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Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART)
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Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART)

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

Deadline for manuscript submissions: 25 November 2024 | Viewed by 3597

Special Issue Editor

Dr. Diana Alecsandru

E-Mail Website
Guest Editor
1. Department of Immunology, IVI RMA Madrid, Madrid, Spain
2. IVI Foundation, Health Research Institute La Fe, Valencia, Spain
Interests: reproductive disorders; immunology; IVF clinical; female fertility; pre-implantation genetics

Special Issue Information

Dear Colleagues,

Infertility is a significant health problem, affecting 8–15% of people worldwide.  Decades ago, assisted reproductive technology (ART) emerged as a tool in the fight against infertility. Though the number of patients undergoing ART has grown substantially and the process itself has been subjected to numerous advancements since its inception, most ART cycles do not result in a live birth. Even when chromosomally normal embryos are transferred, only about 50% gets implanted. Apart from ageing, which is the primary issue affecting fertility in today's society, other underlying conditions such as male factor, endometriosis, ovulation disorders, tubal disease, uterine factor, metabolic, immune and inflammatory disorders also affect negatively fertility and ART outcomes.

Pregnancy involves the coexistence of two genetically different identities in a suitable environment. This exceptional situation requires specific changes in the uterine microenvironment, at the morphological, metabolic, immunological, vascular, biochemical and even genetic levels. Research in this field is concerned with  preventive procedures (fertility preservation at a young age), shortening the diagnosis time, as well as improving the diagnostic techniques and treatment measures.

This Special Issue aims to collate both original research and review articles that highlight the clinical advancements in infertility and ART. Some potential topics include artificial intelligence, diagnosis and treatment of maternal environment, and the maternal–fetal cross-talk.

Dr. Diana Alecsandru
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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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
  • ART
  • implantation failure
  • endometrial factor
  • decidualization
  • early placentation
  • maternal–fetal cross-talk
  • maternal immune tolerance
  • maternal–fetal match
  • artificial intelligence

Published Papers (5 papers)

