Lower Urinary Tract Symptoms in Greek Women After Menopause: The LADY Study.

INTRODUCTION AND HYPOTHESIS: The genitourinary syndrome of menopause (GSM), apart from symptoms related to vulvovaginal atrophy (VVA), also consists of lower urinary tract symptoms (LUTS). Based on the common embryological origin of the genital and lower urinary system, the presence of estrogen receptors, and the high prevalence of VVA and LUTS in the menopausal population, the two conditions can coexist. This study is aimed at investigating the prevalence and risk factors of LUTS in a sample of Greek peri- and postmenopausal women. METHODS: Four hundred and fifty (450) women, aged 40-70 years, attending three outpatient gynecology clinics for routine examination, completed a structured interview and responded to a validated questionnaire (International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms, ICIQ-FLUTS). RESULTS: Urinary urgency or frequency affected 51.6% and dysuria 43.6% of the participants. Mild urgency or frequency was described by 25.6%, moderate by 14.4%, and severe by 11.6% of the women. Mild dysuria was reported by 26.26%, moderate by 5.8%, and severe by 11.6%. Age, weight, BMI, and number of pregnancies and abortions correlated with a higher ICIQ-FLUTS score. Women with moderate/severe symptoms of VVA, such as irritation, a burning sensation, and pruritus of the vulva or vagina, had a higher ICIQ-FLUTS score than women without such symptoms (beta coefficient 2.42, CI 1.204, 3.635, p < 0.001). CONCLUSIONS: Lower urinary tract symptoms are very common among peri- and postmenopausal women and are linked to symptoms of VVA. Our data support the need for prompt evaluation of women transitioning to menopause, as these symptoms compromise the quality of life.

Effect of Stress on Each of the Stages of the IVF Procedure: A Systematic Review.

The aim of this systematic review was to examine if chronic or acute stress, measured by questionnaires or physiological biomarkers, has a separate impact on each different stage in the IVF process. A systematic search of peer-reviewed literature was performed in three databases with keywords. Preselection included 46 articles, and in all, 36 articles were included. Most studies concluded that stress has a negative effect on IVF treatment. The egg retrieval time point was most affected by chronic and acute stress. Through this research, there may be an association between chronic stress and the fertilization stage. Only chronic stress impacted the embryo transfer stage and further evidence suggested that stress decreased during this stage. The pregnancy rate stage was weakly associated with stress. Follicular cortisol was found to affect three stages. Chronic and acute stress significantly and negatively affected the egg retrieval time point. Chronic stress was associated with a lesser extent with the fertilization point, and no significant relationship between acute stress and the embryo transfer and pregnancy rate stages were found. Follicular cortisol was found to affect the process. This review contributes to the research of the relationship between stress and IVF success.

Infertility Improvement after Medical Weight Loss in Women and Men: A Review of the Literature.

Infertility is a modern health problem. Obesity is another expanding health issue associated with chronic diseases among which infertility is also included. This review will focus on the effects of weight loss by medical therapy on fertility regarding reproductive hormonal profile, ovulation rates, time to pregnancy, implantation rates, pregnancy rates, normal embryo development, and live birth rates. We comprised medicine already used for weight loss, such as orlistat and metformin, and emerging medical treatments, such as Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA). Their use is not recommended during a planned pregnancy, and they should be discontinued in such cases. The main outcomes of this literature review are the following: modest weight loss after medication and the duration of the treatment are important factors for fertility improvement. The fecundity outcomes upon which medical-induced weight loss provides significant results are the female reproductive hormonal profile, menstrual cyclicity, ovulation and conception rates, and pregnancy rates. Regarding the male reproductive system, the fertility outcomes that feature significant alterations after medically induced weight loss are as follows: the male reproductive hormonal profile, sperm motility, movement and morphology, weight of reproductive organs, and sexual function. The newer promising GLP-1 RAs show expectations regarding fertility improvement, as they have evidenced encouraging effects on improving ovulation rates and regulating the menstrual cycle. However, more human studies are needed to confirm this. Future research should aim to provide answers about whether medical weight loss therapies affect fertility indirectly through weight loss or by a possible direct action on the reproductive system.

