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OBJECTIVE: This study is to discover hormone pathways active in early cleaving human embryos. METHODS: A list of 152 hormones and receptors were compiled to query the microarray database of mRNAs in 8-cell human embryos, two lines of human embryonic stem cells plus human fibroblasts before and after induced pluripotency. RESULTS: Over half of the 152 hormones and receptors were silent on the arrays of all cell types, and more were detected at high or moderate levels on the 8-cell arrays than on the pluripotent cell or fibroblast arrays. Eight hormone family genes were uniquely detected at least 22-fold higher on the 8-cell arrays than the stem cell arrays: AVPI1, CCK, CORT, FSTL4, GIP, GPHA2, OXT, and PPY suggesting novel roles for these proteins in early development. Oxytocin was detected by pilot immunoassay in culture media collected from Day 3 embryos. Robust detection of CRHR1 and EPOR suggests the 8-cell embryo may be responsive to maternal CRH and EPO. The over-expression of POMC and GHITM suggests POMP peptide products may have undiscovered roles in early development and GHITM may contribute to mitochondrial remodeling. Under-detected on the 8-cell arrays at least tenfold were two key enzymes in steroid biosynthesis, DHCR24 and FDPS. CONCLUSIONS: The 8-cell human embryo may be secreting oxytocin, which could stimulate its own progress down the fallopian tube as well as play a role in early neural precursor development. The 8-cell embryo does not synthesize reproductive steroid hormones. As previously reported for growth factor families, the early embryo over-expresses more hormones than hormone receptors.
Subject(s)
Fibroblasts , Oxytocin , Female , Humans , Oxytocin/genetics , Oxytocin/metabolism , Fibroblasts/metabolism , Embryo, Mammalian , Microarray Analysis , Steroids/metabolismABSTRACT
With current advances in medical treatment, reproductive issues have become more important for women with chronic immune-mediated diseases. Most, if not all, patients report that their disease affects their personal relationships, their decision to have children, and the size of their family. These decisions are multi-factorial, influenced mainly by concerns over the effect of pregnancy on the rheumatic disease, the impact of disease activity during pregnancy on foetal health, the patient's ability to care for the child, and the possible harmful effects medication could have on the child, both pre- and post-natally during breastfeeding. Apart from that, women's health issues tend to be overlooked in favour of the management of the underlying rheumatic disease. To this end, we convened an expert panel to review the published literature on women's health and reproductive issues and provide evidence- and eminence-based points to consider for the treating physicians. We conclude that there is a need for a change in mind-set from one which 'cautions against pregnancy' to one which 'embraces pregnancy' through the practice of individualised, pre- and post-conceptual, multi-disciplinary care.
Subject(s)
Family Planning Services , Fertility , Infertility, Female/therapy , Reproductive Techniques, Assisted , Rheumatic Diseases/complications , Women's Health , Congresses as Topic , Family Planning Services/methods , Female , Fertility Preservation , Humans , Immunosuppressive Agents/adverse effects , Infertility, Female/diagnosis , Infertility, Female/immunology , Infertility, Female/physiopathology , Pregnancy , Rheumatic Diseases/drug therapy , Rheumatic Diseases/immunology , Rheumatic Diseases/physiopathology , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: This prospective cohort study, conducted from pregnancy to six months postpartum and grounded in STROBE methodology, quantitatively explores the relationship between antenatal breastfeeding intentions and subsequent breastfeeding outcomes among high-risk pregnant women, compared to a low-risk pregnancy group. METHODS: The study was conducted in one of the largest public hospitals in Attica that provides care to pregnant women, enrolling 380 participants divided into high-risk (n = 200) and low-risk (n = 180) cohorts. Data were collected over 20 months (starting from the end of May 2020 until January 2022), spanning from pregnancy to six months postpartum, via comprehensive questionnaires. RESULTS: Statistical analysis revealed a pronounced correlation between prenatal breastfeeding intentions and actual breastfeeding behaviors across both groups. Specifically, 81.1% of women in the high-risk group and 82.5% in the low-risk group expressed intentions of exclusively breastfeeding during pregnancy. By six months postpartum, 54.9% of the high-risk and 64.3% of the low-risk pregnancy group managed to sustain breastfeeding. Extended antenatal hospitalization emerged as a statistically significant factor (p = 0.045) negatively impacting exclusive breastfeeding intentions among high-risk pregnancies. CONCLUSION: The findings illuminate the critical influence of antenatal intentions on breastfeeding outcomes, particularly among high-risk pregnancies. Moreover, the study identifies the detrimental effect of prolonged hospital stays on breastfeeding aspirations. These insights underscore the necessity for nuanced, supportive interventions aimed at bolstering breastfeeding rates, thereby advancing maternal and neonatal health objectives aligned with World Health Organization recommendations.
