The association of assisted reproductive technology with fetal malpresentation: a systematic review and meta-analysis.

BACKGROUND: Since its introduction, assisted reproductive technology (ART) has developed into a common clinical practice around the world; yet it still raises a lot of questions. Throughout time, many researchers have investigated its association with several obstetric incidences and its consequences on perinatal outcomes. The aim of the current meta-analysis was to estimate the correlation between ART procedures and malpresentation of the fetus in singleton pregnancies. METHODS: The study was conducted according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines and prospectively registered under the PROSPERO database (CRD42023458084). Five databases (Embase, MEDLINE®, APA PsycInfo, Global Health, Health Management Information Consortium (HMIC)) and two additional sources were searched from inception to 31 May 2023. Quality of the included studies was assessed using the ROBINS-1 scale, whilst quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Summative and subgroup data as well as heterogeneity were generated by the Cochrane platform RevMan Web. RESULTS: Overall, 11 studies were included in the study with a total of 3,360,134 deliveries. Results indicate a higher risk of malpresentation at delivery in fetuses conceived through ART than those conceived naturally (RR: 1.50, (95% confidence interval (CI):1.30, 1.73)). This risk decreased when adjustments for potential confounders were applied (RR = 1.12, 95% CI 1.02, 1.23). CONCLUSIONS: Based on observational studies, this meta-analysis indicated that singleton pregnancies conceived through ART are associated with higher risk of malpresentation than those conceived naturally, albeit the difference was lower when potential confounders were examined. Thus, future large studies are required to better understand possible reversible and irreversible factors of this relationship.

Efficacy and safety of metformin during pregnancy: an update.

During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.

Antiphospholipid syndrome in cardiovascular disease and cancer.

Antiphospholipid syndrome is an autoimmune disorder which is characterized by the presence of heterogeneous antiphospholipid antibodies. There is an evidence on antiphospholipid (aPL) antibodies related to thromboembolic events in cancer patients. In fact, the thrombotic complications in patients with malignancy occur at a rather high frequency, compared to other risk factors. In parallel with standard therapies available, there is need of case-by-case monitoring of each patient and the introduction of new therapies and need for more clinical trials which will address many questions for the optimal management of patients. This paper presents a basic review of the literature on the aPL antibodies associated with cardiovascular disease and cancer, as well as its complications, which are reported so far in the bibliography.

Surgical management of abdominal wall sheath and rectus abdominis muscle endometriosis: a case report and literature review.

Introduction: Endometriosis, defined as the presence of endometrial glands and stroma outside the uterine cavity, mainly affects the pelvic viscera and peritoneum. Endometriosis can also occur at sites of surgical incisions on the abdominal wall, mainly in women with a history of cesarean section (CS). The incidence of abdominal wall endometriosis after CS reaches 1%. Clinical suspicion, along with imaging, plays a crucial role in diagnosis. The preferred treatment involves extensive surgical excision with clear margins, ensuring a definitive diagnosis through histopathology examination. Case presentation: This case report is of a 44-year-old woman with a history of two CS procedures who developed pain and pigmentation at the incisional site one year after the last CS. Thirteen years after the surgical excision of an abdominal wall endometriosis (AWE) mass, followed by hormone therapy, she presented in our hospital with worsening pain for further management. Pelvic MRI findings were consistent with AWE. During surgery, the abdominal wall endometriosis foci were removed, and the defect in the aponeurosis was repaired using a dual-sided mesh in a tension-free procedure. Conclusion: Although AWE is a rare condition, we foresee an increase in cases because of the ever-increasing CS rates and the important association between AWE and CS. Healthcare practitioners should remain vigilant for this condition in women of reproductive age who exhibit cyclic pain, a palpable mass in the abdomen, and a background of previous uterine surgeries.

Laparoscopic Management of Cornual Ectopic Pregnancy: A Step-by-step Approach.

