Clomiphene citrate as a new modality in management of vaginal bleeding with depomedroxyprogesterone acetate (DMPA): A randomized controlled trial.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users. MATERIALS AND METHODS: We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use. RESULTS: Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups. CONCLUSIONS: Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.

Effects of letrozole alone or in combination with gonadotropins on ovulation induction and clinical pregnancy in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS). METHODS: Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS). RESULTS: Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome. CONCLUSION: Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.

Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity.

The present experiment aimed to identify the potential protective role of empagliflozin (EMPA) on haloperidol (HAL)-induced ovarian damage in female rats because of its anti-inflammatory, antioxidant, and antiapoptotic effects. EMPA was administered in the presence and absence of HAL. Thirty-two adult female albino rats were divided into four groups. Control group, EMPA group: received EMPA (10 mg/kg/day) p.o., HAL group: received HAL (2 mg/kg/day) p.o., HAL + EMPA group: HAL (2 mg/kg/day) combined with EMPA for 28 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) levels were measured. Ovarian oxidative stress parameters, besides inflammatory and apoptotic biomarkers, and ovarian Sirtuin-1 (Sirt-1) were evaluated. Ovarian histopathological examination and heat shock protein 70 (Hsp70) immunohistochemical study were performed. HAL significantly increased serum levels of FSH, LH, and ovarian inflammatory, apoptotic, and oxidative stress biomarkers and decreased serum AMH levels and Sirt-1 expression. Histopathological findings of ovarian damage and high Hsp70 immunoexpression were detected. EMPA significantly normalized the distributed hormonal levels, oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and a decrease in Hsp70 immunoexpression. Accordingly, EMPA protected against HAL-induced ovarian toxicity by modulating the Sirt-1/Hsp70/TNF-α/caspase-3 signaling pathway.

Does Ultrasound Guidance Provide Pain Relief During Intrauterine Contraceptive Device Insertion? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate ultrasound guidance effect in pain relief during intrauterine device (IUD) insertion. METHODS: Four different databases were searched from inception till June 2022. We selected randomized controlled trials (RCTs) that compared transabdominal ultrasound guidance versus traditional non-guided IUD insertion among women undergoing IUD placement for contraception. We used Revman software during performing our meta-analysis. Our primary outcome was the pain score during IUD insertion as evaluated by the Visual Analog Scale (VAS). Our secondary outcomes were the procedure insertion time, satisfaction, and incidences of complications and misplaced IUDs. RESULTS: Seven RCTs were retrieved with a total number of 1267 patients. There was a significant reduction in the VAS pain score during IUD insertion among the ultrasound-guided group (MD = -1.91, 95% CI [-3.08, -0.73], P = .001). The procedure insertion time was significantly shorter within the ultrasound guidance group compared with the control group (MD = -1.35, 95% CI [-1.81, -0.88], P < .001). Moreover, more women were significantly satisfied with the procedure among the ultrasound-guided group (P < .001). In addition, ultrasound-guided IUD insertion was linked to significant decline in incidences of complications and misplaced IUDs. CONCLUSION: Ultrasound guidance can be used as a modified technique during IUD insertion as it decreases pain, procedure time, and rates of complications and misplaced IUDs with better patient satisfaction.

The acceptability of using IUDs among Egyptian nulliparous women: a cross-sectional study.

BACKGROUND: Although intrauterine contraceptive device is highly effective, safe, long term and reversible method of contraception, the general population and physicians refuse. IUDs for nulliparous women due to persistent rumors about its side effects and complications. The aim of this study was to assess the acceptability of IUD use in nulliparous women by both women and health care providers in Egypt. METHODS: Five hundred thirty nulliparous women and 200 physicians were interviewed in 10 family planning clinics in Suez and Minia cities - Egypt. The knowledge and attitudes of women and health care providers towards IUD use in nulliparous women were assessed through a well designed questionnaire over 2 years. Those women who accepted using IUD were then followed up for 6 months. RESULTS: Most of nulliparous women sought for contraception reported a negative impression of IUD method (96.2%). 82.5% of physicians had the same attitude. The reasons for refusing IUD among nulliparous women are fear of side effects including infection (52.8%), and bleeding (37.7%).Also, fear of subsequent infertility 51.9% of women. Regarding the providers, increased pelvic inflammatory disease (PID) represented the highest percentage (70%) for non acceptability, followed by difficult insertion (52.5%). Ninety women who accepted use IUD were followed up 6 months later, 94.4% were still using the method and77.8% were happy with the results. CONCLUSION: The main barriers that hinder the use of IUD in nulliparous women are the women insufficient knowledge and attitude of their physicians. Good client counseling. Good training for physician to improve their experience would help increase the use of such effective and safe method.

