Fetal aortic isthmus Doppler assessment to predict the adverse perinatal outcomes associated with fetal growth restriction: systematic review and meta-analysis.

PURPOSE: Fetal growth restriction (FGR) management and delivery planning is based on a multimodal approach. This meta-analysis aimed to evaluate the prognostic accuracies of the aortic isthmus Doppler to predict adverse perinatal outcomes in singleton pregnancies with FGR. METHODS: PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and Google scholar were searched from inception to May 2021, for studies on the prognostic accuracy of anterograde aortic isthmus flow compared with retrograde aortic isthmus flow in singleton pregnancy with FGR. The meta-analysis was registered on PROSPERO and was assessed according to PRISMA and Newcastle-Ottawa Scale. DerSimonian and Laird's random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2 statistics. RESULTS: A total of 2933 articles were identified through the electronic search, of which 6 studies (involving 240 women) were included. The quality evaluation of studies revealed an overall acceptable score for study group selection and comparability and substantial heterogeneity. The risk of perinatal death was significantly greater in fetuses with retrograde Aortic Isthmus blood flow, with a RR of 5.17 (p value 0.00001). Similarly, the stillbirth rate was found to have a RR of 5.39 (p value 0.00001). Respiratory distress syndrome had a RR of 2.64 (p value = 0.03) in the group of fetuses with retrograde Aortic Isthmus blood flow. CONCLUSION: Aortic Isthmus Doppler study may add information for FGR management. However, additional clinical trial are required to assess its applicability in clinical practice.

Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm. METHODS: A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates. RESULTS: Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001). CONCLUSION: Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise.

Pharmacological and non-pharmacological pain relief for office hysteroscopy: an up-to-date review.

In-office hysteroscopy is considered the standard technique for visualization of the uterine cavity and the diagnosis of intrauterine pathologies. Moreover, nowadays, it is possible to treat a vast number of intracavitary diseases in the office, without the need for the inpatient setting. However, in some cases, pain might occur, and this is the most common reason for not completing the procedure. Over the last 20 years, many efforts have been carried out to miniaturize the instrumentation and to improve the techniques in order to avoid discomfort. Nonetheless, hysteroscopy still provokes distress for many patients. For this reason, pharmacological and non-pharmacological treatments for intraoperative and postoperative pain relief have been widely used for in-office hysteroscopy, with different results in various groups of women. The purpose of this review was to analyze the current literature on pharmacological aids (non-steroidal anti inflammatory drugs, cyclooxygenase-2 inhibitors, antispasmodics, local anesthetics, prostaglandins, opioids) and non-pharmacological interventions (transcutaneous electrical nerve stimulation, uterine stretching, uterine pressure, warming of distension medium, hypnosis, music, vocal-local) and to evaluate their impact on the relief from pain experienced during in-office hysteroscopy.

Environmental pollution due to cadmium: measure of semen quality as a marker of exposure and correlation with reproductive potential.

PURPOSE: Contradictory reports exist in the literature regarding an association of cadmium with parameters of semen quality. The aim of the study was to assess cadmium levels in both blood and seminal plasma and to analyze the relationships between cadmium concentrations and lifestyle and semen parameters. MATERIAL AND METHODS: Fifty healthy male volunteers were recruited to provide semen and blood samples. Each patient completed an extensive questionnaire regarding his occupation, residence, social status, diet, water source, smoking habits, and medical and surgical history. Semen analysis was carried out according to WHO guidelines. Detection of cadmium in both semen and blood samples was carried out by means of atomic absorption spectrophotometer. RESULTS: Mean concentrations of cadmium were 8.18 ± 1.6 ng/ml in blood samples and 2.56 ± 0.9 ng/ml in semen samples. Cadmium blood levels were significantly higher in men from industrialized areas and in current smokers, but were not correlated with semen levels. A significant positive correlation was found between cadmium blood levels, number of immotile spermatozoa, and teratozoospermia index (TZI). Significant inverse relationships between cadmium blood concentration and type-a and type a + b motility were found. CONCLUSIONS: The present data show a significant correlation between blood cadmium concentrations, cigarette smoking, occupational exposure, and parameters of semen quality. Such a reduction in spermiogenetic function could be an early marker of a toxic effect by cadmium pollution.

The possible role of zinc in the etiopathogenesis of endometriosis.

