REPRODUCTIVE ENDOCRINOLOGY

Protection of the rights of children born using reproductive technologies

T.Z. Harasymiv — 2025-09-18

Background. The use of assisted reproductive technologies (ART) gives rise to additional problems of a social, ethical and legal nature, in particular, an important unresolved issue is the status of children born using these technologies. Medical law in Ukraine has numerous gaps in legal regulation, and the sphere of assisted reproduction is no exception, which affects the issue of ensuring the best interests of the child.
Objective of the study: to carry out an intercomplementary analysis of the problem of protecting the rights of children born using reproductive technologies in the context of highlighting aspects of their social, ethical, medical and legal status.
Materials and methods. The research methodology includes a complex of philosophical (dialectical; ethical-normative; phenomenological) and special scientific (statistical, comparative-legal, dogmatic) methods.
Results. The authors harmonized the terms and concepts of the issue, analyzed the legal regulation of ART and studied individual aspects of the social and legal status of children born using this method. The article also examines the problems of information accessibility of their genetic information and paternity data, and presents the legal and psychosocial aspects of the right to identity of such a group of children. The problem of legal regulation of the posthumous use of reproductive cells has been studied in detail precisely in the context of ensuring the best interests of the child and balancing these interests with the reproductive rights of parents. The authors separately emphasize the importance of legal awareness of medical professionals, compliance between them and recipients and donors, cooperation between doctors and lawyers in various forms, which will contribute to the creation of the necessary conditions for general well-being, the implementation of reproductive rights, psychosocial comfort and legal protection of children born using ART.
Conclusions. Based on the results of the analysis of the declared problem, the need for child-centeredness, non-discrimination in any form and the need for further scientific research into the feasibility of updating the current legislation by adopting a profile Law on ART, changing the requirements for donors of reproductive cells, guaranteeing the right to identity by prohibiting anonymous donation and introducing quotas on the number of families for using gametes from one donor, balanced regulation of posthumous reproduction, allowing the use of gametes of military personnel as donors and making changes to family and civil legislation regarding the regulation of the status of children born using ART, parents and donors.

A modern view on potential directions in the research of breast microcalcifications

A.Y. Kovtun — 2025-09-18

Background. The majority of breast calcifications are not dangerous and represents benign changes in the breast that do not require further follow-up
and additional examinations. However, in a third of cases with suspicious microcalcifications (МС), oncopathology can be diagnosed after verification. The morphological type of calcifications and their distribution are determined by benign and malignant pathologies. Factors such as age, hormonal background, and density of the breast parenchyma play an important role in the appearance of certain breast findings and pathologies.
Objective of the study: to analyze the prospects of possible directions of research into suspicious MC of the breast and factors contributing to their formation. Materials and methods. An analysis of radiological and pathomorphological studies was carried out in 129 women with suspicious MC, aged from 31 to 85 years, with an average age of 49.0 years. Sampling was performed under ultrasound and X-ray guidance, depending on the ability to visualize the suspicious area with MC.
Results. The vast majority of the 129 women were young and middle-aged (according to the WHO classification, 2017) – 49 (37.98%) and 63 (48.84%) patients, respectively. 92 (71.32%) women had dense breasts, and 37 (28.68%) women had non-dense breasts. According to the localization of MC in the breast, there was a significant predominance in the upper-outer quadrant, where 85 (65.89%) cases of suspicious MC were visualized. The upper-outer quadrant prevailed in all age groups: young age – 38 (77.58%) cases, middle age – 38 (60.32%) cases, elderly and senior – 9 (52.94%). The most common types of MC grouping were grouped in 88 (68.22%) cases, and segmental – 26 (20.16%) cases. For all age groups, grouped calcifications had the most common presentation: young age – 31 (63.27%) cases, middle age – 44 (69.84%) cases, elderly and senior – 13 (76.47%) cases. Segmental and grouped types of suspicious MC are most characteristic in dense breast – 19 (20.65%) and 65 (70.65%) cases, respectively. Pleomorphic MC were the most common type of calcifications among all age groups: young age – 35 (71.43%) cases, middle age – 44 (69.84%) cases, elderly and senior – 11 (64.71%) cases. There was a predominance of punctate and pleomorphic types of suspicious MC for dense breast – 17 (18.48%) and 65 (70.65%) cases, respectively. Of the 129 suspicious findings, malignant pathology was diagnosed in 36 (27.9%) cases, and 93 (72.1%) cases were associated with benign findings.
Conclusions. It is advisable to conduct studies that could assess the presence of a statistically significant effect on the manifestation of the morphological type of suspicious MC and their type of grouping depending on the density of the breast parenchyma, localization in the breast and the age of the patients. Additionally, it is necessary to assess the effect of breast density on the frequency of the appearance of suspicious MC and the increase in the risk of breast cancer.

