Role of cetrorelix in the prevention and treatment of ovarian hyperstimulation syndrome: a prospective case control study

Background: Ovarian hyperstimulation syndrome (OHSS) has intrigued clinicians for many years because of its devastating consequences. As an iatrogenic condition resulting from elective ovarian stimulation in the quest for pregnancy, the need to completely prevent the syndrome is evident. Gonadotropin releasing hormone (GnRH) antagonist Cetrorelix has found to be effective in treatment of OHSS and some studies have found it to be helpful in prevention of this condition. Hence, we designed a hospital-based study to investigate the effect of Cetrorelix in preventing and treating OHSS in in-vitro fertilization � embryo transfer (IVF朎T) patients at risk of OHSS undergoing long and short protocol.Methods: The study includes total 102 patients undergoing controlled ovarian stimulation COS for IVF/ICSI. All cases were stimulated using long and short protocol. Depending on whether a GnRH antagonist was given after ovum pick-up (OPU) the patients were divided in two groups: Cetrorelix (antagonist) group (n=51) and control group (n=51). The study group was treated with Cetrorelix 0.25 mg for 5 days commencing on the day of ovum pick up.Results: Incidence of mild OHSS was significantly higher (p=0.01) whereas moderate to severe OHSS was significantly lower in the antagonist group (p<0.05). None of the patients had critical OHSS.Conclusions: GnRH antagonist Cetrorelix administration in early luteal phase in patients undergoing long or short protocol is effective in prevention and treatment of OHSS.

Addition of gonadotropin releasing hormone antagonist for women undergoing intrauterine insemination: a randomized controlled trial

Background: Intrauterine insemination (IUI) is a widely acceptable fertility treatment modality. GnRH antagonists have been proven effective in restricting the LH surge. The aim of the study was to assess whether the addition of gonadotropin releasing hormone antagonist (Cetrorelix) would improve clinical pregnancy rate in women undergoing IUI. Methods: This prospective randomized controlled trial was conducted at a Sudha fertility center where 730 women with primary or secondary infertility were subjected to controlled ovarian stimulation with tablet letrozole 5mg once daily for 5 days and then human menopausal gonadotrophins 75 IU/150 IU administered intramuscularly for both the groups and for study group alone Cetrorelix (0.25 mg/day, started when the leading follicle was ?16 mm; GnRH antagonist) was given additionally. A double insemination was performed at 36 hours and 60 hours after hCG was given (5,000 IU, intramuscularly) in both groups. Chi-square and independent t test was done.Results: Baseline characteristics in both the groups were almost equal without any statistically significant difference. Significant difference (p=0.017) was found on calculating with statistics among both groups on analyzing LH on hCG day. Clinical pregnancy rates (29.3%) were higher among the study group compared with the control group (21.7%).Conclusions: From the present study results it shows that addition of GnRH antagonists to controlled ovarian stimulation IUI significantly decreases the incidence of premature luteinization and increases the clinical pregnancy rates and live birth rate.

The regulation of ovarian reserve function by Zuogui pills combined with cetrorelix / 药学学报

The purpose of this study was to investigate how Zuogui pills from the Kidney-tonifying and Nourishing Yin formula, in combination with the gonadotrophin-releasing hormone antagonist cetrorelix, affected the ovarian local oxidative stress response in decreasing ovarian reserve (DOR) mice. All animal experiments were carried out in accordance with the guidelines and standards established by Jinan University's Experimental Animal Management Committee. Cyclophosphamide (CTX)-treated DOR mice were given Zuogui pills, cetrorelix, or a combination of the two drugs intragastrically. After treatment, there were changes in the estrous cycle, serum sex hormone levels, oxidative stress-related indexes, growth biochemical factor levels, and SIRT1/P53/P21 expression. In comparison to the model group, the Zuogui pills and the cetrorelix+Zuogui pills group had significantly prolonged estrous periods and shortened interestrous periods, and the cetrorelix+Zuogui pills group had a significantly shortened cycle length. Follicle-stimulating hormone (FSH) decreased and estradiol (E2) increased in all treatment groups compared to the model group, oxidative stress indexes nitric oxide synthase (NOS), nitric oxide (NO), and reactive oxygen species (ROS) decreased, growth biochemical factors brain derived neurotrophic factor (BDNF) and growth differentiation factor 9 (GDF-9) concentrations increased significantly, and leukemia inhibitory factor (LIF) showed no significant change. SIRT1/P53/P21 immunohistochemical results revealed that, when compared to the model group, the expression of SIRT1 increased while the expression of P53 and P21 proteins decreased in all treatment groups, with the cetrorelix+Zuogui pills group having the largest decrease, with significant differences in all indicators. We conclude that cetrorelix combined with Zuogui pills for kidney nourishing and Yin recipe improved the oxidative stress response in the follicle by regulating the SIRT1/P53/P21 pathway, reducing peroxide product production, protecting ovarian function, and regulating ovarian hormone secretion, and its efficacy is superior to that of cetrorelix or Zuogui pills alone.

