REPRODUCTIVE ENDOCRINOLOGY

Order of the Ministry of Health of Ukraine No. 1400 “On approval of the Standard of Medical Care “Spontaneous pregnancy (spontaneous abortion)”

REPRODUCTIVE ENDOCRINOLOGY — 2025-12-30

Діагноз: Спонтанний викидень (спонтанний аборт).
Коди стану або захворювання. НК 025:2021 «Класифікатор хвороб та споріднених проблем охорони здоров’я»:
O02.1 Завмерла вагітність
O03 Спонтанний аборт
O03.0 Спонтанний аборт, Неповний аборт, ускладнений інфекцією статевих шляхів та тазових органів
O03.1 Спонтанний аборт, Неповний аборт, ускладнений тривалою або надмірною кровотечею
O03.2 Спонтанний аборт, Неповний аборт, ускладнений емболією
O03.3 Спонтанний аборт, Неповний аборт з іншими та неуточненими ускладненнями
O03.4 Спонтанний аборт, Неповний аборт без ускладнень
O03.5 Спонтанний аборт, Повний або неуточнений аборт, ускладнений інфекцією статевих шляхів та тазових органів
O03.6 Спонтанний аборт, Повний або неуточнений аборт, ускладнений тривалою чи надмірною кровотечею
O03.7 Спонтанний аборт, Повний або неуточнений аборт, ускладнений емболією
O03.8 Спонтанний аборт, Повний або неуточнений аборт з іншими та неуточненими ускладненнями
O03.9 Спонтанний аборт, Повний або неуточнений аборт, без ускладнень
O20 Кровотеча в ранні терміни вагітності
O20.0 Загрозливе невиношування

ESHRE guideline on ovarian stimulation for IVF/ICSI – 2025

European Society of Human Reproduction and Embryology (ESHRE) — 2025-12-30

The aim of the ovarian stimulation guideline is to provide clinicians with evidence-based information on the different options for ovarian stimulation for in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI), taking into account issues such as the ‘optimal’ ovarian response, live birth rates, safety, patient compliance, and individualisation. Special attention has also been given to pre- and adjuvant treatments in low responders and the prevention of ovarian hyperstimulation syndrome in high responders.
The guideline provides recommendations on all steps of ovarian stimulation: pre-stimulation management, pituitary suppression and gonadotropin stimulation, monitoring during ovarian stimulation, triggering of fifinal oocyte maturation and luteal support and the prevention of ovarian hyperstimulation syndrome.
As an update to the original guideline published in 2019, it contains new key question on fertility preservation that has been split into three parts, to reflect the best available evidence on fertility preservation for women facing gonadotoxic treatment, elective oocyte cryopreservation or oocyte donation. In addition, several new interventions were added to the existing key questions. Overall, these changes resulted in 46 new recommendations.
The guideline was developed according to the structured methodology for development of ESHRE guidelines.

The role of inositol in reproductive health

L.K. Sokolova — 2025-12-30

This review highlights the mechanisms of action and current evidence on the effectiveness of inositol for the treatment of reproductive disorders.
The results of the studies showed that inositol plays an important role in the functioning of the reproductive system in both women and men. In women, myo-inositol (MI) acts as a second messenger of follicle-stimulating hormone in signaling pathways that regulate the proliferation and maturation of granulosa cells. MI also affects the production of anti-MГјllerian hormone, which plays a key role in the maturation of the egg, its passage through the fallopian tubes and the formation of high-quality embryos. The ovaries have a specific ratio of MI to D-chiro-inositol (DCI), which ensures their normal functioning. Excess DCI can impair the quality of oocytes and blastocysts, so its level needs to be strictly regulated.
In men, DCI affects steroidogenesis, stimulating the synthesis of androgens by Leydig cells of the testicles. It also regulates the expression of the aromatase enzyme, which leads to a decrease in estrogen synthesis. A change in the MI:DCI ratio can cause hormonal imbalance, characteristic of conditions such as polycystic ovary syndrome, female and male infertility. The use of MI and DCI in a ratio of 40:1 demonstrates the highest effectiveness in reducing all manifestations of polycystic ovary syndrome. This combination is considered first-line therapy for women with polycystic ovary syndrome and excess body weight, as it contributes to the normalization of metabolic indicators and improvement of clinical outcomes. The effectiveness of this combination of inositol stereoisomers is due to their synergistic effect: DCI reduces peripheral hyperinsulinemia, while MI restores ovulatory function. As a result, combination therapy reduces the risk of metabolic syndrome, improves hormonal balance and increases insulin sensitivity.
Due to high efficacy, good tolerability, minimal side effects and low toxicity, inositols can be safely and widely used in these reproductive disorders.