CytoSaLPs score: a promising new tool for the detection and screening of extrauterine high grade serous carcinoma.

BACKGROUND: A recent theory supports that high-grade serous epithelial ovarian cancer derives from the fimbrial end of the fallopian tube and during the last decade, a few studies have examined the fallopian tube cytology. Our study aims to determine the cytomorphological characteristics of both benign and non-benign salpingeal samples, in order to establish fallopian cytology as a valuable diagnostic test for women with high risk for development of ovarian/fallopian/peritoneal cancer. METHODS: Our study included patients undergoing salpingoophorectomy or total hysterectomy and salpingoophorectomy for any gynecological pathology. Using a soft brush, fallopian tube smears from the fimbrial end were collected ex vivo. The Cytologists of our Institution described the morphological characteristics of the fallopian cells by adopting a proposed Table, which had a calibration system ranging from 3 to 29. This Table is referred to as the CytoSaLPs Score. Our study compared the two diagnostic cytological methods, the one of the conventional cytology and the other using the CytoSaLPs Score, having as gold standard the tubal's pathological findings. RESULTS: A total of 230 tubal specimens from 144 patients were included in this study. The Score's mean for the benign and non-benign arm was 12.8 and 18.7 respectively. The cut-off point for both arms was 16.5. The CytoSaLPs Score tool showed significantly higher specificity (87.50% vs. 75.96, p-value < 0.001) and positive predictive value PPV (40.91% vs. 26.47%, p-value < 0.001) compared to conventional cytology. Regarding the accuracy, the Score's superiority is highlighted (86.96% vs. 76.52%, p-value < 0.001). CONCLUTIONS: The evaluation of tubal cytology using the CytoSaLPs Score could be used as a reliable diagnostic method. Further evaluation with larger studies is warranted.

Metabolic Mechanisms and Potential Therapeutic Targets for Prevention of Ovarian Aging: Data from Up-to-Date Experimental Studies.

Female infertility and reproduction is an ongoing and rising healthcare issue, resulting in delaying the decision to start a family. Therefore, in this review, we examine potential novel metabolic mechanisms involved in ovarian aging according to recent data and how these mechanisms may be addressed through new potential medical treatments. We examine novel medical treatments currently available based mostly on experimental stem cell procedures as well as caloric restriction (CR), hyperbaric oxygen treatment and mitochondrial transfer. Understanding the connection between metabolic and reproductive pathways has the potential to offer a significant scientific breakthrough in preventing ovarian aging and prolonging female fertility. Overall, the field of ovarian aging is an emerging field that may expand the female fertility window and perhaps even reduce the need for artificial reproductive techniques.

GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation.

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radiotherapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments.

The Gestational Effects of Maternal Bone Marker Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review.

Fetal exposure in adverse environmental factors during intrauterine life can lead to various biological adjustments, affecting not only in utero development of the conceptus, but also its later metabolic and endocrine wellbeing. During human gestation, maternal bone turnover increases, as reflected by molecules involved in bone metabolism, such as vitamin D, osteocalcin, sclerostin, sRANKL, and osteoprotegerin; however, recent studies support their emerging role in endocrine functions and glucose homeostasis regulation. Herein, we sought to systematically review current knowledge on the effects of aforementioned maternal bone biomarkers during pregnancy on fetal intrauterine growth and metabolism, neonatal anthropometric measures at birth, as well as on future endocrine and metabolic wellbeing of the offspring. A growing body of literature converges on the view that maternal bone turnover is likely implicated in fetal growth, and at least to some extent, in neonatal and childhood body composition and metabolic wellbeing. Maternal sclerostin and sRANKL are positively linked with fetal abdominal circumference and subcutaneous fat deposition, contributing to greater birthweights. Vitamin D deficiency correlates with lower birthweights, while research is still needed on intrauterine fetal metabolism, as well as on vitamin D dosing supplementation during pregnancy, to diminish the risks of low birthweight or SGA neonates in high-risk populations.

