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Hot Topics in Reproductive Medicine Research
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Hot Topics in Reproductive Medicine Research

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

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 54196

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Aldo E. Calogero

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
Interests: endocrinology of reproduction and sexuality
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Claudio Manna

E-Mail Website
Guest Editor
1. Biofertility IVF and Infertility Center, Rome, Italy
2. Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy
Interests: assisted reproduction; preimplantation genetic tests for aneuploidies; infertility; male infertility; obstetric outcome; polycystic ovarian syndrome; endometrium; endometriosis

Special Issue Information

Dear Colleagues,

Infertility affects approximately 10–15% of couples of reproductive age worldwide. Several factors contribute to its increasing trend in Western countries. Unfortunately, the etiology of infertility remains elusive in a high proportion of patients and therefore the treatments are poorly effective.

Additionally, the results of assisted reproductive techniques (ARTs) show evident limitations even using pre-implantation genetic diagnosis for aneuploidies, prolonged embryo cultures, selection of embryos, etc. Furthermore, there are concerns about obstetric, neonatal, and adult health risks of the children obtained by ART. The endometrium and the placenta certainly deserve more attention. Despite the growing trend in the use of ART, very frequent conditions, such as inflammation of the male genital tract and varicocele, female diseases such as polycystic ovarian syndrome and endometriosis, and their treatments cannot be underestimated.

Another important aspect is the selection of embryos to be used for embryo transfer after ART. Considering the multifactorial aspects involved in reproduction, new approaches are being studied to select the “best” ones in terms of reproductive success. These include the use of artificial intelligence.

This Special Issue aims to focus on some hot issues in reproductive medicine and to re-evaluate infertility etiology, the available clinical-therapeutic strategies (including ART), and decision-making algorithms in the light of the most recent evidence.

Prof. Dr. Aldo E. Calogero
Prof. Dr. Claudio Manna
Guest Editors

Manuscript Submission Information

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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

  • assisted reproduction
  • preimplantation genetic tests for aneuploidies
  • infertility
  • male infertility
  • obstetric outcome
  • polycystic ovarian syndrome
  • endometrium
  • endometriosis

Published Papers (17 papers)

