Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. Methods: To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Results: Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Conclusions: Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes.
This case presents a rare form of an ectopic pregnancy after retrograde migration of the transferred blastocyst to the fallopian tube. The presence of hydrosalpinx and extremely advanced maternal age further increases the risk. This case highlights the possibility of blastocyst migration even after ultrasound guidance during embryo transfer.
Chronic inflammation is increasingly recognized as a critical factor in female reproductive health; influencing natural conception and the outcomes of assisted reproductive technologies such as in vitro fertilization (IVF). An essential component of innate immunity, the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is one of the major mediators of inflammatory responses, and its activation is closely linked to oxidative stress. This interaction contributes to a decline in oocyte quality, reduced fertilization potential, and impaired embryo development. In the ovarian milieu, oxidative stress and NLRP3 inflammasome activation interact intricately, and their combined effects on oocyte competence and reproductive outcomes are significant. The aims of this review are to examine these molecular mechanisms and to explore therapeutic strategies targeting oxidative stress and NLRP3 inflammasome activity, with the goal of enhancing female fertility and improving clinical outcomes in reproductive health.
Poor ovarian response (POR) remains a significant challenge in the field of assisted reproductive technology (ART), as the quantity and quality of oocytes retrieved directly influence embryo implantation, clinical pregnancy, and live birth rates. Metabolomics has become a valuable tool for elucidating the molecular mechanisms underlying diminished ovarian reserve (DOR) and POR. This review aims to synthesize findings from metabolomic studies examining metabolite expression patterns in serum and follicular fluid samples from women with POR. A literature search was performed using the Medline/PubMed and Scopus databases, employing keywords related to metabolomics and POR. In total, nine studies met the inclusion criteria for this review. These studies identified several metabolites with differential expression in serum and follicular fluid samples between women with normal ovarian response and those with POR. Although the metabolomic profiles varied significantly among studies, consistent alterations in prostaglandin related metabolites were observed in two of the nine studies reviewed. These findings suggest that, pending further validation, these metabolites may serve as potential biomarkers for ovarian response. Metabolomics has significantly advanced our understanding of the mechanisms underlying ovarian function and holds promise for identifying effective biomarkers that could improve the prediction and management of POR.
Background/Objectives: The purpose of this study was to systematically review the potential effects of a pregnant woman’s excessive gestational weight gain on adverse perinatal outcomes affecting the mother and the fetus/neonate. Methods: Medline/PubMed, Scopus, CADTH Grey Matters and National Archive of PhD Theses were systematically searched for all relevant studies published. Assessments of the risk of bias in the included studies were made according to the tool “The Newcastle–Ottawa Scale (NOS)”. Results: Five publications met all the inclusion criteria and were included in this review. The risk of bias in all the included studies was low. One study supports the detrimental effect of excessive gestational weight gain on the risk of gestational diabetes mellitus, one study on the risk of preterm birth, five studies on the risk of macrosomia-high birthweight of the neonate, three studies on the risk of a large-for-gestational-age neonate, three studies on the risk of hypertensive disorders of pregnancy, one study on the risk of gestational hypertension and preeclampsia, five studies on the risk of delivery by cesarean section and one study on the risk of neonatal hypoglycemia requiring treatment. One study supports the beneficial effect of excessive gestational weight gain on the risk of preterm birth, two studies on the risk of a small-for-gestational-age neonate and two studies on the risk of low birthweight of the neonate. Conclusions: The study presents the most recent and strong evidence regarding the negative effect of excessive gestational weight gain on most adverse perinatal outcomes. However, excessive gestational weight gain has a beneficial effect in a very limited number of outcomes.
Background: Endometrial stromal sarcomas (ESS) are rare uterine mesenchymal tumors that histologically resemble endometrial stroma of functioning endometrium. The key characteristic of those tumors is the difficulty to diagnose preoperatively that leads to high rate of misdiagnosis. The aim of this case report is to present an extremely rare mutation of these already rare tumors and urge for more personalized therapies in the future. Case Description: We present a case of a 62-year-old postmenopausal patient initially diagnosed with high-grade ESS (HG-ESS). In her routine follow-up, her computerized tomography (CT) and positron emission tomography-CT (PET-CT) scan showed a relapse in the vaginal vault and enlarged left iliac lymph nodes. The patient did not respond to chemotherapy and suffered from severe abdominal pain and her quality of life severely deteriorated. A cytoreduction laparotomic surgery was decided with complete resection (R0) of the tumor in the pelvis with no visible residual disease. Chemosensitivity and gene expression analysis report showed a high tumor mutation burden with 11 mutations/Mb and the detection of COL1A1-PDGF/3 fusion. COL1A1-PDGF/3 fusion is an extremely rare mutation observed in ESS with only a handful of cases in the literature and is suggestive of potential therapeutic benefit from imatinib administration. HG-ESS have frequent recurrences and intermediate prognosis. Conclusions: Recurrent or advanced tumors should be treated aggressively with chemotherapy and radiation. Effort for complete resection and targeted therapy should be offered to the patients. Discovery of rare mutations might offer better personalized therapies in the future. Despite its radicality, cytoreductive surgery is a valid option in cases where life quality has severely deteriorated, offering a few qualitative months of life to the patient.