Heterotopic pregnancy after bilateral salpingectomy, IVF and multiple embryos transfer. A case report and systematic review of the literature.

Heterotopic pregnancy after bilateral salpingectomy is an extremely rare complication of in vitro fertilisation/embryo transfer cycles. We report a case of a ruptured abdominal pregnancy on the omentum which was the stimulus to conduct the first systematic review on this complication according to 'PRISMA' guidelines (PROSPERO R.No CRD42020134104). PubMed, EMBASE and OpenAIRE databases were systematically reviewed for studies reporting (a) cases or case series of, (b) heterotopic pregnancies after, (c) prior bilateral salpingectomy, and (d) embryo transfer cycles. Twenty-two articles met the selection criteria including, with our case, 28 cases. Based on the results, clinical manifestations and laboratory findings can be unspecific or misleading. Transvaginal ultrasound is the main diagnostic tool as the ectopic foetus is more frequently located in the intramural part of the fallopian tubes, the tubal stump or the ovaries. Laparotomy or laparoscopy are the main treatment options with adequate perinatal outcome.

PGT-A: who and when? Α systematic review and network meta-analysis of RCTs.

PURPOSE: Wide controversy is still ongoing regarding efficiency of preimplantation genetic testing for aneuploidy (PGT-A). This systematic review and meta-analysis, aims to identify the patient age group that benefits from PGT-A and the best day to biopsy. METHODS: A systematic search of the literature was performed on MEDLINE/PubMed, Embase and Cochrane Central Library up to May 2020. Eleven randomized controlled trials employing PGT-A with comprehensive chromosomal screening (CCS) on Day-3 or Day-5 were eligible. RESULTS: PGT-A did not improve live-birth rates (LBR) per patient in the general population (RR:1.11; 95%CI:0.87-1.42; n=1513; I2=75%). However, PGT-A lowered miscarriage rate in the general population (RR:0.45; 95%CI:0.25-0.80; n=912; I2=49%). Interestingly, the cumulative LBR per patient was improved by PGT-A (RR:1.36; 95%CI:1.13-1.64; n=580; I2=12%). When performing an age-subgroup analysis PGT-A improved LBR in women over the age of 35 (RR:1.29; 95%CI:1.05-1.60; n=692; I2=0%), whereas it appeared to be ineffective in younger women (RR:0.92; 95%CI:0.62-1.39; n=666; I2=75%). Regarding optimal timing, only day-5 biopsy practice presented with improved LBR per ET (RR: 1.37; 95% CI: 1.03-1.82; I2=72%). CONCLUSION: PGT-A did not improve clinical outcomes for the general population, however PGT-A improved live-birth rates strictly when performed on blastocyst stage embryos of women over the 35-year-old mark.

Navigating assisted reproduction treatment in the time of COVID-19: concerns and considerations.

The COVID-19 pandemic has fueled numerous debates in the field of assisted reproductive technology (ART) as the effect of SARS-CoV-2 on pregnancy and infancy is still considered uncharted territory. Various theses and recommendations on what optimal practice is have emerged, as evidenced by surveys, webinars, and recent publications. ART specialists are faced with dilemmas in light of the lack of concrete scientific evidence required to pave the way towards future safe practice. Meanwhile, infertile couples were similarly left in limbo unable to exercise their reproductive autonomy unlike fertile couples-where achieving a pregnancy via natural conception is a matter of decision. ART treatment being classified as non-essential has only recently re-started, facing new challenges while enabling pregnancy at a time of uncertainty. This article highlights matters of bioethical nature to be considered in the ART world at the time of COVID-19 while presenting an all-inclusive critique of the current status. When pursuing pregnancy through IVF treatment during the pandemic, distancing and caution have the lead role in an effort to defend the health of the intended parents and future children. To promote patient autonomy along with our ethical, moral, and legal duty towards our patients, emphasis should be given on ascertaining shared decision-making, and ensuring that an appropriate all-inclusive informed consent is signed prior to initiating any IVF treatment.

