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Abstract

Background: Early pregnancy loss (EPL) is one of the significant issues of reproductology. It seems to be a purely immunological phenomenon, which concerns especially the first weeks of gestation. Embrioprotective factors are activated from the first day of pregnancy. One is progesterone-induced blocking factor (PIBF), which maintains the pregnancy.
Objective: To assess the prognostic value of PIBF in EPL, in naturally conceived women and in women undergoing In Vitro Fertilization (IVF).
Methods: This prospective observational study included 86 patients. Fifty naturally conceived women (Group A) and 36 pregnant women after IVF (Group B) were divided into three subgroups each: AI (patients with progressive pregnancy); AII (patients with EPL; AIII (patients with biochemical pregnancy (BP); BI (patients with progressive pregnancy), BII (patients with EPL), and BIII (patients with BP). Beta human chorionic gonadotropin (β-hCG), PIBF and progesterone (PG) levels were measured in women’s blood serum on the 12th to 14th day after ovulation and embryo transfer (ET), respectively. Statistical analysis was performed using a one-way ANOVA test. Differences were considered significant when p was <0.05.
Results: In subgroup AI, the mean level of PIBF was statistically significantly higher (15.94 ± 5.0 ng/mL) compared to patients with EPL (AII: 7.13 ± 5.04 ng/mL) and BP (AIII: 5.62 ± 2.76 ng/mL, p<0.05), but no significant difference was found in PIBF levels between women with EPL and BP (AII vs. AIII, p>0.05). Similarly, after IVF, PIBF was statistically higher in subgroup BI (30.14 ± 10.21 ng/mL) than in the EPL (BII: 21.11 ± 5.37 ng/mL, p<0.05) and BP subgroups (BIII: 20.72 ± 4.24 ng/mL, p<0.05). No significant differences were found in PIBF levels between EPL and BP subgroups (BII vs. BIII, p>0.05). There was no significant correlation between PIBF and PG in the subgroups of Groups A and B.
Conclusions: PIBF emerges as a prognostic indicator for EPL, encompassing even its preclinical stage. PG may be considered a prognostic marker for clinical pregnancy.