Interstitial and cornual pregnancies are dangerous, yet rare, forms of ectopic pregnancy, accounting for 2%-4% of all ectopic pregnancies. A 38-year-old female, para 1, gravida 3 had undergone another in vitro fertilisation (IVF) cycle (a salpingectomy performed elsewhere for treating a hydrosalpinx before a previous IVF attempt). Duration of pregnancy is 6 weeks and 5 days, a transvaginal ultrasound revealed an embryo with a positive foetal heartbeat, located in the left cornuum. As no conservative treatment option could be followed, we proceeded with laparoscopic removal of ectopic pregnancy through cornual resection. Since a specific surgical methodology has not yet been established, presenting more step-by-step surgical approaches that can be used in clinical practice is of high importance. We present a step-by-step surgical approach that we have implemented in cases of cornual pregnancy in our department.

Commercially Available Molecular Approaches to Evaluate Endometrial Receptivity: A Systematic Review and Critical Analysis of the Literature.

Despite the advances in the field of reproductive medicine, implantation failure represents a challenging condition affecting 10-30% of patients subjected to in vitro fertilization (IVF). Research has focused on the identification of molecules playing crucial roles in endometrial receptivity, with the aim of designing predictive tools for efficient detection of the implantation window. To that end, novel molecular genomic and transcriptomic approaches have been introduced as promising tools to enable personalized approaches with the aim of optimizing embryo transfer dating. However, the clinical value of these approaches remains unclear. The aim of this study is to provide a systematic review and critical analysis of the existing evidence regarding the employment of commercially available novel approaches to evaluate endometrial receptivity. An Embase and PubMed/Medline search was performed on 1 February 2022. From the 475 articles yielded, only 27 were included and analyzed. The considerable heterogeneity of the included articles indicates the uniqueness of the implantation window, showcasing that the optimal time for embryo transfer varies significantly between women. Moreover, this study provides information regarding the technical aspects of these advanced molecular tools, as well as an analysis of novel possible biomarkers for endometrial receptivity, providing a basis for future research in the field.

Current Approaches to the Management of Patients with Endometrial Cancer.

The incidence of endometrial cancer (EC) is rising and healthcare professionals need to be informed about the latest data on the constant developments in the field of its management. With particular interest in the classification and management of EC, we surveyed current literature, national and international data, and guidelines, as well as the latest studies to present the most recent data regarding the management of EC. It became evident that despite the consensus on low-risk EC, there are still controversies surrounding the management of high-risk EC, especially regarding the role of sentinel lymph node biopsy (SLNB). Our aim is to present the old and new perspectives in the management of EC, the different available surgical routes, the possible desire for fertility preservation, the role of adjuvant therapies and the focus on the advantages and the limitations of the implementation of SLNB in therapeutic strategies. It became evident throughout our search and based on literature data that minimally invasive surgery (MIS) leads to satisfying outcomes, thus becoming gradually the preferred route of surgery, while SLNB could provide essential information and guidance about the overall management needed in cases of both low-risk and high-risk EC.

The Current Evidence Regarding COVID-19 and Pregnancy: Where Are We Now and Where Should We Head to Next?

Despite the volume of publications dedicated to unraveling the biological characteristics and clinical manifestations of SARS-CoV-2, available data on pregnant patients are limited. In the current review of literature, we present an overview on the developmental course, complications, and adverse effects of COVID-19 on pregnancy. A comprehensive review of the literature was performed in PubMed/Medline, Embase, and Cochrane Central databases up to June 2021. This article collectively presents what has been so far reported on the identified critical aspects, namely complications during pregnancy, delivery challenges, neonatal health care, potential routes of viral transmission, including vertical transmission or breastfeeding, along with the risks involved in the vaccination strategy during pregnancy. Despite the fact that we are still largely navigating uncharted territory, the observed publication explosion in the field is unprecedented. The overwhelming need for data is undoubtable, and this serves as the driver for the plethora of publications witnessed. Nonetheless, the quality of data sourced is variable. In the midst of the frenzy for reporting on SARS-CoV-2 data, monitoring this informational overload is where we should head to next, considering that poor quality research may in fact hamper our attempts to prevail against this unparalleled pandemic outbreak.

