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Life
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Human Infertility and Reproductive Endocrinology: 2nd Edition
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Human Infertility and Reproductive Endocrinology: 2nd Edition

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Reproductive and Developmental Biology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 10850

Special Issue Editor

Dr. Giuseppe Grande

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Guest Editor
Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy
Interests: reproductive endocrinology; male infertility; andrology; hypogonadism; proteomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The second volume of this Special Issue follows on from the success of the first. We invite you to publish your research in this edition of “Human Infertility and Reproductive Endocrinology” (https://www.mdpi.com/journal/life/special_issues/6R8KIXVW2L).

Infertility is a common clinical problem, affecting 13% to 15% of couples worldwide. In addition, infertility is considered a public problem, not only affecting couples’ lives, but also healthcare services and the social environment. The male factor is solely responsible for about 20% of infertile couples and contributory to another 30–40%. The female factor is responsible, solely or associated with the male factor, for about 50% of the cases.

This Special Issue will focus on human fertility and infertility, both at the molecular and clinical levels, including the hormonal regulation of male and female fertility, diagnosis and treatment of diseases causing infertility, and the clinical management of infertile couples.

Dr. Giuseppe Grande
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infertility
  • reproduction
  • reproductive endocrinology
  • male infertility
  • female infertility

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Published Papers (5 papers)