Subject(s)
Breast Feeding , Intention , Postpartum Period , Humans , Female , Breast Feeding/psychology , Breast Feeding/statistics & numerical data , Pregnancy , Prospective Studies , Adult , Greece , Postpartum Period/psychology , Young Adult , Pregnant Women/psychology , Surveys and Questionnaires , Pregnancy, High-Risk/psychologyABSTRACT
BACKGROUND: the objective of this longitudinal study (from pregnancy to the end of the sixth month postpartum) is to elucidate the association between maternal self-efficacy, defined as a mother's confidence in her ability to breastfeed, and breastfeeding outcomes. METHODS: This prospective cohort study was conducted among high-risk pregnant women (including those with conditions such as gestational diabetes, hypertension, pre-eclampsia, and other pathological medical conditions) and normal-risk pregnant women in Greece. The high-risk group included 164 women, while the normal-risk group comprised 154 women. Data were collected using validated psychometric scales, including the Breastfeeding Self-Efficacy Scale-Short Form, State-Trait Anxiety Inventory, Edinburgh Postnatal Depression Scale, Maternal Antenatal Attachment Scale, and Iowa Infant Feeding Attitude Scale. RESULTS: Higher maternal self-efficacy was significantly associated with a longer duration and greater exclusivity of breastfeeding. A statistically significant relationship between the type of breastfeeding and the degree of breastfeeding self-efficacy was observed at multiple postpartum milestones: in the first and third 24 h postpartum, and at the end of the sixth week, third month, and sixth month postpartum. CONCLUSION: The findings underscore the critical role of maternal self-efficacy in breastfeeding success, influenced by individual psychological factors and broader socio-cultural contexts. Strengthening maternal self-efficacy is essential for improving breastfeeding outcomes.
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Caesarean scar pregnancy represents one of the rarest locations of ectopic pregnancies. It occurs when the blastocyst is implanted in a scar from a previous caesarean section. A dramatic increase of its prevalence has been observed for the last decades, reaching about 21% globally. Early diagnosis and treatment are crucial to avoid maternal morbidity and mortality. Our case presents the characteristic appearance of a caesarean scar pregnancy with full implantation of the gestational sac in the scar, which was managed successfully with laparotomy.
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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.
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Background: Telomere attrition and mitochondrial dysfunction are two fundamental aspects of aging. Calorie restriction (CR) is the best strategy to postpone aging since it can enhance telomere attrition, boost antioxidant capacity, and lower the generation of reactive oxygen species (ROS). Since ROS is produced by mitochondria and can readily travel to cell nuclei, it is thought to be a crucial molecule for information transfer between mitochondria and cell nuclei. Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). Telomere damage results from mitochondrial failure, whereas nuclear DNA remains unaffected. This research aims to investigate potential associations between these three variables and how they might relate to body mass index. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, male participants who were categorized into three body mass index (ΒΜΙ) groups-normal, overweight, and obese-had their sperm samples tested. Results: For both the normal and overweight groups, our results show a negative connection between relative telomere length and ΒΜI. As an illustration of a potential connection between mitochondrial health and telomere maintenance, a positive correlation was found for the obese group. Only the obese group's results were statistically significant (p < 0.05). More evidence that longer telomeres are associated with lower mitochondrial content can be found in the negative connection between telomere length and mitochondrial content in both the normal and overweight groups. However, the obese group showed a positive association. The data did not reach statistical significance for any of the three groups. These associations may affect sperm quality since telomere length and mitochondrial concentration are indicators of cellular integrity and health. Moreover, the ratio of mtDNA to nDNA was positively correlated with the relative telomere lengths of the obese group, but negatively correlated with the normal and overweight groups. In every group that was studied, the results were not statistically significant. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome compared to the nuclear DNA in sperm. Conclusions: Essentially, the goal of our work is to determine whether mitochondria and telomere length in human sperm interact. Understanding these connections may aid in the explanation of some male infertility causes and possibly contribute to the creation of new treatment modalities for problems pertaining to reproductive health. The functional implications of these connections and their applications in therapeutic settings require further investigation.
