The role of cytomegaloviral infection in young females with ovarian resistance

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Introduction. The study is aimed at the evaluation of the effects of cytomegaloviruses (CMV) on the development of ovarian resistance (OR) and at the development of a package of diagnostic and therapeutic measures in patients with such pathology.

Material and Methods. Thirty two female patients of 17 to 23 years old with hypomenstrual syndrome and amenorrhea were examined. The group of patients was homogeneous with respect to the level and quality of life. Thorough examination of the medical histories and data of USI (poorly developed follicular structures, follicles of 1, 2 or 3 mm in diameter) and hormonal investigations (high levels of FSH and LH hormones and low levels of E2 were found in all patients, E2 to FSH ratio less than 20) made it possible to suggest a lack of activation of ovarian estrogen receptors. In order to make a final diagnosis, laparoscopy was made in, and gonadal biopsy was taken from, 24 patients. The laparoscopy revealed that the shape of the ovaries was almost rounded and the follicular apparatus was poorly developed. Primordial and preantral follicles were detected in the samples of ovarian biopsy during a pathohistological investigation. Polymerase Chain Reaction (PCR) was employed during laparoscopy to test the peritoneal fluid and samples of ovarian biopsy and urogenital discharge for DNA of CMV, and enzyme-linked immune assay was employed to detect Ig M and IgG antibodies against CMV. DNA of CMV was found in the samples of ovarian biopsy of 7 patients (21,8%), in the peritoneal fluid of 5 patients (15,6%), and IgM against CMV was found in 4 patients (12,5%) and diagnostic IgG titre - in 28 patients (87,5%). IgG titre fluctuated in the range from 1,47 to 10,9 with the reference values of IgG titre of 0,9. We have noticed that patients showing detected levels of DNA of CMV in the studied material and diagnostic titres of IgG against CMV or IgM had also more marked clinical signs of hypomenstrual syndrome and changes in the hormone levels. All patients in the group received the following therapy: human immunoglobulin against cytomegaloviruses - 1,5 ml, i/m, 5 times every fifth day, Laferon - 2 million IU, i/m, 10 times, Thiotriazoline, 2,5% - 2 ml i/m, vitamin E - 100 mg, 10 times, tincture of Echinacea Purpurea - 2,75 ml triple daily, Solco Trichovac - 1 dose, Viferon - 3 x 2 suppositoria (every 12 hours) per rectum, 10 times, UV irradiation of the blood 5 times. Three sessions of therapy were administered with an interval of 15 days. In the studied group of patients, the use of active estrogen - estradiol - was pathogenetically reasonable for the purposes of estrone competition in order to achieve an adequate reaction of the target organs. Transdermal Divigel preparation was preferred. The dose of 1 mg daily was used. The duration of administration was 21 days, and the minimal therapeutic doses of gestagens were added to the scheme of treatment on the 15th day of administration of Divigel; gestagen therapy continued for 10 to 12 days.

Results. Upon one month of treatment, a monitoring examination was performed in the group of the studied patients. During such examination, DNA of CMV was found in 2 patients (6,2%), IgM antibodies against CMV were not detected, IgG antibodies against CMV were found in 11 patients (34,3%). IgG titre was ranging 1,34 to 4,47. Hormonal investigation showed a reduction of the levels of FSH and LH in 23 patients, and the level of E2 came close to the lower limit of the normal values, and the E2 to FSH ratio increased to 22-34 (in phase 1 of the cycle). A repeated monitoring examination was performed in three months following the completion of therapy: DNA of CMV was found in none of the patients of the studied group, IgM antibodies against CMV were not detected, IgG antibodies against CMV were found in 2 patients (6,2%). IgG titre was ranging 0,4 to 0,9 in 30 patients (93,7%).

Hormonal investigation showed normal levels of FSH and LH and E2 in 25 patients, and the E2 to FSH ratio increased to 27-40 (in phase 1 of the cycle). USI showed that the structure of the ovaries was within the age-related normal margins.

Conclusions. The obtained results make it possible to conclude:

• CMV has negative impact on the reproductive system;
• CMV is a factor causing ovarian resistance;
• Patients with hypomenstrual syndrome shall be tested for CMV infection by using PCR and enzyme-linked immune assay methods in order to confirm the diagnosis of ovarian resistance;
• For the purposes of making a final diagnosis, laparoscopy and gonadal biopsy and withdrawal of material from the abdomen for PCR (CMV diagnosis) are required;
• Estrogen-gestagen therapy as a certain phase of treatment of patients with developing ovarian resistance if pathogenetically justified; in such cases, administration of transdermal Divigel is preferred;
• We have offered a method of treatment of ovarian resistance in patients with CMV infection showing very high efficacy.

About the authors

A. S. Protsenko

Regional Centre for Rehabilitation of the Human Reproductive Function

Author for correspondence.
Email: info@eco-vector.com
Ukraine, Zaporozhyje

N. V. Avramenko

Regional Centre for Rehabilitation of the Human Reproductive Function

Email: info@eco-vector.com
Ukraine, Zaporozhyje

O. V. Strelko

Regional Centre for Rehabilitation of the Human Reproductive Function

Email: info@eco-vector.com
Ukraine, Zaporozhyje

G. P. Khodak

Regional Centre for Rehabilitation of the Human Reproductive Function

Email: info@eco-vector.com
Ukraine, Zaporozhyje

V. N. Protsenko

Regional Centre for Rehabilitation of the Human Reproductive Function

Email: info@eco-vector.com
Ukraine, Zaporozhyje

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