Recurrent miscarriage: strategies for overcoming the problem in the pre-pregnancy stage

I.A. Zhabchenko — 2025-09-18

The article highlights the relevance of the problem of miscarriage in the world and in Ukraine in modern conditions. Particular attention is paid to the problem of recurrent miscarriage (RM), which is faced by approximately 1–3% of all couples of reproductive age.
Approximately 50% of miscarriages occur for unknown reasons. Currently, the known causes of RM are genetic, anatomical, endocrine, immune, infectious factors, male factor, etc. Over the past 10–15 years, views on antiphospholipid syndrome as the cause of RM have changed significantly.
It is believed that most sporadic early pregnancy losses are associated with chromosomal abnormalities of the fetus and are not signs of problems in the woman’s body. Views on the significant role in the development of RM of such negative factors as smoking, alcohol, drug addiction, low socio-economic status, deficiency / excess body weight, stress remain unchanged.
A real way out of this situation can be adequately organized and timely conducted high-quality pre-pregnancy preparation, which is a complex of diagnostic, preventive and therapeutic measures aimed at assessing the health status and preparing the couple for conception, pregnancy and the birth of a healthy child. The best time for a new pregnancy is currently considered to be the period of 3–6 months after a spontaneous abortion. Compared with conception that occurred later, at this time the frequency of recurrent miscarriage, ectopic pregnancy, premature birth, low birth weight, cesarean section and induced labor is significantly lower.
Taking into account risk factors, key recommendations for pre-pregnancy preparation of women with RM were formulated. The basic principle is that testing and treatment after a first pregnancy loss is not recommended, as it is usually a sporadic event. The remaining recommendations include: a comprehensive approach (determination of the state of somatic health, detection of extragenital pathology and its correction with the involvement of related specialists if necessary); lifestyle modification and supplementation of vitamins and microelements; routine vaccination; genetic testing; correction of anatomical disorders of the female reproductive organs; correction of antiphospholipid syndrome and hereditary thrombophilias; elimination of infectious factors; restoration of normal vaginal biocenosis; correction of endocrine factors; correction of the male factor and psychoemotional disorders.
Special attention is focused on the role of progesterone in the prevention of RM. Most experts agree on the advantages of various forms (vaginal, sublingual) of micronized progesterone, which has been proven by numerous studies.

Markers of epithelial-mesenchymal transformation in placentas with fetal growth retardation