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BACKGROUND: Infertility affects about 80 million individuals worldwide and 10-15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. METHODS: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. RESULTS: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. CONCLUSIONS: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children.
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Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with infertility. The aim of the present review is to focus on mammalian oocyte maturation events and the association between oocyte growth and miRNA expression. PubMed/Medline, Google Scholar and Scopus databases were searched, and 33 studies were included. Regarding the correlation among miRNA expression and the regulation of granulosa cells and cumulus cells, the most important miRNAs were let-7b, let-7c and miR-21. Additionally, the loss of Dicer, an enzyme involved in miRNA biogenesis, is probably a crucial factor in oogenesis, oocyte maturation and embryogenesis. Furthermore, miRNAs interfere with different cellular mechanisms like apoptosis, steroidogenesis, genome integrity, angiogenesis, antioxidative response and, consequently, oocyte maturation. Hence, it is of major importance to clarify the role and mechanism of each miRNA as understanding its action may develop new tools and establish new diagnostic and treatment approaches for infertility and ovarian disorders.
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Background: Recurrent pregnancy loss refers to the spontaneous demise of two or more pregnancies before the 24 weeks of gestation. In almost half of the cases of recurrent miscarriages, the causes remain unknown since there is no reliable way of prognosis, early diagnosis, or treatment. Recent research has detected differential expression of certain miRNAs in reproductive system pathologies. Methods: The aim of the present review is to focus on microRNAs and their relationship with idiopathic recurrent miscarriages and to correlate miRNA expression with recurrent miscarriage and examine their potential role as biomarkers. Pubmed/Medline and Scopus databases were searched up to 31st January 2024 with terms related to recurrent pregnancy loss and miRNAs. Results: In total, 21 studies were selected for the review. A total of 75 different miRNAs were identified, showing a statistically significant differential expression. Around 40 miRNAs had increased expression, such as miR-520, miR-184 and miR-100-5p, 21 decreased, such as let-7c, and 14 had either increased or decreased expression depending on the study, such as miR-21. Conclusions: The dysregulation of miRNA expression is strongly associated with recurrent miscarriages. The circulating in the peripheral blood miRNAs, miR-100-5p and let-7c, might be utilized as biomarkers and establish a valuable non-invasive prognostic and diagnostic tool in the future.
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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.