Effects of cetrorelix versus ganirelix in gonadotropin-releasing hormone antagonist cycles for preventing premature luteinizing hormone surges and on clinical outcomes of IVF-ET cycles / 南方医科大学学报

OBJECTIVE@#To compare the effects of cetrorelix and ganirelix in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles for preventing premature luteinizing hormone (LH) surges and on clinical outcomes of IVF-ET cycles.@*METHODS@#We retrospectively analyzed 2572 GnRH-ant cycles of fertilization and embryo transfer from January, 2013 to December, 2016, including 1368 cycles with cetrorelix treatment and 1204 cycles with ganirelix treatment. The baseline characteristics of the patients and the clinical outcomes of the two groups were compared.@*RESULTS@#Compared with those receiving ganirelix treatment, the patients with cetrorelix treatment had a significantly younger age (33.10 33.89 years, 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% 3.2%) and similar spontaneous ovulation rate (0.6% 0.5%), clinical pregnancy rate (47.7% 45.9%) and live birth rate (37.5% 33.6%) following fresh embryo transfer ( > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% 0.1%, =0.006).@*CONCLUSIONS@#Cetrorelix and ganirelix can achieve comparable effects for preventing premature LH surges and can achieve similar clinical outcomes of GnRH-ant cycles, but ganirelix is associated with a significantly higher incidence of moderate to severe ovarian hyperstimulation syndrome.

Regulation of BuShen ZhuYun Decotion on gonadotropin in rat pituitary cells / 医学研究生学报

Objective The mechanism of luteal phase defect remains unclear. To investigate the mechanism of BuShen ZhuYun Decoction on the gonadotropin secretion in the pituitary gland, we observed the effects of medicated serum of BuShen ZhuYun Decotion on the secretion of gonadotropin-follicle-stimulating hormone (FSH) and luteotropic hormone (LH) in rat pituitary cells.Methods The BuShen ZhuYun Decotion was administered to the female SD rats by gavage to prepare the serum containing BuShen ZhuYun Decoction. The CCK-8 method was used to detect the effect of cetrorelix acetate powder for injection, medicated serum and gonadotropin releasing hormone (GnRH) on cell activity. In the maximum non-toxic concentration, we used cetrorelix acetate powder for injection to block the GnRH receptor (GnRHR) in pituitary cells and established the GnRHR antagonistic model. Then we treat the model group with medicated serum (model group). Moreover, we established the blank group (normal pituitary cells), the cetrorelix group (intervented with cetrorelix for 6 hours), and medicated serum group (intervented with medicated serum for 24 hours). 20nmol/L GnRH was used to stimulate cells for 6h. The contents of FSH and LH in the supernatant of each group and the mRNA expression of FSHβ, LHβ and GnRHR were detected.Results Compared with that of the blank group, the supernatant levels of FSH and LH in the Cetrorelix group decreased significantly \[(3.91±0.36) mIU/mL vs (2.26±0.22) mIU/mL, (8.94±0.57) mIU/mL vs (3.35±0.59) mIU/mL, P<0.05)\]. In contrast, the levels of LH significantly increased \[(8.94±0.57) mIU/mL vs (10.79±0.60) mIU/mL, P<0.05)\]; Compared with the cetrorelix group, the levels of FSH and LH in both medicated serum group and model group increased significantly (P<0.05). Compared with the blank group, the mRNA level of FSH and LH in the cetrorelix group decreased significantly \[(0.95±0.23) mIU/mL vs (0.58±0.12) mIU/mL, (0.98±0.14) mIU/mL vs (0.27±0.21) mIU/mL, P<0.01) \], and the mRNA expression of GnRHR increased in the cetrorelix group \[(0.97±0.13) mIU/mL vs (1.77±0.26) mIU/mL, P<0.01) \]; The mRNA levels of FSH and LH in the medicated serum group were increased (P<0.05). Compared with the cetrorelix group, the mRNA expression of FSHβ mRNA and LHβ were both increased in the medicated serum group and model group (P<0.05), the mRNA expression of GnRHR decreased (P<0.01).Conclusion It is suggested that the therapeutic mechanism of BuShen ZhuYun Decotion may be related to the improvement of GnRH receptor expression.