PURPOSE OF INVESTIGATION: Aim of the study was to evaluate the possible involvement of zinc in the complex pathogenic process behind the onset and perpetuation of endometriotic lesions. To study the level of zinc serum between a group of patients affected by endometriosis and a group of healthy patients. MATERIALS AND METHODS: The study included 86 women: 42 patients whose histodiagnosis had revealed pelvic endometriosis and 44 healthy patients. The authors measured the serum zinc concentration for all patients. RESULTS: The group of patients with endometriosis presented serum zinc concentration of 1010 +/- 59.24 microg/l. The observation group presented a serum zinc concentration of 1294 +/- 62.22 microg/l. CONCLUSION: The results showed that serum zinc levels in women with endometriosis are decreased and this seems to actually confirm that this microelement can possibly affect the multifactorial pathogenesis of the disease. As a matter of fact, zinc interferes with many biological processes, among which inflammation and immunity, which seem to be the base of the development of the lesions. Therefore, the authors believe that this hypothesis requires more attention and further investigation to determine its reasonableness. If the results are confirmed, this study opens up future prospects as for the treatment of endometriosis, taking into account also the role of zinc in the onset of male sterility and the development of testicles. Zinc could in fact be used as marker to detect women at high risk of endometriosis and for the elaboration of a new treatment for sterility, from which these women often suffer.

Pregnancy management in Behçet's disease treated with uninterrupted infliximab. Report of a case with fetal growth restriction and mini-review of the literature.

BACKGROUND: The mutual impact of Behçet's disease (BD) and pregnancy is variable and still unclear. Among the safe drugs administered, the newer infliximab (IFX) was rarely experienced in pregnancy, particularly in the third trimester. CASE: The authors report a pregnancy with fetal growth restriction at 36 weeks in a 31-year-old primigravida with symptomatic BD, treated with uninterrupted monthly IFX and daily enoxaparin. The patient was induced at 38 weeks and had an uneventful vaginal delivery of a healthy baby. The postpartum period and following six months were uneventful for mother in terms of BD exacerbation, and newborn in terms of potential risks of neonatal BD and/or infections due to late immunosuppressive IFX administration. CONCLUSION: Because of the inconstant mutual impact, BD pregnancies should be precautionary considered at "potential high-risk" and need a careful and close monitoring by a multidisciplinary team with specific expertise.

Asymptomatic large bladder diverticulum.

The authors report a case of a 61-year-old woman diagnosed with large bladder diverticulum. Diagnosis was performed only after a series of investigations carried out for the occasional finding of hypercreatininaemia. Although the significant volumes of post void residual (PVR) and the relevant urine stagnation in the diverticulum, subjective symptomatology was absent and urinalysis and urine culture were negative. The scheduled therapeutic plan consisted of fosfomycin three grams every ten days for sixmonths, self-catheterization twice a day, voiding on a time schedule, and adequate fluid intake. The monthly scheduled follow-up at one year showed good general health, good compliance with the therapy, no urinary tract infections, a decrease in creatininemia to 1.2 mg/dl, and regression of nephrohydrosis to a mild stage. In conclusion, the absence of symptoms and negative urinalysis or urine culture allows expectant management despite the considerable size of the bladder diverticulum.

Low-dose estrogen and drospirenone combination: effects on metabolism and endothelial function in postmenopausal women with metabolic syndrome.

PURPOSE: Metabolic syndrome and endothelial dysfunction play a relevant role in the cardiovascular risk in post-menopause. The aim of the study was to assess the effects of a low-dose hemihydrate estradiol and drospirenone combination on cardiovascular risk parameters in postmenopausal women with metabolic syndrome. MATERIALS AND METHODS: Twenty-eight healthy women (group A) and 28 women with metabolic syndrome (group B) were treated with hemihydrate estradiol one mg + drospirenone two mg. At recruitment and after six months, clinical and laboratory parameters of metabolic syndrome were evaluated. Endothelial function was assessed measuring the flow-mediated dilatation of the brachial artery and the intima-media thickness of the common carotid artery. RESULTS: After six months an overall improvement of metabolism was observed in both groups reaching statistical significance for triglycerides, total cholesterolemia, and systolic pressure in group B. A trend to lower baseline flow-mediated dilatation was also found in group B. CONCLUSIONS: Drospirenone improves cardiovascular risk factors and does not impair endothelial function in menopausal women with metabolic syndrome.