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BACKGROUND: There is an emerging need to systematically investigate the causes for the increased cesarean section rates in Greece and undertake interventions so as to substantially reduce its rates. To this end, the ability of the participating Greek obstetricians to follow evidence-based guidelines and respond to other educational and behavioral interventions while managing labor will be explored, along with barriers and enablers. Herein discussed is the protocol of a stepped-wedge designed intervention trial in Greek maternity units with the aforementioned goals in mind, named ENGAGE (ENhancinG vAGinal dElivery in Greece). METHODS: Twenty-two selected maternity units in Greece will participate in a multicenter stepped-wedge randomized prospective trial involving 20,000 to 25,000 births, with two of them entering the intervention period of the study each month (stepped randomization). The maternity care units entering the study will apply the suggested interventions for a period of 8-18 months depending on the time they enter the intervention stage of the study. There will also be an initial phase of the study lasting from 8 to 18 months including observation and recording of the routine practice (cesarean section, vaginal birth, and maternal and perinatal morbidity and mortality) in the participating units. The second phase, the intervention period, will include such interventions as the application of the HSOG (the Hellenic Society of Obstetrics and Gynecology) Guidelines on labor management, training on the correct interpretation of cardiotocography, and dealing with emergencies in vaginal deliveries, while the steering committee members will be available to discuss and implement organizational and behavioral changes, answer questions, clarify relevant issues, and provide practical instructions to the participating healthcare professionals during regular visits or video conferences. Furthermore, during the study, the results will be available for the participating units in order for them to monitor their own performance while also receiving feedback regarding their rates. Τhe final 2-month phase of the study will be devoted to completing follow-up questionnaires with data concerning maternal and neonatal morbidities that occurred after the completion of the intervention period. The total duration of the study is estimated at 28 months. The primary outcome assessed will be the cesarean section rate change and the secondary outcomes will be maternal and neonatal morbidity and mortality. DISCUSSION: The study is expected to yield new information on the effects, advantages, possibilities, and challenges of consistent clinical engagement and implementation of behavioral, educational, and organizational interventions described in detail in the protocol on cesarean section practice in Greece. The results may lead to new insights into means of improving the quality of maternal and neonatal care, particularly since this represents a shared effort to reduce the high cesarean section rates in Greece and, moreover, points the way to their reduction in other countries. TRIAL REGISTRATION: NCT04504500 (ClinicalTrials.gov). The trial was prospectively registered. Ethics Reference No: 320/23.6.2020, Bioethics and Conduct Committee, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Subject(s)
Cesarean Section , Delivery, Obstetric , Randomized Controlled Trials as Topic , Humans , Female , Pregnancy , Greece , Prospective Studies , Practice Patterns, Physicians' , Obstetrics , Multicenter Studies as Topic , Labor, Obstetric , Time Factors , Health Knowledge, Attitudes, Practice , Attitude of Health Personnel , Guideline AdherenceABSTRACT
PURPOSE: To investigate two of the most studied estrogen receptor alpha polymorphisms (PvuII and XbaI) in combination, in order to evaluate their impact on an ART program outcome. METHODS: 203 normally ovulating women who underwent IVF or ICSI treatment were genotyped for PvuII and XbaI polymorphisms in ESR1 intron 1 using Real-Time PCR. The relationship between the presence of polymorphic alleles and the ovulation induction parameters and outcome was examined. RESULTS: Women were grouped according to the number of polymorphic alleles they carried in two groups (0-2 versus 3-4 polymorphic alleles). The presence of 3 or more polymorphic alleles was associated with significantly lower E2 levels on the day of hCG administration and a significantly lower rate of good quality embryos. CONCLUSION: There is an association between ESR1 polymorphisms and some ART parameters such as the level of E2 on the day of hCG administration and the quality of the embryos. These results underline the importance of ESR1 as a candidate gene for the prediction of ovarian response to IVF/ICSI protocols. Future research work concerning several more genes is necessary for a better evaluation of patients before entering an IVF/ICSI program.
Subject(s)
Estrogen Receptor alpha/genetics , Polymorphism, Genetic , Reproductive Techniques, Assisted/standards , Adult , Alleles , Female , Fertilization in Vitro , Genetic Predisposition to Disease , Genotype , Humans , Introns , Ovulation Induction , Real-Time Polymerase Chain Reaction , Sperm Injections, IntracytoplasmicABSTRACT
Background: Human papilloma virus (HPV) is considered a successful pathogen as it has the ability to evade host immune responses and establish long-term persistent infection. It has been reported that programmed death ligand 1 (PDL-1) expression is correlated with HPV-positivity and is increased with lesion progression or tumor metastasis in cervical cancer. The expression of microRNAs (miRNAs) is often deregulated in cancer, and their potential targets are affected. Methods: RNA was extracted from formalin-fixed paraffin-embedded (FFPE) cervical samples of different histological types, previously typed for the presence of HPV. A specific quantitative polymerase chain reaction (qPCR) protocol with SYBR Green was used to check for the expression of four miRNAs that were computationally predicted to target PDL-1. Results and conclusion: hsa-miR-20a-5p and hsa-miR-106b-5p showed an expression increase with the severity of the lesions, while hsa-miR-125b-5p depicted a significant decrease in its expression in cancerous samples when compared to normal samples.
