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Medicina
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Management and Diagnosis of Infertility and Recurrent Abortions in Obstetrics...
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Management and Diagnosis of Infertility and Recurrent Abortions in Obstetrics and Gynecology

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

Deadline for manuscript submissions: 20 August 2025 | Viewed by 1365

Special Issue Editors

Prof. Dr. Peter Drakakis

E-Mail Website
Guest Editor
Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
Interests: reproductive medicine; assisted reproduction techniques; early pregnancy; recurrent pregnancy loss; recurrent implantation failure; infertility
Special Issues, Collections and Topics in MDPI journals
Dr. Anastasios Potiris

E-Mail Website
Guest Editor Assistant
Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
Interests: reproductive medicine; assisted reproduction techniques; recurrent pregnancy loss; recurrent implantation failure; infertility
Dr. Sofoklis Stavros

E-Mail Website
Guest Editor Assistant
Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
Interests: reproductive medicine; early pregnancy; recurrent pregnancy loss; recurrent implantation failure; gynecological ultrasound; infertility

Special Issue Information

Dear Colleagues,

Recurrent pregnancy loss (RPL) affects approximately 1–4% of women attempting pregnancy in Europe and the United States. Recurrent pregnancy loss or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. Despite its wide prevalence, shedding light on RPL pathophysiology and risk factors remains challenging. There are diverse causes leading to recurrent pregnancy loss, including several factors such as genetic, anatomical, hormonal, and immunological. On the other hand, infertility is defined as the inability to conceive after 12 or more months of regular unprotected sexual intercourse. Even though the origin of infertility varies, 40% of its etiology is related to female causes. Female infertility may be related to obesity, menstrual disorders, endometriosis, diminished ovarian reserve, and tubal occlusion, although several other factors have been validated to contribute to female infertility, including oxidative stress.

The causes of infertility are varied and can be classified into several categories: genetic, anatomical, hormonal, immunological, and lifestyle. Genetic abnormalities, such as chromosomal translocations, account for a portion of RPL cases, while anatomical issues, like uterine abnormalities, can lead to implantation failure. Hormonal imbalances, such as those associated with polycystic ovary syndrome (PCOS), and immunological factors, including antiphospholipid syndrome, can also contribute to these conditions. Furthermore, lifestyle factors—such as obesity, smoking, and excessive alcohol consumption—can play a significant role in reproductive health.

The primary objectives of this Special Issue are:

  1. Investigating and understanding recurrent pregnancy loss at the genetic or molecular level.
  2. Enhancing research efforts focused on the etiology and treatment options of RPL and infertility.
  3. Developing comprehensive, multidisciplinary treatment protocols that address these conditions' physical and emotional aspects.
  4. Understanding pregnancy complications and adverse outcomes related to infertility and RPL.
  5. Understanding male and female factors and their impact during ART.
  6. Understanding ectopic pregnancy and other complications in early pregnancy.

Recurrent pregnancy loss and infertility are pressing issues that require urgent and sustained attention from the medical community, researchers, and the public. We can improve the lives of those affected by these conditions through education, research, comprehensive treatment protocols, and support systems. This Special Issue aims to create a holistic framework that addresses the medical aspects and acknowledges and supports the emotional journey of individuals and couples dealing with RPL and infertility.

Prof. Dr. Peter Drakakis
Guest Editor

Dr. Anastasios Potiris
Dr. Sofoklis Stavros
Guest Editor Assistants

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. Medicina 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 2200 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

  • male and female infertility
  • recurrent pregnancy loss (RPL)
  • recurrent implantation failure (RIF)
  • assisted reproductive technologies (ART)
  • early pregnancy

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Published Papers (3 papers)

