Assisted Reproductive Technology and Infertility Treatment: Current Updates and Perspectives

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: 30 January 2025 | Viewed by 8559

Special Issue Editors


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Guest Editor
Obstetric-Gynecologic Clinic, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
Interests: assisted reproduction; infertility; ovarian stimulation; poor responders; fertility preservation
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Laboratory of Physiology, Faculty of Medicine, School of Health Sciences Democritus University of Thrace, 69100 Alexandroupolis, Greece
2. Embryokosmogenesis, Medically Assisted Reproduction Unit, 4th km Alexandroupolis-Borders, 68131 Apalos, Alexandroupolis, Greece
Interests: assisted reproduction; infertility; natural products; immunobiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

ART is used extensively as an aid in overcoming infertility problems. Evidence-based research suggests that 8–12% of couples worldwide are trying to conceive spontaneously despite experiencing fertility problems. A remarkable percentage of people turn to assisted reproduction consultation and help from medical solutions to bring about the conception and birth of a baby of their own. Each ART cycle is complex and consists of several steps. Thus, it is crucial that this system is based on sufficient evidence and detailed guidelines. This Special Issue aims to discuss the development of assisted reproduction techniques, including their proper indication. Experimental, innovative and widely used technology supports the inter-professional team disclosure. The contradictions and their subsequent management provide the underlying background for personalised assistance in IVF and associated procedures. The success rate, benefits, risks, cost and ethics of ART are also important parts of in vitro fertilization methods and indicate the essential surveillance and vigilance in quality control. The conclusive aim of this Special Issue is to overview the most up-to-date evidence on ART to optimise guidelines and protocols in order to improve assisted reproduction technology practices and outcomes.

Prof. Dr. Nikos Nikolettos
Dr. Angeliki Tiptiri-Kourpeti
Guest Editors

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Keywords

  • assisted reproduction technology (ART)
  • infertility
  • treatment
  • reproduction
  • IVF

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Published Papers (7 papers)

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Research

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11 pages, 555 KiB  
Article
Risk Factors for Prematurity and Congenital Malformations in Assisted Reproductive Technology Pregnancies—A Retrospective Study
by Raluca Tocariu, Alexandru Dinulescu, Ana Prejmereanu, Călina Maier, Anca-Magdalena Coricovac, Evelyn-Denise Archir, Lucia Elena Niculae and Elvira Brătilă
J. Clin. Med. 2024, 13(21), 6470; https://doi.org/10.3390/jcm13216470 - 29 Oct 2024
Viewed by 544
Abstract
Background: Assisted reproductive technology (ART) nowadays plays a major role in the treatment of infertility, with the most frequently used techniques being in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The objective of this study is to analyze pregnancies achieved using these [...] Read more.
Background: Assisted reproductive technology (ART) nowadays plays a major role in the treatment of infertility, with the most frequently used techniques being in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The objective of this study is to analyze pregnancies achieved using these ART techniques and their correlations with the prematurity and congenital malformations rates. Methods: This is an observational retrospective longitudinal study that includes 814 newborns conceived through an ART, namely IVF or ICSI. Results: Using a multivariate logistic regression analysis mode, there is a higher prematurity rate in twin pregnancies OR 16 (95% CI 10.7, 23.8), donor conception OR 1.8 (95% CI 1.1, 3.3) and PIH pregnancy OR 2.6 (95% CI 1.5, 4.5). The odds of malformations in these ART pregnancies are increased by the stage of the embryo (day 3) OR 2.6 (95% CI 1.3, 5.2), fresh embryo transfer OR 2 (95% CI 1.2, 3.4) and donor conception OR 2.3 (95% CI 1.2, 4.4). The ART used (IVF/ICSI) does not influence the prematurity or birth defects rate. Conclusions: Donor conception is found to increase the odds of both prematurity and congenital malformations. The ART used (IVF/ICSI) does not influence the prematurity or birth defects rate. Full article
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9 pages, 2380 KiB  
Article
Effect of Waiting Period on Initial Adverse Vaginal Microbiome Composition in IVF-ICSI Patients
by Alexandra Petra Bielfeld, Dunja Maria Baston-Buest, Philippos Edimiris and Jan-Steffen Kruessel
J. Clin. Med. 2024, 13(17), 5024; https://doi.org/10.3390/jcm13175024 - 25 Aug 2024
Viewed by 709
Abstract
Background/Objectives: In this observational prospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, the spontaneous reversal capacity and the effect of waiting time on an adverse vaginal microbiome profile in subfertile patients were investigated. Methods: Vaginal [...] Read more.
Background/Objectives: In this observational prospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, the spontaneous reversal capacity and the effect of waiting time on an adverse vaginal microbiome profile in subfertile patients were investigated. Methods: Vaginal swabs of 76 patients were obtained before starting a fertility treatment using a commercially available test to perform a microbiome analysis. Patients with a favorable microbiome profile (“medium” or “high profile”) according to the manufacturer’s algorithm proceeded with the fertility treatment. Patients with an unfavorable microbiome profile (“low profile”) postponed their fertility treatment and were sampled up to four times in each successive cycle or until a shift to a more favorable profile was detected. Results: Initially, 54/76 subjects had a high or medium profile and 23/76 had a low profile. Within 3 months, 75% of patients with an initial low profile shifted to a more favorable profile (7/23 dropouts). The presence of Lactobacillus crispatus in the initial sample was associated with a higher likelihood of a spontaneous shift to a more favorable profile. Conclusions: The vaginal microbiome is subject to strong fluctuations. Even an unfavorable microbiome profile can develop into a favorable microbiome profile within a few months without treatment. Full article
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11 pages, 247 KiB  
Article
Poor Response to Gonadotropin Stimulation and Perinatal Outcomes in Fresh In Vitro Fertilization Embryo Transfer Cycles—A Retrospective Cohort Study
by Alyssa Hochberg, Avital Wertheimer, Rita Zlatkin, Onit Sapir, Eyal Krispin, Tzippy Schohat, Eran Altman, Avi Ben-Haroush and Yoel Shufaro
J. Clin. Med. 2024, 13(10), 2985; https://doi.org/10.3390/jcm13102985 - 19 May 2024
Viewed by 1090
Abstract
Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17–39 who underwent [...] Read more.
Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17–39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007–2022). Patients were classified as one of the following categories: poor responders—daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders—4–15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes. Full article

