Female Infertility: Clinical Diagnosis and Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 3106

Special Issue Editor


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Guest Editor
Center for Reproductive Medicine, University of Liege, Boulevard du 12ème de Ligne 1, 4000 Liege, Belgium
Interests: oncofertility; fertility preservation; implantation failure; ovulatory disorders; endometriosis; infertility; IVF
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Special Issue Information

Dear Colleagues,

Advancements in the diagnosis and treatment of female infertility over the past few decades have been truly remarkable. Innovations such as exploring the endometrial microbiome, genetic screening, and diagnosing conditions like endometriosis via micro-RNA are transforming the field. Additionally, emerging techniques for the prediction of the embryo with the best implantation potential, regardless of its morphological development, and the improvement of sperm selection are enhancing pregnancy success rates. Cutting-edge approaches like preimplantation genetic testing and advanced sperm selection methods promise significant clinical improvements. Integrating these new technologies and methods into treatment protocols offers unprecedented opportunities for couples facing reproductive challenges. For this Special Issue, we invite authors to submit articles on these revolutionary clinical advances, contributing to the future of reproductive medicine by helping to develop new strategies that continually improve infertility care.

Dr. Laurie Henry
Guest Editor

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Keywords

  • infertility
  • assisted reproductive techniques
  • diagnosis
  • implantation
  • gametes

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Published Papers (5 papers)

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Research

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13 pages, 2663 KiB  
Article
The Effects of Filgrastim and Hyaluronic Acid on the Endometrium in Experimentally Induced Asherman Syndrome Rat Models: A Prospective Laboratory Study
by Merve Genco, Mehmet Genco, Fisun Vural and Nermin Koç
J. Clin. Med. 2025, 14(10), 3334; https://doi.org/10.3390/jcm14103334 (registering DOI) - 11 May 2025
Abstract
Background/Objectives: The aim of the present study was to explore the histopathological effects and tissue Vascular Endothelial Growth Factor (VEGF) levels of filgrastim and hyaluronic acid treatment in a rat model with experimentally induced Asherman syndrome. Methods: In this study, 26 female Sprague [...] Read more.
Background/Objectives: The aim of the present study was to explore the histopathological effects and tissue Vascular Endothelial Growth Factor (VEGF) levels of filgrastim and hyaluronic acid treatment in a rat model with experimentally induced Asherman syndrome. Methods: In this study, 26 female Sprague Dawley rats were used. First, a rat model of Asherman syndrome was established in two rats, and the remaining rats were randomly divided into three groups. A total of 0.1 mL trichloroacetic acid was applied to the right uterine horns of all groups to induce adhesion formation.Group I received no treatment, Group II received intrauterine hyaluronic acid treatment (0.01), Group III received subcutaneous Filgrastim treatment (50 μg/kg/day), and Group IV received both intrauterine hyaluronic acid and subcutaneous Filgrastim treatment. Histopathological analysis of uterine horns in the rats with and without Asherman syndrome, inflammation, glandular count, and fibrosis levels were examined. Tissue VEGF levels were investigated immunohistochemically. Results: Hyaluronic acid treatment resulted in an increase only in uterine lumen diameter and VEGF levels, while Filgrastim treatment led to an increase in uterine wall diameter, lumen diameter, gland count, and VEGF levels, as well as a decrease in fibrosis and inflammation scores. Combined treatment with filgrastim and hyaluronic acid showed an increase in lumen diameter, gland count, and VEGF levels, along with a decrease in inflammation and fibrosis scores (p < 0.05). Filgrastim treatment resulted in better effects for Asherman syndrome compared to hyaluronic acid treatment. There were no beneficial effects seen with the combined therapy. Conclusions: Filgrastim treatment resulted in better outcomes for Asherman syndrome compared to hyaluronic acid treatment. The combined therapy did not show additional benefits beyond what was achieved with Filgrastim treatment alone. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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Review