Arterial hypertension and female sexual dysfunction in postmenopausal women.

PURPOSE: To evaluate female sexual dysfunction in hypertensive postmenopausal women and the effects of antihypertensive therapy. MATERIALS AND METHODS: Female sexual dysfunction was assessed by the Female Sexual Function Index (FSFI) in three groups of postmenopausal patients: normotensive women (group A: 240 women), hypertensive women without therapy (group B: 220 women), hypertensive women on therapy (group C: 80 women). RESULTS: The incidence of female sexual dysfunction was increased in group B compared to groups A and C. Healthy patients showed higher FSFI scores compared to hypertensive patients (groups B and C). Hypertensive-treated patients accounted for higher scores in all items compared to hypertensive patients without therapy. CONCLUSIONS: Essential hypertension significantly affects female sexual function. Physicians should recognize and properly manage FSD in hypertensive women.

Nonhormonal management of postmenopausal women: effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile.

PURPOSE OF INVESTIGATION: The aim of this prospective randomized study was to evaluate a red clover based isoflavones supplementation in the treatment of climacteric syndrome and its effects on cardiovascular risk serum profile. MATERIALS AND METHODS: The study included 150 healthy postmenopausal women that were randomly assigned to receive phytoestrogens tablets, amounting in a total daily intake of 60.8 mg red clover isoflavones plus 19.2 mg soy isoflavones (n = 75), or placebo (n = 75). The authors evaluated teh following: daily number of hot flushes and Kupperman Index at baseline and after one and three months; serum total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and antithrombin III (ATIII) at baseline and after three and six months. RESULTS: One hundred twenty-eight patients completed the study: 67 in the active group and 61 in the placebo group. The treatment led to a progressive significant reduction (p < 0.05) of the number of hot flushes in the active group compared to placebo already after one month, while Kupperman Index was statistically reduced after three months. No significant variation in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, PT, PTT, fibrinogen, and ATIII were found. CONCLUSION: The present findings suggest that a red clover based isoflavones supplementation in healthy postmenopausal women is promptly effective on climacteric syndrome, improves neurovegetative symptoms, safe on cardiovascular risk serum profile, and does not modify lipids and coagulation.

An apparently benign vulvar mass: possibly a rare malignancy.

BACKGROUND: Vulvar dermatofibrosarcoma is a rare fibrous tumor of intermediate grade malignancy, with a tendency for local recurrence, and rarely metastasizes. Management should be multidisciplinary. This is a report of an apparently benign vulvar mass with delayed diagnosis of vulvar dermatofibrosarcoma. CASE REPORT: A 42-year-old woman was referred to our hospital because of a vulvar tumor lasting 16 years, although several gynecological procedures and a total laparoscopic hysterectomy had been performed two years before. During this long period the lesion did not change morphological features and remained asymptomatic. Only a benign vulvar mass was diagnosed. Then, the swelling became evident showing erythematous skin with an aspect of "peau d'orange", leading the patient to consult a specialist. A firm vulvar swelling was observed in the anterior third of right labia majora continuing with about 3 cm of cord on top, quite movable above the underlying tissue but not on the overlying tissue. A wide excision was performed. The pathological examination showed positive margins. One month later an extensive deeper excision was performed. Histology confirmed a diagnosis of dermatofibrosarcoma. Immunohistochemistry was strongly positive for CD34. CONCLUSION: Vulvar lesions always require complete pathologic examination even in case of features of benign tumor to exclude a dermatofibrosarcoma. The role of the pathologist is essential to ensure negative microscopic margins and to avoid local recurrence.

[Endocrine disruptors and reproductive health]. / Interferenti endocrini e salute riproduttiva.

Endocrine disruptors (EDs) are dangerous chemicals widely used daily and spread in the environment and able to impair male and female fertility by interfering with the endocrine regulation of reproductive system. Many epidemiological studies showed the role of the EDs in the pathogenesis of reproductive pathologies such as infertility, recurrent abortions, malformations and endometriosis. Personal data show a significant correlation between phthalates and bisphenols and endometriosis. Further studies are needed to assess a clear relationship between environmental exposure to ED and reproductive pathologies and to find exposure's markers for environmental pollutants in biological fluids with the aim to have useful instruments for monitoring and preserving the reproductive health of women at risk of occupational/environmental exposure to ED.