T.O. Stepanenko — 2025-09-18

Objective of the study: to study the phenomenon of epithelial-mesenchymal transformation in the placenta with fetal growth retardation (FGR).
Materials and methods. A study of placentas from 40 singleton births with FGR, divided into 4 groups, was conducted. Group I included pregnant women with FGR diagnosed before 32 weeks without concomitant gestational complications, group II included patients with FGR diagnosed up to 32 weeks and preeclampsia criteria, group III included pregnant women with FGR diagnosed after 32 weeks without concomitant gestational complications, group IV included pregnant women with FGR diagnosed after 32 weeks and concomitant preeclampsia. The control group consisted of 10 healthy parturient women.
The intensity of cytokeratin 7 and vimentin expression in extravillous and villous trophoblast cells and amnion was determined by an immunohistochemical direct immunoperoxidase method using microscopic morphometry in placental samples.
Results. In the extravillous trophoblast of the placenta against the background of FGR and preeclampsia and isolated early fetal growth retardation, increased expression of cytokeratin 7 was recorded: 0.471 standard units (SI) of light in group I, 0.437 SI of light in group II, 0.424 SI of light in group IV, 0.345 SI of light in the control group. At the same time, in the villous trophoblast, against the background of isolated FGR, a reduced expression of cytokeratin 7 was recorded: 0.345 SI of light in group I and 0.357 in group III versus 0.498 SI of light in the control group, and for concomitant preeclampsia even lower – 0.248 SI of light in group II and 0.239 SIof light in group IV.
Vimentin expression in extravillous trophoblast in FGR and preeclampsia, as well as in isolated early FGR, was lower than in the control group – 0.271 SI of light in group I, 0.237 SI of light in group II, 0.224 SI of light in group IV and 0.345 SI of light in healthy placentas. In villous trophoblast, vimentin expression was higher in placentas with FGR (0.375 SI of light in group I, 0.348 SI of light in group II, 0.387 SI of light in group III and 0.339 SI of light in group IV) than in healthy placentas (0.248 SI of light).
Conclusions. In the extravillous trophoblast of placentas with FGR and preeclampsia, as well as with isolated early FGR, insufficient acquisition of mesenchymal properties by cells (insufficient expression of vimentin) and preservation of epithelial properties (increased expression of cytokeratin 7) are observed. In the villous trophoblast of placentas with isolated FGR, excessive acquisition of mesenchymal cells and loss of epithelial properties were detected, and in the presence of concomitant preeclampsia, these changes are even more pronounced.

Australian living evidence guideline: endometriosis – 2025

Reproductive Endocrinology — 2025-09-18

The Australian Living Evidence Guideline for Endometriosis, published in May 2025 by RANZCOG, offers the latest scientific evidence for detecting, diagnosing, and managing endometriosis. A Living Evidence Guideline incorporating current research to provide evidence-based recommendations to health care practitioners who diagnose and manage people with suspected or confirmed endometriosis or adenomyosis.
The new guideline aims to improve consistency of care for people living with endometriosis, and will reduce reliance on invasive laparoscopic surgery, which had been the gold standard in endometriosis detection and diagnosis for decades. Instead, these evidence-based guidelines prioritise less invasive medical imaging techniques to facilitate earlier diagnosis and treatment of endometriosis and ultimately reduce the pain and cost for the patients affected by the disease.
This guideline emphasizes non-invasive diagnostic methods and includes specific resources for primary care providers and patients.
Key features of the guideline included such positions:

Focus on non-invasive diagnosis. The guideline promotes the use of transvaginal ultrasound and MRI as first-line diagnostic tools, reducing reliance on laparoscopic surgery.
Patient-centered approach. It includes resources to help patients understand endometriosis, navigate their care journey, and manage symptoms, including emotional and psychological well-being.
Specific recommendations for primary care. A quick reference guide and flowchart are provided to support general practitioners in the early detection and management of endometriosis.
Living guideline model. The guideline is regularly updated with new evidence to ensure it reflects the latest research and best practices.
Emphasis on education. The guideline stresses the importance of educating patients about endometriosis, its management, and the potential impact of treatments like hormonal contraception.
Addresses related conditions. The guideline also addresses adenomyosis, a related condition often associated with endometriosis.

Miscarriage, recurrent mmiscarriage and ectopic pregnancy. Clinical guideline – 2025

Reproductive Endocrinology — 2025-09-18

This guideline has been developed by the Miscarriage, Recurrent Miscarriage and Ectopic Pregnancy Guideline Development Group of the Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and approved by the Women’s Health Committee and Council in March 2025.
Objectives: to provide clinical guidance and advice to registered health professionals providing care to women with suspected or confirmed early pregnancy loss, including miscarriage, recurrent miscarriage and tubal
or non-tubal ectopic pregnancy.
Scope: Early pregnancy losses including miscarriage (and threatened miscarriageii), recurrent miscarriage and all ectopic pregnancies both tubal and non-tubal. The gestational age limit for this guideline is up to 14 weeks, except for investigation of recurrent miscarriage where the gestational age limit is up to 20 weeks.
The information is intended to provide general advice to practitioners. This information should not be relied on as a substitute for proper assessment with respect to the circumstances of each case and the needs of any woman. This document reflects emerging clinical and scientific advances as of the date issued and is subject to change.