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16 pages, 688 KiB  
Review
The Role of Artificial Intelligence in Female Infertility Diagnosis: An Update
by Necati Findikli, Catherine Houba, David Pening and Anne Delbaere
J. Clin. Med. 2025, 14(9), 3127; https://doi.org/10.3390/jcm14093127 - 30 Apr 2025
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Abstract
Female infertility is a multifaceted condition affecting millions of women worldwide, with causes ranging from hormonal imbalances and genetic predispositions to lifestyle and environmental factors. Traditional diagnostic approaches, such as hormonal assays, ultrasound imaging, and genetic testing, often require extensive time, resources, and [...] Read more.
Female infertility is a multifaceted condition affecting millions of women worldwide, with causes ranging from hormonal imbalances and genetic predispositions to lifestyle and environmental factors. Traditional diagnostic approaches, such as hormonal assays, ultrasound imaging, and genetic testing, often require extensive time, resources, and expert interpretation. In recent years, artificial intelligence (AI) has emerged as a transformative tool in the field of reproductive medicine, offering advanced capabilities for improving the accuracy, efficiency, and personalization of infertility diagnosis and treatment. AI technologies demonstrate significant potential in analyzing vast and complex datasets, identifying hidden patterns, and providing data-driven insights that enhance clinical decision-making processes in assisted reproductive technologies (ART) services. This narrative review explores the current advancements in AI applications in female infertility diagnostics and therapeutics, highlighting key technological innovations, their clinical implications, and existing limitations. It also discusses the future potential of AI in revolutionizing reproductive healthcare. As AI-based technologies continue to evolve, their integration into reproductive medicine is expected to pave the way for more accessible, cost-effective, and personalized fertility care. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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14 pages, 750 KiB  
Review
The Effects of Endometriosis on Oocyte and Embryo Quality
by Necati Findikli, Sandie Janssens, Giovanna Fasano, Isabelle Demeestere, Maxime Fastrez, Catherine Houba and Anne Delbaere
J. Clin. Med. 2025, 14(7), 2339; https://doi.org/10.3390/jcm14072339 - 28 Mar 2025
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Abstract
Endometriosis is a complex and multifaceted gynecological disorder characterized by the abnormal growth and presence of endometrial-like tissue outside the confines of the uterine cavity. It can lead to a wide range of distressing symptoms, including chronic pelvic pain, heavy and/or irregular menstrual [...] Read more.
Endometriosis is a complex and multifaceted gynecological disorder characterized by the abnormal growth and presence of endometrial-like tissue outside the confines of the uterine cavity. It can lead to a wide range of distressing symptoms, including chronic pelvic pain, heavy and/or irregular menstrual bleeding, and significant challenges with fertility. While the association between endometriosis and infertility is well recognized, the precise mechanisms through which the disease affects oocyte and embryo quality remain controversial. Studies that utilized transcriptomic, metabolomic, and ultrastructural analyses indicated dysregulated energy metabolism, oxidative stress, mitochondrial dysfunction, and inflammatory alterations in the ovarian microenvironment. The impact of endometriosis on fertilization, embryo development, and implantation remains debated, with conflicting findings across different study designs. Some investigations reported impaired oocyte morphology, reduced fertilization rates, and poorer embryo quality, while others suggested that endometriosis does not significantly affect ART outcomes when confounding factors are controlled. Recent studies highlight the importance of distinguishing the disease severity, lesion location, and prior surgical interventions when assessing reproductive outcomes. The need for standardized methodologies in evaluating oocyte and embryo quality, alongside personalized treatment approaches, is emphasized. Further research is warranted to elucidate the precise molecular mechanisms underlying these effects and to develop targeted therapeutic strategies aimed at improving ART success in women with endometriosis. This narrative review provides a thorough examination of the previous research on the impact of endometriosis on oocyte and embryo quality, highlighting both the known mechanisms and the areas that require further investigation. This will help to guide future research and clinical management strategies to improve reproductive outcomes for women with endometriosis. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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13 pages, 2646 KiB  
Review
Endometriosis and Infertility: Gynecological Examination Practical Guide
by Alice Moïse, Milana Dzeitova, Laurent de Landsheere, Michelle Nisolle and Géraldine Brichant
J. Clin. Med. 2025, 14(6), 1904; https://doi.org/10.3390/jcm14061904 - 12 Mar 2025
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Abstract
Endometriosis, a prevalent gynecological condition affecting 10–15% of reproductive-age women, involves the growth of endometrial-like tissue outside the uterine cavity. This chronic inflammatory disease can significantly impact fertility by disrupting ovulation, tubal transport, and implantation. Clinical manifestations vary widely, ranging from asymptomatic cases [...] Read more.
Endometriosis, a prevalent gynecological condition affecting 10–15% of reproductive-age women, involves the growth of endometrial-like tissue outside the uterine cavity. This chronic inflammatory disease can significantly impact fertility by disrupting ovulation, tubal transport, and implantation. Clinical manifestations vary widely, ranging from asymptomatic cases to severe pelvic pain, dysmenorrhea, and dyspareunia. Accurate diagnosis remains challenging, often requiring a combination of patient history, clinical examination, and imaging studies. This paper will discuss the clinical approach to endometriosis during a first-line gynecological appointment, focusing on patient history, including detailed assessment of menstrual, pelvic, and bowel symptoms, and clinical examination; thorough gynecological examination, including abdominal and pelvic palpation, speculum examination, and bimanual examination; imaging evaluation (particularly of the role of ultrasound in identifying and characterizing endometriotic lesions, including the use of the #ENZIAN classification for deep infiltrating endometriosis and evaluation of fertility impact); and discussion of the Endometriosis Fertility Index (EFI) as a tool for assessing fertility potential. This comprehensive approach aims to guide clinicians in identifying and managing endometriosis effectively, improving patient outcomes and optimizing fertility management strategies. Methods: A literature search for suitable articles published from January 1974 to 2024 in the English language was performed using PubMed. Results: Endometriosis is associated with infertility rates ranging from 20% to 68%, with mechanisms including pelvic adhesions, chronic inflammation, and immune dysregulation. The revised American Society for Reproductive Medicine (rASRM) classification and #ENZIAN classification were identified as essential tools for staging and characterizing the disease. Transvaginal ultrasound (TVS) demonstrated high diagnostic accuracy for deep infiltrating endometriosis, with a sensitivity of up to 96% and specificity of 99%. EFI emerged as a valuable predictor of natural conception post-surgery. Additionally, the review underscores the frequent co-occurrence of adenomyosis in women with endometriosis, which may further compromise fertility. Despite advancements in imaging techniques and classification systems, the variability in symptom presentation and disease progression continues to challenge early diagnosis and effective management. Conclusions: Endometriosis is a prevalent gynecological condition affecting women of reproductive age and is associated with infertility. This paper describes the diagnostic approach to endometriosis during a first-line gynecological appointment, focusing on clinical history, physical examination, and the role of imaging, particularly ultrasound, in identifying and characterizing endometriosis lesions. The adoption of standardized classification systems such as #ENZIAN and EFI enhances disease staging and fertility prognosis, allowing for tailored treatment strategies. Despite improvements in non-invasive diagnostic methods, challenges persist in correlating symptom severity with disease extent, necessitating continued research into biomarkers and novel imaging techniques. Additionally, the frequent coexistence of adenomyosis further complicates fertility outcomes, underscoring the need for comprehensive management strategies. Further research is needed to enhance early detection strategies and optimize fertility preservation techniques for affected women. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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Other

