Premature ovarian insufficiency: etiological factors, clinical aspects, and optimization of in vitro fertilization programs (A literature review)

Abstract

Relevance:   Premature Ovarian Insufficiency (POI) represents one of the most significant disorders of reproductive health, characterized by early cessation of ovarian function and pronounced hypoestrogenism. According to systematic reviews and meta-analyses, the prevalence of POI ranges from 0.9% to 3.7%, indicating its considerable clinical and social impact. In recent years, there has been an upward trend in incidence, driven by the combined influence of genetic, metabolic, iatrogenic, and environmental factors. Considering that POI is among the leading causes of infertility and that the effectiveness of assisted reproductive technologies in this group remains limited, the search for new diagnostic and therapeutic strategies is of high importance.

Furthermore, POI is associated with a pronounced negative impact on the somatic and psycho-emotional well-being of women. In the context of the increasing trend toward delayed childbearing, its medical and social significance continues to rise steadily.

The study aimed to systematize current evidence on the causes, pathophysiological mechanisms, and consequences of premature ovarian insufficiency, and to analyze specific considerations for conducting in vitro fertilization programs in women with premature ovarian insufficiency.

Materials and Methods: A systematic review of publications from 2020 to 2025 was conducted using the PubMed, Scopus, Web of Science, and Cochrane Library databases, including clinical studies, systematic reviews, meta-analyses, and current recommendations from ESHRE and ASRM.

Results: According to the updated ASRM and ESHRE guidelines (2024), POI is diagnosed in women under 40 years of age who present with amenorrhea or oligomenorrhea lasting ≥4 months and a follicle-stimulating hormone level >25 IU/L. The mean age at diagnosis ranges from 30 to 35 years, and the prevalence varies from 0.9% to 3.7%, depending on the population studied and the diagnostic criteria applied. The etiological spectrum of POI includes genetic, autoimmune, iatrogenic, metabolic, and environmental factors, with up to 50% of cases remaining idiopathic. The most significant risk factors are a family history of early menopause, FMR1 gene mutations, autoimmune diseases, exposure to chemotherapy and radiotherapy, as well as metabolic disorders and nutrient deficiencies, warranting further investigation of their pathogenetic associations. The effectiveness of assisted reproductive technology (ART) programs using autologous oocytes remains extremely low; therefore, the use of donor gametes and fertility-preserving technologies is considered the most promising strategy. The future management of patients with POI is expected to rely on personalized protocols, molecular-genetic screening, and innovative approaches to restore ovarian function.

Conclusion: POI is a multifactorial condition with complex reproductive and systemic consequences. Current evidence highlights the predominant role of genetic, autoimmune, iatrogenic, and environmental factors in the development of POI, warranting further investigation of their pathogenetic interrelations. The effectiveness of ART programs using autologous oocytes remains extremely low; therefore, the use of donor gametes and fertility-preserving technologies is considered the most promising approach. Considering that the refusal of donor oocyte use among women with POI is driven by complex psychosocial, ethical, and cultural factors—including the loss of genetic identity, partner or family pressure, religious beliefs, and emotional discomfort associated with third-party gamete use—the future management of POI patients will rely on the implementation of personalized treatment protocols, molecular-genetic screening, and innovative strategies aimed at restoring ovarian function.