mmunohistochemical and molecular genetic profiling in determining pathogenetic variants of malignant epithelial ovarian tumors

I.R. Hrytsay — 2025-09-18

Objective of the study: to investigate immunohistochemical and molecular markers in tumor samples representing different pathomorphological types of ovarian cancer (OC) and assess their predictive value.
Materials and methods. A retrospective analysis was conducted on 37 tumor samples obtained from patients with OC through primary cytoreductive surgery, diagnostic laparoscopy with biopsy, or trephine biopsy of distant metastases. The study utilized an immunohistochemical panel assessing the expression of WT-1, p53, Napsin A, and progesterone receptors, along with a molecular genetic panel targeting mutations in HRR, TP53, and other key genes.
Results. Histological analysis identified the following tumor distribution: high-grade serous carcinoma (HGSC) вЂ“ 19 cases (51.4%), endometrioid carcinoma (ENOC) – 7 (18.9%), clear cell carcinoma (CCC) – 7 (18.9%), and unclassified tumors – 4 (10.8%).
The distribution was revised following immunohistochemical analysis: HGSC – 21 cases (56.8%), ENOC – 7 (18.9%), CCC – 6 (16.2%), and low-grade serous carcinoma (LGSC) – 3 (8.1%). A discrepancy between pathomorphological and immunohistochemical diagnoses was observed in 21.6% of cases; however, immunohistochemical technique enabled a definitive subtype diagnosis in 97.3% of cases.
Among 21 HGSC cases, TP53 mutations were detected in 11 (50%) patients, BRCA1 in 5 (22.7%), BRCA2 in 2 (9.1%), CDK12 in 2 (9.1%), and one case each of AR (4.5%) and PIK3CA (4.5%).
In ENOC cases, BRCA1 mutations were found in 2 (25.6%) patients, TP53 in 3 (42.9%), and one case each – RAD51C (14.7%) and KRAS (14.7%).
In CCC, molecular profiling revealed mutations in the following genes: TP53 –1 case (16.7%), NBN – 1 case (16.7%), RAD51C – 1 case (16.7%). Overall, TP53 mutations were identified in 11 (52.4%) cases using next-generation sequencing, while p53 protein abnormalities were observed in 14 (66.7%) cases via immunohistochemical analysis.
Conclusions. Immunohistochemistry is essential for the accurate classification of malignant epithelial ovarian tumors. Concurrently, molecular profiling provides critical insights into homologous recombination repair deficiencies and reveals key mutations not only in HGSC but also in ENOC and CCC subtypes. Together, these tests support personalized treatment selection, including tailored chemotherapy regimens and targeted therapies, potentially enhancing treatment response and patient outcomes.

Personalized management strategies for patients with perimenopausal disorders under war-related stress

T.F. Tatarchuk — 2025-09-18

Objective of the study: to investigate the frequency of menopausal transition symptoms in women aged 40–52 years under chronic stress due to the war in Ukraine.
Materials and methods. An online survey of women aged 40–52 years presenting with menstrual cycle disturbances was conducted on the initiative of the Association of Gynecologists-Endocrinologists of Ukraine. Between May and September 2024, 1685 questionnaires were collected, of which 1374 were complete and included in the analysis. The standardized online questionnaire included items on place of residence, clinical profile, menopausal symptoms, and somatic health characteristics. Parametric statistical methods were used for data analysis.
Results. Most respondents were aged 46–52 years (59.6%). Overweight was observed in 45.9% and obesity in 24.2%. Menstrual cycle disturbances persisted for 2–11 months in 87.4% of respondents, with 76.6% attributing these changes to severe stress.
Over 80% of women in both age groups reported fatigue, decreased activity, and irritability; anxiety and panic attacks occurred in 29–52% of cases. Sleep disturbances were present in the majority (73–75%), and cognitive difficulties affected more than half of respondents regardless of age.
Genitourinary menopausal syndrome symptoms were reported by over 50% of women, while sexual disorders (decreased libido and loss of interest in sexual activity) were noted by about two-thirds of respondents.
Conclusions. The study demonstrated a high prevalence and inverted pattern of climacteric symptoms, with the early onset of cognitive dysfunction and manifestations of genitourinary menopausal syndrome already at a young age (40–45 years). This indicates that chronic psycho-emotional stress of war is a significant aggravating factor that potentially accelerates and intensifies the clinical manifestations of the menopausal transition in women in Ukraine. The obtained results justify the need to reconsider management approaches for patients in this age group, with an emphasis on proactive identification of complaints, educational efforts, and timely initiation of therapy to prevent the progression of menopausal disorders.

