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Biomedicines
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New Advances in Human Reproductive Biology
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New Advances in Human Reproductive Biology

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 2358

Special Issue Editor

Dr. Nikolaos Machairiotis

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Guest Editor
Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
Interests: endometriosis; pain; inflammation; inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reproductive biology involves the scientific study of the reproductive system. Improved understanding of reproductive biology can lead to new treatments for reproductive disorders, such as infertility.

Infertility is a challenge faced by millions of couples worldwide, and advances in IVF (in vitro fertilization) technology have been a ray of hope for many. With cutting-edge developments in 2025, it is important to understand the latest breakthroughs that are transforming assisted reproductive technology.

Increased demand for in vitro fertilization due to socio-demographic trends and supply facilitated by new technologies converged to transform the way a substantial proportion of humans reproduce.

Continuous research and development in human reproduction and its molecular mechanisms form the basis for its evolution and development.

Ultimately, this Special Issue not only aims to contribute to the existing literature but also seeks to inspire ongoing efforts to enhance the development of human reproductive biology.

Dr. Nikolaos Machairiotis
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines 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

  • gametogenesis
  • fertilization
  • egg retrieval
  • embryo implantation
  • epigenetics
  • microRNAs in fertility
  • hormonal signaling
  • stem cells and fertility
  • assisted reproductive technologies
  • molecular and polymorphism in fertility
  • reproductive health novelty

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Published Papers (3 papers)

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Research

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18 pages, 575 KB  
Article
The Molecular Landscape of Nitric Oxide in Ovarian Function and IVF Success: Bridging Redox Biology and Reproductive Outcomes
by Diamandis Athanasiou, Charalampos Voros, Ntilay Soyhan, Georgia Panagou, Maria Sakellariou, Despoina Mavrogianni, Eleni Sivylla Bikouvaraki, George Daskalakis and Kalliopi Pappa
Biomedicines 2025, 13(7), 1748; https://doi.org/10.3390/biomedicines13071748 - 17 Jul 2025
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Abstract
Background: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO3−) and nitrite (NO2−) may indicate real-time follicular function during IVF. Methods: [...] Read more.
Background: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO3−) and nitrite (NO2−) may indicate real-time follicular function during IVF. Methods: In this prospective study, we included 89 women who underwent controlled ovarian stimulation. The Griess test was used to measure NO2-NO3 concentrations in follicular fluid collected on the day of oocyte retrieval. Non-parametric and correlation tests were used to investigate the associations between oocyte yield, maturity (MII), fertilization (2PN), embryo development, and hormone levels. Results: Higher NO2-NO3 levels were substantially associated with increased total oocyte count, MII oocytes (p = 0.014), and 2PN embryos (p = 0.029). This suggests a strong relationship between NO bioavailability and oocyte competence. NO2-NO3 levels showed a positive correlation with estradiol (p < 0.001) and progesterone (p < 0.001), suggesting a possible function in granulosa cell steroidogenesis. Conclusions: Follicular NO metabolites are candidate functional indicators for oocyte quality evaluation and intrafollicular steroidogenic activity. Their predictive value may improve customized IVF treatment, especially in individuals with complicated ovarian phenotypes such as PCOS or decreased ovarian reserve. Full article
(This article belongs to the Special Issue New Advances in Human Reproductive Biology)
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Review

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34 pages, 441 KB  
Review
Rescuing Fertilization Failure in ICSI: A Narrative Review of Calcium Ionophore Activation, PLCζ Testing, and Embryo Morphokinetics
by Charalampos Voros, Despoina Mavrogianni, Diamantis Athanasiou, Ioakeim Sapantzoglou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Georgios Papadimas, Charalampos Tsimpoukelis, Ioannis Papapanagiotou, Dimitrios Vaitsis, Aristotelis-Marios Koulakmanidis, Maria Anastasia Daskalaki, Vasileios Topalis, Nikolaos Thomakos, Marianna Theodora, Panagiotis Antsaklis, Fotios Chatzinikolaou, Dimitrios Loutradis and Georgios Daskalakis
Biomedicines 2025, 13(8), 2007; https://doi.org/10.3390/biomedicines13082007 - 18 Aug 2025
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Abstract
Fertilisation failure following intracytoplasmic sperm injection (ICSI) is a significant challenge in assisted reproductive technology (ART), particularly in the absence of an identifiable cause. Artificial oocyte activation (AOA), typically with calcium ionophores, has emerged as a potential solution in scenarios characterised by a [...] Read more.
Fertilisation failure following intracytoplasmic sperm injection (ICSI) is a significant challenge in assisted reproductive technology (ART), particularly in the absence of an identifiable cause. Artificial oocyte activation (AOA), typically with calcium ionophores, has emerged as a potential solution in scenarios characterised by a deficiency of phospholipase C zeta (PLCζ). This narrative review consolidates the latest clinical and experimental data regarding the application of calcium ionophores for oocyte activation, the significance of PLCζ testing in instances of unexplained fertilisation failure, and the impact of AOA on the morphokinetics and developmental potential of embryos. AOA has demonstrated an enhancement in fertilisation, cleavage, and pregnancy outcomes in specific patient populations, including individuals with diminished ovarian reserve or those who have previously attempted conception unsuccessfully. Although AOA appears to have no impact on embryo morphokinetics, certain studies indicate slight alterations in early cleavage features. The available statistics indicate that there are no significant safety concerns about outcomes for babies. This finding underscores the significance of tailored ART methodologies that incorporate molecular diagnostics and targeted AOA therapies. It emphasises the necessity for additional prospective trials to enhance patient selection and long-term safety surveillance. Full article
(This article belongs to the Special Issue New Advances in Human Reproductive Biology)

