Premature Ovarian Insufficiency Determined by X Chromosome Anomalies

Abstract

Background: Premature ovarian insufficiency (POI) is a condition defined by loss of ovarian activity before the age of 40 years, accompanied by menopausal symptoms. It is marked by amenorrhea or oligomenorrhea, absence of ovulation, elevated gonadotropins, and low estradiol levels. POI can be classified into spontaneous non-iatrogenic and iatrogenic forms. The prevalence of non-iatrogenic POI in the population ranges from 1% to 3.5%. The X chromosome’s Numerical and structural abnormalities are key etiological factors.
Objective: To determine the clinical peculiarities and types of POI caused by X chromosome anomalies.
Material and Methods: The study included 26 patients aged 16 to 24 with non-iatrogenic spontaneous POI. Of these, 12 patients were diagnosed with numerical or structural abnormalities of the X chromosome based on clinical, laboratory, and instrumental studies. In some cases, x-chromosome abnormalities were detected using G-banding in peripheral blood lymphocyte cultures; fluorescence in situ hybridization (FISH) and molecular cytogenetic methods were employed.
Results: Among the 26 patients with non-iatrogenic spontaneous POI, four were diagnosed with Turner syndrome. These patients exhibited severe growth retardation, somatic anomalies typical of Turner syndrome, and sexual development according to Tanner’s scheme (Ma0PaAx0Me0), including markedly elevated gonadotropins and decreased estradiol levels, By US – streak gonads and uterus, without follicles. Two patients were identified with a 45, X karyotype, while another had a 46, X, i(Xq) karyotype. Additionally, a mosaic karyotype with a 45, X cell line was detected in 5 patients (4 with 45, X/46, XX and 1 with 45, X/47, XXX). Structural abnormalities of the X chromosome, specifically deletions, were found in 2 patients. Patients with mosaicism and structural abnormalities of the X chromosome exhibited mild growth retardation and premature ovarian failure, which was characterized by primary amenorrhea, hypergonadotropinemia, and a significantly reduced number of antral follicles. Only one patient with a 45, X /47, XXX mosaic karyotype experienced secondary amenorrhea and spontaneous puberty. One patient with tetrasomy X (karyotype 48, XXXX) and POI presented with tall stature, mental retardation, secondary amenorrhea, hypergonadotropinemia, and a few follicles in the ovaries. To initiate puberty, all patients were treated with monotherapy using natural estrogen analogs, followed by replacement therapy with estrogen-gestagens until the age of natural menopause.
Conclusion:
• For all patients with non-iatrogenic premature ovarian insufficiency, despite the absence of subjective signs of estrogen deficiency and the characteristic signs of Turner’s syndrome, karyotyping is recommended.
• Oocyte donation is the optimal method to achieve fertility in patients with premature ovarian insufficiency and numerical and structural anomalies of the X chromosome.
• In patients with X chromosome anomalies at an early stage of diagnosis of chromosomal anomalies and in cases of an acceptable number of ovarian follicles, cryopreservation of reproductive materials may be considered with the using genetic testing of the embryo.