Getting to Know Endometriosis-Related Infertility Better: A Review on How Endometriosis Affects Oocyte Quality and Embryo Development.

Endometriosis-related infertility describes a case of deteriorated fecundity when endometriosis is diagnosed. Numerous mechanisms have been proposed in an effort to delineate the multifaceted pathophysiology that induces impairment of reproductive dynamics in patients with endometriosis. In this critical analysis, authors present the plethora of molecular events that are entailed and elaborate on how they potentially impair the oocyte's and embryo's competence in patients with endometriosis. Reactive oxygen species, dysregulation of the immune system and cellular architectural disruption constitute the crucial mechanisms that detrimentally affect oocyte and embryo developmental potential. The molecular level impairment of the reproductive tissue is discussed, since differentiation, proliferation and apoptosis constitute focal regulatory cellular functions that appear severely compromised in cases of endometriosis. Mapping the precise molecular mechanisms entailed in endometriosis-related infertility may help delineate the complex nature of the disorder and bring us a step closer to a more personalized approach in understanding, diagnosing and managing endometriosis-related infertility.

Common Malignancies During Pregnancy: A Comprehensive Review.

Malignant disease complicates pregnancy in up to 1 per 1,000-2,000 cases. Pregnancy itself does not constitute a predisposing factor for malignancy. Management and treatment of patients suffering from a malignancy during pregnancy still represents a challenge in everyday clinical practice. Recent advances in imaging, diagnostic and overall treatment modalities have tailored the management of patients, specifically those who wish to maintain the pregnancy. The aim of this review was to provide clinicians with concise information on the management of the most common malignancies during pregnancy. We performed a review of the current literature including review articles, original research articles and guidelines, which are used for the management of the most common malignancies during pregnancy. Breast, cervical and ovarian malignant tumours are the most common during pregnancy. However, the overall outcome and survival per stage for these cancers do not appear to be influenced by pregnancy. Ethical, emotional and treatment dilemmas may be encountered during treatment planning. Individualization of treatment planning should be made by a multidisciplinary team but the final decision rests with the parents.

Concordance between systematic reviews of randomized controlled trials in assisted reproduction: an overview.

STUDY QUESTION: Are systematic reviews published within a 3-year period on interventions in ART concordant in their conclusions? SUMMARY ANSWER: The majority of the systematic reviews published within a 3-year period in the field of assisted reproduction on the same topic had discordant conclusions. WHAT IS KNOWN ALREADY: Systematic reviews and meta-analyses have now replaced individual randomized controlled trials (RCTs) at the top of the evidence pyramid. There has been a proliferation of systematic reviews and meta-analyses, many of which suffer from methodological issues and provide varying conclusions. STUDY DESIGN SIZE DURATION: We assessed nine interventions in women undergoing ART with at least three systematic reviews each, published from January 2015 to December 2017. PARTICIPANTS/MATERIALS SETTING METHODS: The systematic reviews which included RCTs were considered eligible for inclusion. The primary outcome was extent of concordance between systematic reviews on the same topic. Secondary outcomes included assessment of quality of systematic reviews, differences in included studies in meta-analyses covering the same search period, selective reporting and reporting the quality of evidence. MAIN RESULTS AND THE ROLE OF CHANCE: Concordant results and conclusions were found in only one topic, with reviews in the remaining eight topics displaying partial discordance. The AMSTAR grading for the majority of the non-Cochrane reviews was critically low whilst it was categorized as high for all of the Cochrane reviews. For three of the nine topics, none of the included systematic reviews assessed the quality of evidence. We were unable to assess selective reporting as most of the reviews did not have a pre-specified published protocol. LIMITATIONS REASONS FOR CAUTION: We were limited by the high proportion of reviews lacking a pre-specified protocol, which made it impossible to assess for selective reporting. Furthermore, many reviews did not specify primary and secondary outcomes which made it difficult to assess reporting bias. All the authors of this review were Cochrane review authors which may introduce some assessment bias. The categorization of the review's conclusions as beneficial, harmful or neutral was subjective, depending on the tone and wording of the conclusion section of the review. WIDER IMPLICATIONS OF THE FINDINGS: The majority of the systematic reviews published within a 3-year period on the same topic in the field of assisted reproduction revealed discordant conclusions and suffered from serious methodological issues, hindering the process of informed healthcare decision-making. STUDY FUNDING/COMPETING INTERESTS: All the authors are Cochrane authors. M.S.K. is an editorial board member of Cochrane Gynaecology and Fertility group. No grant from funding agencies in the public, commercial or not-for-profit sectors was obtained.