Resolution of the III Ukrainian Forum of Experts on Abnormal Uterine Bleeding

T.F. Tatarchuk — 2025-09-18

Abnormal uterine bleeding (AUB) is the leading reason for seeking medical attention among women aged 30 to 50. Given the demographic crisis that Ukraine is currently facing, there is
an urgent need to develop a strategy to preserve the reproductive health of the population and update the national regulatory framework. This should take into account modern scientific achievements to unify clinical approaches.
The resolution of this Forum aims to improve clinical approaches to the management of patients with menstrual disorders and AUB, to implement personalized treatment, which is designed to improve the reproductive health of Ukrainian women in conditions of full-scale war.
The resolution summarizes the recommendations of international associations, highlights the advantages of using gestagens in the treatment of AUB, applies an interdisciplinary approach to discussing AUB management - from hematological and endocrinological perspectives, and considers the issue of prevention of venous thromboembolic complications in gynecological patients. In order to optimize the management of patients with AUB, the Forum experts improved the AUB management algorithm. The main difference was the clarification of the period for which the patient has a request and willingness to take contraceptives.
The main direction of AUB pharmacotherapy is the use of hormonal drugs such as combined oral contraceptives and gestagens. Among gestagens, high efficacy and safety of dydrogesterone has been proven. Given the fact that most patients with AUB have concomitant pathology, interdisciplinary cooperation and integration of a patient-oriented approach are important, which is the key to preserving the reproductive potential of Ukrainian women.

Resolution of the II Ukrainian Forum of Experts on Endometriosis

T.F. Tatarchuk — 2025-09-18

Endometriosis is a chronic, incurable disease that requires a long-term and individualized approach to the management of patients from menarche to menopause. This disease significantly reduces the quality of life of most patients, affects sexual and family life, is the cause of infertility and increases the risk of ovarian cancer in older age. In addition to physical discomfort, endometriosis has a significant negative impact on mental health, causing the development of depression and anxiety, which can aggravate chronic pelvic pain.
In Ukraine, work is underway to update the national clinical protocol for the management of endometriosis. The working group, approved by the order of the Ministry of Health of Ukraine, uses the updated NICE (2024) and ESHRE (2022) guidelines to prepare current regulatory documents. The goal is to standardize approaches, take into account the latest scientific data and comprehensive management, which includes, in addition to medical aspects, also reproductive and social rehabilitation.
The ESHRE (2022) and NICE (2024) guidelines move away from laparoscopy as the “gold standard” of diagnosis. Instead, they emphasize the importance of clinical examination, imaging (ultrasound, MRI) and empirical treatment.
Drug therapy should be aimed at controlling symptoms. It is important to take into account individual characteristics, patient wishes, side effect profile and cost. Dydrogesterone has been recognized as effective
and safe for the treatment of endometriosis-associated pain, especially in patients who wish to plan a pregnancy, since it does not suppress ovulation. Nonsteroidal anti-inflammatory drugs, including high doses of ibuprofen, may be used to relieve pain.
Surgery involves removing the endometriosis lesions and is an important tool in cases of ineffective pharmacotherapy. However, surgery does not guarantee complete pain relief and has a high risk of recurrence, especially in young women. Repeated operations can significantly reduce ovarian reserve.
For women with endometriosis-related infertility, assisted reproductive technologies, including in vitro fertilization, can be used. The endometriosis fertility index is a useful tool for deciding on the optimal method of achieving pregnancy.
For successful management of patients, it is critical to develop a long-term plan that includes medical and surgical interventions, lifestyle modification, and the integration of psychological support. Raising women’s awareness of their condition, along with cognitive-behavioral therapy, and relaxation techniques, has been proven effective in reducing pain and improving the quality of life of such patients.