Features of the course of gestational processes in women with adenomyosis

V.P. Mishchenko — 2025-12-30

Background. The relevance of the topic of the features of gestational processes in women with adenomyosis lies in the high frequency of occurrence in practical medicine of infertility, miscarriage, gestational complications by trimesters of gestation, obstetric bleeding in childbirth, etc. Adenomyosis in the vast majority of women clinically occurs in parallel with concomitant gynecological, somatic diseases, negatively affects the psycho-emotional state of women.
Objective of the study: determination of the features of the course of gestational processes in women with adenomyosis of I–II degree.
Materials and methods. We observed 51 women of reproductive age. Of these, 34 had adenomyosis of the I-II degree of severity, who were divided into subgroups depending on the management algorithm. The remaining 17 pregnant women without gynecological pathology were included in the control group.
Results. The average duration of the adenomyosis was 5–7 years. More than 80% of the participants with adenomyosis underwent treatment within the last three years. These patients had a high frequency of somatic and gynecological pathology, a high level of gestational complications, including chorionic/placental abruption, hypotonic bleeding during childbirth. The indicators were significantly better in the group of women who received preconception preparation.
Conclusions. Women with adenomyosis and reproductive plans are subject to systematic dispensary supervision, including the use of etiopathogenetic therapy and timely complex stage-by-stage personalized preconception preparation for pregnancy. The algorithm for managing pregnant women with adenomyosis should be exclusively personalized depending on the clinical general condition of the mother and fetus, data from instrumental and laboratory examinations in the dynamics of observation. Delivery must take place under obstetric supervision due to the risk of bleeding.
Women with adenomyosis should undergo preconception preparation 4–6 months before pregnancy, which includes hormone therapy (micronized progesterone), vitamin D in combination with the trace element magnesium, folate in physiological doses, macro- and microelement complexes for pregnant women, nutritional support, and measures to maintain mental health.

Experience of correction of latent (non-anaemic) iron deficiency in adolescent girls and young women

G.I. Reznichenko — 2025-12-30

Objective of the study: to evaluate the effectiveness of treatment and quality of life of adolescent girls and young women with latent iron deficiency using the iron (III) hydroxide-polymaltose complex.
Materials and methods. 654 women aged 16вЂ“20 years were examined: 55 patients (8.4%) were diagnosed with iron deficiency anemia, 342 (52.3%) did not have iron deficiency, 257 (39.3%) had latent iron deficiency, of whom 37 used the iron (III) hydroxide-polymaltose complex for 3 months (study group). 83 women without iron deficiency were included in the control group.
The levels of ferritin, serum iron, C-reactive protein, malondialdehyde and phospholipids in erythrocytes, permeability of erythrocyte membranes, catecholamine and insulin-depositing function of erythrocytes, sex hormones, cortisol, immunoglobulin A, the state of the vaginal microbiome and quality of life were determined.
Results. In patients with latent iron deficiency, changes in the functional state of various organs and systems were found, and quality of life was reduced compared to individuals without iron deficiency. The use of the iron (III) hydroxide-polymaltose complex in this cohort high effectiveness in restoring ferritin and serum iron levels, which contributed to the normalization of the hormonal profile and lipid peroxidation in erythrocytes, the function and structure of erythrocyte membranes, the restoration of the vaginal microbiome and immunoglobulin A and the quality of life.
Conclusions: The use of the iron (III) hydroxide-polymaltose complex has shown its effectiveness in correcting latent iron deficiency and its consequences, thus improving the quality of life of patients.

Multimodal impact of myo- and D-chiro-inositol combined with glutathione and bioactive folate (Quatrefolic®) on the course of hyperandrogenic PCOS phenotypes

T.F. Tatarchuk — 2025-12-30

Objective of the study: to evaluate the efficacy of a combination of myo-inositol (РњР†) and D-chiro-inositol (DCI) (in a 40:1 ratio) supplemented with glutathione and a bioactive form of folic acid (QuatrefolicВ®) on sex hormone-binding globulin (SHBG) levels, markers of hyperandrogenism, insulin resistance, and anthropometric parameters in women with hyperandrogenic polycystic ovary syndrome (PCOS) phenotypes and signs of metabolic dysfunction-associated steatotic liver disease.
Materials and methods. The study included 59 women of reproductive age with classical PCOS phenotypes and ultrasound evidence of hepatic steatosis. Patients were divided into two groups: the main group (n = 30) received a complex of MI + DCI (2000/50 mg) + glutathione (50 mg) + QuatrefolicВ® (400 Вµg) twice daily; the comparison group (n = 29) followed lifestyle modification recommendations only. Anthropometric data (body mass index and waist circumference, insulin resistance (HOMA-IR index), total testosterone, and SHBG were assessed, with the calculation of the free androgen index at baseline and after 4 months of intervention. Impact on ovulatory dysfunction was evaluated by luteinizing hormone dynamics and ultrasound evidence of ovulation.
Results. The main group receiving the comprehensive therapy demonstrated a statistically significant advantage over the lifestyle modification group. SHBG levels increased by 138% (from 26,35 В± 4,56 tРѕ 62,88 В± 11,54 nmol/L), leading to a radical 2,87-fold reduction in the free androgen index. Significant reductions in body mass index, waist circumference (3,88 cm vs. 1,52 cm in the comparison group), and normalization of the HOMA-IR index (2,18 В± 0,25) were observed, indicating effective management of insulin resistance and visceral obesity. Along with androgenic profile correction, gonadotropic function normalized: luteinizing hormone levels decreased 2,87-fold (from 19,8 В± 2,8 to 6,9 В± 1,9 U/L). The cumulative result of the therapy was the restoration of ovulatory cycles in 73.3% of patients (p < 0,001), confirming the efficacy of the multimodal impact on the hepato-ovarian axis in women with PCOS.
Conclusion. The addition of glutathione and QuatrefolicВ® to standard inositol therapy (in a 40:1 ratio) demonstrates a pronounced synergistic effect. This approach restores hepatic synthetic function, normalizes SHBG levels, and effectively corrects hormonal and metabolic disturbances in PCOS patients with concomitant hepatic steatosis, significantly outperforming standard lifestyle modification guidelines.

