Pharmacological Protection of Ovaries During Program Drug Chemotherapy in Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Patients

Aim. To assess the efficacy of ovarian protection and options for fertility preservation with the use of gonadotropin-releasing hormone agonists (a-GnRH) in patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphomas (NHLs) during program drug chemotherapy.

Materials & Methods. The study enrolled 247 female patients (187 with cHL and 60 with NHLs) undergoing program drug chemotherapy from 2019 to 2023. The patients were aged 13–42 years (median 24 years). Prior to chemotherapy and after it was completed, the serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol levels were measured. Besides, antral follicle count was estimated by pelvic ultrasound. To provide ovarian protection during chemotherapy, a-GnRH was administered to 67 (27 %) out of 247 patients. Ovarian reserve was assessed based on ultrasound and AMH, FSH, and estradiol levels in 2–3 months after completing the program of drug chemotherapy or after spontaneous menstrual recovery.

Results. Menstrual cycle recovered in 194 (78.5 %) out of 247 patients, regardless of lymphoid malignancy variant. Among them, there were 79.7 % (n = 149) of cHL patients and 75 % (n = 45) of NHL patients. Accordingly, ovarian function was lost in 20.3 % (n = 38) of cHL patients and 25 % (n = 15) of NHL patients. Predictors of ovarian function recovery appeared to be age ≤ 28 years and AMH level > 2.45 ng/mL. Pharmacological protection of ovaries did not impact the probability of menstrual cycle recovery. Regardless of immunomorphological variant of lymphoid malignancy, a regular menstrual cycle was completely restored in 48 (71.6 %) out of 67 a-GnRH recipients and in 146 (81.1 %) out of 180 patients without a-GnRH treatment.

Conclusion. Most of cHL and NHL patients of early reproductive age (≤ 30 years) have a fair chance of menstrual cycle recovery after completing the program drug chemotherapy similar to BEACOPP, EACODD(PP)-14, R-CHOP, R-Da-EPOCH and other regimens. Ovarian reserve cannot be preserved by means of a-GnRH administration during chemotherapy. High baseline FSH and low baseline AMH levels indirectly indicate evidence of impaired ovarian reserve. Patients belonging to this category are those who, if intensive combined cytostatic therapy regimens are planned, should undergo prior oocyte/embryo retrieval with subsequent cryopreservation due to the risk of premature loss of ovarian function.

• I.E. Antukh VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, ул. Академика Опарина, д. 4, Москва, Российская Федерация, 117997
• Valeriya Olegovna Shpirko NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian ; ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478
• T.A. Nazarenko VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, ул. Академика Опарина, д. 4, Москва, Российская Федерация, 117997
• Ya.O. Martirosyan VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, ул. Академика Опарина, д. 4, Москва, Российская Федерация, 117997
• A.M. Biryukova VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, ул. Академика Опарина, д. 4, Москва, Российская Федерация, 117997
• S.V. Khokhlova VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997 ; ФГБУ «НМИЦ акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова» Минздрава России, ул. Академика Опарина, д. 4, Москва, Российская Федерация, 117997
• G.S. Tumyan NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

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