Original Article

Therapeutic approaches of chronic endometritis at presence of adenomyosis

Abstract

Background: Adenomyosis as well as chronic endometritis (CE) are inflammatory diseases that attract attention due to their frequent prevalence among young women, causing dysmenorrhea, and abnormal uterine bleeding. Their combination leads to reproductive failure, affection of the psycho-emotional state, limitation of social activities (due to pelvic pain, polymenorrhagia, post-hemorrhagic anemia). This issue requires additional investigation to optimize diagnosis and treatment.
Objective: Investigate and compare the effectiveness of different treatment approaches for adenomyosis in combination with CE.
Methods: A study was conducted among 108 women with CE, among them 70 patients were diagnosed with uterine adenomyosis. Patients were divided into three groups: the main group 1 (MG1), the main group 2 (MG2) and the control group (CG). MG1 included women with adenomyosis and CE who received adenomyosis therapy with dydrogesterone. MG2 included women with adenomyosis and CE who took dienogest. The CG included all other patients with CE who received antibacterial therapy (doxycycline). All women underwent treatment control and evaluation of therapy effectiveness at 3 and 6 months after the end of therapy.
Results: After 3 months of treatment, 85.7% of MG1 and 82.9% of MG2 had a negative test for CE, compared to 86.8% of CG (p= 0.887), indicating that the difference between the groups was not statistically significant. Also, after 6 months patients were negative for CE in 93.9% of MG1, 91.4% in MG2, and 97.4% in CG (p=0.340), showing comparable distribution of patients with CЕ.
Conclusion: The study shows that in cases of adenomyosis and CE occurring simultaneously, the administration of dydrogesterone or dienogest has the same therapeutic effect on CE as antibacterial therapy.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting between 5 to 10 percent of women, characterized by anovulation and androgen excess. At least two of the following three Rotterdam criteria are needed to diagnose PCOS: 1) Irregular menstrual cycles or absence of ovulation, clinical signs of biochemical evidence of hyperandrogenism, 3) polycystic ovarian morphology. Patients with this disease tend to have a higher incidence of metabolic disorders such as insulin resistance, obesity, dyslipidemia and metabolic syndrome (MetS). Given the hyperandrogenic state and metabolic alterations of women with PCOS, it is essential to carefully tailor therapeutic options for optimal management. Among the available pharmacological interventions are hormonal contraceptives, insulin sensitizers (metformin or supplements such as carnitines, inositols or α-lipoic acid), antiandrogens (flutamide, finasteride, spironolactone and cyproterone acetate [CPA]) or drugs that induce ovulation (clomiphene citrate, letrozole or gonadotrophins injections). Treatment plans should consider each patient's unique characteristics, their metabolic status, manifestations of hyperandrogenism, and personal goals, such as menstrual regulation, weight control or aesthetic improvement desire. In patients who have no desire to become pregnant, the first therapeutic line in addition to lifestyle changes (diet and physical activity) is hormonal contraception. The best option is combined oral contraceptives (COCs) with anti-androgenic progestins like CPA, dienogest (DNG), nomegestrol acetate (NOMAC), drospirenone (DRSP), or norgestimate (NGM) paired with estrogens that offer a more effective control of hyperandrogenic symptoms and endometrial protection. Non-oral options such as the vaginal ring, transdermal patches, or progestin-only contraceptives, while offering menstrual regulation, are generally less effective in treating acne, hirsutism, and seborrhea. When androgen excess persists despite contraceptive use, anti-androgenic medications such as spironolactone, flutamide or finasteride, may help achieve optimal results. Moreover, in the presence of metabolic alterations, a combination therapy with insulin sensitizers and hormonal contraceptives, should be considered.

Abstract

Introduction: The menstrual cycle has taken centre stage as researchers include more female participants in studies and focus on hormonal profiles. This interest necessitates renewed efforts to determine cycle phases using serial hormonal testing. The validity of salivary and urinary methods for detecting menstrual hormones remains unclear, despite current attention in the literature. Therefore, the objective of this scoping review was to examine the validity and precision of salivary estradiol and progesterone, and urinary luteinizing hormone assays in menstrual cycle hormone detection.
Method: The JBI methodology for scoping reviews and PRISMA guidelines were used to conduct a search from 1999 to June 17, 2022, in MEDLINE, Embase, CINAHL, CENTRAL, Scopus, and ProQuest Dissertations and Theses Global. Studies were screened independently, and decisions for inclusion were unanimous. Data charting and synthesis were used to explore the data.
Results: Eight studies examined salivary hormones, and eight examined urinary luteinizing hormone, for a total of 16 included studies. Menstrual phase definitions, validity, precision, hormone values, ranges, and comparability of assays were extracted in tabular format and separated by assay type. Raw and converted hormone values were reported.
Conclusion: This scoping review highlights inconsistencies in definitions and the scarcity of hormone values reported for menstrual cycle phases since the early 2000s. This limitation, along with the lack of reported validity and precision measures, makes study comparisons challenging. A strength of the studies was the inclusion of intra-assay coefficient reporting. Further research is needed on the development of salivary and urinary assays for menstrual cycle hormone detection.

Abstract

Contraceptive usage remains prevalent in Europe, with the Italian population displaying a variety of contraceptive practices, including reliance on less effective methods and an unmet need for contraception. The Evra® transdermal contraceptive patch has been underutilized in recent years, despite its proven efficacy and convenience. This paper examines the contraceptive landscape in Italy, highlighting the need for improved counseling practices to address the unmet need for contraception. Additionally, it explores the role of the Evra® patch as a viable alternative, emphasizing its advantages and potential to meet the diverse contraceptive needs of Italian women, including postpartum women that do not breastfeed, users seeking to regulate bleeding patterns, as well as individuals that request convenient non-daily options. By addressing barriers such as misinformation, limited awareness, and provider biases, healthcare systems can better support women in selecting contraceptive methods that align with their preferences, lifestyles, and reproductive goals. The Evra® patch emerges as a promising option, offering high efficacy, convenience, and suitability for various user profiles. Integrating structured counseling practices and promoting non-daily contraceptive options like the Evra® patch can significantly contribute to reducing the unmet need for contraception and improving reproductive health outcomes in Italy.