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Research

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14 pages, 1263 KiB  
Article
Poor Sperm Chromatin Condensation Is Associated with Cryopreservation-Induced DNA Fragmentation and Cell Death in Human Spermatozoa
by Jade Hallam, Peter Burton and Katherine Sanders
J. Clin. Med. 2024, 13(14), 4156; https://doi.org/10.3390/jcm13144156 - 16 Jul 2024
Viewed by 476
Abstract
Background/Objectives: Semen cryopreservation is routinely performed in fertility clinics for a variety of reasons, including fertility preservation and storage of donor sperm, yet the freeze–thaw process leads to cellular damage via ice crystal formation, osmotic shock, and supraphysiological levels of oxidative stress. [...] Read more.
Background/Objectives: Semen cryopreservation is routinely performed in fertility clinics for a variety of reasons, including fertility preservation and storage of donor sperm, yet the freeze–thaw process leads to cellular damage via ice crystal formation, osmotic shock, and supraphysiological levels of oxidative stress. Sperm resistance to damage during the freeze–thaw process varies widely, yet the intrinsic factors associated with sperm cryotolerance are largely unknown. The study aimed to investigate whether poor chromatin condensation renders sperm vulnerable to DNA fragmentation and cell death induced by the freeze–thaw process. Methods: Participants (n = 51) from the general community who met the inclusion criteria collected a semen sample after 3–8 days of abstinence. Neat semen samples underwent traditional semen analysis, aniline blue (AB)-eosin staining for chromatin condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay for DNA fragmentation, and the Annexin V assay for apoptosis/necrosis, prior to being cryopreserved using the liquid nitrogen vapour method and stored at −196 °C. Stored samples were later thawed at room temperature and processed using density gradient centrifugation. Motile sperm concentration, DNA fragmentation and apoptosis/necrosis were analysed in post-thaw samples. Results: As indicated by a significant interaction effect in linear mixed models, an increased proportion of AB-positive sperm in the pre-freeze sample exacerbated the adverse effect of freezing on sperm DNA fragmentation (p = 0.004), late apoptosis (p = 0.007), and necrosis (p = 0.007). AB-staining was positively correlated with all three parameters in the post-thaw sample (all rs ≥ 0.424, all p < 0.01) and remained significant after adjusting for neat sperm concentration (all partial rs ≥ 0.493, all p < 0.01). Similarly, AB-staining was significantly correlated with the percentage point change in sperm DNA fragmentation (rs = 0.366, p = 0.014) and necrosis (rs = 0.403, p = 0.009), both of which remained significant after adjusting for neat sperm concentration (both partial rs ≥ 0.404, both p < 0.01), and borderline significantly correlated with percentage point change in late apoptosis (rs = 0.307, p = 0.051). Conclusions: Sperm with poorly condensed chromatin may be more susceptible to cellular damage during the freeze–thaw process, independent of pre-freeze sperm concentration. These findings may help to explain the intrinsic variation in sperm resistance to cryodamage within and between individuals that is poorly understood. Full article
(This article belongs to the Special Issue Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART))
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13 pages, 1306 KiB  
Article
Advancing Age May Decrease Mitochondrial Activity in Cumulus Cells
by Suwichaya Jitngamsujarit, Lingling Salang, Charupong Saengboonmee, Supannika Sorin, Kanyarat Thithuan, Thanida Pongsritasana and Sineenart Sukkasame
J. Clin. Med. 2024, 13(10), 2800; https://doi.org/10.3390/jcm13102800 - 9 May 2024
Viewed by 657
Abstract
Background: The goal of this study was to compare mitochondrial activity in cumulus cells (CCs) between young and advancing-aged women, the factors that affect mitochondrial activity, and their association with blastocyst quality. Materials and methods: This prospective study included 80 infertile women who [...] Read more.
Background: The goal of this study was to compare mitochondrial activity in cumulus cells (CCs) between young and advancing-aged women, the factors that affect mitochondrial activity, and their association with blastocyst quality. Materials and methods: This prospective study included 80 infertile women who underwent ICSI between May and October 2023. Participants were divided into two groups: older and younger than 38. The oocyte mitochondrial activity from CCs was evaluated using MitoTracker, and the mean fluorescence intensity (MFI) was also evaluated. Results: The univariate and multivariate analyses revealed a significant difference in the MFI between the woman ≥ 38 age group and the lower age group (162.68 ± 79.87 vs. 228.39 ± 121.38; p-value = 0.005; 95%CI 19.97, 111.45). The factors that affected the MFI were women ≥ 38 years of age (p-value = 0.005; 95%CI −111.45, −19.91), total gonadotropin dosages (p-value = 0.006; 95%CI −0.08, 0.01), and gonadotropin-releasing hormone agonist (GnRHa) triggering (p-value = 0.006; 95%CI 36.46, 210.06). However, only women aged ≥38 years remained statistically significant after a multivariable regression analysis (p-value = 0.014; 95%CI −121.00, −14.30). In addition, only male age (mean age ± SD = 38.26 ± 5.13) was associated with high blastocyst quality in univariate and mixed multivariate analyses (OR 0.91; 95%CI 0.56, 3.04). The chemical pregnancy rate was not significantly different between the two age groups (34.5% vs. 56.7%; p-value = 0.162; 95%CI 0.2, 1.30). Conclusion: Advancing age decreased mitochondrial activity in CCs but did not affect blastocyst quality. By contrast, male age may be a predictor of high-grade blastocyst quality. Full article
(This article belongs to the Special Issue Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART))
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12 pages, 668 KiB  
Article
Time-Lapse Incubation for Embryo Culture-Morphokinetics and Environmental Stability May Not Be Enough: Results from a Pilot Randomized Controlled Trial
by Gilat C. Sacks, Henny Mozes, Ruth Ronn, Talia Elder-Geva, Oshrat Schonberger, Ido Ben-Ami and Naama Srebnik
J. Clin. Med. 2024, 13(6), 1701; https://doi.org/10.3390/jcm13061701 - 15 Mar 2024
Viewed by 794
Abstract
Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016–2020. In total, 102 patients were [...] Read more.
Background: Does the Time-lapse Incubator (TLI) add value to reproductive outcomes when its two components, undisturbed culturing and morphokinetic embryo grading, are separated. Methods: A prospective pilot, randomized, controlled, double-blinded, single-center study was conducted during the years 2016–2020. In total, 102 patients were randomized into three groups: (1) conventional incubation with morphological evaluation only (n = 34), (2) TLI with both morphological and morphokinetic evaluations (n = 32), and (3) TLI with morphological evaluation only (n = 36). All arms were cultured in ESCO-MIRI® incubators. A total of 1061 injected mature oocytes were evaluated (420 in arm 1, 285 in arm 2, and 356 in arm 3). The primary outcome was live birth rates. Secondary outcomes included clinical and cumulative pregnancy rates as well as embryo quality. Embryos in arm 3 were retrospectively evaluated for their morphokinetic score. Results: No significant difference was found in the live birth rate for single embryo transfer cycles (SET) (35% vs. 31.6% vs. 24%, p = 0.708) or double embryo transfer (DET) cycles (41.7% vs. 38.5% vs. 36.4%, p = 0.966). Comparable pregnancy rates, clinical pregnancy rates, and cumulative pregnancy were found for similar top-quality embryos for days 2, 3, and blastocyst stages across groups. A similar number of embryos were suitable for either transfer or cryopreservation within the different groups. For 62.8% of the embryos in arm 3, the morphokinetic and morphologic evaluations were similar. In only 2/36 (5.6%) treatment cycles, the use of morphokinetic scoring may have helped the patient avoid undergoing an additional treatment cycle. In the other cases, morphokinetic scoring would not have changed the end point of pregnancy. Conclusions: The two components of the TLI system—undisturbed culturing and morphokinetic embryo grading—do not appear to have a significant additional value in reproductive outcome, although these results should be validated by an RCT. Full article
(This article belongs to the Special Issue Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART))
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Review