Gestational diabetes mellitus (GDM) is a prevalent medical complication in pregnancy that is rapidly escalating worldwide, with epidemic implications. This systematic review aims to identify fetal brain changes using neurosonography and pinpoint potential markers for the early diagnosis of GDM. We conducted a literature search from 6 January 2013 to 4 September 2024 to identify studies examining fetal brain development using ultrasound in pregnancies affected by GDM compared to uncomplicated pregnancies. The outcome measures included the cavum septum pellucidum (CSP), corpus callosum (CC), lateral ventricle (LV), cisterna magna (CM), transcerebellar diameter (TCD), cerebral fissures (CF), and others. For pregnancies affected by GDM, results were reported. Five studies were included. The findings suggest that the width of the CSP was larger in fetuses of mothers with GDM compared to the control group, and the mean widths of LVs were also larger in the fetuses of diabetic mothers compared to the control group. The influence of GDM on fetal brain development as assessed by neurosonography necessitates thorough investigation in future studies.
Background and Objectives: Caesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy in which the early pregnancy implants at the site of the uterine scar. Methotrexate (MTX) in lower doses can be used to treat CSPs. However, MTX administration is associated with a spectrum of side effects that include hematological toxicities. This case report presents a CSP treated with an intragestational injection of MTX and subsequently developed pancytopenia. Materials and Methods: A 23-year-old woman at six weeks and six days of pregnancy was referred as a potential case of CSP. After establishing the diagnosis, she was treated with a transvaginal ultrasound-guided intragestational administration of 80 mg MTX (adjusted to 50 mg/m2 body surface area) under sedation. Results: On day four after the MTX injection, she developed oral ulcers, fever, and pruritic phlyctenular maculopapular rash. Subsequently, the patient developed febrile neutropenia and was admitted to the Intensive Care Unit. On day six, a subsequent exacerbation of the rash was observed with the formation of blisters and purplish spots with concurrent odynophagia and sialorrhea. Ultimately, the patient developed pancytopenia due to bone marrow suppression. Fifteen days after MTX administration, the patient recovered and was discharged from the hospital hemodynamically stable, afebrile, with dropping β-hcg levels, and in good clinical condition. Conclusions: Although methotrexate administration is the preferred option for the treatment of cesarean scar pregnancies, clinicians should be aware of the fact that its use entails potential risks, even when it is used locally. To our knowledge, this case is the first description of pancytopenia due to bone marrow suppression following a single low dose of intragestational methotrexate injection.
Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin-6, tumor necrosis factor-alpha, and interleukin-10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL. Several studies indicate an increased risk of recurrent pregnancy loss in cytokine polymorphisms, specifically for interleukin-6, tumor necrosis factor-alpha, and interleukin-10.
We present a 39-centimeter thecoma with ascites and elevated Ca-125 values which is compatible with an atypical/incomplete Meigs' syndrome. Giant ovarian masses with elevated Ca-125 values and ascites are an alarming combination, although Gynecologists should be aware that there are also benign entities that mimic advanced stage ovarian cancer.
Human papillomavirus (HPV) infections are significantly associated with multiple adverse reproductive outcomes such as miscarriages. Pregnant women are more susceptible to an HPV infection and its prevalence increases as pregnancy progresses. In this present review, we summarize the existing evidence indicating the potential impact of an HPV infection on the occurrence of recurrent pregnancy loss (RPL). Comprehensive research of the literature was performed in the Medline/PubMed and Scopus databases. A total of 185 articles were identified and 40 full-text articles were assessed. Four studies were eligible to be included in this literature review. To our knowledge, this is the first review aiming to summarize the current state of evidence regarding the possible association of HPV infections and RPL. Recurrent pregnancy loss constitutes a distressing reproductive event and scientific research has made significant efforts to determine the causes and mechanisms that could lead to RPL. It is still unclear whether the papillomavirus infection is associated with an increased risk for recurrent miscarriages. Research in the field revealed conflicting results and their deductions are limited by methodological limitations. Given the high prevalence of HPV infections and their potential role in the occurrence of adverse outcomes during pregnancy, further research is required to clarify the possibility of an HPV infection being a potential risk factor for recurrent miscarriages.