Impact of a new carrageenan-based vaginal microbicide in a female population with genital HPV-infection: first experimental results.

OBJECTIVE: The objective of this study was to assess safety, satisfaction, and anti-viral effect of a new carrageenan-based vaginal microbicide in a population of fertile female patients with genital human papillomavirus (HPV) infection. PATIENTS AND METHODS: Forty healthy and sexually active women aged 18-45 years with genital HPV infection were enrolled. Each subject was treated with a gel formulated with 0.02% carrageenan and Propionibacterium extract (CGP) (Carvir, Depofarma SpA, Mogliano Veneto, Treviso, Italy). The subjects were evaluated at baseline, after the I cycle of therapy and after the II cycle. At final status, treatment acceptability and satisfaction were evaluated using a 5-point Likert scale. Furthermore, the rate of HPV genital infection clearance at final follow-up was evaluated. These data were compared with the HPV genital infection clearance rate in a control group of patients not subjected to any therapy. RESULTS: Overall, 68 HPV infections were detected at baseline, among 40 subjects enrolled. The HPV 16 genotype was the most frequent (12%) followed by HPV 18 (10%), and HPV 53 (9%). At the end of the study, 22 (55%) patients were very satisfied, 14 (35%) were satisfied, 3 (7.5%) were uncertain, and only 1 (2.5%) was dissatisfied, with 0 very dissatisfied. Only 2 patients complained of a local adverse event. Analysing infection clearance at the end of the study, 60% of patients became HPV negative. Among these, 13 cases were high-risk HPV infection. There were 16 patients with persistent infection ("non-responders"). No patient developed a "de novo" genital lesion. After controlling for age, the intervention had an adjusted OR of 4.9 (95% CI 1.6-15.1) to clear HPV. CONCLUSIONS: The results of this work suggest that Carvir vulvovaginal microbicide gel is safe and well-tolerated. Furthermore, this experience supports the hypothesis that CG has a role in accelerating the normal clearance of genital HPV infection in women with a positive HPV-DNA test.

[Endometrial survey during phytoestrogens therapy in postmenopausal women]. / La sorveglianza endometriale in corso di terapia con fitoestrogeni in postmenopausa.

AIM: The aim of this study was to verify the effects on endometrium of short-term phytoestrogens therapy in postmenopausal women. METHODS: This randomized study compared two groups of 50 patients undergone respectively to phytoestrogens therapy or placebo. An endometrial survey was performed on the study groups by ultrasound and hysteroscopy at baseline and at 6 and 12 months. RESULTS: The ultrasonographic findings and the hysteroscopic biopsies in the 47 women submitted to phytoestrogens therapy that completed the follow-up showed an atrophic and/or inactive endometrial mucosa less than in one patients (2.1%) with endometrial thickness and proliferative endometrium bioptical sample after 12 months of treatment; no cases of endometrial hyperplasia were found. CONCLUSION: In the authors' 12 month experience, phytoestrogens therapy in postmenopausal women was safe for endometrial stimulation because did not cause any significant alteration of the mucosa in a short-term administration.

Low-dose hormone therapy in the perimenopause.

OBJECTIVE: To evaluate the effects of low-dose hormone therapy (LD-HT) on bleeding pattern and vasomotor symptoms in perimenopausal women. METHODS: In a prospective, open-label study at an University clinic, 120 perimenopausal women suffering from irregular menstrual cycles and hot flushes were randomized to micronized 17beta-estradiol 1 mg plus dydrogesterone 10 mg sequential added (LD-HT; group A: 60 subjects) or dydrogesterone 10 mg from day 15 to 28 (group B: 60 subjects). Number and severity of hot flushes and bleeding pattern were assessed throughout the study. RESULTS: Women in group A experienced a significant reduction in number of hot flushes while no significant variation was observed in group B. The incidence of cyclic bleeding was 86% in group A and 76% in group B, the mean duration was significantly lower in group A than in group B. CONCLUSIONS: LD-HT may control both irregular bleeding and hot flushes in perimenopausal women.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

OBJECTIVE: To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. STUDY DESIGN: This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. RESULTS: At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. CONCLUSIONS: In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.

Seminal anti-Müllerian hormone levels during recombinant human follicle-stimulating hormone treatment in men with idiopathic infertility undergoing assisted reproduction cycles.

