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Biomedicines
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Advances in Reproductive Medicine and Health
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Advances in Reproductive Medicine and Health

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

Deadline for manuscript submissions: 31 March 2027 | Viewed by 10225

Editors

Dr. Athanasios Zikopoulos

E-Mail Website
Guest Editor
Medical School, National and Kapodistrian University of Athens, Athens, Greece
Interests: human reproduction; infertility; oxidative stress; reproductive endocrinology; assisted reproductive technologies (ARTs); embryo quality; oocyte biology; endometriosis; polycystic ovary syndrome (PCOS); recurrent pregnancy loss; biomarkers of reproductive health
Special Issues, Collections and Topics in MDPI journals
Dr. Sofoklis Stavros

E-Mail Website
Guest Editor
Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, 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
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infertility is a devastating, multifactorial issue affecting 12 to 15% of reproductive-age couples. This Special Issue aims to explore recent advancements in reproductive medicine and health, focusing on innovations in assisted reproductive technologies (ART), fertility preservation, and the impact of novel laboratory investigations on reproductive outcomes. This Special Issue covers topics related to in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT), cryopreservation techniques, recurrent implantation failures, recurrent miscarriages, early pregnancy complications after ART, use of stem cells, gene editing, gene expression, protein and miRNA expression, and their impact on reproductive and perinatal outcomes.

The objectives of the Special Issue are as follows:

  • Latest technological and clinical developments in assisted reproductive technologies (ART);
  • Efficacy and safety of modern fertility preservation and stimulation methods;
  • From gene to protein expression: Advances related to better understanding of infertility and personalized care;
  • Ethical and policy challenges associated with reproductive medicine;
  • Future trends and experimental strategies in reproductive medicine.

Ultimately, this Special Issue seeks to explore and evaluate how these advancements improve reproductive outcomes, affect perinatal outcomes, and lead towards personalized and holistic care of infertile couples.

Dr. Athanasios Zikopoulos
Dr. Sofoklis Stavros
Dr. Anastasios Potiris
Guest Editors

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-anonymized 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

  • reproductive medicine
  • assisted reproductive technology
  • fertility preservation
  • IVF
  • early pregnancy
  • miscarriages
  • proteomics
  • metabolomics
  • transcriptomics
  • infertility
  • bioethics
  • cryopreservation
  • personalized medicine