Recurrent implantation failure (RIF) poses a significant challenge in assisted reproductive technology (ART) outcomes. The endometrium plays a crucial role in embryo implantation, and its protein expression profile is integral in determining receptivity. Proteomics has emerged as a valuable tool in unraveling the molecular intricacies underlying endometrial receptivity and RIF. The aim of the present review is to analyze the contribution of proteomics to the understanding of endometrial protein expression in women with RIF, based on the results of significant proteomic studies. Medline/Pubmed databases were searched using keywords pertaining to proteomics combined with terms related to RIF. 15 studies were included in the present review. Several proteins have been found to exbibit differential expression in endometrial biopsies and fluid samples between fertile women and women with RIF during the receptive endometrial phase. The profile of endometrial proteins varied significantly among the studies. Nevertheless, similar changes in the expression levels of annexin-6, progesterone receptor, MMP-2, and MMP-9 in the endometrium of women with RIF, were found in more than one study indicating that certain proteins could potentially be effective biomarkers of endometrial receptivity. Proteomics contributes significantly to the understanding of protein expression in the endometrium of women with RIF and the analysis of proteins in endometrial fluid are promising for improving the clinical management of RIF.
Obesity and cancer represent two pandemics of current civilization, the progression of which has followed parallel trajectories. To time, thirteen types of malignancies have been recognized as obesity-related cancers, including breast (in postmenopausal women), endometrial, and ovarian cancer. Pathophysiologic mechanisms that connect the two entities include insulin resistance, adipokine imbalance, increased peripheral aromatization and estrogen levels, tissue hypoxia, and disrupted immunity in the cellular milieu. Beyond the connection of obesity to carcinogenesis at a molecular and cellular level, clinicians should always be cognizant of the fact that obesity might have secondary impacts on the diagnosis and treatment of gynecologic cancer, including limited access to effective screening programs, resistance to chemotherapy and targeted therapies, persisting lymphedema, etc. Metabolic bariatric surgery represents an attractive intervention not only for decreasing the risk of carcinogenesis in high-risk women living with obesity but most importantly as a measure to improve disease-specific and overall survival in patients with diagnosed obesity-related gynecologic malignancies. The present narrative review summarizes current evidence on the underlying pathophysiologic mechanisms, the clinical data, and the potential applications of metabolic bariatric surgery in all types of gynecologic cancer, including breast, endometrial, ovarian, cervical, vulvar, and vaginal.
Bisphenols, particularly bisphenol A (BPA), are among the most thoroughly investigated endocrine disrupting chemicals (EDCs). BPA was the first synthetic estrogen to be identified, exerting its estrogenic effects through interaction with human estrogen receptors (ERs). The aim of the present narrative review is to summarize the most recent literature regarding the adverse effects of bisphenols on female fertility and pregnancy outcomes. A review of the literature in the PubMed/Medline and Scopus databases was conducted in November 2024 and 15 studies were included in the present review. BPA levels were higher in women with diminished ovarian reserve, polycystic ovary syndrome, and recurrent miscarriages. Furthermore, one study showed a significant association between BPA levels and the onset of gestational diabetes mellitus. Higher levels of BPA are associated with disruptions to the female reproductive system, such as ovarian function, reduced number of antral follicles, and lower anti-Müllerian hormone (AMH) levels. Bisphenols A and S were associated with an increased risk of developing gestational diabetes mellitus. Bisphenols A and F were correlated with an increased risk of lower birth weight and bisphenol F seemed to be associated with an increased risk of preterm delivery. Ultimately, further research is necessary to fully understand the extent of the harmful effects that bisphenols have separately and as mixtures on the female reproductive system.
Background: Endometriosis is characterized by the presence of endometrial tissue outside the uterus. Beyond medical treatment, surgical intervention is also a viable consideration. However, current guidelines do not clearly indicate whether laparoscopic cystectomy, ablative methods (CO2 laser vaporization, plasma energy), or sclerotherapy is the preferred option. Methods: We conducted searches in two databases (PubMed and Europe PMC) to retrieve articles containing the keywords ‘surgical intervention for Endometrioma, ovarian reserve, pregnancy rates, fertility’, published between 1 January 2000 and 31 December 2023. We included articles presenting information on surgical intervention for endometrioma and its correlation with infertility parameters. Articles describing conservative treatment were excluded. Data were extracted by two authors using predefined criteria. Results: The initial database search produced 1376 articles, which were narrowed down to 41 relevant articles meeting the eligibility criteria. Conclusions: Laparoscopic cystectomy appears to impact postoperative anti-mullerian hormone levels, showing a stronger correlation with larger cysts and individual factors. CO2 laser vaporization demonstrates favorable results compared to traditional cystectomy. Combining GnRH agonist treatment with assisted reproduction treatment after cystectomy could be considered an alternative method. Plasma energy causes less damage to ovarian function, with pregnancy outcomes comparable to cystectomy. Sclerotherapy shows promising results for ovarian reserve preservation, recurrence rates, and safety. Further studies comparing these techniques are necessary to provide guidance to clinicians.
