Infertility is an increasingly important issue for patients surviving cancer. Significant improvements in cancer management have led to greater numbers of patients living healthy and fulfilling lives for many years after a diagnosis of cancer, and the ability to bear children is a major component of well-being. Infertility is particularly challenging in gynaecological cancer, where multiple treatment modalities are often employed. Surgery may involve the removal of reproductive organs and subsequent chemotherapy may also lead to infertility. Mitigation of this through the use of cryopreservation of embryos, oocytes or ovarian tissue before chemotherapy may enable subsequent pregnancy in the patient or a surrogate mother. Suppression of ovarian function during chemotherapy is less well established, but promises a reduction in infertility without the risks associated with surgery. Similarly, evolving chemotherapy regimens with replacement of alkylating agents will reduce the incidence of infertility. With a combination of these techniques, an increasing proportion of patients may be able to conceive after completion of treatment, and there is no evidence of an increase in congenital abnormalities. This review discusses chemotherapy-induced infertility, interventions and success rates, and demonstrates that individualisation of management is required for optimum outcome.

• Infertility
• Chemotherapy
• Gynaecological malignancies
• Ovarian
• Cryopreservation

AIM: To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect.

METHODS: Wistar rats were administered physiological saline (4 mL/kg) or MK615 solution (4 mL/kg) for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection (ip) of D-galactosamine hydrochloride (D-GalN) (600 mg/kg). Plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and liver tissues were used for histopathological analysis. Fifty-eight patients with liver disorders [hepatitis C (n = 40), non-alcoholic fatty liver disease (n = 15), and autoimmune liver disease (n = 3)] were orally administered commercially available Misatol ME-containing MK615 (13 g/d) daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various biochemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint.

RESULTS: D-GalN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GalN, the plasma levels of ALT (475.6 ± 191.5 IU/L vs 225.3 ± 194.2 IU/L, P < 0.05) and AST (1253.9 ± 223.4 IU/L vs 621.9 ± 478.2 IU/L, P < 0.05) in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly decreased compared with pre-intake baseline levels from 103.5 ± 58.8 IU/L to 71.8 ± 39.3 IU/L (P < 0.05) and from 93.5 ± 55.6 IU/L to 65.5 ± 34.8 IU/L (P < 0.05), respectively. A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 26 (45%) of the 58 patients, while 25 (43%) patients exhibited similar AST level reductions. The chronic hepatitis C group exhibited significant ALT and AST level reductions from 93.4 ± 51.1 IU/L to 64.6 ± 35.1 IU/L (P < 0.05) and from 94.2 ± 55.5 IU/L to 67.2 ± 35.6 IU/L (P < 0.05), respectively. A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 20 (50%) of the 40 patients. ALT levels in both the combined ursodeoxycholic acid (UDCA) treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GalN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders.

CONCLUSION: These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.

• Prunus mume
• MK615
• Liver damage
• Hepatitis C
• Non-alcoholic fatty liver disease