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Review

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20 pages, 1153 KiB  
Review
Paternal Contributions to Recurrent Pregnancy Loss: Mechanisms, Biomarkers, and Therapeutic Approaches
by Aris Kaltsas, Athanasios Zikopoulos, Vladimir Kojovic, Fotios Dimitriadis, Nikolaos Sofikitis, Michael Chrisofos and Athanasios Zachariou
Medicina 2024, 60(12), 1920; https://doi.org/10.3390/medicina60121920 - 22 Nov 2024
Abstract
Background and Objectives: Recurrent pregnancy loss (RPL) affects numerous couples worldwide and has traditionally been attributed mainly to maternal factors. However, recent evidence highlights significant paternal influences on pregnancy viability and outcomes. This review aims to comprehensively examine male contributions to pregnancy [...] Read more.
Background and Objectives: Recurrent pregnancy loss (RPL) affects numerous couples worldwide and has traditionally been attributed mainly to maternal factors. However, recent evidence highlights significant paternal influences on pregnancy viability and outcomes. This review aims to comprehensively examine male contributions to pregnancy loss, focusing on underlying mechanisms, novel biomarkers, and integrated strategies for improved reproductive success. Materials and Methods: A comprehensive narrative review was conducted by searching databases including PubMed and Embase for the literature published from January 2004 to October 2024. Studies focusing on paternal influences in RPL—encompassing oxidative stress, genetic and epigenetic mechanisms, health conditions, lifestyle factors, environmental exposures, and advancements in sperm proteomics—were included. Inclusion criteria were peer-reviewed articles in English that directly addressed paternal factors in RPL; studies not meeting these criteria were excluded. Results: The review identified that paternal factors such as advanced age, metabolic and cardiovascular health issues, chronic diseases, lifestyle habits (e.g., smoking, alcohol consumption, poor diet), and environmental exposures significantly affect sperm integrity through mechanisms like oxidative stress, DNA fragmentation, and epigenetic alterations. Advanced paternal age and poor health conditions are associated with increased risks of miscarriage and adverse pregnancy outcomes. Novel sperm proteomic biomarkers have been identified, offering potential for enhanced diagnostics and personalized interventions. Integrated approaches involving multidisciplinary assessments, preventive strategies, and genetic counseling are essential for effectively addressing RPL. Conclusions: Integrating paternal factors into clinical evaluations is crucial for effectively addressing recurrent pregnancy loss. Recognizing and modifying paternal risk factors through lifestyle changes, medical interventions, and environmental management can improve pregnancy outcomes. The findings underscore the need for incorporating paternal assessments into standard care and highlight the importance of future research focusing on standardizing diagnostic protocols, expanding studies on paternal contributions, and integrating proteomic biomarkers into clinical practice to facilitate personalized treatment strategies. Full article
(This article belongs to the Special Issue Management and Diagnosis of Infertility and Recurrent Abortions in Obstetrics and Gynecology)
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24 pages, 1588 KiB  
Review
Alloimmune Causes of Recurrent Pregnancy Loss: Cellular Mechanisms and Overview of Therapeutic Approaches
by Cristina Uța, Alexandru Tîrziu, Elena-Larisa Zimbru, Răzvan-Ionuț Zimbru, Marius Georgescu, Laura Haidar and Carmen Panaitescu
Medicina 2024, 60(11), 1896; https://doi.org/10.3390/medicina60111896 - 19 Nov 2024
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Abstract
Recurrent pregnancy loss (RPL) is a complex early pregnancy complication affecting 1–2% of couples and is often linked to immune dysfunction. Aberrations in T and B cell subpopulations, as well as natural killer (NK) cell activity, are particularly influential, with studies showing that [...] Read more.
Recurrent pregnancy loss (RPL) is a complex early pregnancy complication affecting 1–2% of couples and is often linked to immune dysfunction. Aberrations in T and B cell subpopulations, as well as natural killer (NK) cell activity, are particularly influential, with studies showing that abnormal NK cell activation and imbalances in T and B cell subtypes contribute to immune-mediated miscarriage risk. Successful pregnancy requires a tightly regulated balance between pro-inflammatory and anti-inflammatory immune responses. In the early stages, inflammation supports processes such as trophoblast invasion and spiral artery remodeling, but this must be tempered to prevent immune rejection of the fetus. In this review, we explore the underlying immune mechanisms of RPL, focusing on how dysregulated T, B, and NK cell function disrupts maternal tolerance. Specifically, we discuss the essential role of uterine NK cells in the early stages of vascular remodeling in the decidua and regulate the depth of invasion by extravillous trophoblasts. Furthermore, we focus on the delicate Treg dynamics that enable the maintenance of optimal immune homeostasis, where the balance, and not only the quantity of Tregs, is crucial for fostering maternal–fetal tolerance. Other T cell subpopulations, such as Th1, Th2, and Th17 cells, also contribute to immune imbalance, with Th1 and Th17 cells promoting inflammation and potentially harming fetal tolerance, while Th2 cells support immune tolerance. Finally, we show how changes in B cell subpopulations and their functions have been associated with adverse pregnancy outcomes. We further discuss current therapeutic strategies aimed at correcting these immune imbalances, including intravenous immunoglobulin (IVIg), glucocorticoids, and TNF-α inhibitors, examining their efficacy, challenges, and potential side effects. By highlighting both the therapeutic benefits and limitations of these interventions, we aim to offer a balanced perspective on clinical applications for women facing immune-related causes of RPL. Full article
(This article belongs to the Special Issue Management and Diagnosis of Infertility and Recurrent Abortions in Obstetrics and Gynecology)
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Other