Review

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12 pages, 271 KiB  
Review
Understanding the Role of Female Genital Tract Microbiome in Recurrent Implantation Failure
by Anastasios Lafioniatis, Athina A. Samara, Peter K. Makaritsis, Stefanos Dafopoulos, Sotirios Sotiriou and Konstantinos Dafopoulos
J. Clin. Med. 2024, 13(11), 3173; https://doi.org/10.3390/jcm13113173 - 28 May 2024
Viewed by 1275
Abstract
The realization of the role of the microbiome of the female reproductive tract in health and disease has opened numerous possibilities for the scientific examination of the intertwining role between the human host and its microbiota. The imbalance in the composition of the [...] Read more.
The realization of the role of the microbiome of the female reproductive tract in health and disease has opened numerous possibilities for the scientific examination of the intertwining role between the human host and its microbiota. The imbalance in the composition of the microbial communities of the vagina and uterus is now recognized as a risk factor for many complications in pregnancy and according to the data from numerous studies, it is possible for this imbalance to play a crucial role in creating a hostile endometrial environment, and therefore, contributing to the etiology of recurrent implantation failure. Nevertheless, our current understanding of these complicated biological phenomena is far from complete, and in the future, there needs to be a systematic and thorough investigation of the diagnosis and therapy of this condition. This will enable scientists who engage in the field of assisted reproduction technologies to accurately identify and cure women in whom dysbiosis hinders the achievement of a healthy pregnancy. Full article
23 pages, 966 KiB  
Review
NGF, EPO, and IGF-1 in the Male Reproductive System
by Chryssa Metallinou, Chrysovalanto Staneloudi, Konstantinos Nikolettos and Byron Asimakopoulos
J. Clin. Med. 2024, 13(10), 2918; https://doi.org/10.3390/jcm13102918 - 15 May 2024
Cited by 1 | Viewed by 1540
Abstract
Several studies have demonstrated interesting results considering the implication of three growth factors (GFs), namely nerve growth factor (NGF), erythropoietin (EPO), and the insulin-like growth factor-I (IGF-1) in the physiology of male reproductive functions. This review provides insights into the effects of NGF, [...] Read more.
Several studies have demonstrated interesting results considering the implication of three growth factors (GFs), namely nerve growth factor (NGF), erythropoietin (EPO), and the insulin-like growth factor-I (IGF-1) in the physiology of male reproductive functions. This review provides insights into the effects of NGF, EPO, and IGF-1 on the male reproductive system, emphasizing mainly their effects on sperm motility and vitality. In the male reproductive system, the expression pattern of the NGF system varies according to the species and testicular development, playing a crucial role in morphogenesis and spermatogenesis. In humans, it seems that NGF positively affects sperm motility parameters and NGF supplementation in cryopreservation media improves post-thaw sperm motility. In animals, EPO is found in various male reproductive tissues, and in humans, the protein is present in seminal plasma and testicular germ cells. EPO receptors have been discovered in the plasma membrane of human spermatozoa, suggesting potential roles in sperm motility and vitality. In humans, IGF-1 is expressed mainly in Sertoli cells and is present in seminal plasma, contributing to cell development and the maturation of spermatozoa. IGF-1 seems to modulate sperm motility, and treatment with IGF-1 has a positive effect on sperm motility and vitality. Furthermore, lower levels of NGF or IGF-1 in seminal plasma are associated with infertility. Understanding the mechanisms of actions of these GFs in the male reproductive system may improve the outcome of sperm processing techniques. Full article
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Other