High serum APRIL levels strongly correlate with disease severity in pediatric atopic eczema.

BACKGROUND: Expression of the tumor necrosis factor (TNF) family member APRIL (a proliferation-inducing ligand) is low in normal tissues but is elevated in various autoimmune diseases. OBJECTIVES: This study explored serum APRIL in children with atopic eczema (AE) during flare and quiescence. METHODS: A case-control study including 50 patients with AE and 40 control subjects was conducted. The severity of AE was assessed according to each of the Leicester Sign Score (LSS), the Simple Scoring System (SSS), the SCORing of Atopic Dermatitis (SCORAD) index, and the Objective SCORAD. Serum measurements of APRIL, total immunoglobulin E, and lactate dehydrogenase were obtained in all subjects. Data were obtained during both flare and quiescence in AE subjects. Data were analyzed using the Mann-Whitney U-test and Pearson's correlation coefficient. P-values of <0.05 were considered to indicate statistical significance. RESULTS: Serum APRIL levels were significantly elevated in children with AE in comparison with control subjects during both flare and quiescence (P < 0.0001 for both). Serum APRIL levels during AE flare and quiescence were positively correlated (P < 0.001). Serum APRIL levels and scores on each of the LSS, SSS, and SCORAD showed significant positive correlations (P < 0.01 for all). CONCLUSIONS: Serum APRIL levels were significantly elevated in children with AE during both flare and quiescence. This confirms the importance of APRIL in the pathophysiology of pediatric AE. Serum APRIL is a reliable marker of the severity of AE in children. APRIL may be a new target in the treatment of AE.

Up regulation of serum tumor necrosis factor-related apoptosis inducing ligand in juvenile-onset systemic lupus erythematosus: relations with disease activity, antibodies to double -stranded DNA, nephritis and neutropenia.

OBJECTIVES: Apoptosis is induced by binding of death receptor ligands, members of the tumor necrosis factor (TNF) superfamily, to their cognate receptors. It is suggested that TNF-related apoptosis inducing ligand (TRAIL) is involved in pathogenesis of juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to assess TRAIL concentrations in sera of JSLE children and to determine their potential relationship with disease activity, anti-double-stranded DNA (anti-dsDNA) levels, neutropenia and renal involvement. METHODS: Circulating levels of TRAIL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 40 JSLE patients (20 with active and 20 with inactive disease) and 20 controls. RESULTS: The mean (SEM) serum TRAIL concentration in JSLE was 1750.7 (440.2) pg/mL. Serum TRAIL concentrations in patients were higher than those in controls (P < 0.01). Serum TRAIL concentrations for children with inactive disease (1854.8 [485.4] pg/mL) and those with activity (1646.6 [390.6] pg/mL) were statistically comparable. JSLE children with positive anti-dsDNA antibodies had significantly higher TRAIL levels (mean = 1846 [456] vs. 1455 [325] pg/mL; P < 0.05). Serum TRAIL concentrations were significantly higher in classes III and IV nephritis compared to classes I and II nephritis (1970 [512] vs. 1330 [331] pg/mL; P < 0.01). Serum TRAIL concentrations in patients with neutropenia were higher than those without neutropenia (1805 [505] vs. 1516 [400] pg/mL; P = 0.042) and in controls (P = 0.024). CONCLUSIONS: Our data indicate that an increased level of TRAIL is a feature of JSLE that correlates with disease activity, anti-dsDNA titers neutropenia and lupus nephritis.

Elevated production of galectin-3 is correlated with juvenile idiopathic arthritis disease activity, severity, and progression.