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Research

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13 pages, 1160 KiB  
Article
Novel Time-Lapse Parameters Correlate with Embryo Ploidy and Suggest an Improvement in Non-Invasive Embryo Selection
by Clara Serrano-Novillo, Laia Uroz and Carmen Márquez
J. Clin. Med. 2023, 12(8), 2983; https://doi.org/10.3390/jcm12082983 - 19 Apr 2023
Cited by 1 | Viewed by 1833
Abstract
Selecting the best embryo for transfer is key to success in assisted reproduction. The use of algorithms or artificial intelligence can already predict blastulation or implantation with good results. However, ploidy predictions still rely on invasive techniques. Embryologists are still essential, and improving [...] Read more.
Selecting the best embryo for transfer is key to success in assisted reproduction. The use of algorithms or artificial intelligence can already predict blastulation or implantation with good results. However, ploidy predictions still rely on invasive techniques. Embryologists are still essential, and improving their evaluation tools can enhance clinical outcomes. This study analyzed 374 blastocysts from preimplantation genetic testing cycles. Embryos were cultured in time-lapse incubators and tested for aneuploidies; images were then studied for morphokinetic parameters. We present a new parameter, “st2, start of t2”, detected at the beginning of the first cell cleavage, as strongly implicated in ploidy status. We describe specific cytoplasmic movement patterns associated with ploidy status. Aneuploid embryos also present slower developmental rates (t3, t5, tSB, tB, cc3, and t5-t2). Our analysis demonstrates a positive correlation among them for euploid embryos, while aneuploids present non-sequential behaviors. A logistic regression study confirmed the implications of the described parameters, showing a ROC value of 0.69 for ploidy prediction (95% confidence interval (CI), 0.62 to 0.76). Our results show that optimizing the relevant indicators to select the most suitable blastocyst, such as by including st2, could reduce the time until the pregnancy of a euploid baby while avoiding invasive and expensive methods. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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10 pages, 256 KiB  
Article
The Impact of Endometrioma on Embryo Quality in In Vitro Fertilization: A Retrospective Cohort Study
by Houjin Dongye, Yizheng Tian, Dan Qi, Yanbo Du and Lei Yan
J. Clin. Med. 2023, 12(6), 2416; https://doi.org/10.3390/jcm12062416 - 21 Mar 2023
Cited by 2 | Viewed by 1157
Abstract
The influence of endometrioma on oocyte and embryo competence is inconclusive. Furthermore, the benefits of surgical treatment remain uncertain. This study aimed to investigate the effect of endometrioma on oocyte and embryo quality from a morphological perspective and further explore whether surgery could [...] Read more.
The influence of endometrioma on oocyte and embryo competence is inconclusive. Furthermore, the benefits of surgical treatment remain uncertain. This study aimed to investigate the effect of endometrioma on oocyte and embryo quality from a morphological perspective and further explore whether surgery could contribute to improving oocyte and embryo competence. A total of 664 IVF cycles with endometrioma (538 cycles underwent surgeries) and 3133 IVF cycles from the control group were included. The propensity score matching was used to balance the baseline differences between groups. There was a lower MII oocyte rate (85.0% versus 87.8%, p < 0.001; 84.9% versus 87.6%, p = 0.001) and a similar good-quality embryos rate in women with endometrioma (and those who underwent surgeries) compared with control group. For women with endometrioma, the rates of blastocyst development (67.1% versus 60.2%; p = 0.013) and good blastocyst development (40.7% versus 35.2%; p = 0.049) were significantly higher in those who had undergone surgical treatment compared with those who had not, but the rates of MII oocytes (79.9% versus 87.7%; p < 0.001) and normal fertilization (55.2% versus 66.2%; p < 0.001) were lower. The study indicates that endometrioma, including its surgical treatment, compromises the oocyte maturity not the embryo quality at the cleavage stage; however, the surgery seems to contribute to improving blastocyst development. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
11 pages, 298 KiB  
Article
Advanced Paternal Age Does Not Affect Medically-Relevant Obstetrical and Perinatal Outcomes following IVF or ICSI in Humans with Donated Oocytes
by Ana Navarro-Gomezlechon, María Gil Juliá, Irene Hervás, Laura Mossetti, Rocío Rivera-Egea and Nicolás Garrido
J. Clin. Med. 2023, 12(3), 1014; https://doi.org/10.3390/jcm12031014 - 28 Jan 2023
Cited by 1 | Viewed by 1343
Abstract
Background: Concomitant with delays in childbearing, concerns have been raised of whether advanced paternal age is associated with adverse reproductive outcomes, but the evidence is controversial in part due to the uncertain threshold in which to consider advanced paternal age and confounding maternal [...] Read more.
