A bitter pill to swallow: adjustments to oral contraceptive pill use in polycystic ovary syndrome.

INTRODUCTION: This Special Report aims to highlight the importance of tailored therapies in women with Polycystic Ovary Syndrome (PCOS), avoiding prescribing generalized or unsuitable therapies based on oral contraceptive pills (OCPs). AREAS COVERED: This article discusses the benefits and risks of OCP-based therapy, highlighting the possible undesirable effects, especially in those patients exhibiting risk factors as women with PCOS, and the importance of carefully evaluated tailored therapeutic approaches. Literature searches were performed with the use of PubMed, Google Scholar, and Web of Science between January and February 2024. EXPERT OPINION: Considering the recent re-analysis of PCOS Rotterdam Criteria by the Expert Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), the traditional Rotterdam phenotypes can be reclassified to achieve more efficacious therapy choices. Using personalized therapies that consider the specific clinical characteristics of the patient allows to improve the management of the syndrome, thus avoiding the generalized use of OCPs, which risk treating only symptoms of PCOS rather than the underlying cause. In cases when contraceptive purpose is desired, patients may benefit from combined therapy with diet or insulin-sensitizer agents, as inositol, to rebalance the metabolic profile, thus reducing the risk of developing future complications.

Hormonal Therapies before in vitro fertilization in women with endometriosis: The Minotaur's Labyrinth and the Ariadne's Thread.

Endometriosis-related infertility is one of the most debated topics in reproductive medicine. In recent years, prolonged pre-cycle hormonal regimens gained attention as a mean of improving the assisted reproduction technologies (ART) success rates in endometriosis patients. GnRH agonists, dienogest, medroxyprogesterone acetate, and aromatase inhibitors are the most studied medications. Conflicting results and a high risk of bias exist in almost all of the conducted studies in the field. However, current evidence suggests that pre-cycle treatment with GnRH agonists may be beneficial for patients with stage III/IV endometriosis. Dienogest and medroxyprogesterone acetate-based progestin-primed ovarian stimulation protocol was shown to be comparable to the prolonged GnRH agonists protocol. Finally, aromatase inhibitors seem to be of limited benefit to the assisted reproductive outcomes of endometriosis patients. Although it is challenging to draw any clinical conclusions, pre-cycle hormonal treatments seem to be best indicated in endometriosis patients who had previously failed ART treatment.

Predictive Role of Progesterone Levels for IVF Outcome in Different Phases of Controlled Ovarian Stimulation for Patients With and Without Endometriosis: Expert View.

The study aimed to review the role of basal, trigger, and aspiration day progesterone levels (PLs) as predictors of in vitro fertilization (IVF) success for patients with and without endometriosis. A non-systematic review was conducted by searching papers published in English during the period of 1990-2023 in MEDLINE and PubMed, Embase, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), and Web of Science. The most widely used IVF predictor success was the trigger day progesterone serum level. Many studies utilize the threshold level of 1.5-2.0 ng/ml. However, the predictive power of only progesterone level failed to show high sensitivity and specificity. Contrary, progesterone level on the trigger day combined with the number of mature retrieved oocytes had the highest predictive power. High baseline progesterone level was associated with poor IVF outcomes. Research on progesterone and IVF success in patients with endometriosis is limited but indicates that endometriosis patients seem to benefit from higher progesterone concentrations (≥ 37.1 ng/ml) in IVF cycles. Currently, there is limited data for a definitive insight into the mportance of progesterone in the estimation of IVF success. Nonetheless, this summarized evidence could serve as up-to-date guidance for the role of progesterone in the prediction of IVF outcomes, both in patients with and without endometriosis.

Menopausal Status Impact on the Quality of Life in Kazakhstani Healthcare Workers: A Cross-sectional Study.