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

13 pages, 1677 KB  
Article
Association of Endometrial HAND2 Expression with β2-Glycoprotein I Antibodies in Recurrent Pregnancy Loss
by Madina Khalmirzaeva, Gulzhakhan Omarova, Almagul Kurmanova, Gaukhar Kurmanova, Gaini Anartayeva, Zhamilya Zhankina, Aidana Tulesheva, Ainura Veliyeva, Botakuz Jarikova and Alfiya Dzheksembekova
Biomedicines 2026, 14(7), 1560; https://doi.org/10.3390/biomedicines14071560 - 12 Jul 2026
Viewed by 330
Abstract
Background: Recurrent pregnancy loss (RPL) is frequently linked to antiphospholipid antibodies, yet many affected women are seronegative for the classical (Sydney) criteria antibodies. In a previously characterized cohort, an extended antiphospholipid antibody panel was positive in 79% of women with RPL, with [...] Read more.
Background: Recurrent pregnancy loss (RPL) is frequently linked to antiphospholipid antibodies, yet many affected women are seronegative for the classical (Sydney) criteria antibodies. In a previously characterized cohort, an extended antiphospholipid antibody panel was positive in 79% of women with RPL, with the strongest associations for antibodies against prothrombin, annexin V and β2-glycoprotein I. Whether this association reflects molecular endometrial dysfunction was unclear. Objective: To examine endometrial expression of ten decidualization- and inflammation-related genes in women with RPL, stratified by APL status, focusing on the dominant antibody specificity: anti-β2-glycoprotein I. Methods: Thirty-nine women with RPL (≥2 losses), a subsample of a published 100-patient cohort, underwent mid-luteal Pipelle endometrial biopsy followed by RT-PCR for C4BPA, CXCL1, HAND2, HPRT1, IFNG, IL15, IL8 (CXCL8), MMP10, TNC and VEGFB. Antibodies were measured by antiphospholipid 10 Dot line immunoblot (Generic Assays, Germany). The analysis used Mann–Whitney U, Fisher’s exact test, Benjamini–Hochberg correction and ROC analysis. Results: Antibody prevalence in the subsample matched the parent cohort (Pearson r = 0.999). Of ten transcripts, only HAND2 showed a nominally significant reduction in APL+ women (median ΔCt −2.04 vs. −1.30; p = 0.037; rank-biserial r = −0.47); this signal did not survive Benjamini–Hochberg correction (q = 0.372). The signal was specific to anti-β2GPI (p = 0.064; AUC 0.700), not to annexin V or prothrombin. A cut-off of HAND2 ΔCt ≤ −1.60 identified APL+ status with 73% sensitivity, 78% specificity and OR 9.62 (95% CI 1.64–56.4; p = 0.015). HAND2 clustered with IL15 (ρ = 0.65) and VEGFB (ρ = 0.70). Conclusions: Anti-β2-glycoprotein I antibodies, the dominant APL specificity in RPL, are associated with reduced endometrial HAND2 expression. This exploratory data outline a candidate molecular pathway linking extended antiphospholipid serology to impaired endometrial receptivity. Full article
(This article belongs to the Special Issue Advances in Reproductive Medicine and Health)
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22 pages, 1558 KB  
Article
Human Amniotic Membrane-Derived Mesenchymal Stem Cell-Conditioned Saline as an Injectable Formulation Improves Ovarian Antioxidant Status and Preimplantation Embryo Development
by Kihae Ra, Eun Young Kim, Sung Keun Kang, Geon A Kim and Se Chang Park
Biomedicines 2026, 14(7), 1522; https://doi.org/10.3390/biomedicines14071522 - 7 Jul 2026
Viewed by 383
Abstract
Background/Objectives: Oxidative stress is a major cause of impaired oocyte quality and early embryo development, a challenge that still needs to be addressed in assisted reproduction. Mesenchymal stem cell secretomes have been investigated as cell-free therapeutics with antioxidant activity and relevant anti-apoptotic [...] Read more.
Background/Objectives: Oxidative stress is a major cause of impaired oocyte quality and early embryo development, a challenge that still needs to be addressed in assisted reproduction. Mesenchymal stem cell secretomes have been investigated as cell-free therapeutics with antioxidant activity and relevant anti-apoptotic effects. This study aimed to evaluate the effects of human amniotic membrane-derived mesenchymal stem cell-conditioned saline (AMSC-CS) as an injectable formulation on oxidative stress–related markers in ovarian tissue and preimplantation developmental outcomes. Methods: AMSC-CS was administered intravenously to female mice in a dose-dependent manner. Safety assessments were conducted to evaluate systemic and target organ toxicity within the dosage range. In vitro fertilization (IVF) outcomes and oxidative status in ovaries, oocytes, and embryos were evaluated following treatment with low, medium, and high doses of AMSC-CS (1, 3, and 5 μL/g). Results: As an injectable formulation, the safety assessments did not reveal systemic or target organ toxicity of AMSC-CS within the dosage range. Medium-to-high doses of AMSC-CS improved the expression of folliculogenesis-related genes and decreased oxidative stress and apoptosis signaling in ovarian tissue. At the high dose, AMSC-CS promoted preimplantation embryo development to the blastocyst and hatched blastocyst stages, along with improved blastocyst quality and reduced oxidative stress in oocytes and blastocysts. Conclusions: These findings suggest that AMSC-CS at medium-to-high doses, as an injectable formulation with antioxidant activity, may be a promising adjunct for assisted reproductive technologies. Full article
