), 186; https://doi.org/10.3390/medicina62010186 - 16 Jan 2026
Viewed by 1145
Abstract
Background and Objectives: Preeclampsia (PE) complicates 2–8% of pregnancies globally, with a higher incidence in developing countries. This condition poses significant risks to maternal and fetal health, contributing substantially to maternal and perinatal mortality, particularly in cases of early-onset PE, which is associated [...] Read more.
Background and Objectives: Preeclampsia (PE) complicates 2–8% of pregnancies globally, with a higher incidence in developing countries. This condition poses significant risks to maternal and fetal health, contributing substantially to maternal and perinatal mortality, particularly in cases of early-onset PE, which is associated with severe complications. This review aims to synthesize current evidence regarding the predictive utility of ophthalmic artery Doppler for preeclampsia. Current strategies focus on early prediction and prevention to mitigate adverse outcomes and reduce the economic burden of hypertensive disorders in pregnancy. The International Federation of Gynecology and Obstetrics (FIGO) recommends first-trimester screening combining maternal risk factors, mean arterial pressure, serum placental growth factor (PlGF), and uterine artery pulsatility index (UtA-PI). High-risk women are advised to take low-dose aspirin (150 mg daily) until 36 weeks of gestation. Materials and Methods: This review explores an innovative predictive tool for PE: ophthalmic artery (OA) Doppler. Results: As a non-invasive and easily accessible method, OA Doppler provides valuable insights into intracranial vascular resistance, offering potential advantages in early risk assessment, particularly for preterm PE, the most severe form of the disease. Conclusions: Our findings suggest that OA Doppler may serve as a promising adjunct in PE screening, enhancing the early identification of high-risk pregnancies and improving clinical outcomes. Further research is warranted to validate its role in routine prenatal care. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
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