Background: Concomitant with delays in childbearing, concerns have been raised of whether advanced paternal age is associated with adverse reproductive outcomes, but the evidence is controversial in part due to the uncertain threshold in which to consider advanced paternal age and confounding maternal factors. This retrospective study aimed to evaluate the effect of paternal age on reproductive outcomes related to the pregnancy and perinatal health of the offspring. Methods: We retrospectively evaluated 16,268 cases of patients who underwent IVF or ICSI (using autologous sperm and donated oocytes, between January 2008 and March 2020, at Spanish IVIRMA clinics. Patients were divided based on paternal age at conception [≤30 (n = 204), 31–40 (n = 5752), and >40 years (n = 10,312)], and the differences in obstetrical and perinatal outcomes were analyzed by descriptive analysis, followed by univariate and multivariate analysis. Results: Fathers 31–40 and >40 years old were associated with lower odds of caesarean delivery [AOR 0.63 (95% CI, 0.44–0.90; p = 0.012) and AOR 0.61 (95% CI, 0.41–0.91; p = 0.017), respectively] and longer pregnancies [ARC 5.09 (95% CI, 2.39–7.79; p < 0.001) and ARC 4.54 (95% CI, 1.51–7.58; p = 0.003), respectively] with respect to fathers ≤30 years old. Furthermore, fathers aged 31–40 years old had lower odds of having a female infant (AOR, 0.70; 95% CI, 0.49–0.99; p = 0.045) than those ≤30. The rest of obstetrical and perinatal outcomes, which we deemed more medically-relevant as they were considered serious for health, were comparable between groups with our adjusted model. Conclusions: Despite this hopeful message to fathers of advanced paternal age, future studies should consider the short- and long-term outcomes of the offspring and try to better elucidate the associations of advanced paternal age with reproductive outcomes and the molecular mechanisms underlying the observed associations. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
13 pages, 634 KiB  
Article
Assisted Reproductive Technology without Embryo Discarding or Freezing in Women ≥40 Years: A 5-Year Retrospective Study at a Single Center in Italy
by Claudio Manna, Federica Barbagallo, Francesca Sagnella, Ashraf Farrag and Aldo E. Calogero
J. Clin. Med. 2023, 12(2), 504; https://doi.org/10.3390/jcm12020504 - 07 Jan 2023
Cited by 3 | Viewed by 1954
Abstract
The protocols commonly used in assisted reproductive technology (ART) consist of long-term embryo culture up to the blastocyst stage after the insemination of all mature oocytes, the freezing of all the embryos produced, and their subsequent transfer one by one. These practices, along [...] Read more.
The protocols commonly used in assisted reproductive technology (ART) consist of long-term embryo culture up to the blastocyst stage after the insemination of all mature oocytes, the freezing of all the embryos produced, and their subsequent transfer one by one. These practices, along with preimplantation genetic testing, although developed to improve the live birth rate (LBR) and reduce the risk of multiple pregnancies, are drawing attention to the possible increase in obstetric and perinatal risks, and adverse epigenetic consequences in offspring. Furthermore, ethical–legal concerns are growing regarding the increase in cryopreservation and storage of frozen embryos. In an attempt to reduce the risk associated with prolonged embryo culture and avoid embryo storage, we have chosen to inseminate a limited number of oocytes not exceeding the number of embryos to be transferred, after two days or less of culture. We retrospectively analyzed 245 ICSI cycles performed in 184 infertile couples with a female partner aged ≥40 from January 2016 to July 2021. The results showed a fertilization rate of 95.7%, a miscarriage rate of 48.9%, and a LBR of 10% with twin pregnancies of 16.7%. The cumulative LBR in our group of couples was 13%. No embryos were frozen. In conclusion, these results suggest that oocyte selection and embryo transfer at the cleaving stage constitute a practice that has a LBR comparable to that of the more commonly used protocols in older women who have reduced ovarian reserve. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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12 pages, 994 KiB  
Article
Association of the Cumulative Live Birth Rate with the Factors in Assisted Reproductive Technology: A Retrospective Study of 16,583 Women
by Qiumin Wang, Dan Qi, Lixia Zhang, Jingru Wang, Yanbo Du, Hong Lv and Lei Yan
J. Clin. Med. 2023, 12(2), 493; https://doi.org/10.3390/jcm12020493 - 06 Jan 2023
Cited by 1 | Viewed by 1534
Abstract
The cumulative live birth rate (CLBR) can better reflect the overall treatment effect by successive treatments, and continuous rather than categorical variables as exposure variables can increase the statistical power in detecting the potential correlation. Therefore, the dose–response relationships might find an optimal [...] Read more.
The cumulative live birth rate (CLBR) can better reflect the overall treatment effect by successive treatments, and continuous rather than categorical variables as exposure variables can increase the statistical power in detecting the potential correlation. Therefore, the dose–response relationships might find an optimal dose for the better CLBR, offering evidence-based references for clinicians. To determine the dose–response relationships of the factors and the optimal ranges of the factors in assisted reproductive technology (ART) associated with a higher CLBR, this study retrospectively analyzed 16,583 patients undergoing the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) from January 2017 to January 2019. Our study demonstrated the optimal ranges of age with a higher CLBR were under 32.10 years. We estimated the CLBR tends to increase with increased levels of AMH at AMH levels below 1.482 ng/mL, and the CLBR reaches a slightly high level at AMH levels in the range from 2.58–4.18 ng/mL. The optimal ranges of basal FSH with a higher CLBR were less than 9.13 IU. When the number of cryopreserved embryos was above 1.055 and the number of total transferred embryos was 2, the CLBR was significantly higher. In conclusion, there is a non-linear dose–response relationship between the CLBR with age, AMH, basal FSH, and the number of cryopreserved embryos and total transferred embryos. We proposed the optimal ranges of the five factors that were correlated with a higher CLBR in the first oocyte retrieval cycle, which may help consultation at IVF clinics. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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12 pages, 2452 KiB  