Abstract

Background: For women with breast and ovarian cancers on aromatase inhibitor, letrozole, there can be negative consequences on bone health such as osteopenia and osteoporosis. Treating oncologists, however, often fail to address this important survivorship issue. The primary objective of this study was to evaluate the current rate of osteoporosis screening and assess the effectiveness of an Electronic Medical Record (EMR)-based reminder at improving the rate of osteoporosis screening and prevention in female oncologic patients receiving letrozole therapy at a Tertiary based institution in Ontario.
Objective: A multidisciplinary Quality Improvement (QI) team used evidence-based interventions to: 1) Determine if oncologic patients on long-term letrozole are receiving appropriate screening and management for osteoporosis prevention; 2) Calculate the rate of oncologic patients on letrozole who receive calcium, vitamin D, and monitoring of bone mineral density (BMD); 3) Identify factors associated with adherence to the standard osteoporosis guidelines; 4) Implement an EMR based reminder with the letrozole order to help remind physicians about prescribing calcium, vitamin D, and consider BMD; and 5) Evaluate the impact, if any, of the EMR based reminder at improving the current standard of care for female oncologic patients receiving long-term letrozole therapy at our local tertiary cancer centre.
Methods: An initial retrospective chart review was performed on a random group of female patients receiving care at our oncology clinic (i.e. the preintervention group) to help identify gaps in adherence to standard osteoporosis guidelines when prescribing letrozole. An intervention was then developed and consisted of an EMR based prompt to remind prescribers of standard guideline recommendations when prescribing letrozole to monitor for osteoporosis, including performing a baseline BMD test, subsequent BMD scans every 1-2 years, and daily supplementation with vitamin D and calcium. Five months after implementation of the intervention, a chart review was performed on a random group of female patients (i.e. the postintervention group) to evaluate the adherence to osteoporosis guidelines following the intervention.
Results: A total of 607 patients were included in the study: 419 patients in the preintervention group and 188 patients in the postintervention group. The osteoporosis screening rate determined by baseline BMD testing was 39.4 % in the preintervention group and 41.5 % in the postintervention group respectively (p=0.668). Our EMR-based intervention failed to improve the osteoporosis screening rate in this high-risk population group. In the pre-intervention group, 5.7 % of women developed osteoporosis on letrozole (p=0.001). Female gender of oncologist provider was associated with higher odds of adherence to screening guideline recommendations. There was no association between oncologist’s years of experience and guideline compliance.
Conclusion: Implementation of an EMR based reminder as a stand-alone Quality Improvement initiative was not successful at improving the osteoporosis screening rates in patients initiating letrozole at our local tertiary cancer centre.

What is already known on this topic
Oncologic patients starting letrozole therapy are at high risk for developing osteoporosis and osteoporotic fractures. These patients should be counselled about daily calcium and vitamin D intake, weight-bearing exercises and smoking cessation. They should undergo baseline and annual BMD monitoring and start antiresorptive therapy such as a bisphosphonate if they develop osteoporosis or fragility fractures. There is some evidence in the literature that simple EMR based interventions can be effective tools at eliciting change in Quality Improvement projects.

What this study adds
An EMR based reminder, used as the sole intervention in a Quality Improvement project, was not effective at improving the rate of osteoporosis screening by treating oncologist initiating letrozole therapy. In our retrospective study of 607 patients receiving letrozole, 4.1% of women developed osteoporosis (p=0.001). Male gender of oncologist provider was associated with lower odds of adherence to osteoporosis screening guideline recommendations (p<0.0001). There was no association between oncologist’s years of experience and guideline compliance (p=0.052).

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