A prospective study was designed to investigate the effects of recombinant human follicle-stimulating hormone (rhFSH) on seminal anti-Müllerian hormone (AMH) levels in men with idiopathic oligoasthenoteratozoospermia (iOAT), researching possible relationships between the seminal AMH behavior and the response to the treatment. Thirty-nine men who were candidates for intracytoplasmic sperm injection (ICSI) because of iOAT were enrolled. Patients were treated on alternately days with 150 IU of rhFSH for at least 3 months before assisted reproduction cycles. Main outcome measures were seminal AMH concentrations before and after rhFSH therapy. After treatment, 16 subjects (responders) showed an improvement in their sperm count compared to baseline (7.6 ± 2.9 vs. 19.3 ± 7.7, p < 0.01) whereas 23 men (non-responders) experienced no sperm modifications. Baseline seminal AMH concentrations were significantly higher in responders than in non-responders (53.0 ± 30.6 vs. 34.6 ± 18.5, p < 0.025). Following therapy, a greater increase in AMH levels was observed in responders compared to non-responders (Δ = 24.8 ± 36.4 vs. Δ = 6.4 ± 11.2, p < 0.028). Seminal AMH levels significantly and positively correlated with sperm count (after rhFSH treatment rho = 0.647, p < 0.001). Our study suggests that rhFSH improves sperm count in a quota of iOAT men, and the subjects who respond to the treatment have higher baseline seminal AMH concentrations than the patients who are not responsive. Seminal AMH could be helpful to select those infertile men who may benefit from rhFSH treatment.

Effects of a short-term suspension of hormone replacement therapy on mammographic density.

OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) and of a short-term suspension of HRT on mammographic density. DESIGN: Prospective clinical study. SETTING: Outpatient menopausal clinic of the Second University of Naples. PATIENT(S): Ninety-seven healthy postmenopausal women. INTERVENTION(S): Thirty-nine menopausal women with intact uterus (group A) were treated with continuous transdermal E(2) plus acetate nomegestrolo sequentially added, 37 women in surgical menopause (group B) were treated with transdermal E(2) continuously administered, and 21 menopausal women did not receive any medication (group C). At the entry and after 12 months, a mammography was performed without suspension of HRT (group A1: 19 women; group B1: 19 women) or after a short-term suspension (group A2: 20 women; group B2: 18 women). MAIN OUTCOME MEASURE(S): Mammographic density evaluated according to a quantitative method. RESULT(S): At the second mammography, seven patients in group A1, four patients in group B1, and one patient in both groups A2 and B2 showed an increase in mammographic density, whereas no mammographic density increase was observed in patients in group C. A statistically significant difference in the mammographic density increase was found between group A1 and group A2; no difference was found between group B1 and B2. CONCLUSION(S): Suspension of HRT for about 3 weeks may reverse mammographic density increase associated with its use.

Chronic administration of imipramine antagonizes deranged circadian rhythm phases in individually housed rats.

The circadian rhythms of hypothalamic serotonin (5HT), tryptophan (TP) and 5-hydroxy-indoleacetic acid (5HIAA), and serum corticosterone were determined in male Wistar rats. The animals underwent a five-week 12:12-hr light/dark cycle conditioning period and were divided into three groups: rats housed four to a cage (group C, control), rats housed individually (group I), and rats housed individually and treated for two weeks with 10 mg/kg/day of imipramine continuously administered by osmotic pumps implanted under the skin (group T). Significant differences were found in the acrophases of 5HT, TP and 5HIAA between group I and group C, and corticosterone mesor was higher in group I than in group C. On the contrary, no differences were observed between group T (individually housed, but given imipramine) and group C. Therefore, chronically administered imipramine antagonizes the circadian changes induced by individual housing.

Circadian rhythms of hypothalamic norepinephrine and of some circulating substances in individually housed adult rats.

The circadian rhythms of hypothalamic norepinephrine (NE) and of circulating norepinephrine, epinephrine (E), corticosterone, aldosterone, and serotonin (5HT) were determined in group-housed and in individually housed male adult rats, adapted to a 12/12 light/dark cycle. After 5 weeks of individual housing, compared to group-housed animals, hypothalamic NE mesor decreased, while circulating NE, E, and corticosterone mesor increased. The circadian rhythms of aldosterone and 5HT were unaffected by individual housing.