Article
Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways
by Maha H. Daghestani, Huda A. Alqahtani, AlBandary AlBakheet, Mashael Al Deery, Khalid A. Awartani, Mazin H. Daghestani, Namik Kaya, Arjumand Warsy, Serdar Coskun and Dilek Colak
J. Clin. Med. 2022, 11(23), 6941; https://doi.org/10.3390/jcm11236941 - 25 Nov 2022
Cited by 3 | Viewed by 1974
Abstract
Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an [...] Read more.
Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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9 pages, 455 KiB  
Communication
Positive Effect of a New Combination of Antioxidants and Natural Hormone Stimulants for the Treatment of Oligoasthenoteratozoospermia
by Vincenzo De Leo, Claudia Tosti, Giuseppe Morgante, Rosetta Ponchia, Alice Luddi, Laura Governini and Paola Piomboni
J. Clin. Med. 2022, 11(7), 1991; https://doi.org/10.3390/jcm11071991 - 02 Apr 2022
Cited by 4 | Viewed by 3220
Abstract
Oligoasthenoteratozoospermia (OAT) accounts for about 90% of male infertility; in many cases this disorder may be associated with oxidative stress, a condition that decreases the success of fertilization. Therefore, the empirical treatment of male infertility is often based on the use of antioxidants. [...] Read more.
Oligoasthenoteratozoospermia (OAT) accounts for about 90% of male infertility; in many cases this disorder may be associated with oxidative stress, a condition that decreases the success of fertilization. Therefore, the empirical treatment of male infertility is often based on the use of antioxidants. The aim of the present study was to assess the effectiveness of three months’ administration of a new nutraceutical preparation on hormone profile, sperm parameters and fertilization capability in men undergoing in vitro fertilization (IVF). A total of 36 OAT patients were daily treated for 3 months with a dose of a formulation containing: Inositol, L-Carnitine, Vitamins C, D, E, Coenzyme Q10 and Selenium. Selected parameters were analysed before (T0) and after (T1) treatment, and IVF outcomes were evaluated. We observed an improvement of sperm concentration, motility, morphology and vitality; blood level of testosterone also showed an increase. A significant increase of fertilization rate was detected in 14 couples, whose male partner were treated with the nutraceutical preparation. The present results indicate that a formulation containing antioxidant and energy supply substances was effective in the treatment of sperm alterations and led to significant recovery of fertilizing capacity. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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14 pages, 2089 KiB  
Article
Astaxanthin Relieves Testicular Ischemia-Reperfusion Injury—Immunohistochemical and Biochemical Analyses
by Marko Bašković, Dajana Krsnik, Marta Himelreich Perić, Ana Katušić Bojanac, Nino Sinčić, Zdenko Sonicki and Davor Ježek
J. Clin. Med. 2022, 11(5), 1284; https://doi.org/10.3390/jcm11051284 - 26 Feb 2022
Cited by 3 | Viewed by 2141
Abstract
Testicular torsion potentially leads to acute scrotum and testicle loss, and requires prompt surgical intervention to restore testicular blood flow, despite the paradoxical negative effect of reperfusion. While no drug is yet approved for this condition, antioxidants are promising candidates. This study aimed [...] Read more.
Testicular torsion potentially leads to acute scrotum and testicle loss, and requires prompt surgical intervention to restore testicular blood flow, despite the paradoxical negative effect of reperfusion. While no drug is yet approved for this condition, antioxidants are promising candidates. This study aimed to determine astaxanthin’s (ASX), a potent antioxidant, effect on rat testicular torsion−detorsion injury. Thirty-two prepubertal male Fischer rats were divided into four groups. Group 1 underwent sham surgery. In group 2, the right testis was twisted at 720° for 90 min. After 90 min of reperfusion, the testis was removed. ASX was administered intraperitoneally at the time of detorsion (group 3) and 45 min after detorsion (group 4). Quantification of caspase-3 positive cells and oxidative stress markers detection were determined immunohistochemically, while the malondialdehyde (MDA) value, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined by colorimetric assays. The number of apoptotic caspase-3 positive cells and the MDA value were lower in group 4 compared to group 2. A significant increase in the SOD and GPx activity was observed in group 4 compared to groups 2 and 3. We conclude that ASX has a favorable effect on testicular ischemia-reperfusion injury in rats. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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Review