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7 pages, 2064 KiB  
Case Report
Methotrexate-Induced Toxicity After Ultrasound-Guided Intragestational Injection in a Patient with Caesarean Scar Pregnancy—A Case Report
by Sofoklis Stavros, Anastasios Potiris, Angeliki Gerede, Athanasios Zikopoulos, Maria Giourga, Christina Karasmani, Athanasios Karpouzos, Theodoros Karampitsakos, Spyridon Topis, Ismini Anagnostaki, Konstantinos Louis, Ioannis Tsakiridis, Themistoklis Dagklis, Peter Drakakis and Ekaterini Domali
Medicina 2024, 60(11), 1900; https://doi.org/10.3390/medicina60111900 - 20 Nov 2024
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Abstract
Background and Objectives: Caesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy in which the early pregnancy implants at the site of the uterine scar. Methotrexate (MTX) in lower doses can be used to treat CSPs. However, MTX administration is [...] Read more.
Background and Objectives: Caesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy in which the early pregnancy implants at the site of the uterine scar. Methotrexate (MTX) in lower doses can be used to treat CSPs. However, MTX administration is associated with a spectrum of side effects that include hematological toxicities. This case report presents a CSP treated with an intragestational injection of MTX and subsequently developed pancytopenia. Materials and Methods: A 23-year-old woman at six weeks and six days of pregnancy was referred as a potential case of CSP. After establishing the diagnosis, she was treated with a transvaginal ultrasound-guided intragestational administration of 80 mg MTX (adjusted to 50 mg/m2 body surface area) under sedation. Results: On day four after the MTX injection, she developed oral ulcers, fever, and pruritic phlyctenular maculopapular rash. Subsequently, the patient developed febrile neutropenia and was admitted to the Intensive Care Unit. On day six, a subsequent exacerbation of the rash was observed with the formation of blisters and purplish spots with concurrent odynophagia and sialorrhea. Ultimately, the patient developed pancytopenia due to bone marrow suppression. Fifteen days after MTX administration, the patient recovered and was discharged from the hospital hemodynamically stable, afebrile, with dropping β-hcg levels, and in good clinical condition. Conclusions: Although methotrexate administration is the preferred option for the treatment of cesarean scar pregnancies, clinicians should be aware of the fact that its use entails potential risks, even when it is used locally. To our knowledge, this case is the first description of pancytopenia due to bone marrow suppression following a single low dose of intragestational methotrexate injection. Full article
(This article belongs to the Special Issue Management and Diagnosis of Infertility and Recurrent Abortions in Obstetrics and Gynecology)
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