Other

Jump to: Research, Review

34 pages, 448 KB  
Systematic Review
Evaluation of the Effectiveness and Accuracy of Non-Invasive Preimplantation Genetic Testing (niPGT) Compared to Invasive Embryo Biopsy
by Charalampos Voros, Menelaos Darlas, Diamantis Athanasiou, Antonia Athanasiou, Aikaterini Athanasiou, Kyriakos Bananis, Georgios Papadimas, Charalampos Tsimpoukelis, Athanasios Gkirgkinoudis, Ioakeim Sapantzoglou, Ioannis Papapanagiotou, Dimitrios Vaitsis, Aristotelis-Marios Koulakmanidis, Vasileios Topalis, Nikolaos Thomakos, Marianna Theodora, Panagiotis Antsaklis, Fotios Chatzinikolaou, Hans Atli Dahl, Georgios Daskalakis and Dimitrios Loutradisadd Show full author list remove Hide full author list
Biomedicines 2025, 13(8), 2010; https://doi.org/10.3390/biomedicines13082010 - 18 Aug 2025
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Abstract
Background: Preimplantation genetic testing for aneuploidy (PGT-A) is a popular approach in assisted reproductive technology that improves embryo selection and implantation rates. Traditional approaches rely on trophectoderm (TE) biopsy, which is an invasive procedure that might jeopardize embryo integrity and create technical constraints [...] Read more.
Background: Preimplantation genetic testing for aneuploidy (PGT-A) is a popular approach in assisted reproductive technology that improves embryo selection and implantation rates. Traditional approaches rely on trophectoderm (TE) biopsy, which is an invasive procedure that might jeopardize embryo integrity and create technical constraints such as mosaicism-related misclassification. Non-invasive preimplantation genetic testing (niPGT) has emerged as a possible alternative, using embryonic cell-free DNA (cfDNA) extracted from wasted culture media or blastocoel fluid to assess chromosomal status without requiring direct embryo manipulation. Methods: This systematic study investigates the molecular mechanisms behind cfDNA release, its biological properties, and the technological concerns that influence its utilization in niPGT. We look at recent advances in next-generation sequencing (NGS), whole-genome amplification (WGA), and bioinformatic techniques that improve cfDNA-based aneuploidy detection. In addition, we compare the sensitivity, specificity, and concordance rates of niPGT to conventional TE biopsy, highlighting the major aspects impacting its diagnostic performance. Results: The release of cfDNA from embryos is influenced by apoptotic and necrotic processes, active DNA shedding, and extracellular vesicle secretion, which results in fragmented chromosomal material of different qualities and quantities. While niPGT has shown promise as a noninvasive screening approach, significant variability in cfDNA yield, maternal DNA contamination, and sequencing biases all have an impact on test accuracy. Studies show that niPGT and TE biopsies have moderate-to-high concordance, although there are still issues in detecting mosaicism, segmental aneuploidies, and DNA degradation artifacts. Conclusions: NiPGT is a safer and less intrusive alternative to TE biopsy, with potential clinical benefits. However, technical advancements are required to improve cfDNA collecting procedures, reduce contamination, and improve sequencing accuracy. Additional large-scale validation studies are needed to create standardized methodologies and ensure that niPGT achieves the diagnostic reliability requirements required for widespread clinical deployment in IVF programs. Full article
(This article belongs to the Special Issue New Advances in Human Reproductive Biology)
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