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17 pages, 1457 KiB  
Review
Can Cryopreservation in Assisted Reproductive Technology (ART) Induce Epigenetic Changes to Gametes and Embryos?
by Romualdo Sciorio, Claudio Manna, Patricia Fauque and Paolo Rinaudo
J. Clin. Med. 2023, 12(13), 4444; https://doi.org/10.3390/jcm12134444 - 02 Jul 2023
Cited by 3 | Viewed by 1975
Abstract
Since the birth of Louise Brown in 1978, more than nine million children have been conceived using assisted reproductive technologies (ARTs). While the great majority of children are healthy, there are concerns about the potential epigenetic consequences of gametes and embryo manipulation. In [...] Read more.
Since the birth of Louise Brown in 1978, more than nine million children have been conceived using assisted reproductive technologies (ARTs). While the great majority of children are healthy, there are concerns about the potential epigenetic consequences of gametes and embryo manipulation. In fact, during the preimplantation period, major waves of epigenetic reprogramming occur. Epigenetic reprogramming is susceptible to environmental changes induced by ovarian stimulation, in-vitro fertilization, and embryo culture, as well as cryopreservation procedures. This review summarizes the evidence relating to oocytes and embryo cryopreservation and potential epigenetic regulation. Overall, it appears that the stress induced by vitrification, including osmotic shock, temperature and pH changes, and toxicity of cryoprotectants, might induce epigenetic and transcriptomic changes in oocytes and embryos. It is currently unclear if these changes will have potential consequences for the health of future offspring. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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13 pages, 805 KiB  
Review
Varicocele: To Treat or Not to Treat?
by Antonio Franco, Flavia Proietti, Veronica Palombi, Gabriele Savarese, Michele Guidotti, Costantino Leonardo, Fabio Ferro, Claudio Manna and Giorgio Franco
J. Clin. Med. 2023, 12(12), 4062; https://doi.org/10.3390/jcm12124062 - 15 Jun 2023
Cited by 2 | Viewed by 6113
Abstract
Varicocele treatment in infertility still remains controversial. It is clear, in fact, that in many patients, varicocele has no impact on fertility. Recent scientific evidence demonstrated that varicocele treatment is beneficial in improving semen parameters and pregnancy rate when an appropriate selection of [...] Read more.
Varicocele treatment in infertility still remains controversial. It is clear, in fact, that in many patients, varicocele has no impact on fertility. Recent scientific evidence demonstrated that varicocele treatment is beneficial in improving semen parameters and pregnancy rate when an appropriate selection of patients is made. The purpose of treating varicocele in adults is mainly to improve current fertility status. On the other hand, the goal of treatment in adolescents is to prevent testicular injury and maintain testicular function for future fertility. Hence, the key to the success of varicocele treatment seems to be a correct indication. The aim of this study is to review and summarize current evidence in managing varicocele treatment focusing on the controversies regarding surgical indications in adolescent and adult patients, and in other specific situations such as azoospermia, bilateral or subclinical varicocele, and prior to ART. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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12 pages, 1715 KiB  
Review
Adverse Pregnancy Outcomes and Maternal Periodontal Disease: An Overview on Meta-Analytic and Methodological Quality
by Vanessa Machado, Madalena Ferreira, Luísa Lopes, José João Mendes and João Botelho
J. Clin. Med. 2023, 12(11), 3635; https://doi.org/10.3390/jcm12113635 - 23 May 2023
Cited by 1 | Viewed by 1559
Abstract
This umbrella review aims to appraise the methodological quality and strength of evidence on the association between maternal periodontitis and adverse pregnancy outcomes (APOs). PubMed, CENTRAL, Web-of-Science, LILACS, and Clinical Trials were searched until February 2023, without date or language restrictions. Two authors [...] Read more.