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15 pages, 1535 KiB  
Systematic Review
Controversial Roles of Autophagy in Adenomyosis and Its Implications for Fertility Outcomes—A Systematic Review
by Julie Vervier, Marlyne Squatrito, Michelle Nisolle, Laurie Henry and Carine Munaut
J. Clin. Med. 2024, 13(24), 7501; https://doi.org/10.3390/jcm13247501 - 10 Dec 2024
Viewed by 1034
Abstract
Background/Objectives: Adenomyosis is a benign condition where ectopic endometrial glandular tissue is found within the uterine myometrium. Its impact on women’s reproductive outcomes is substantial, primarily due to defective decidualization, impaired endometrial receptivity, and implantation failure. The exact pathogenesis of the disease remains [...] Read more.
Background/Objectives: Adenomyosis is a benign condition where ectopic endometrial glandular tissue is found within the uterine myometrium. Its impact on women’s reproductive outcomes is substantial, primarily due to defective decidualization, impaired endometrial receptivity, and implantation failure. The exact pathogenesis of the disease remains unclear, and the role of autophagy in adenomyosis and its associated infertility is not well understood. The aim of this systematic review was to conduct an exhaustive search of the literature to clarify the role of autophagy in the pathogenesis of adenomyosis. Methods: A systematic search was conducted in Medline, Embase, and Scopus databases up to the date of 20 August 2024. We included all English-written publications assessing the role of autophagy in the pathogenesis of adenomyosis. Results: Seventeen eligible articles were identified, including reviews and experimental studies involving human samples and murine models. The results showed that the role of autophagy in adenomyosis is controversial, with studies showing both increased and decreased levels of autophagy in adenomyosis. Conclusions: Autophagy plays a dual role in cell survival and death. Increased autophagy might support the survival and proliferation of ectopic endometrial cells, while decreased autophagy could prevent cell death, leading to abnormal growth. Oxidative stress may trigger pro-survival autophagy, mitigating apoptosis and promoting cellular homeostasis. Hormonal imbalances disrupt normal autophagic activity, potentially impairing endometrial receptivity and decidualization and contributing to infertility. The balance of autophagy is crucial in adenomyosis, with its dual role contributing to the complexity of the disease. Limitations: A few studies have been conducted with heterogeneous populations, limiting comparative analyses. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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