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.

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.

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.

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.

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.

Fertility preservation in endometrial cancer patients: options, challenges and perspectives.

Several different approaches have been designed by physicians in order to preserve fertility in younger patients with endometrial carcinoma. There are various options offering different advantages, but hysteroscopic resection of pathologic endometrial tissue with placement of a Levonorgestrel Intrauterine Device has proven to be the most successful in allowing patients to conceive and give birth afterwards. However, conservative treatments should only be considered in patients with low-grade and low-stage endometrial tumours. There are many published studies which have sought out a preferable approach to treating endometrial cancer whilst preserving fertility. However, more research on this matter is needed to allow a better understanding as to which techniques/approaches are optimal. In this review, we will summarise the current available treatment options for endometrial cancer in patients of reproductive age.

Current role of Pipelle endometrial sampling in early diagnosis of endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in developed countries. The most prevalent, however not pathognomonic symptom of the disease is abnormal uterine bleeding. The diagnosis of endometrial cancer is based on the histologic results of endometrial sampling. Endometrial biopsy could be obtained using different modalities: hysteroscopy-directed endometrial biopsy, uterine curettage or office endometrial biopsy. Outpatient endometrial biopsy using different devices for the evaluation of abnormal uterine bleeding is gaining popularity. The most popular office-based device for endometrial sampling procedure is the Pipelle device. Currently, Pipelle endometrial sampling is widely used to diagnose endometrial cancer in women with abnormal uterine bleeding and/or postmenopausal bleeding. The method became very useful due to easiness and simplicity of the procedure, availability of a device, as well as high sensitivity in detecting endometrial cancer. Many studies compared the validity and accuracy of Pipelle biopsy with dilation and curettage in the detection of various endometrial pathologies. Published results state that Pipelle biopsy and uterine curettage are almost equally reliable in the evaluation of endometrial pathologies. Moreover, Pipelle biopsy appears more beneficial as it does not require hospital admission and anaesthesia. However, it is proven the Pipelle technique has a limited capacity to identify endometrial polyps, and some authors, based on their study, claim that dilation and curettage is a more reliable method in terms of correlation with the final histological results. In addition, there are many factors affecting the efficiency of the endometrial biopsy. Failure to get samples that are adequate for histological examination is one of the problems associated with Pipelle sampling. The above mentioned contradictory conclusions by different researchers and lack of guidance to avoid inadequate sampling present the demand for further studies on the comparison of Pipelle biopsy and uterine curettage efficiency and accuracy.

Ovulation induction in infertile women with endometriotic ovarian cysts: current evidence and potential pitfalls.

Endometriosis is a chronic benign gynecological disease with symptoms that can severely impact quality of life and well-being. Women affected by endometriotic ovarian cyst could have associated infertility problems. Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, due to the disease pathophysiologic mechanisms. Generally, infertility management include surgical procedure (usually with minimally invasive approach) and ovulation induction with intrauterine insemination or in vitro fertilization. Fertility preservation technologies also include oocyte or embryo freezing and ovarian tissue cryopreservation. Approach to patients with endometriotic cysts still remains controversial, and a multidisciplinary approach is a key factor to achieve the best outcome with appropriate patient counselling. Such management by a multidisciplinary team is a key factor in achieving the successful outcome.

Evaluation of Uterine Artery Embolization on Myoma Shrinkage: Results from a Large Cohort Analysis.

OBJECTIVE: There are still contradictory opinions on the success rates of uterine artery embolization (UAE) for the treatment of myomas. In this scenario, our study aims to assess the effect of UAE on myoma shrinkage. MATERIALS AND METHODS: The study included 337 women in reproductive age affected by a single symptomatic intramural myoma and declined surgery, undergoing UAE. The uterus and myoma diameters and volumes were determined on ultrasonographic scans before and 3, 6, and 12 months after the procedure. RESULTS: The mean uterine volume before intervention was 226.46 ± 307.67 mm3, whereas myoma volume was 51.53 ± 65.53 mm3. Further myoma progression was registered in only four patients. In remaining women, uterus volume in average decreased for 149.99 ± 156.63 mm3, whereas myomas decreased for 36.57 ± 47.96 mm3. The mean volume reduction rate of the uterus was 49.54 ± 35.62 and for myoma was 57.58 ± 30.71. A significant decrease in both uterine and myoma volume was registered in every stage of the follow-up. The highest average decrease in uterine volume was in the first 3 months and myoma volume between 3 and 6 months following UAE. After 12 months follow-up, successful outcome (volume regression >50% respect to the baseline) was registered for uterus in 97.4% and for myoma in 67.9% of investigated patients. CONCLUSION: UAE was proven to allow a good success rate and can be considered as an effective alternative procedure for myoma treatment.