Clinical, morphological and molecular markers in the formation of prognosis in patients with cervical cancer

I.E. Yezhova — 2025-12-30

Cervical cancer (CC) remains one of the leading causes of cancer mortality among women in the world, despite significant progress in prevention, screening and
treatment. Due to risk factors associated with the development of CC (smoking, early onset of sexual activity, sexually transmitted infections, number of sexual partners, oral contraceptive use, and immunosuppression), this disease is characterized by an early asymptomatic course. Despite the current methods of treatment of CC (surgical, radiological, chemotherapeutic, as well as the introduction of immunotherapy and targeted drugs in recent years), the prognosis for CC remains unfavorable. The choice of the correct treatment regimen depending on the prognostic and predictive factors of the course of CC is the most important stage. Classical clinicopathological prognostic factors do not sufficiently explain the variability of the course of the disease in patients with similar tumor characteristics, especially at intermediate risk.
This review analyzes both known factors of prognosis of CC (stage of the disease, depth of stromal invasion, lymphovascular invasion, lymph node involvement, spread to the parametrium), and new markers, the role of which is actively studied: perineural invasion, tumor-free distance. Current data on known and promising prognostic biomarkers are summarized: the presence of human papillomavirus, viral load, proteins p16, p53, Ki-67, markers of hypoxia and angiogenesis HIF-1Î±, VEGF, serum antigens SCC Ag, CYFRA 21-1, hematological indices of systemic inflammation (NLR, PLR, PIV) and components of the tumor microenvironment, such as tumor-infiltrating lymphocytes
(TILs), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAF), programmed death ligand 1 (PD-L1). The role of the new biological markers microRNAs is associated with the development of many malignant neoplasms, in particular CC.
The integration of these markers into clinical practice significantly increases the accuracy of predicting the course of CC, allows for a better assessment of the risk of recurrence and potential response to therapy, and also contributes to the individualization of treatment tactics. The presented review emphasizes the need for further multicenter studies to standardize and implement new prognostic markers into clinical practice.

Intramural uterine leiomyomas in early anamnesis

N.P. Tsip — 2025-12-30

Background. Uterine leiomyomas are benign smooth muscle tumors with significant global economic and healthcare impact. While typical in the fourth decade of a woman’s life, cases diagnosed in patients around 20 years old suggest unique biological mechanisms, including genetic predisposition (MED12 and HMGA2 gene mutations) and epigenetic reprogramming. Clinical case. A retrospective analysis of two clinical cases of intramural uterine leiomyomas, incidentally diagnosed in women aged 20 years, with tracking of their clinical evolution over 20 years is presented.
Both patients remained asymptomatic for more than two decades, successfully realizing reproductive function. However, after the age of 40, both women experienced rapid tumor growth (up to 7–10 cm in diameter) and severe abnormal uterine bleeding.
Treatment included preoperative therapy with gonadotropin-releasing hormone agonist (Zoladex) followed by successful conservative myomectomy. Menstruation in both patients resumed within a few months after the completion of postoperative gonadotropin-releasing hormone agonist therapy, and none of them was found to have disease recurrence during 15–16 months of follow-up.
Histopathological examination revealed different variants of uterine leiomyomas: multiple proliferating leiomyomas in clinical case 1 (indicating a probable pathway associated with a MED12 gene mutation) and solitary cell leiomyoma in clinical case 2 (indicating a probable pathway associated with an HMGA2 gene mutation).
Conclusions. Early-onset uterine leiomyoma exhibits a long indolent phase followed by aggressive symptomatic transformation in the perimenopausal period. A combined approach of gonadotropin-releasing hormone agonists and myomectomy is an effective organ-preserving strategy. Long-term follow-up and personalized molecular analysis are crucial for managing these patients.