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BACKGROUND: ZEB1 plays a role in epithelial-to-mesenchymal transition and acts as a repressor of E-cadherin, TGF-ß, and Wnt/ß-catenin. Since ZEB1 protein is expressed in estrogen-responsive tissues, and expression of the gene in the normal ovary and endometrium is positively correlated with high estrogen levels, we performed a direct analysis of granulosa cell samples to determine whether there are any significant changes in zeb1 expression during folliculogenesis. METHODS: ZEB1 expression levels were measured in the granulosa cells of 56 infertile women undergoing IVF treatment. RNA extraction from granulosa cells was performed along with reverse transcription quantitative polymerase chain reaction (RT-qPCR) with SYBR Green I to determine zeb1 gene expression levels. Statistical analysis was performed by using t-test, while possible correlations of the expression of ZEB1 protein with body mass index (BMI), age, number of oocytes, and oocyte maturation were investigated. RESULTS: Zeb1 gene expression levels correlate significantly with body mass index (BMI) and age, but not with oocyte number and oocyte maturation stage. Obese women demonstrate a higher expression level of zeb1 gene compared to normal and overweight women. Moreover, zeb1 gene is overexpressed in women aged 35-40 years old and is under-expressed in women >40 years old. CONCLUSIONS: ZEB1 expression should be further investigated as it may unveil new potential findings of the zeb1 gene's role in female fertility and its use as a biomarker in fertility workups.
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BACKGROUND: The aim of this case-control study is to investigate possible associations between GSTM1 polymorphism and redox potential with sperm parameters. METHODS: The study group consisted of sperm samples from 51 infertile men according to the WHO guidelines. The control group included 39 samples from men with normal seminal parameters. DNA was extracted and genotyped for the detection of the GSTM1 polymorphism. An evaluation of the static redox potential (sORP) using the MiOXSYSTM system was conducted. RESULTS: The frequency of the GSTM1-null genotype was higher in infertile male individuals (60.78%) than in the controls (41.03%) and was associated with a 2.228-fold increased risk for male infertility. Fertile controls carrying the GSTM1-null genotype presented a lower percentage of typical sperm morphology and lower slow progressive motility. An excess of redox potential was observed in infertile males compared to fertile ones. In the control group higher sORP values had a positive correlation with immotility percentage and a negative correlation regarding total motility. In the study group sORP values had a negative correlation with total count, concentration, and slow progressive motility. CONCLUSIONS: The present study highlights that GSTM1 polymorphism and redox potential affect both fertile and in fertile males. Moreover, redox potential levels could be used as an additional indicator along with the routine semen analysis for a comprehensive screening between infertile and fertile men.
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Endocrine Disrupting Compounds or Chemicals (EDCs) constitute an extensive and varied group of mostly non-natural chemicals that have the ability to imitate any aspect of hormone action, perturbing many physiological functions in humans and animals. As for female fertility, several EDCs are associated with adverse effects in the regulation of steroidogenesis, higher miscarriage rates as well as lower fertilization and embryo implantation rates and some of them are considered to decrease the number of high-quality embryos in assisted reproductive technology (ART) pregnancy. The most common EDCs are pesticides, hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) and especially phthalates and bisphenols which are used in thousands of products as plasticizers. Among all, Bisphenol A (BPA) is one of the most permeating and well-studied EDCs. BPA's action resembles that of estradiol affecting negatively the female reproductive system in various ways. This review summarizes the most recent literature on the impact of EDCs in female fertility.