The COVID-19 pandemic has posed significant risks to pregnant women and those recently pregnant, leading to heightened mortality and morbidity rates. Vaccination has emerged as a pivotal strategy in reducing COVID-19-related deaths and illnesses worldwide. However, the initial exclusion of pregnant individuals from most clinical trials raised concerns about vaccine safety in this population, contributing to vaccine hesitancy. This review aims to consolidate the existing literature to assess the safety and efficacy of COVID-19 vaccination in pregnant populations and neonatal outcomes. Diverse studies were included evaluating various aspects of safety for women and their newborns, encompassing mild to severe symptoms across different vaccines. The findings indicate the overall safety and efficacy of COVID-19 vaccination, with minimal adverse outcomes observed, including mild side effects like pain and fever. Although most studies reported the absence of severe adverse outcomes, isolated case reports have raised concerns about potential associations between maternal COVID-19 vaccination and conditions such as fetal supraventricular tachycardia and immune-mediated diseases. Our review underscores the importance of ongoing surveillance and monitoring to ensure vaccine safety in pregnant women. Overall, COVID-19 vaccination during pregnancy remains a safe and effective strategy, emphasizing the need for continued research and vigilance to safeguard maternal and fetal health.
The review aims to describe the effect of thyroid diseases on fertility. There are many causes of infertility in couples and thyroid dysfunction is a critical cause. Thyroid hormones and the hypothalamic-pituitary-ovarian axis interact in several ways and thyroid hormones may modulate ovarian functions. Hypothyroidism causes ovulatory dysfunction and luteal hypoplasia due to decreased progesterone production. Levothyroxine supplementation restores the ovulatory function and ultimately resolves the fertility issues. Regarding the elevated concentrations of antithyroid antibodies in infertile women, high concentrations are associated with a three- to four-fold increased risk of recurrent miscarriages. Moreover, women with positive antithyroid antibodies tend to develop thyroiditis postpartum. In assisted reproduction cycles the presence of antithyroid antibodies is correlated with poorer embryo quality, lower fertilization rates and increased risk of spontaneous abortion. Lastly, hyperthyroid women, especially with thyrotoxicosis, have menstrual disorders such as oligomenorrhea and polymenorrhea. In hyperthyroid women the incidence of infertility is higher.
Background/Objectives: Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This article aims to summarize the key findings of the literature regarding the role of miRNAs in human embryo implantation, emphasizing their involvement in critical stages such as decidualization, endometrial receptivity and trophoblast adhesion. Methods: This review includes primary research articles from the past decade. The studies utilize a range of experimental methodologies, including gene expression analysis and in vitro studies. Results: MicroRNAs, like miR-320a, miR-149, and miR30d secreted by preimplantation embryos and blastocysts significantly influence endometrial receptivity by promoting essential cellular processes, such as cell migration and trophoblast cell attachment, while others—miR17-5p, miR-193-3p, miR-372, and miR-542-3p—secreted from the endometrium regulate the decidualization phase. During the apposition and adhesion phases, miRNAs play a complex role by promoting, for example, miR-23b-3p, and inhibiting—as do miR-29c and miR-519d-3p—important biological pathways of these stages. During invasion, miR-26a-5p and miR-125-5p modulate important genes. Conclusions: This review underscores the critical impact of miRNAs in the regulation of embryo implantation and early pregnancy. The ability of miRNAs to modulate gene expression at various stages of reproduction presents promising therapeutic avenues for improving assisted reproductive technologies outcomes and addressing infertility. Further research into miRNA-based diagnostic tools and therapeutic strategies is essential to enhance our understanding of their role in reproductive health and to exploit their potential for clinical applications.
Uveal melanomas represent approximately 5% of all human melanomas. Omental metastases are often diagnosed as secondary metastatic sites and only a few cases have been described as the first single manifestation of distant metastasis. In this case image, we illustrate the interesting appearance of the metastatic localization of metastatic uveal melanoma.
Calcifying fibrous pseudotumors (CFT) are rare benign lesions diagnosed by histological and immunohistochemical studies. Our case presents a rare detection of a CFT in the parietal peritoneum. These lesions can be falsely interpreted as myomas or adnexal masses and thus gynecologists should be aware of the existence of CFTs.