The Conundrum of Poor Ovarian Response: From Diagnosis to Treatment.

Despite recent striking advances in assisted reproductive technology (ART), poor ovarian response (POR) diagnosis and treatment is still considered challenging. Poor responders constitute a heterogeneous cohort with the common denominator of under-responding to controlled ovarian stimulation. Inevitably, respective success rates are significantly compromised. As POR pathophysiology entails the elusive factor of compromised ovarian function, both diagnosis and management fuel an ongoing heated debate depicted in the literature. From the criteria employed for diagnosis to the plethora of strategies and adjuvant therapies proposed, the conundrum of POR still puzzles the practitioner. What is more, novel treatment approaches from stem cell therapy and platelet-rich plasma intra-ovarian infusion to mitochondrial replacement therapy have emerged, albeit not claiming clinical routine status yet. The complex and time sensitive nature of this subgroup of infertile patients indicates the demand for a consensus on a horizontally accepted definition, diagnosis and subsequent effective treating strategy. This critical review analyzes the standing criteria employed in order to diagnose and aptly categorize POR patients, while it proceeds to critically evaluate current and novel strategies regarding their management. Discrepancies in diagnosis and respective implications are discussed, while the existing diversity in management options highlights the need for individualized management.

The Impact of Autoantibodies on IVF Treatment and Outcome: A Systematic Review.

The role of autoantibodies in in vitro fertilization (IVF) has been discussed for almost three decades. Nonetheless, studies are still scarce and widely controversial. The aim of this study is to provide a comprehensive systematic review on the possible complications associated to autoantibodies (AA) impeding the chances of a successful IVF cycle. An Embase, PubMed/Medline and Cochrane Central Database search was performed on 1 December 2018, from 2006 until that date. From the 598 articles yielded in the search only 44 relevant articles ultimately fulfilled the inclusion criteria and were qualitatively analyzed. Five subsets of results were identified, namely, thyroid related AA, anti-phospholipid antibodies, anti-nuclear antibodies, AA affecting the reproductive system and AA related to celiac disease. It may be implied that the majority of auto-antibodies exert a statistically significant effect on miscarriage rates, whereas the effects on clinical pregnancy and live birth rates differ according to the type of auto-antibodies. While significant research is performed in the field, the quality of evidence provided is still low. The conduction of well-designed prospective cohort studies is an absolute necessity in order to define the impact of the different types of autoantibodies on IVF outcome.

Postponing Pregnancy Through Oocyte Cryopreservation for Social Reasons: Considerations Regarding Clinical Practice and the Socio-Psychological and Bioethical Issues Involved.