What is the true place of a double stimulation and double oocyte retrieval in the same cycle for patients diagnosed with poor ovarian reserve? A systematic review including a meta-analytical approach.

PURPOSE: This systematic review including a meta-analytical approach aims to investigate the safety and efficacy of employing a double ovarian stimulation (DuoStim) and a subsequent double oocyte retrieval in the same menstrual cycle, in poor ovarian reserve (POR) patients. METHODS: A systematic search of literature was performed in the databases of PubMed/MEDLINE, Embase, and Cochrane Central Library up until March 2019. Both prospective and retrospective cohort studies considered suitable for inclusion reported on women with POR undergoing a DuoStim in the follicular (FPS) and luteal phase (LPS) of the same menstrual cycle. Following the systematic review of the literature, a meta-analytical approach was attempted. RESULTS: This study indicates that DuoStim is correlated with a higher number of retrieved oocytes, mature MII oocytes, and good-quality embryos in comparison to conventional stimulation. Additionally, LPS seems to be correlated with an equal or an even higher overall performance in comparison to FPS. CONCLUSION: DuoStim favors an enhanced clinical outcome in regard to the total number of yielded oocytes, mature oocytes, and available embryos, along with the quality of obtained embryos. Sourced data indicate that LPS is not correlated with a higher aneuploidy rate. This option may present as promising for the time-sensitive nature of POR patients' management, by enabling a higher oocyte yield during a single menstrual cycle.

Could the Age Difference of a Single Calendar Year between Patients Undergoing IVF at 34, 35 or at 36 Years Old Affect the IVF Outcome? A Retrospective Data Analysis.

Background and Objectives: Clinicians are called to overcome age-related challenges in decision making during In Vitro Fertilization (IVF) treatment. The aim of this study was to investigate the possible impact of a single calendar year difference among patients aged 34, 35 and 36 on IVF outcomes. Materials and Methods: Medical records between 2008 and 2019 were analyzed retrospectively. The study group consisted of women diagnosed with tubal factor infertility. Sample size was divided in three categories at 34, 35 and 36 years of age. Embryo transfer including two blastocysts was performed for every patient. Comparisons were performed regarding hormonal profile, response to stimulation, quality of transferred embryos, positive hCG test and clinical pregnancy rate. Results: A total of 706 women were eligible to participate. Two-hundred and forty-eight women were 34, 226 were 35 while the remaining 232 were 36 years old. Regarding the hormonal profile, the number of accumulated oocytes and the quality of embryos transferred, no statistically significant difference was documented between the three age groups. Women aged 34 and 35 years old indicated a significantly increased positive hCG rate in comparison to women aged 36 years old (p-value = 0.009, p-value = 0.023, respectively). Women aged 34 and 35 years old presented with a higher clinical pregnancy rate in comparison to those aged 36 years old (p-value = 0.04, p-value = 0.05, respectively). Conclusion: A calendar year difference between patients undergoing IVF treatment at 34 or 35 years of age does not appear to exert any influence regarding outcome. When treatment involves patients above the age of 35, then a single calendar year may exert considerable impact on IVF outcome. This observation indicates that age 35 may serve as a valid cut-off point regarding IVF outcome.

Assessing Clinical Embryology Research: A Global Bibliometric Analysis.