This umbrella review aims to appraise the methodological quality and strength of evidence on the association between maternal periodontitis and adverse pregnancy outcomes (APOs). PubMed, CENTRAL, Web-of-Science, LILACS, and Clinical Trials were searched until February 2023, without date or language restrictions. Two authors independently screened studies, extracted data, performed the risk-of-bias analysis, and estimated the meta-analytic strengths and validity and the fail-safe number (FSN). A total of 43 SRs were identified, of which 34 conducted meta-analyses. Of the 28 APOs, periodontitis had a strong association with preterm birth (PTB), low birth weight (LBW), and gestational diabetes mellitus (GDM), PTB and LBW showed all levels of strength, and pre-eclampsia showed only suggestive and weak strength. Regarding the consistency of the significant estimates, only 8.7% were likely to change in the future. The impact of periodontal treatment on APOs was examined in 15 SRs, 11 of which conducted meta-analyses. Forty-one meta-analyses were included and showed that periodontal treatment did not have a strong association with APOs, although PTB revealed all levels of strength and LBW showed only suggestive and weak evidence. Strong and highly suggestive evidence from observational studies supports an association of periodontitis with a higher risk of PTB, LBW, GDM, and pre-eclampsia. The effect of periodontal treatment on the prevention of APOs is still uncertain and requires future studies to draw definitive and robust conclusions. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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20 pages, 2659 KiB  
Review
The Impact of a Very Short Abstinence Period on Conventional Sperm Parameters and Sperm DNA Fragmentation: A Systematic Review and Meta-Analysis
by Federica Barbagallo, Rossella Cannarella, Andrea Crafa, Claudio Manna, Sandro La Vignera, Rosita A. Condorelli and Aldo E. Calogero
J. Clin. Med. 2022, 11(24), 7303; https://doi.org/10.3390/jcm11247303 - 08 Dec 2022
Cited by 11 | Viewed by 2933
Abstract
Purpose: In recent years, a growing number of studies have supported the beneficial effects of a very short abstinence period on sperm parameters, especially in patients with oligoasthenozoospermia. However, the results are controversial and no consensus exists regarding whether to request a second [...] Read more.
Purpose: In recent years, a growing number of studies have supported the beneficial effects of a very short abstinence period on sperm parameters, especially in patients with oligoasthenozoospermia. However, the results are controversial and no consensus exists regarding whether to request a second semen collection in clinical practice. Therefore, this systematic review and meta-analysis aimed to evaluate the influence of a very short abstinence period (within 4 h) on conventional sperm parameters and sperm DNA fragmentation (SDF) rate. Materials and Methods: The literature search was performed using Scopus and PubMed databases. The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. All eligible studies were selected according to the Population, Intervention, Comparison/Comparator, Outcomes, and Study design (PICOS) model. The quality of evidence of the included studies was analyzed through the Cambridge Quality Checklists. The standardized mean difference (SMD) was used to analyze the outcomes. Cochran-Q and I2 statistics were used to evaluate statistical heterogeneity. Results: We assessed for eligibility 1334 abstracts, and 19 studies were finally included. All 19 articles evaluated the effects of a very short abstinence period on sperm parameters and, among these, 5 articles also evaluated the effects on SDF rate. The quantitative analysis showed a significant reduction in semen volume after a very short abstinence period in both normozoospermic men and patients with oligozoospermia, asthenozoospermia, and/or teratozoospermia (OAT) patients. We found a statistically significant increase in sperm concentration and total and progressive motility in the second ejaculation of patients with OAT. In contrast, the SDF rate decreased significantly in the second ejaculate of OAT patients. Conclusions: This is the first systematic review and meta-analysis investigating the impact of a very short abstinence period on sperm parameters and SDF rate. The results suggest that collecting a second consecutive ejaculation after a very short time from the first could represent a simple and useful strategy for obtaining better-quality spermatozoa, especially in patients with abnormal sperm parameters. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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11 pages, 873 KiB  