Oocyte freezing for 'social reasons' refers to women of reproductive age who are aiming to prolong, protect and secure their fertility. The term emerged to describe application of the highly promising technique, namely vitrification on oocytes retrieved through controlled ovarian stimulation (COS) from women intending to preserve their fertility for social reasons. These women opt to cryopreserve their oocytes at a point in their life when they need to postpone childbearing on the grounds of so called 'social' reasons. These reasons may include a highly driven career, absence of an adequate partner, financial instability, or personal reasons that make them feel unprepared for motherhood. This is a sensitive and multifaceted issue that entails medical, bioethical and socio-psychological components. The latest trend and the apparent increase noted on oocyte freezing for 'social reasons' has prompted our team of fertility specialists, embryologists, obstetricians, gynecologists and psychologists to proceed with a thorough, critical and all-inclusive comprehensive analysis. The wide range of findings of this analysis involve concerns of embryology and epigenetics that shape decisions made in the IVF laboratory, issues regarding obstetric and perinatal concerns on the pregnancy concluding from these oocytes and the respective delivery management and neonatal data, to the social and bioethical impact of this trend's application. This literature review refers to matters rising from the moment the 'idea' of this option is 'birthed' in a woman's thoughts, to proceeding and executing it clinically, up until the point of the pediatric follow up of the children born. We aim to shed light to the controversial issue of oocyte freezing, while objectively exhibit all aspects regarding this complex matter, as well as to respectfully approach how could the prospect of our future expectations be shaped from the impact of its application.

Making IVF more effective through the evolution of prediction models: is prognosis the missing piece of the puzzle?

Assisted reproductive technology has evolved tremendously since the emergence of in vitro fertilization (IVF). In the course of the recent decade, there have been significant efforts in order to minimize multiple gestations, while improving percentages of singleton pregnancies and offering individualized services in IVF, in line with the trend of personalized medicine. Patients as well as clinicians and the entire IVF team benefit majorly from 'knowing what to expect' from an IVF cycle. Hereby, the question that has emerged is to what extent prognosis could facilitate toward the achievement of the above goal. In the current review, we present prediction models based on patients' characteristics and IVF data, as well as models based on embryo morphology and biomarkers during culture shaping a complication free and cost-effective personalized treatment. The starting point for the implementation of prediction models was initiated by the aspiration of moving toward optimal practice. Thus, prediction models could serve as useful tools that could safely set the expectations involved during this journey guiding and making IVF treatment more effective. The aim and scope of this review is to thoroughly present the evolution and contribution of prediction models toward an efficient IVF treatment. ABBREVIATIONS: IVF: In vitro fertilization; ART: assisted reproduction techniques; BMI: body mass index; OHSS: ovarian hyperstimulation syndrome; eSET: elective single embryo transfer; ESHRE: European Society of Human Reproduction and Embryology; mtDNA: mitochondrial DNA; nDNA: nuclear DNA; ICSI: intracytoplasmic sperm injection; MBR: multiple birth rates; LBR: live birth rates; SART: Society for Assisted Reproductive Technology Clinic Outcome Reporting System; AFC: antral follicle count; GnRH: gonadotrophin releasing hormone; FSH: follicle stimulating hormone; LH: luteinizing hormone; AMH: anti-Müllerian hormone; DHEA: dehydroepiandrosterone; PCOS: polycystic ovarian syndrome; NPCOS: non-polycystic ovarian syndrome; CE: cost-effectiveness; CC: clomiphene citrate; ORT: ovarian reserve test; EU: embryo-uterus; DET: double embryo transfer; CES: Cumulative Embryo Score; GES: Graduated Embryo Score; CSS: Combined Scoring System; MSEQ: Mean Score of Embryo Quality; IMC: integrated morphology cleavage; EFNB2: ephrin-B2; CAMK1D: calcium/calmodulin-dependent protein kinase 1D; GSTA4: glutathione S-transferase alpha 4; GSR: glutathione reductase; PGR: progesterone receptor; AMHR2: anti-Müllerian hormone receptor 2; LIF: leukemia inhibitory factor; sHLA-G: soluble human leukocyte antigen G.

Intrauterine HPV transmission: a systematic review of the literature.