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Research

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10 pages, 371 KB  
Article
Gut Dysbiosis in Infertile Patients with Persistent Male Accessory Gland Infection
by Giuseppe Grande, Andrea Graziani, Raffaele Scafa, Luca De Toni, Andrea Garolla and Alberto Ferlin
Life 2025, 15(6), 894; https://doi.org/10.3390/life15060894 - 31 May 2025
Cited by 2 | Viewed by 1812
Abstract
Male tract infections (MTIs) are a common clinical condition, often presenting without any signs nor symptoms of disease. As advised by the European Urology Guidelines dealing with this topic, patients are typically treated with antibiotics alone. Nevertheless, in between 40% and 50% of [...] Read more.
Male tract infections (MTIs) are a common clinical condition, often presenting without any signs nor symptoms of disease. As advised by the European Urology Guidelines dealing with this topic, patients are typically treated with antibiotics alone. Nevertheless, in between 40% and 50% of cases, antibiotic therapy is not effective in eradicating the semen infection. Therefore, persistent semen infection is frequently found upon semen culture evaluation following antibiotic therapy. In this study, we aimed to analyze the fecal microbiota of male infertile patients with persistent MTI in order to verify the prevalence of gut dysbiosis in these patients. We therefore enrolled 20 infertile patients with persistent MTIs after a proper cycle of antibiotic treatment. All patients performed the study for gut microbiota analysis after about 30 days after the last dose of antibiotic treatment. Gut microbiota analysis revealed that 50% of patients with persistent MTI presented a reduction in microbial biodiversity. Indeed, a situation of gut dysbiosis was reported in 75% of patients. In details, the Firmicutes–Bacteroidetes ratio was reduced in 70% of such patients, including 40% of patients where a severe reduction was observed due to an elevated abundance of Bacteroidetes (putrefactive dysbiosis). The most frequent enterotype was Prevotella-dominant (43%). We demonstrated for the first time that patients with recurrent MTIs have enterotypes associated with increased gut permeability and systemic inflammation. Further studies are required to analyze the molecular machinery by which gut dysbiosis exerts its role in patients with MTIs, in particular persistent MTIs, and how supplementation with probiotics might impact in terms of restoring eubiosis, in terms of eradicating the infection, and reducing prostate inflammation and eventually in terms of improving semen evaluation in male infertile patients. Full article
(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)
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14 pages, 2200 KB  
Article
CD56-Positive NK Cells and CD138-Positive Plasma Cells in Basal Decidua of Term Placentas in Singleton Pregnancies After Assisted Reproductive Technology Treatment of Endometriosis-Related Infertility
by Stipe Dumancic, Marinela Bakotin Jakovac, Marko Drazen Mimica, Sandra Zekic Tomas and Jelena Marusic
Life 2025, 15(2), 240; https://doi.org/10.3390/life15020240 - 5 Feb 2025
Cited by 3 | Viewed by 3460
Abstract
A eutopic endometrium in endometriosis shows altered immune responses, including abnormalities of NK cells and expression of plasma cells, related to reproductive issues. This study investigated the counts of CD56-positive NK cells and CD138-positive plasma cells in the basal decidua of term placentas [...] Read more.
A eutopic endometrium in endometriosis shows altered immune responses, including abnormalities of NK cells and expression of plasma cells, related to reproductive issues. This study investigated the counts of CD56-positive NK cells and CD138-positive plasma cells in the basal decidua of term placentas in singleton pregnancies after endometriosis-related infertility conceived by assisted reproductive technology (ART). This single-center, case-control study involved immunohistochemical analysis of CD56-positive NK cells and CD138-positive plasma cells in basal decidua using primary monoclonal mouse antibodies, followed by secondary antibodies using a standardized protocol. CD56 and CD138 immunohistochemically positive cells were reported as the total cell count for each studied antibody expressed per 1 mm2 of basal decidua (Olympus BX46 and Olympus Image Analyzer). Placental samples containing basal decidua from 36 participants with endometriosis-related infertility who conceived by ART, 31 participants with male factor infertility who conceived by ART and 40 healthy controls were included. Endometriosis decidua showed the lowest median count of CD56-positive NK cells (11.5 / mm2, p = 0.039) in BD compared to male factor group (25 / mm2) and healthy controls (24.5 / mm2). No differences were found for CD138-positive plasma cells counts between study groups. Basal decidua in pregnancies after endometriosis-related infertility showed reduced total count of CD56-positive NK cells, without differences in the CD138-positive plasma cell counts compared to control groups. Future studies should investigate how changes in NK cells throughout pregnancy affect the development of perinatal complications and placental pathologies in women with endometriosis, which could uncover potential diagnostic and therapeutic targets. Full article
(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)
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13 pages, 255 KB  
Article
Retrospective Analysis of Effective Management Strategies for Primary Amenorrhea of Reproductive Age in Saudi Arabia
by Hanadi Bakhsh
Life 2024, 14(6), 772; https://doi.org/10.3390/life14060772 - 17 Jun 2024
Viewed by 2808
Abstract
Primary amenorrhea, the absence of menstruation by age 15, can have significant implications for reproductive health and overall well-being. This retrospective study aimed to evaluate the effectiveness of various management strategies for primary amenorrhea among women of reproductive age in Saudi Arabia. Medical [...] Read more.
Primary amenorrhea, the absence of menstruation by age 15, can have significant implications for reproductive health and overall well-being. This retrospective study aimed to evaluate the effectiveness of various management strategies for primary amenorrhea among women of reproductive age in Saudi Arabia. Medical records of 63 eligible patients from 2018 to 2023 were analyzed, assessing diagnostic methods, treatment modalities, and associated outcomes. The findings revealed that hormonal therapy was the most commonly employed management strategy (50.0%) and demonstrated the highest rate of achieving menstrual regularity (62.5%). Surgical interventions were utilized in 28.1% of cases, with a 50.0% rate of symptom resolution. Lifestyle modifications were less frequent (21.9%) but showed a moderate rate of symptom resolution (35.7%). Logistic regression analysis identified age, underlying etiology, and management strategy as significant predictors of treatment success. Subgroup analyses highlighted the efficacy of hormonal therapy and lifestyle modifications for genetic etiologies, while surgical interventions were more effective for anatomical causes. The study underscores the importance of a comprehensive diagnostic approach and personalized treatment plans tailored to individual patient characteristics. Despite limitations, the findings contribute to the understanding of optimal management strategies for primary amenorrhea and emphasize the need for multidisciplinary collaboration in addressing this complex condition. Full article
(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)