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10 pages, 1518 KiB  
Study Protocol
Impact of Hysteroscopic Polypectomy on IVF Outcomes in Women with Unexplained Infertility
by Olga Triantafyllidou, Ilias Korompokis, Stamatia Chasiakou, Panagiotis Bakas, Theodoros Kalampokas, Mara Simopoulou, Despoina Tzanakaki, Emmanouil Kalampokas, Evangelia Panagodimou, Maria Xepapadaki, Panagiotis Christopoulos, Georgios Valsamakis and Nikolaos F Vlahos
J. Clin. Med. 2024, 13(16), 4755; https://doi.org/10.3390/jcm13164755 - 13 Aug 2024
Viewed by 1183
Abstract
Objective: To assess the effect of hysteroscopic polypectomy on the in vitro fertilization (IVF) results in infertile women with at least one prior negative IVF outcome. Methods: This retrospective cohort study included women who had attended the “2nd Department of Obstetrics and Gynecology [...] Read more.
Objective: To assess the effect of hysteroscopic polypectomy on the in vitro fertilization (IVF) results in infertile women with at least one prior negative IVF outcome. Methods: This retrospective cohort study included women who had attended the “2nd Department of Obstetrics and Gynecology of the National and Kapodistrian University of Athens” and “Iaso” Maternity Hospital from October 2019 to January 2023 for infertility treatment. The medical records of 345 women aged 18–45 years old without abnormal findings in hysterosalpingography (HSG) and with at least one previous failed IVF procedure were analyzed. The male factor was excluded, as well as a prior hysteroscopic removal of polyps. In 67 women, polyps were suspected during initial two-dimensional ultrasound (2D-US) examination. The final sample of the study comprised 40 patients, in which endometrial polyps were removed by hysteroscopy with the use of resectoscope. All patients underwent ovarian stimulation and IVF in the consecutive cycle using a short GnRh antagonist protocol. Main Results: After hysteroscopic polypectomy, 29 (72.5%) out of 40 patients had a positive pregnancy result: 26 (65%) clinical and 3 (7.5%) biochemical pregnancies were documented. There was a statistically significant difference between the number of clinical pregnancies before and after polypectomy (p < 0.001), as well as between the total number of pregnancies (p < 0.001). Secondary Results: Women with positive outcome were significantly younger and had significantly lower FSH levels (p < 0.007). They also had significantly higher AMH (p < 0.009) and peak estradiol levels (p < 0.013) and yielded more M II oocytes (p < 0.009) and embryos (p < 0.002). Conclusions: Hysteroscopic polypectomy in women with a suspected endometrial polyp using 2D ultrasound and a history of prior failed IVF attempt improves IVF outcomes in terms of the clinical and total number of pregnancies. Full article
19 pages, 3002 KiB  
Systematic Review
The Effect of Open and Closed Oocyte Vitrification Systems on Embryo Development: A Systematic Review and Network Meta-Analysis
by Konstantinos Pantos, Evangelos Maziotis, Anna Trypidi, Sokratis Grigoriadis, Kristi Agapitou, Agni Pantou, Konstantinos Nikolettos, Georgia Kokkini, Konstantinos Sfakianoudis, Kimball O. Pomeroy and Mara Simopoulou
J. Clin. Med. 2024, 13(9), 2651; https://doi.org/10.3390/jcm13092651 - 30 Apr 2024
Viewed by 1407
Abstract
Background/Objectives: Open and closed vitrification systems are commonly employed in oocyte cryopreservation; however, there is limited evidence regarding a comparison of their separate impact on oocyte competence. This study uniquely brings to the literature, data on the effect of open versus closed [...] Read more.
Background/Objectives: Open and closed vitrification systems are commonly employed in oocyte cryopreservation; however, there is limited evidence regarding a comparison of their separate impact on oocyte competence. This study uniquely brings to the literature, data on the effect of open versus closed vitrification systems on laboratory and clinical outcomes, and the effect of cooling and warming rates. Methods: A systematic search of the literature was performed using the databases PubMed/MEDLINE and the Cochrane Central Library, limited to articles published in English up to January 2023. A network meta-analysis was conducted comparing each vitrification system versus fresh oocytes. Results: Twenty-three studies were included. When compared to fresh oocytes, both vitrification devices resulted in lower fertilization rates per MII oocyte retrieved. When comparing the two systems in terms of survival rates, no statistically significant difference was observed. However, interestingly open systems resulted in lower cleavage and blastocyst formation rates per 2 pronuclear (2PN) oocyte compared to fresh controls, while at the same time no statistically significant difference was detected when comparing closed devices with fresh oocytes. Conclusions: In conclusion, closed vitrification systems appear to exert a less detrimental impact on the oocytes’ competence, which is reflected in the blastocyst formation rates. Proof of superiority of one system versus the other may lead to standardization, helping to ultimately determine optimal practice in oocyte vitrification. Full article
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