PURPOSE: To evaluate the percentage of intrauterine vertical human papillomavirus (HPV) transmission among HPV-positive mothers and the relative risk of intrauterine vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women. METHODS: This systematic review was made according to the PRISMA statement. We searched PubMed and Scopus and the final articles were selected by two reviewers. Data from the selected articles were plotted, and the pooled percentage of antenatal vertical HPV transmission among HPV-positive mothers as well as the pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women were calculated. RESULTS: 9 studies including 421 HPV-positive mothers and their offsprings were selected from 434 potential papers. Following meta-analysis, the pooled percentage of antenatal vertical HPV transmission was 4.936% (95% CI 1.651-9.849), with moderate heterogeneity between the studies (I2 = 72.22%). The pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women was 0.912, with no statistical significance (95% CI 0.226-3.674) and homogeneity between the studies (I2 = 24.48%).

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises.

Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. It comprises approximately 15-20% of breast cancers (BCs). Unfortunately, TNBC's treatment continues to be a clinical problem because of its relatively poor prognosis, its aggressiveness and the lack of targeted therapies, leaving chemotherapy as the mainstay of treatment. It is essential to find new therapies against TNBC, in order to surpass the resistance and the invasiveness of already existing therapies. Given the fact that epigenetic processes control both the initiation and progression of TNBC, there is an increasing interest in the mechanisms, molecules and signaling pathways that participate at the epigenetic modulation of genes expressed in carcinogenesis. The acetylation of histone proteins provokes the transcription of genes involved in cell growth, and the expression of histone deacetylases (HDACs) is frequently up-regulated in many malignancies. Unfortunately, in the field of BC, HDAC inhibitors have shown limited effect as single agents. Nevertheless, their use in combination with kinase inhibitors, autophagy inhibitors, ionizing radiation, or two HDAC inhibitors together is currently being evaluated. HDAC inhibitors such as suberoylanilidehydroxamic acid (SAHA), sodium butyrate, mocetinostat, panobinostat, entinostat, YCW1 and N-(2-hydroxyphenyl)-2-propylpentanamide have shown promising therapeutic outcomes against TNBC, especially when they are used in combination with other anticancer agents. More studies concerning HDAC inhibitors in breast carcinomas along with a more accurate understanding of the TNBC's pathobiology are required for the possible identification of new therapeutic strategies.

Epidural fentanyl does not affect cervical dilation and progress of first stage of vaginal delivery: a randomized, double-blind study.

OBJECTIVE: Local anesthetics combined with opioids are commonly used in labor epidural analgesic schemes. This study investigated if the addition of fentanyl to epidural ropivacaine can affect cervical dilation and progress of vaginal delivery. METHODS: Sixty-two nulliparous parturients were randomized to receive epidurally 8 ml ropivacaine 0.2% combined with fentanyl 20 µg (F/R-group, n = 31) or with normal saline 0.4 ml (R-group, n = 31), every hour. Rescue doses of 5 ml ropivacaine 0.2% were also administered. Measurements were performed every 60 min until full cervical dilation. The primary end-point was the time to reach 10-cm cervical dilation. Secondary outcomes were Bishop scores, mode of delivery, total ropivacaine dose, pain, and satisfaction scores (numerical scale, 0-10). RESULTS: Data from 60 parturients (29 in the F/R and 31 in the R-group) were analyzed. The F/R-group had 26 vaginal deliveries (four instrumentally assisted), and three cesarean deliveries. The R-group had 27 vaginal deliveries (six instrumentally assisted) and 4 cesarean deliveries. Time to 10-cm cervical dilation did not differ between the groups (4 ± 2.4 h in the F/R-group vs 4.4 ± 2.1 h in the R-group, p = .341). The number of women remaining in the study every hour until full cervical dilation and Bishop scores for a 4-h period did not differ between the groups (p = .617). Total ropivacaine dose was comparable between the groups, but the F/R-group reported significantly lower pain (p = .01) and higher satisfaction scores (p = .001). CONCLUSIONS: The addition of fentanyl to ropivacaine 0.2% solution did not affect cervical dilation and progress of the first stage of labor, but improved both analgesia and satisfaction.