The role of mutations in the PI3K/AKT/mTOR- signal pathway in decreasing ovarian reserve in reproductive patients with deep infiltrative endometriosis



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Abstract

The most common reason for patients with endometriosis seeking medical help is infertility, which affects 25-50% of patients with this disease. One of the essential factors of infertility in deep infiltrative endometriosis is the depletion of the ovarian reserve. To study the effect of deep infiltrative endometriosis on the state of the ovarian reserve in patients of reproductive age, as well as to assess the range of mutations in the PIK3CA gene among patients with infiltrative endometriosis. The main group consisted of 50 patients of reproductive age with deep infiltrative endometriosis, 18 of whom with ovarian endometriomas. The comparison group included 25 patients of reproductive age with inconsistency of the uterine scar after cesarean section. The level of anti-Mullerian hormone, follicle-stimulating hormone and estradiol in the blood was determined, as well as the number of antral follicles in the ovaries was counted during trans-vaginal ultrasound. The search for activating mutations of the PIK3CA gene was carried out by the method of new generation DNA sequencing in tissue samples of ovarian endometriomas and in biopsies of healthy ovarian tissue. The anti-Mullerian hormones level was lower in patients with infiltrative endometriosis than in patients in the comparison group by 1.0 ng/ml (2.6 ± 2.2 ng/ml in the main group, 3.6 ± 3.5 ng/ ml in the comparison group), however, the difference did not reach statistical significance, p>0.05. The number of antral follicles according to ultrasound data was significantly lower in the main group (8.5 ± 4.5) than in the comparison group (12.2 ± 4.1), p=0.001. This difference was statistically significant both for patients with ovarian endometriomas (6.0 ± 4.2, p<0.001) and for patients without ovarian involvement (9.8 ± 4.2, p=0.04). Our study did not reveal PIK3CA gene mutations in any of the ovarian endometrioma tissue samples and healthy ovarian tissue biopsies in patients of both groups. The presence of deep infiltrative endometriosis is associated with a decrease in ovarian reserve in patients of reproductive age, regardless of the presence of endometrioid ovarian lesions. Population studies are needed to identify mutations of this gene in endometriosis, as well as to study mutations of other genes encoding proteins regulating the antiapoptic signaling pathway PI3K/ AKT/mTOR, to identify the mechanism of depletion of the ovarian reserve in infiltrative form of external genital endometriosis.

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About the authors

O. A Melkozerova

Ural Scientific Research Institute of Maternity and Child Care

E. O Okulova

Ural Scientific Research Institute of Maternity and Child Care

A. A Mikhelson

Ural Scientific Research Institute of Maternity and Child Care

T. B Tretyakova

Ural Scientific Research Institute of Maternity and Child Care

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