Review
Placental Volume and Uterine Artery Doppler in Pregnancy Following In Vitro Fertilization: A Comprehensive Literature Review
by Serena Resta, Gaia Scandella, Ilenia Mappa, Maria Elena Pietrolucci, Pavjola Maqina and Giuseppe Rizzo
J. Clin. Med. 2022, 11(19), 5793; https://doi.org/10.3390/jcm11195793 - 29 Sep 2022
Cited by 3 | Viewed by 2376
Abstract
The number of pregnancies achieved using in vitro fertilization (IVF) is rapidly increasing around the world. The chance of obtaining a successful pregnancy is also significantly improved due to technological advances and improvement in infertility treatment. Despite this success, there is evidence that [...] Read more.
The number of pregnancies achieved using in vitro fertilization (IVF) is rapidly increasing around the world. The chance of obtaining a successful pregnancy is also significantly improved due to technological advances and improvement in infertility treatment. Despite this success, there is evidence that pregnancy conceived by IVF has an increased risk of adverse maternal and perinatal outcome mainly represented by the development of hypertensive diseases, pre-eclampsia, and fetal growth restriction. Although different cofactors may play a role in the genesis of these diseases, the development of the placenta has a pivotal function in determining pregnancy outcomes. Advances in ultrasound technology already allows for evaluation in the first trimester, the impedance to flow in the uterine artery, and the placental volume using Doppler and three-dimensional techniques. This review article aims to describe the modification occurring in placental volume and hemodynamics after IVF and to summarize the differences present according to the type of IVF (fresh vs. frozen-thawed embryos). Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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14 pages, 2337 KiB  
Review
PCOS Physiopathology and Vitamin D Deficiency: Biological Insights and Perspectives for Treatment
by Giuseppe Morgante, Ilenia Darino, Amelia Spanò, Stefano Luisi, Alice Luddi, Paola Piomboni, Laura Governini and Vincenzo De Leo
J. Clin. Med. 2022, 11(15), 4509; https://doi.org/10.3390/jcm11154509 - 02 Aug 2022
Cited by 23 | Viewed by 8708
Abstract
Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated [...] Read more.
Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated with insulin resistance and increased diabetes risk. Since women with PCOS and hirsutism seem to have lower levels of VD than women with PCOS without hirsutism, a correlation between VD deficiency and hyperandrogenism may be suggested. Interestingly, VD is crucial for many human physiological functions, including to counteract inflammation and oxidative stress. Some studies evaluated effects of VD supplementation on glucose homeostasis variables, hormonal status, lipid concentrations, and biomarkers of inflammation and oxidative stress among VD-deficient women. Moreover, VD has been shown to play a role in egg quality and fertility. This review aims to show the relationship between VD and the endocrine and metabolic profile of PCOS patients, as well as its implications for their fertility. The supplement of VD to the common therapy can lead to an improvement of the insulin resistance and lipid metabolism, a reduction of circulating androgens, as well as a better response to the induction of ovulation in PCOS women. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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18 pages, 1718 KiB  
Review
Epigenetic Risks of Medically Assisted Reproduction
by Romualdo Sciorio and Nady El Hajj
J. Clin. Med. 2022, 11(8), 2151; https://doi.org/10.3390/jcm11082151 - 12 Apr 2022
Cited by 14 | Viewed by 5029
Abstract
Since the birth of Louise Joy Brown, the first baby conceived via in vitro fertilization, more than 9 million children have been born worldwide using assisted reproductive technologies (ART). In vivo fertilization takes place in the maternal oviduct, where the unique physiological conditions [...] Read more.