Gonadotropin releasing hormone antagonist administration for treatment of early type severe ovarian hyperstimulation syndrome: a case series

OBJECTIVE: To report an efficacy of gonadotropin releasing hormone (GnRH) antagonist administration after freezing of all embryos for treatment of early type ovarian hyperstimulation syndrome (OHSS). METHODS: In 10 women who developed fulminant early type OHSS after freezing of all embryos, GnRH antagonist (cetrorelix 0.25 mg per day) was started at the time of hospitalization and continued for 2 to 4 days. Fluid therapy and drainage of ascites was performed as usual. RESULTS: Early type OHSS was successfully treated without any complication. At hospitalization, the median (95% confidence interval [CI]) of the right and the left ovarian diameter was 10.0 cm (7.6 to 12.9 cm) and 8.5 cm (7.5 to 12.6 cm). After completion of GnRH antagonist administration, it was decreased to 7.4 cm (6.2 to 10.7 cm) (P=0.028) and 7.8 cm (5.7 to 12.2 cm) (P=0.116), respectively. The median duration of hospital stay was 6 days (3 to 11 days). Trans-abdominal drainage of ascites was performed in 2 women and drainage of ascites by percutaneous indwelling catheter was performed in 4 women. No side effect of GnRH antagonist was noted. CONCLUSION: GnRH antagonist administration appears to be safe and effective for women with fulminant early type OHSS after freezing all embryos. Optimal dose or duration of GnRH antagonist should be further determined.

Cessation of Gonadotropin-Releasing Hormone Antagonist on Triggering Day: An Alternative Method for Flexible Multiple-Dose Protocol

This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.

GnRH Antagonist Multiple Dose Protocol in Controlled Ovarian Hyperstimulation for In Vitro Fertilization and Embryo Transfer Compared with GnRH Agonist Long Protocol / 대한산부인과학회잡지

OBJECTIVE: To evaluate the efficacy of GnRH antagonist multiple dose protocol (MDP) in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) comparing with the standard GnRH agonist long protocol (GnRH-a LP). METHODS: From January 2000 to September 2002, 57 infertile women with tubal factor alone who had undergone IVF-ET were enrolled in the present study. Study group consisted of 28 patients in 28 cycles in which GnRH antagonist Cetrorelix 0.25 mg was given daily when the leading follicle reached 14 mm in mean diameter until the human chorionic gonadotropin (hCG) injection. Control group consisted of 29 patients in 29 cycles in which COH was performed using standard GnRH-a luteal LP. RESULTS: Patient's characteristics were comparable in both groups. Premature luteinization was not developed in all patients in each group. The number of ampules and duration of exogenous gonadotropins required were significantly lower in the study group than those in the control group (por=14 mm diameter on the day of hCG injection, the number of oocytes retrieved, fertilization rate, and the number of grade I, II embryos between the two groups, but the numbers of mature oocytes retrieved and fertilized oocytes were significantly lower in the study group than in the control group (p<0.01, p<0.01). The clinical pregnancy rate seemed to be lower in the study group, but the difference did not achieve significance (28.6% vs 34.5%). There were also no differences in the miscarriage rate and multiple pregnancy rate between the two groups. CONCLUSION: This study demonstrates that GnRH antagonist Cetrorelix MDP can result in the comparable pregnancy outcome as the GnRH-a LP and furthermore reduce the total dose of gonadotropins and duration of stimulation.