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14 pages, 584 KiB  
Review
Dysmorphic Uterus: More Questions than Answers
by Aikaterini Selntigia, Livia Pellegrini, Francesco Gebbia and Daniela Galliano
J. Clin. Med. 2024, 13(15), 4333; https://doi.org/10.3390/jcm13154333 - 25 Jul 2024
Viewed by 182
Abstract
A T-shaped uterus is a rare uterine malformation that is classically associated with diethylstilbesterol (DES) exposure. Surprisingly, the prevalence of T- and Y-shaped uterus has increased in recent years despite the absence of a diagnostic consensus and a correlation with the reproductive outcomes [...] Read more.
A T-shaped uterus is a rare uterine malformation that is classically associated with diethylstilbesterol (DES) exposure. Surprisingly, the prevalence of T- and Y-shaped uterus has increased in recent years despite the absence of a diagnostic consensus and a correlation with the reproductive outcomes has been observed. A systematic electronic database search for all English-language studies published on reproductive outcomes associated with dysmorphic uteri over the past 10 years using PubMed, Google Scholar, and Scopus was performed. This uterine malformation is associated with impaired reproductive outcomes, including primary infertility, miscarriage, ectopic pregnancy, and preterm birth. Hysteroscopic metroplasty is a simple surgical procedure that could potentially improve outcomes in subfertile women, but the data are not robust. Studies reported significant improvements in implantation and pregnancy rates after corrective metroplasty in women undergoing in vitro fertilization. However, multicenter, prospective, randomized, and controlled trials are needed to validate these findings and to help define clear diagnostic criteria, surgical indications, and appropriate follow-up of reproductive outcomes after the procedure. Full article
(This article belongs to the Special Issue Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART))
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24 pages, 1936 KiB  
Review
The Impacts of Inflammatory and Autoimmune Conditions on the Endometrium and Reproductive Outcomes
by Isabel Cuadrado-Torroglosa, Juan A. García-Velasco and Diana Alecsandru
J. Clin. Med. 2024, 13(13), 3724; https://doi.org/10.3390/jcm13133724 - 26 Jun 2024
Viewed by 983
Abstract
Background: A healthy pregnancy begins with an adequate endometrial state, even before the arrival of a blastocyst. Proper endometrial priming and the development of a tolerogenic decidua are key steps in creating the perfect environment for implantation and pregnancy. In these processes, [...] Read more.
Background: A healthy pregnancy begins with an adequate endometrial state, even before the arrival of a blastocyst. Proper endometrial priming and the development of a tolerogenic decidua are key steps in creating the perfect environment for implantation and pregnancy. In these processes, the involvement of the maternal immune system seems to be of great relevance, modulating the different decidual immune populations to prepare the endometrium for a potential pregnancy. However, certain local pathologies of an inflammatory and autoimmune nature appear to have a direct impact on these phenomena, thus altering patients’ reproductive outcomes. Methods: This literature review analyzes original articles, reviews, systematic reviews, and meta-analyses published between 1990 and 2024, concerning the impact of different inflammatory and autoimmune conditions on endometrial status and fertility. The included papers were obtained from Medline (Pubmed) and the Cochrane library. Results: There is evidence that endometriosis, adenomyosis, and chronic endometritis, through the promotion of a chronic inflammatory environment, are capable of altering endometrial immune populations, and, thus, processes essential for early pregnancy. Among other effects, these conditions have been linked to impaired decidualization, alterations in progesterone responsiveness, and hindered placentation. Similarly, antiphospholipid syndrome (APS), thyroid dysfunction, diabetes, and other pathologies related to glucose and gluten metabolism, due to their autoimmune nature, also appear to have a local impact on the uterine environment, affecting reproductive success through different mechanisms, including altered hormonal response and, again, impaired decidualization. Conclusions: The management of inflammatory and autoimmune diseases in assisted reproduction patients is gaining importance due to their direct impact on the endometrium. It is necessary to follow current expert recommendations and established therapeutic approaches in order to improve patients’ prospects, ranging from antibiotic treatment in chronic endometritis to heparin and aspirin in APS, as well as hormonal treatments for endometriosis/adenomyosis or a gluten-free diet in celiac disease. All of them and the rest of the therapeutic perspectives, both current and under investigation, are presented throughout this work, assessing the possible improvements for reproductive outcomes. Full article
(This article belongs to the Special Issue Clinical Advancements in Infertility Treatments and Assisted Reproductive Technology (ART))
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