BACKGROUND: Menopausal quality of life (MenQoL) is a common concern that primary healthcare workers often encounter. Menopause has a significant impact on women's health, but studies examining its effect on the MenQoL of menopausal healthcare employees have produced conflicting results. OBJECTIVE: The aim of this study was to compare the quality of life related to menopausal status (pre-, peri-, or postmenopausal) in healthcare workers from various clinical settings in Kazakhstan. DESIGN: This was a cross-sectional study. PARTICIPANTS: In total, 222 menopausal healthcare workers (physicians, nurses/midwives, administrative staff, and cleaners) were enrolled from hospitals affiliated with the University Medical Center (UMC) in Kazakhstan. MAIN MEASURES: The outcome variable was assessed using the Menopausal Quality of Life Questionnaire (MENQOL), which evaluates MenQoL across four domains of menopausal symptoms: physical, psychological, vasomotor, and sexual. KEY RESULTS: The most frequently reported menopausal symptoms were physical ones, such as feeling tired or worn out (70.7%), followed by feeling a lack of energy (65.3%) and dry skin (64.1%). The postmenopause group had the highest mean MenQoL score in the vasomotor domain (mean 3.46 ± 1.84). There was a borderline statistical significance when comparing postmenopause and perimenopause groups in the physical domain. The pairwise comparison of mean sexual scores revealed that postmenopause women had the highest average score (3.3 ± 2.36) compared to both premenopause (mean 2.3 ± 1.82) and perimenopause (mean 2.22 ± 1.58) groups (p < 0.05). CONCLUSIONS: Menopausal status has influence on the MenQoL of healthcare workers. The study findings could have important implications for policymakers as they provide insight into the factors influencing the quality of life of menopausal healthcare employees. Creating a more menopause-friendly work environment may not only enhance the well-being of healthcare personnel but also improve their overall job satisfaction and performance.

Effects of Low Luteinizing Hormone Serum Levels on Oocyte Retrieval, Fertilization Rate, and Embryo Quality during Controlled Ovarian Stimulation: Results from a Prospective Cohort Analysis.

OBJECTIVES: Luteinizing hormone (LH) plays a key role in normal follicular development and oocyte maturation in controlled ovarian stimulation. LH stimulates the proliferation and differentiation of theca cells for the secretion of androgens, synergistically increasing estrogen production. This study aimed to investigate the effects of low LH concentrations on oocyte retrieval, fertilization, and embryo development in patients undergoing in vitro fertilization/intracytoplasmic sperm injection. DESIGN: We prospectively (ClinicalTrials ID: NCT05755529) analyzed patients undergoing in vitro fertilization/intracytoplasmic sperm injection, subdividing them into three groups according to their age. Serum LH levels were evaluated on day 3, during stimulation (day 10) and before ovulation induction (day 12). PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty-three consecutive women were scheduled for IVF and received ovarian stimulation with follitropin alfa (Gonal F, Merck Serono, Germany) and ganirelix (Fyremaldel, Sun Pharma, Italy). Statistical analysis was performed with InStat 3.10, GraphPad software, San Diego, CA, USA. Normal distribution was tested by the Shapiro-Wilk test. Continuous variables were expressed as the mean and standard deviation. Categorical variables are expressed as frequencies and percentages. RESULTS: Our data analysis suggests that serum LH levels progressively decrease during controlled ovarian stimulation, and this effect is more evident in the early phase of this procedure. From this perspective, circulating LH levels may significantly decrease during the late follicular phase due to the negative feedback of ovarian hormones from multiple follicular developments or after the suppressive effects of gonadotropin-releasing hormone antagonists. LIMITATIONS: Although our study confirms that exogenous LH can be considered a strategy in women with reduced LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome, the generalizability of the results is limited by the low number of participants enrolled. CONCLUSIONS: Exogenous LH may be considered a strategy in women with a decrease in LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome.

Unveiling the Role of the Work Environment in the Quality of Life of Menopausal Physicians and Nurses.

BACKGROUND: There is a lack of scientific evidence regarding the specific challenges faced by menopausal medical professionals in different work settings. This study aims to investigate the relationship between work environment and the menopausal quality of life (QoL) in physicians and nurses. METHODS: This survey was conducted using the Menopausal Quality of Life Questionnaire (MENQOL) with a sample of 35 menopausal physicians and 95 nurses employed in health facilities in Astana and Kyzylorda cities, Kazakhstan. RESULTS: Physicians reported a higher frequency of menopausal symptoms compared to nurses. The difference was statistically significant (p < 0.05) for symptoms such as decreased productivity (60.00% vs. 38.20%), flatulence or gas pains (71.43% vs. 48.39%), weight gain (79.41% vs. 61.80%), changes in skin appearance (79.59% vs. 50.00%), and changes in sexual desire (58.82% vs. 33.70%). Physicians with managerial duties had a significantly higher occurrence of vasomotor symptoms compared to non-managerial physicians (mean 3.35 ± 2.14 vs. 1.69 ± 0.89) and also had a higher mean psychological score (mean 3.26 ± 1.28 vs. 2.29 ± 1.19). CONCLUSIONS: These findings reflect differences between the menopause effects related to work environment for doctors and nurses, and shed light on the specific challenges faced by them during menopause. In addition, it is important to consider socio-demographic and workplace-related factors in investigating their impact on the QoL.

Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study.

The aim of this study was to evaluate the effect of maternal age and body mass index (BMI) on induction of labor with oral misoprostol for premature rupture of membrane (PROM) at term. We have conducted retrospective cross-sectional study, including only term (37 weeks or more of gestation) PROM in healthy nulliparous women with a negative vaginal-rectal swab for group B streptococcus, a single cephalic fetus with normal birthweight, and uneventful pregnancy that were induced after 24 h from PROM. Ninety-one patients were included. According to the multivariate logistic regression, age and BMI odds ratio (OR) for induction success were 0.795 and 0.857, respectively. The study population was divided into two groups based on age (<35 and ≥35 years) and obesity (BMI <30 and ≥30). Older women reported a higher induction failure rate (p < 0.001); longer time to cervical dilation of 6 cm (p = 0.03) and delivery (p < 0.001). Obese women reported a higher induction failure rate (p = 0.01); number of misoprostol doses (p = 0.03), longer time of induction (p = 0.03) to cervical dilatation of 6 cm (p < 0.001), and delivery (p < 0.001); and higher cesarean section (p = 0.012) and episiotomy rate (p = 0.007). In conclusion, maternal age and BMI are two of the main factors that influence oral misoprostol efficacy and affect the failure of induction rate in term PROM.

Reproductive and Obstetric Outcomes after Fertility-Sparing Treatments for Cervical Cancer: Current Approach and Future Directions.

Cervical cancer is one of the leading causes of cancer-related death in women of reproductive age. The established fertility-sparing approaches for the management of early-stage cervical cancer for women who plan pregnancy are associated with a decline in fecundity and an increased risk of pregnancy complications. This article aims to offer an overview of fertility-sparing approaches and the management of potential subfertility and pregnancy complications after these treatments. An extensive search for the available data about infertility and cervical cancer, fertility-sparing techniques in patients with cervical cancer, fertility treatment, obstetrical complications, and pregnancy outcomes in cervical cancer patients was completed. Fertility-preserving procedures such as loop electrosurgical excision procedure (LEEP), cold-knife conization, and trachelectomy in women diagnosed with cervical cancer can be considered as safe and effective treatments that preserve reproductive potential. Current fertility-preserving procedures, based on the balance of the oncological characteristics of patients as well as their desire for reproduction, allow one to obtain acceptable reproductive and obstetric outcomes in women treated for cervical cancer. Nevertheless, careful monitoring of pregnancies obtained after fertility-preserving procedures is recommended, since this cohort of patients should be considered at higher risk compared with a healthy population.

Effects of transdermal versus oral hormone replacement therapy in postmenopause: a systematic review.

PURPOSE: To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women. METHODS: We performed a systematic review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer. RESULTS: The systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route. CONCLUSIONS: Available evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route.

Impact of lifestyle and diet on endometriosis: a fresh look to a busy corner.

Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.

The influence of advanced age and obesity on pregnancy course and outcome in patients with diabetes mellitus.

Introduction: Older women are at greater risk of suffering from a series of comorbidities such as obesity, diabetes, and hypertension that could negatively affect pregnancy course and outcomes. This study aims to investigate the impact of maternal age and pre-pregnancy body mass index (BMI) on pregnancy outcomes of women with diabetes mellitus (DM). Material and methods: The study included 323 diabetic pregnant women. All complications throughout pregnancy and the early neonatal period were noted. The women were divided into groups according to age decade and BMI. Results: 84.8% of women reported pregnancy complications, with a higher prevalence in obese women (p = 0.003). However, most children had a good outcome with few early neonatal complications (36.85%). Old and obese women with DM often showed complications, and their newborns had higher birth weight (p = 0.003) and more neonatal complications (p = 0.041). Maternal BMI (p = 0.016; OR = 1.064), but not age (p = 0.801), was found to be a significant predictor of pregnancy complications. Conclusions: Pregnant women with DM should be considered as high-risk patients. Advanced age and increased BMI prior to pregnancy are risk factors for pregnancy complications. Maternal obesity is the most important predictor of pregnancy complications in women with DM. Pregnancy outcome can be good for both mothers and children with a timely and adequate approach.

Pregnancy outcomes in women with diabetes mellitus - the impact of diabetes type and treatment.