Background and Objectives: The evaluative strength of available bibliometric tools in the field of clinical embryology has never been examined in the literature. The aim is to bring insight regarding the identity of clinical embryology research, introducing concerns when solely relying on the methodology of bibliometric analysis. Methods: An all-inclusive analysis of the most bibliometrically highlighted scientific contributions regarding the cornerstones of clinical embryology was performed employing the Scopus, Web of Science (WoS) and PubMed databases, between 1978-2018. An analysis of the number of publications, respective citations and h-index, g-index, along with m-quotient is presented. The top 30 contributing authors for each distinctive area of research are listed. An attempt at visualizing the yearly published articles, clusters, and collaborations of authors, along with the geographic origin of publications, is also presented. Results: Combining all searches and keywords yielded 54,522 results. In the Scopus database, employing the keyword "In Vitro Fertilization" yielded 41,292 results. The publications of the top five authors in each research field were analytically presented and compared to the total number of publications for each respective field. The research field of Preimplantation Genetic Diagnosis/Screening/Testing was allocated the highest percentage of publications produced by the top five authors. Regarding journal bibliometrics, based on the year 2017 metrics, there are only 29 journals according to WoS that refer to "Reproductive Biology", ranking it 187th among 235 disciplines. The USA produced the highest number of publications (12,537). Conclusion: Results indicate an explosion of interest published in the literature regarding the field of clinical embryology. Further analysis on collaborations and the trends involved should be of added value as productivity between countries varies significantly. This may guide researchers, in vitro fertilization professionals, and prospective authors during literature search, while proving useful regarding manuscript design and concurring on keywords and abstract content.

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.

Predictive value of repeated measurements of luteal progesterone and estradiol levels in patients with intrauterine insemination and controlled ovarian stimulation.

OBJECTIVE: The objective of this study is to assess if the difference of repeated measurements of estradiol and progesterone during luteal phase predict the outcome of intrauterine insemination. DESIGN: Prospective study. SETTING: Reproductive clinic. PATIENTS: 126 patients with infertility. INTERVENTION(S): Patients underwent controlled ovarian stimulation with recombinant FSH (50-150 IU/d). The day of IUI patients were given p.o natural micronized progesterone in a dose of 100 mg/tds. RESULTS: The area under the receiver characteristic operating curve (ROC curve) in predicting clinical pregnancy for % change of estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI: 0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a specificity of 75. CONCLUSIONS: The % change of estradiol and progesterone between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of 89.2% and 83.4%, respectively. The addition of % of progesterone to % change of estradiol does not improve the predictive ability of % estradiol and should not be used.

A case of postmenopausal androgen excess.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece.

PURPOSE: BRCA mutation carriers can benefit from targeted clinical interventions. On the other hand, families with evident aggregation of breast cancer (BC) cases and a BRCA-negative genetic test can still be considered as of elevated risk, since the underlying genetic factor remains unidentified. In the present study, we compared clinical and demographic characteristics between BRCA1 mutation carriers (BRCA1mut) and non-carriers (non-BRCA1) in a Greek group of BC patients (n=321). METHODS: Data were collected and analyzed from 321 women with BC, with 131 patients screened for pathogenic mutations in the high-penetrant genes BRCA1 and BRCA2. Collected data included demographics, pedigrees, tumor histopathology and immunohistochemistry findings. RESULTS: In BRCA1mut patients, their mothers and grand- mothers were diagnosed at a younger age compared to non-BRCA1-carriers. Additionally, BRCA1mut patients were diagnosed with mainly estrogen receptor (ER) negative (p<0.001), Her-2 negative (p<0.05) and triple negative (p<0.01) tumors. The youngest generation was diagnosed with familial breast cancer (FBC) 9.7 years earlier than their mothers (p<0.001). Age at BC diagnosis negatively correlated with the nuclear grade of breast tumors (r=-0.3, p<0.05). Among parous individuals, the number of full-term pregnancies significantly correlated with the age at BC onset (r=0.19, p<0.05). CONCLUSION: Despite their similarities, FBC cases with identified BRCA1 mutations exhibit a clearly distinct profile. We have identified an anticipation effect in FBC patients, with significantly reduced age at diagnosis in younger generations. Increased parity seems to prevent early BC onset. This is the first study comparing clinical and demographic characteristics of FBC BRCA1mut and non-carriers in a Greek cohort.

