Abstract
BackgroundAdditional treatment with a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) before IVF-ET (ultralong GnRHa therapy) has been reported to improve the outcome of IVF-ET in endometriosis patients. However, the mechanism of ultralong GnRHa therapy is unclear. It is suggested that inflammatory cytokines and oxidative stress contribute to infertility in endometriosis patients. Therefore, in order to search a possible mechanism of ultralong GnRHa therapy, we investigated the effect of ultralong GnRHa therapy on intrafollicular concentrations of tumor necrosis factor alpha (TNFα), oxidative stress markers, and antioxidants in patients with endometriosis.MethodsTwenty-three infertile women with Stage III or IV endometriosis were recruited for this study. Eleven patients received three courses of GnRHa (1.8 mg s.c. every 28 days), followed by a standard controlled ovarian hyperstimulation (COH) for IVF-ET (ultralong group). The other 12 patients received a standard COH with mid-luteal phase GnRHa down-regulation (control group). The numbers of matured follicles and retrieved oocytes, fertilization rates, implantation rates, clinical pregnancy rate, and intrafollicular concentrations of TNFα, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL) as oxidative stress markers, and melatonin and Cu,Zu-superoxide dismutase (Cu,Zn-SOD) as antioxidants were compared between the two groups.ResultsThe numbers of mature follicles and retrieved oocytes, and fertilization rates did not differ between the two groups. Implantation rates and pregnancy rates tended to be higher in the ultralong group (21.4% and 27.3%, respectively) compared with the control group (8.3% and 8.3%, respectively). TNFα concentrations in the follicular fluid were significantly lower in the ultralong group (5.8 ± 3.2 pg/ml) than those in the control group (10.6 ± 3.2 pg/ml). Follicular concentrations of 8-OHdG concentrations were significantly lower in the ultralong group (5.7 ± 1.6 ng/ml) than those in the control group (6.6 ± 1.5 ng/ml), while melatonin concentrations were significantly higher in the ultralong group (139 ± 46 pg/ml) compared with the control group (86 ± 27 pg/ml).ConclusionsUltralong GnRHa therapy reduces the detrimental effects of cytotoxic cytokines and oxidative stress in the ovary in patients with endometriosis.
Highlights
Additional treatment with a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) before in vitro fertilization and embryo transfer (IVF-ET) has been reported to improve the outcome of IVF-ET in endometriosis patients
TNFα concentrations in the follicular fluid were significantly lower in the ultralong group (5.8 ± 3.2 pg/ml) than in the control group (10.6 ± 3.2 pg/ml) (Figure 1)
The present result clearly showed that the concentrations of a cytotoxic cytokine (TNFα) and oxidative stress (8-OHdG) in follicular fluids were significantly lower in the ultralong GnRHa therapy group than in the control group, suggesting a potential mechanism that additional GnRHa treatment before IVF-ET improves the pregnancy outcome of IVF-ET by reducing the detrimental effects of cytotoxic cytokines and oxidative stress in the peritoneal environment or implantation environment in patients with endometriosis
Summary
Additional treatment with a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) before IVF-ET (ultralong GnRHa therapy) has been reported to improve the outcome of IVF-ET in endometriosis patients. Possible causes of the infertility include poor quality of oocytes and embryos [3], impaired fertilization [4,5], and impaired implantation [6], each of which can be induced by inflammation and other inflammatory cytokines in the endometrium [13,14]. This surge of inflammatory cytokines has been proposed as a cause of endometriosis-related implantation failure [13,14]. Endometriosis patients showed high concentrations of TNFα in ovarian follicular fluids, which is associated with poor oocyte quality or impaired fertilization [11]. These findings strongly suggest that oxidative stress contributes to infertility in endometriosis patients
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