Introduction: It has been estimated that approximately 16% of pregnancies worldwide are affected by pre-existing or gestational insulin-dependent (type 1) or independent (type 2) diabetes mellitus (DM). Diabetes mellitus in pregnancy remains a high-risk condition for both mother and child. This study aimed to investigate pregnancy outcomes regarding DM types. Material and methods: The study included 323 DM patients delivered for 6 years (2012-2017). General and obstetric history data and all complications throughout the pregnancy and the early neonatal period were noted. Based on DM type, women were divided into 4 groups: pre-pregnancy/pre-existing DM, insulin-dependent or independent, and gestational diabetes mellitus with or without insulin therapy. Results: The majority of women had pre-existing insulin-independent DM (type II 62%). Some types of pregnancy/maternal complications were registered in almost 85% of examined pregnancies. However, all babies were live born and mostly with good outcome (36.85% with early neonatal complications). Diabetes mellitus type could not predict the occurrence of neonatal complications (p = 0.342). Pre-existing insulin-dependent DM increased the risk for pregnancy complications (p = 0.031; OR = 1.656). Conclusions: Diabetes mellitus type has a limited impact on pregnancy outcomes and the occurrence of maternal and neonatal complications. With adequate therapy the pregnancy outcome can be good regardless of DM type.

Impact of governmental support to the IVF clinical pregnancy rates: differences between public and private clinical settings in Kazakhstan-a prospective cohort study.

OBJECTIVES: Infertility rates have been increasing in low-income and middle-income countries, including Kazakhstan. The need for accessible and affordable assisted reproductive technologies has become essential for many subfertile women. We aimed to explore whether the public funding and clinical settings are independently associated with in vitro fertilisation (IVF) clinical pregnancy and to determine whether the relationship between IVF clinical pregnancy and clinical settings is modified by payment type. DESIGN: A prospective cohort study. SETTING: Three private and two public IVF clinics located in major cities. PARTICIPANTS: Women aged ≥18 seeking first or repeated IVF treatment and agreed to complete a survey were included in the study. Demographical and previous medical history data were collected from a survey, while clinical data from medical records. The total response rate was 14%. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical pregnancy was defined as a live intrauterine pregnancy identified by ultrasound scan at 8 gestational weeks. The outcome data were missing for 22% of women. RESULTS: Out of 446 women in the study, 68.2% attended private clinics. Two-thirds of women attending public clinics and 13% of women attending private clinics were publicly funded. Private clinics retrieved, on average, a higher number of oocytes (11.5±8.4 vs 8.1±7.2, p<0.001) and transferred more embryos (2.2±2.5 vs 1.4±1.1, p<0.001) and had a statistically significantly higher pregnancy rate compared with public clinics (79.0% vs 29.7%, p<0.001). Publicly funded women had on average a higher number of oocytes retrieved and a statistically significantly higher probability of clinical pregnancy (RR=1.23, 95% CI 1.02 to 1.47) than self-paid women, after adjusting for covariates. There was no statistically significant interaction between clinical setting and payment type. CONCLUSIONS: Private clinics and public funding were independently associated with higher IVF clinical pregnancy rates. There is also a need to further investigate whether the increase in public funding will influence clinical pregnancy rates.

Pipelle endometrial sampling success rates in Kazakhstani settings: results from a prospective cohort analysis.

The aim of this study was to evaluate the feasibility of Pipelle endometrial sampling and to explore factors influencing Pipelle success rate in the clinical settings of Kazakhstan. This prospective analysis included 87 patients who had undergone Pipelle biopsy due to medical indications for endometrial sampling. We analysed physician and patient-related factors potentially influencing the success rate of this method. Pipelle endometrial biopsy overall success rate was 82.76%. The indications for the procedure and patients' age were key factors influencing Pipelle sampling success (p < .001). The success rate was the highest in the group with abnormal uterine bleeding as a biopsy indication in the reproductive age group (93.19%; p < .001).Pipelle biopsy was found to be an acceptable option for endometrial sampling in our clinical setting; at the same time, physicians should consider the potential influencing factors on its success rate like indications for the procedure, BMI and patients' age as well as their menopausal status. In order to provide precise future directions, there is a need to study a larger number of patients.IMPACT STATEMENTWhat is already known on this subject? Compared to dilation and curettage sampling conducted in the operation room, Pipelle endometrial sampling is relatively inexpensive, associated with less morbidity, safe, accurate, and can be performed in an office setting.What do the results of this study add? This is the first prospective data analysis about Pipelle endometrial sampling in Kazakhstani population.What are the implications of these findings for clinical practice and/or further research? Enabling the timely diagnosis of current endometrial pathology, Pipelle endometrial sampling approach may have an important impact on healthcare safety and efficiency, and improve overall treatment outcomes and the quality of life of Kazakhstani population if used consistently.

Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives.

The human endometrium is a unique tissue undergoing important changes through the menstrual cycle. Under the exposure of different risk factors in a woman's lifetime, normal endometrial tissue can give rise to multiple pathologic conditions, including endometriosis and endometrial cancer. Etiology and pathophysiologic changes behind such conditions remain largely unclear. This review summarizes the current knowledge of the pathophysiology of endometriosis and its potential role in the development of endometrial cancer from a molecular perspective. A better understanding of the molecular basis of endometriosis and its role in the development of endometrial pathology will improve the approach to clinical management.

Periodontal Pathogens and Preterm Birth: Current Knowledge and Further Interventions.

Preterm labor is defined as a birth before 37 weeks of gestation and occurs in 5-20% of pregnancies. Preterm labor, as multifactorial entity associated with a high risk of neonatal morbidity and mortality, is influenced by maternal, fetal and environmental factors. Microbiological studies suggest that infectious pathogens may account for 25-40% of preterm birth. Infections of different sites, like genital, urinary tract infections, and pneumonia, are linked to the preterm labor. The most recent epidemiological studies consistently report that maternal periodontal disease is associated with preterm delivery, as well as the association between the presence of pathogenic oral bacteria in the placenta and adverse pregnancy outcomes. On the other hand, some previously published papers found periodontal bacteria in placentas of term pregnancies. In spite of a huge research done on the topic, both experimental and clinical, there are many controversial opinions about the role of periodontal infections in preterm birth. Thus, this comprehensive review addresses this very important topic and evaluates novel strategies of preventive and therapeutic approaches.

The Effect of Stress, Anxiety and Depression on In Vitro Fertilization Outcome in Kazakhstani Public Clinical Setting: A Cross-Sectional Study.

Although it is clear that infertility leads to heightened stress for patients, the impact of depressed mood and anxiety on treatment outcome is inconsistently reported. The aim of this study was to evaluate the effect of stress, depression and anxiety on in vitro fertilization (IVF) outcomes in Kazakhstani public assisted reproductive technology (ART) clinics. The prospective cohort study was performed between June 2019 and September 2020 using questionnaires to assess psychological stress, depressed mood and anxiety in women referred to IVF clinics in two public clinical centers in Kazakhstan, Nur-Sultan and Aktobe. Our study sample comprised 142 women with the average age of 33.9 ± 4.9 years, and infertility duration 6.0 ± 3.5 years. More than half of respondents had Center for Epidemiological Studies Depression Scale (CES-D) scores higher than 16, indicating their risk of developing clinical depression. Ninety-one percent of women from Aktobe city were at risk for clinical depression (p < 0.001). Aktobe city respondents had higher stress subscale scores and anxiety scale scores (p < 0.001) than Nur-Sultan respondents. Statistical analysis showed that IVF outcome was not significantly associated with depression and stress, while the higher anxiety scale scores were negatively associated with clinical pregnancy after IVF.

Contemporary Fertility-Sparing Management Options of Early Stage Endometrioid Endometrial Cancer in Young Nulliparous Patients.

Incidence of endometrial cancer (EC) has been increasing in recent years, especially in high-income countries. The disease commonly affects peri- and postmenopausal women; however, about 5% of women are diagnosed with EC in their reproductive age. Due to both the increasing incidence of EC among reproductive age women and trends to delayed childbearing, fertility-sparing treatment for young patients with EC has become extremely important for researchers and practitioners. Because the classic treatment with total hysterectomy and bilateral saplingo-oophorectomy is not an appropriate approach for young women demanding fertility preservation, several fertility-sparing options have been developed and summarized in this review. Utilization of different medications and their combination (progestagens, gonadotropin releasing hormones analogues, and metformin in different formulations) are tested and found as efficient for fertility-sparing treatment. New minimally invasive surgical techniques, combined with progestagens, are also confirmed as valuable. There are many novel conservative and surgical treatment approaches under investigation. Assuming that molecular biomarkers can be both diagnostic and prognostic to assist in prediction of response to a certain therapy, prognostic risk groups' stratification along with specific biomarkers' identification will ensure low recurrence and decrease mortality rates in young women with EC.