Effect of a low dose combined oral contraceptive pill on the hormonal profile and cycle outcome following COS with a GnRH antagonist protocol in women over 35 years old.

This prospective study examines if pre-treatment with two different doses of an oral contraceptive pill (OCP) modifies significantly the hormonal profile and/or the IVF/ICSI outcome following COS with a GnRH antagonist protocol. Infertile patients were allocated to receive either OCP containing 0.03 mg of ethinylestradiol and 3 mg of drospirenone, or OCP containing 0.02 mg of ethinylestradiol and 3 mg of drospirenone prior to initiation of controlled ovarian stimulation (COS) with recombinant gonadotropins on a variable multi-dose antagonist protocol (Ganirelix), while the control group underwent COS without OCP pretreatment. Lower dose OCP was associated with recovery of FSH on day 3 instead of day 5, but the synchronization of the follicular cohort, the number of retrieved oocytes and the clinical pregnancy rate were similar to higher dose OCP.

Role of hysteroscopy prior to assisted reproduction techniques.

STUDY OBJECTIVE: To determine whether diagnostic hysteroscopy before assisted reproduction techniques (ΑRT) in women without known disease of the uterine cavity is necessary. DESIGN: Prospective cohort clinical study. SETTING: Reproductive medicine clinic. PATIENTS: The study group consisted of 217 infertile women attending the Reproductive Clinic for examination before undergoing ART, either in vitro fertilization or intracytoplasmic sperm injection. INTERVENTIONS: Patients underwent transvaginal sonography (TVS) and hysterosalpingography (HSG) for initial evaluation. If there were no abnormal intrauterine findings, diagnostic hysteroscopy was additionally performed. MEASUREMENTS AND MAIN RESULTS: The safety and diagnostic value of hysteroscopy before ART was examined. Diagnostic hysteroscopy was performed successfully, without complications, in all 217 women. Ninety-five (43.7%) had a history of ART failures (group 1), and 122 (56.3%) had undergone no previous ART attempts (group 2). In 148 women (68.2%), findings at hysteroscopy were normal, whereas in 69 (31.8%), hysteroscopy revealed intrauterine lesions (polyps, septa, submucosal leiomyomas, or synechiae) that led to operative hysteroscopy. The most common intrauterine abnormality was the presence of endometrial polyps in 26 patients (12%). The total percentage of abnormal intrauterine findings was higher in women with a history of repeated ART failures in comparison with those with no history of ART attempts. No statistically significant difference in the outcome of in vitro fertilization or intracytoplasmic sperm injection was observed between women with normal hysteroscopic findings and patients with hysteroscopically corrected endometrial disease. CONCLUSION: Sensitivity of diagnostic hysteroscopy is significantly higher than TVS and HSG in the diagnosis of intrauterine lesions. Diagnostic hysteroscopy should be performed before ART in all patients, including women with normal TVS and/or HSG findings, because a significant percentage of them have undiagnosed uterine disease that may impair the success of fertility treatment.

Childhood Obesity, Hypothalamic Inflammation, and the Onset of Puberty: A Narrative Review.

The onset of puberty, which is under the control of the hypothalamic-pituitary-gonadal (HPG) axis, is influenced by various factors, including obesity, which has been associated with the earlier onset of puberty. Obesity-induced hypothalamic inflammation may cause premature activation of gonadotropin-releasing hormone (GnRH) neurons, resulting in the development of precocious or early puberty. Mechanisms involving phoenixin action and hypothalamic microglial cells are implicated. Furthermore, obesity induces structural and cellular brain alterations, disrupting metabolic regulation. Imaging studies reveal neuroinflammatory changes in obese individuals, impacting pubertal timing. Magnetic resonance spectroscopy enables the assessment of the brain's neurochemical composition by measuring key metabolites, highlighting potential pathways involved in neurological changes associated with obesity. In this article, we present evidence indicating a potential association among obesity, hypothalamic inflammation, and precocious puberty.