Since the birth of Louise Joy Brown, the first baby conceived via in vitro fertilization, more than 9 million children have been born worldwide using assisted reproductive technologies (ART). In vivo fertilization takes place in the maternal oviduct, where the unique physiological conditions guarantee the healthy development of the embryo. During early embryogenesis, a major wave of epigenetic reprogramming takes place that is crucial for the correct development of the embryo. Epigenetic reprogramming is susceptible to environmental changes and non-physiological conditions such as those applied during in vitro culture, including shift in pH and temperature, oxygen tension, controlled ovarian stimulation, intracytoplasmic sperm injection, as well as preimplantation embryo manipulations for genetic testing. In the last decade, concerns were raised of a possible link between ART and increased incidence of imprinting disorders, as well as epigenetic alterations in the germ cells of infertile parents that are transmitted to the offspring following ART. The aim of this review was to present evidence from the literature regarding epigenetic errors linked to assisted reproduction treatments and their consequences on the conceived children. Furthermore, we provide an overview of disease risk associated with epigenetic or imprinting alterations in children born via ART. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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12 pages, 1651 KiB  
Systematic Review
Efficacy of Autologous Intrauterine Infusion of Platelet-Rich Plasma in Patients with Unexplained Repeated Implantation Failures in Embryo Transfer: A Systematic Review and Meta-Analysis
by Muzi Li, Yan Kang, Qianfei Wang and Lei Yan
J. Clin. Med. 2022, 11(22), 6753; https://doi.org/10.3390/jcm11226753 - 15 Nov 2022
Cited by 7 | Viewed by 1842
Abstract
(1) Background: Controversial conclusions have been made in previous studies regarding the influence of autologous platelet-rich plasma (PRP) in the reproductive outcomes of women with repeated implantation failures (RIF) who are undergoing embryo transfer (ET). (2) Methods: This study aimed to evaluate the [...] Read more.
(1) Background: Controversial conclusions have been made in previous studies regarding the influence of autologous platelet-rich plasma (PRP) in the reproductive outcomes of women with repeated implantation failures (RIF) who are undergoing embryo transfer (ET). (2) Methods: This study aimed to evaluate the effect of PRP intrauterine infusion in patients with unexplained RIF, who are undergoing in vitro fertilization (IVF) or intracytoplasmic injection (ICSI), by a systematic review and meta-analysis. (3) Results: A fixed-effects model was used, and 795 cases and 834 controls were included in these studies. The pooling of the results showed the beneficial effect of PRP which were compared with those of the control in terms of the clinical pregnancy rates (n = 10, risk ratio (RR) = 1.79, 95% confidence intervals (CI): 1.55, 2.06; p < 0.01, I2 = 40%), live birth rates (n = 4, RR = 2.92, 95% CI: 2.22, 3.85; p < 0.01, I2 = 83%), implantation rates (n = 3, RR = 1.74, 95% CI: 1.34, 2.26; p < 0.01, I2 = 0%), and positive serum β-HCG 14 days after the ET (n = 8, RR = 1.77, 95% CI: 1.54, 2.03; p < 0.01, I2 = 36%). However, we did not find that the miscarriage rates indicated a significant difference between the two groups (n = 6, RR = 1.04, 95% CI: 0.72, 1.51; p = 0.83, I2 = 0%). (4) Conclusions: The findings of this systemic review and meta-analysis suggest that PRP appears to improve the results of IVF/ICSI treatments in the cases of unexplained RIF. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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23 pages, 4133 KiB  
Systematic Review
DNA Methylation in Offspring Conceived after Assisted Reproductive Techniques: A Systematic Review and Meta-Analysis
by Rossella Cannarella, Andrea Crafa, Laura M. Mongioì, Loredana Leggio, Nunzio Iraci, Sandro La Vignera, Rosita A. Condorelli and Aldo E. Calogero
J. Clin. Med. 2022, 11(17), 5056; https://doi.org/10.3390/jcm11175056 - 28 Aug 2022
Cited by 13 | Viewed by 2053
Abstract
Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all [...] Read more.
Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD −0.81 (−1.53; −0.09), I2 = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring. Full article
(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)
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