OBJECTIVES: Galectin-3 is a carbohydrate-binding protein that plays many important regulatory roles in inflammation, immunity and cancers. Recent studies indicate that galectin-3 plays a role in rheumatoid arthritis (RA) pathogenesis and progression. Therefore, we sought to characterize the expression pattern and role of galectin-3 in juvenile idiopathic arthritis (JIA) and to explore whether galectin-3 investigated in serum and synovial fluid was associated with clinical, laboratory and radiological variables of JIA disease activity and severity. METHODS: Levels of galectin-3 in serum and synovial fluid from patients with JIA and controls were determined by enzyme-linked immunosorbent assay. RESULTS: Median (interquartile range) serum galectin-3 concentrations (ng/mL) were increasingly higher across the following groups: healthy controls (8.1 [4.9-16.7]), total JIA children with inactive disease (18.6 [9.7-28.8], P = 0.00039 vs. controls) and active disease (35.8 [15.8-60.8], P = 0.000012 vs. controls) (inactive vs. active, P = 0.00016). Highest serum expression was found in polyarthritic children. Galectin-3 concentrations in paired sera and synovial fluid samples could be related to each other. Serum and synovial concentrations of galectin-3 were positively correlated with total number of joints with active arthritis and with overall articular severity score. Patients with Larsen index and total radiographic score ≥ 1 had significant higher serum galectin-3 levels than patients with indices and scores < 1. CONCLUSIONS: These results suggest that serum levels of galectin-3 are increased in active JIA children and galectin-3 can be a new biomarker indicating JIA disease activity, severity and progression, although its increment is not disease-specific.

Serum OX40 ligand levels in asthmatic children: a potential biomarker of severity and persistence.

The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T-helper type 2 (Th2) polarization. However, involvement of these molecules in Th2-dominated allergen-induced childhood asthma remains unclear. Therefore, we sought to examine OX40L expression in pediatric asthma across disease activity and attack severity. Serum OX40L concentrations were measured by ELISA in 50 children with atopic asthma (during and in between acute attacks), and in 40 healthy children serving as controls. The median and mean (SD) serum OX40L levels (1487 and 1560 [543] pg/mL) were significantly higher in asthmatic children during acute attacks in comparison with children in between attacks (731 and 689 [321] pg/mL) and in comparison with controls (193 and 157 [60.3] pg/mL). OX40L values were higher among children who presented with acute severe asthma exacerbations than in children with mild or moderate asthma exacerbations. During stability, patients with severe persistent asthma had significantly higher levels when compared with patients with moderate or mild persistent asthma. A positive correlation could be elicited between OX40L levels during exacerbations and the corresponding values during remission. Serum OX40L levels correlated negatively with peak expiratory flow rate and positively with absolute eosinophil count. Up-regulation of OX40L may play a critical role in development of childhood atopic asthma and is in favor of asthma severity. OX40L may represent a useful biomarker of monitoring allergic inflammation. OX40L is one of the most promising targets of immune intervention for treatment of these diseases.

Serum mucosa-associated epithelial chemokine (MEC/CCL28) in atopic dermatitis: a specific marker for severity.

BACKGROUND: Mucosa-associated epithelial chemokine (MEC; CCL28) is considered to be pivotal in mediating the migration of CC chemokine receptor 3- and 10- (CCR3- and CCR10)-expressing, skin-homing, memory, cutaneous lymphocyte-associated antigen-positive (CLA(+)) T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases, such as atopic dermatitis (AD). AIM: This controlled longitudinal study was designed to evaluate the expression of CCL28 in serum in childhood AD and bronchial asthma (BA), and its possible relationship to disease severity and activity. METHODS: Serum CCL28 levels were measured in 36 children with AD, 23 with BA, 14 with both conditions, and 21 healthy age- and sex-matched controls. Sixteen patients in the AD group were followed up and resampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables. RESULTS: Serum CCL28 levels in AD, whether during flare [median, 1530 pg/mL; mean +/- standard deviation (SD) = 1590.4 +/- 724.3 pg/mL] or quiescence (median, 1477 pg/mL; mean +/- SD = 1575.2 +/- 522.1 pg/mL), were significantly higher than those in healthy children (median, 301 pg/mL; mean +/- SD = 189.6 +/- 92.8 pg/mL); however, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median, 340 pg/mL; mean +/- SD = 201.6 +/- 109.5 pg/mL) were significantly lower than those in the AD group, and comparable with those in healthy controls. Serum CCL28 levels in severe AD were significantly higher than those in mild and moderate cases, and correlated positively with the calculated severity scores [Leicester Sign Score (LSS) and Scoring Atopic Dermatitis (SCORAD)]. CCL28 levels during the exacerbation of AD were positively correlated with the corresponding values during remission, the peripheral absolute eosinophil counts, and serum lactate dehydrogenase levels. Serum CCL28 levels were not correlated with the serum total immunoglobulin E values in AD. CONCLUSIONS: Our data reinforce the concept that CCL28 might contribute to the pathogenesis of AD, probably through the selective migration and infiltration of effector/memory T-helper-2 cells in the skin. CCL28 may also represent an objective prognostic marker for disease severity. Further studies may pave the way for CCL28 antagonism among adjuvant therapeutic strategies.