Review

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24 pages, 341 KB  
Review
The Role of Granulocyte Colony-Stimulating Factor in Endometrial Preparation for Embryo Implantation in In Vitro Fertilization
by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Iwakeim Sapantzoglou, Aristotelis-Marios Koulakmanidis, Vaitsis Dimitrios, Diamantis Athanasiou, Vasiliki Kanaka, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Charalampos Tsimpoukelis, Athanasios Karpouzos, Maria Anastasia Daskalaki, Nikolaos Kanakas, Marianna Theodora, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakisadd Show full author list remove Hide full author list
Life 2026, 16(2), 351; https://doi.org/10.3390/life16020351 - 18 Feb 2026
Cited by 1 | Viewed by 712
Abstract
Granulocyte colony-stimulating factor (G-CSF) has been suggested as a supplementary approach for endometrial preparation in IVF. Clinical results continue to be inconsistent. This narrative review synthesises molecular and clinical information to elucidate the function of G-CSF in modifying endometrial receptivity and to identify [...] Read more.
Granulocyte colony-stimulating factor (G-CSF) has been suggested as a supplementary approach for endometrial preparation in IVF. Clinical results continue to be inconsistent. This narrative review synthesises molecular and clinical information to elucidate the function of G-CSF in modifying endometrial receptivity and to identify patient categories most likely to benefit. A thorough assessment was conducted on published research on G-CSF administration in women with treatment-resistant thin endometrium, recurrent implantation failure, and unselected IVF populations. The research demonstrates that G-CSF has phenotype-dependent effects. Improvements in pregnancy and live birth rates are inconsistent and seem dependent on the reversibility of underlying tissue disease; nevertheless, G-CSF reliably increases endometrial thickness in instances of thin endometrium and may restore eligibility for transfer. G-CSF improves implantation and early pregnancy outcomes in repeated implantation failure patients without modifying endometrial morphology, indicating a functional mechanism linked to immune-stromal synchronisation rather than structural expansion. In contrast, randomised controlled studies show no therapeutic benefit in unselected IVF groups. Discrepancies in research outcomes may mostly be attributed to variations in patient phenotype, initial endometrial function, and the therapy setting. Thus, G-CSF should be considered a specific approach for endometrial conditioning rather than just a supplementary component of IVF. Full article
(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)
18 pages, 1475 KB  
Review
Impact of Cadmium Toxicity on Testicular Function: Risk of Male Infertility
by Iva Arato, Elena Eugeni, Giuseppe Basta, Tiziano Baroni, Riccardo Calafiore, Francesca Mancuso and Giovanni Luca
Life 2026, 16(1), 181; https://doi.org/10.3390/life16010181 - 22 Jan 2026
Cited by 1 | Viewed by 936
Abstract
The World Health Organization estimates that about 15% of couples in their adult years in industrialized countries experience infertility, which is described as the inability of a sexually active and non-contraceptive couple to achieve spontaneous pregnancy within a year. Environmental pollution is a [...] Read more.
The World Health Organization estimates that about 15% of couples in their adult years in industrialized countries experience infertility, which is described as the inability of a sexually active and non-contraceptive couple to achieve spontaneous pregnancy within a year. Environmental pollution is a significant health concern worldwide and one of the possible risk factors leading to male infertility. Cadmium is a common heavy toxin derived from industrial activities, a ubiquitous environmental pollutant, and can cause severe harm to various organs including the testis. Cadmium toxicity can lead to severe impairment of male germ cells in both rodents and humans, which can result in azoospermia. The negative effects of cadmium on the testicles are caused by its induction of oxidative stress, spermatogenic apoptosis, and testicular inflammation or its detriment to androgenic and sperm cell functions, which damages the vascular endothelium and blood–testis barrier. Overall, this review describes the detrimental impact of cadmium on the testicles and its effect on male infertility. Therefore, by considering recent research findings and identifying future research directions, this review underlines the need to develop new treatments for male infertility related to heavy metal exposure. Full article
(This article belongs to the Special Issue Human Infertility and Reproductive Endocrinology: 2nd Edition)
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