(This article belongs to the Special Issue Advances in Reproductive Medicine and Health)
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8 pages, 192 KB  
Article
Comparison of Different Progesterone Protocols for Luteal Support in Frozen-Thawed Embryo Transfer Preparation
by Gokalp Oner, Enes Karaman, Busra Kulular, Yasemin Dadas and Hande Nur Doganay
Biomedicines 2025, 13(10), 2487; https://doi.org/10.3390/biomedicines13102487 - 13 Oct 2025
Cited by 3 | Viewed by 6281
Abstract
Objective: To evaluate five luteal support protocols in women with low serum progesterone (<10 ng/mL) undergoing HRT-FET. Methods: Randomized controlled trial at two centers including 200 women under 35 with unexplained infertility. Groups: (1) 600 mg vaginal, (2) 800 mg vaginal, (3) [...] Read more.
Objective: To evaluate five luteal support protocols in women with low serum progesterone (<10 ng/mL) undergoing HRT-FET. Methods: Randomized controlled trial at two centers including 200 women under 35 with unexplained infertility. Groups: (1) 600 mg vaginal, (2) 800 mg vaginal, (3) 600 mg vaginal + 50 mg IM, (4) 600 mg vaginal + 25 mg SC, (5) 600 mg vaginal + 30 mg oral. Results: Groups 3 and 4 achieved significantly higher serum progesterone (p < 0.001), higher clinical pregnancy (70%, 68%), and higher live birth (84%, 83%) compared to Groups 1, 2, and 5. Early pregnancy loss was lower in Groups 3 and 4. Conclusions: Combined vaginal and injectable progesterone improved outcomes compared to monotherapy. Full article
(This article belongs to the Special Issue Advances in Reproductive Medicine and Health)
13 pages, 1782 KB  
Article
The Detrimental Impact of Bisphenol S (BPS) on Trophoblastic Cells and the Ishikawa Cell Lines: An In Vitro Model of Cytotoxic Effect and Molecular Interactions
by Eirini Drakaki, Despoina Mavrogianni, Anastasios Potiris, Stavroula Xydi-Chrysafi, Panagiotis Kotrotsos, Nikolaos Thomakos, Alexandros Rodolakis, Georgios Daskalakis and Ekaterini Domali
Biomedicines 2025, 13(8), 1938; https://doi.org/10.3390/biomedicines13081938 - 8 Aug 2025
Cited by 1 | Viewed by 1293
Abstract
Background/Objectives: Bisphenols (BPs) and especially bisphenol S (BPS), an analog of bisphenol A (BPA), are widely used and induce oxidative stress, resulting in the inhibition of cell proliferation and induction of apoptosis which all are crucial for reproduction, the progression of pregnancy, [...] Read more.
Background/Objectives: Bisphenols (BPs) and especially bisphenol S (BPS), an analog of bisphenol A (BPA), are widely used and induce oxidative stress, resulting in the inhibition of cell proliferation and induction of apoptosis which all are crucial for reproduction, the progression of pregnancy, and fertility. The present study integrates trophoblastic cells as an in vitro model to provide evidence and investigate the molecular interactions regarding placenta-related pregnancy complications after cytotoxic exposure to BPS. Methods: Human endometrial epithelial adenocarcinoma Ishikawa cell lines and trophoblastic cells were cultured. Cells obtained from the cultures were divided into plates and incubated for 24 h with different concentrations of bisphenol S (BPS). Cell viability was measured using the Countess Automated Cell Counter and the viability of Ishikawa cells was assessed after 48 h and for trophoblasts after 24 h. The effect of siRNA on NANOG expression was evaluated using qRT-PCR. Quantification of DNMT and NANOG was performed by qPCR and the G6PD gene was used as an internal control. Results: Real-time PCR results showed that the expression of the DNMT1 gene varies depending on the concentration of BPS in trophoblastic cells. In Ishikawa cell lines, real-time PCR results showed that DNMT1 gene expression was higher due to cell increase, but the measured fold change did not differ significantly. Data analysis indicated a statistically significant difference between CpDNMT1 in trophoblasts with and without BPS, where higher values were observed in the case of BPS presence (p = 0.019). The largest difference was observed between CpDNMT1 trophoblasts without BPS and CpDNMT1 Ishikawa with BPS (p < 0.001). Silencing the NANOG gene resulted in a reduced expression of DNMT1, while the G6PD gene was still detected. Conclusions: The results of this study highlight the cytotoxic effects of BPS and consequently its effect on trophoblast viability. The results of NANOG-DNMT1 gene expression related to BPS exposure reinforces our understanding of EDC-induced placental dysfunction. Full article
(This article belongs to the Special Issue Advances in Reproductive Medicine and Health)
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