Subject(s)
Endocrine Disruptors , Pregnancy , Animals , Humans , Female , Endocrine Disruptors/toxicity , Phenols/toxicity , Benzhydryl Compounds/toxicity , FertilityABSTRACT
BACKGROUND: COVID-19 is a modern worldwide pandemic that affected and continues to affect millions of people around the world. Since the discovery that angiotensin-converting enzyme 2 (ACE2) is the binding site for COVID-19 to achieve cell entry, there has been a continuous debate about the effect of COVID-19 infection in first and second trimester abortions. The aim of this review is to investigate the impact of COVID-19 infection on the incidence of miscarriage. Furthermore, we seek to identify potential pathophysiological mechanisms of early pregnancy loss present in infected women. METHODS: A literature review was conducted on different databases, including PubMed, Google Scholar, Ovid, Science Direct, Scopus, and Cochrane library, between 1 January 2020 and 31 August 2023. A total of 364 articles were identified and 32 articles were ultimately included in the review. RESULTS: There are several case studies that provide evidence that early pregnancy loss is associated with COVID-19 infection. These findings are not further confirmed by the majority of systematic reviews and meta-analyses, which demonstrate that the total number of miscarriages do not differ significantly between infected and non-infected groups. Furthermore, there are also case reports that associate COVID-19 infection with late second trimester abortions. CONCLUSIONS: Given that the virus persists globally, it is important to gain a better understanding of its associated risks in the reproductive process, and larger, more homogeneous, and controlled studies are required to obtain more robust data that can be meta-analyzed to obtain an overview of this potential relationship.
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BACKGROUND: ANRIL rs4977574 gene polymorphism has been associated with arterial thrombosis and cardiovascular disease development. ANRIL rs4977574 gene polymorphism could also be associated with recurrent pregnancy loss (RPL) since there is increasing evidence in favor of a potential shared pathophysiological mechanism with cardiovascular disease, potentially through arterial thrombosis. This study's goal is to investigate the differences in ANRIL rs4977574 gene polymorphism between women with and without RPL, if any, as well as a potential association with the number of pregnancy losses. METHODS: DNA was isolated from peripheral blood samples, and the sequence containing the polymorphism of interest was amplified with PCR. Results were visualized under UV light following electrophoresis in 3% agarose gel with ethidium bromide. ANRIL rs4977574 (A>G) prevalence was compared between 56 women with and 69 without RPL. Results were adjusted for women's age and BMI, while a stratified analysis was performed according to number of pregnancy losses. RESULTS: Allele A was significantly more prevalent in the control group compared to RPL women [31 (44.9%) vs. 14 (25%), p = 0.021]. Although not reaching statistical significance, a gradually decreasing prevalence of allele A with an increasing number of pregnancy losses was observed [31 (44.9%) in control, eight (30.7%) with two, six (23.1%) with three, and 0 (0.0%) with four pregnancy losses, p = 0.078]. Results were also similar following adjustment. CONCLUSIONS: This is the first study that demonstrates an association between RPL presence and ANRIL rs4977574 gene polymorphism (lower prevalence of allele A), while a difference according to the number of pregnancy losses cannot be excluded.
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Background: Ovarian/fallopian tube cancer is the deadliest gynecological malignancy. Most cases are diagnosed at an advanced stage, typically after the cancer has spread to the peritoneal cavity, or via lymphatic drainage. The presence of distant lymph node metastasis in the inguinal region is a rare manifestation of lymphatic metastasis. Since the 2014 FIGO staging revision, ovarian cancer patients with inguinal metastasis are classified as stage IVB. However, the clinical significance of such an upstaging remains under investigation. Materials and Methods: Both Scopus and PubMed / MEDLINE databases were utilized, by inputting the following combination of keywords: (Ovarian cancer OR Fallopian tube cancer) AND (Inguinal lymph node AND Metastasis) on June 31st, 2023. The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. Results: Twelve patients from equal number of case reports were included in our review. Mean age of diagnosis was 56,5 years old, with 3 out of 12 women to be premenopausal at the time of diagnosis. Regarding the histologic type, 67% (8 out of 12) of the cases were serous adenocarcinoma and 4 patients (33%) were diagnosed with fallopian tube malignancy. All patients, except one, were treated with primary cytoreductive surgery. In all patients optimal cytoreductive surgery was achieved. All patients, except one, received adjuvant chemotherapy. Regarding the disease-free survival, mean DFS is calculated approximately at 2 years (23,1 months). Conclusion: Inguinal lymph node metastases from ovarian / fallopian tube malignancy as initial site of metastasis is extremely rare. However, patients with inguinal masses should be investigated for ovarian / fallopian malignancy. Further investigation ought to be conducted to enlighten the pathway and the oncological significance of inguinal lymph node metastasis in ovarian cancer patients.