Fertility Preservation in Benign Gynecological Diseases: Current Approaches and Future Perspectives.

Although fertility preservation is a growing topic in the management of oncological diseases, different benign gynecological pathologies are able to compromise the ovarian reserve due to mechanisms related to the pathology itself or secondary to the performed treatments. Endometriosis, benign ovarian tumors, adnexal torsion, familiarity and genetic syndromes are all benign conditions that can compromise the ovarian reserve. Endometriosis and particularly endometriomas provide a direct damage to ovarian reserve, with different mechanisms, and an indirect damage related to surgery. Similarly, benign ovarian tumors can provide a detrimental effect on ovarian reserve for the surgical treatment, especially for bilateral or recurrent tumors, and in case of secondary adnexal torsion with late diagnosis. Different fertility preservation options are available and should be considered particularly in cases with bilateral or recurrent pathology and/or surgery. In general, the identification of patients at risk of early ovarian failure, for benign gynecological disease or based on known genetic causes or familiarity, is of paramount importance in order to apply fertility preservation techniques before the complete depletion of ovarian reserve.

Organochlorine pesticides exposure in female adolescents: potential impact on sexual hormones and interleukin-1 levels.

The objective of this study was to assess the potential impact of organochlorine pesticides (OCPs) on IL-1 axis in exposed female adolescents through an observational cross-sectional study. The study was conducted in Sary-Agach District (OCPs exposed girls) and Sairam District (OCPs unexposed controls), South Kazakhstan. The study included 524 female adolescents aged 10-17 years (OCPs exposed, n = 253; OCPs unexposed, n = 271). The main outcome was assessment of OCPs blood levels (correlating to pubertal development and sexual hormonal status) and IL-1 levels. The delayed sexual development and the hormonal profile in OCPs exposed female adolescents correlated to the blood levels of OCPs. Interestingly, serum IL-1α and IL-1ß in girls living in contaminated areas correlated to OCPs blood levels as well. Both OCPs and IL-1 blood levels in exposed female adolescents resulted to be increased, but further research is required to establish if that might represent an additional factor contributing to puberty disorders and/or reproductive health issues.

New models for prediction of micronuclei formation in nuclear medicine department workers.

BACKGROUND: Ionizing radiation causes detrimental health effects such as cancer and genetic damage. The study aim was to determine predictors for micronuclei (MN) occurrence and frequency in peripheral blood lymphocytes of health workers professionally exposed to radiation. METHODS: Health workers, age matched, selected for the study on regular check-ups, were divided according to the radiation exposure. The exposed group involved nuclear medicine department employees (54) and the control group comprised workers from other departments (36). Data about workers characteristics and habits, received annual doses (AD), total years of service (TYS) and exposed years of service (EYS) were taken from each subject. Blood samples were taken and micronuclei (MN) number in peripheral blood lymphocytes was calculated using CBMN assay according to standard protocols. RESULTS: Most workers were female, technicians, with mean age of 45.67 years and EYS about 15 years. Health workers exposed to radiation had significantly more MN than controls (p = 0.001). Female gender, older age, higher received annual doses, longer EYS and TYS increased the MN number. Technicians and laboratory workers have higher risk for MN occurrence. Significant predictors of MN formation according to constructed model were workers age, sex, AD and EYS. One EYS year increases MN frequency 1.017 times, while receiving 0.1 mSy raises MN frequency by 26 %. EYS accurately predicts 86.30 % of MN frequencies and AD 64.60 %. CONCLUSIONS: The model, developed for the first time in this study, showed that received annual doses and duration of exposure to radiation can be used for prediction of MN numbers.