Comparison of bevacizumab and cabergoline in the treatment of ovarian hyperstimulation syndrome in a rat model

Abstract

The aim of this study is to investigate the effects of bevacizumab in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline. The study was performed with 24 rats in four main groups (one non-stimulated control and three OHSS treatment groups; bevacizumab, cabergoline and placebo). The rats were randomly assigned to four experimental groups (six rats per group). Efficacy of treatment was assessed on 29th day by measuring weight gain, number of eggs, presence of ascites and ovarian weight. Peritoneal fluid levels of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay. Ovarian weights were significantly higher in the OHSS groups than the control group. Ovarian weights in OHSS placebo group were found to be higher than those in OHSS-treatment groups (p?=?0.002). VEGF levels were found increased in the OHSS-placebo group compared with the control group (p?<?0.05). This increase was not seen in the OHSS groups treated with either bevacizumab or cabergoline. We demonstrate in this study that bevacizumab can lower VEGF production and ovarian weight in rats treated with gonadotropins.     

Spontaneous ovarian hyperstimulation caused by a follicle-stimulating hormone-secreting pituitary adenoma

OBJECTIVE: To report a case of spontaneous ovarian hyperstimulation resulting from an FSH-secreting pituitary adenoma. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 29-year-old previously healthy, nulligravid woman. INTERVENTION(S): Transphenoidal resection of the adenoma. MAIN OUTCOME MEASURE(S): Clinical remission. RESULT(S): After transphenoidal resection of the adenoma, the patient had an uneventful postoperative recovery with complete resolution of ovarian hyperstimulation and associated symptoms. Postoperative magnetic resonance imaging demonstrated residual tumor within the cavernous sinus. CONCLUSION(S): Follicle-stimulating hormone-secreting pituitary adenoma may present as acute spontaneous ovarian hyperstimulation.     

Lifesaving dose increment of cabergoline in life-threatening spontaneous ovarian hyperstimulation syndrome resistant to all interventions

Objective: Spontaneous ovarian hyperstimulation syndrome (SOHSS) is an extremely rare complication that deserves a multidisciplinary approach together with a thorough investigation for the correct diagnosis of the underlying pathology. The aim of this study was to present a case of severe SOHSS resistant to all interventions and to discuss the available interventions to overcome such a rare and serious clinical situation.

Case report: We report a case of severe, life-threatening spontaneous OHSS with a normal nine weeks singleton pregnancy in a 25-year-old nulliparous woman, which resulted with pregnancy termination and continuation of disease progression until the dose of cabergoline was increased to 1.5?mg/day.

Conclusion: This case report emphasizes that patients with life-threatening SOHSS resistant to all medical and surgical interventions may benefit from higher doses of cabergoline. Although spontaneous OHSS is extremely rare, it is potentially a life-threatening clinical entity in its severe form and needs time management and detailed examination of the underlying causes.     

Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome

Objective: The aim of this work was to investigate the value of laparoscopic ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined with cabergoline (Cb), as a prophylaxis against the re-development of ovarian hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI cycle.

Study design: It is a prospective controlled study, where 250 CCR-PCOD women (n?=?250) with a history of severe OHSS before, had been recruited for the study. LOD had been performed for 120 (n?=?120) of the recruited women before ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25?mg) was added when a leading follicle reaches 14–16?mm combined with oral Cb in a dose 0.5?mg a day before hCG, and for 8?d for another 130 (n?=?130) women, and considered as group B. Pregnancy was diagnosed with BhCG level ≥25?IU/L,?±?14?d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2 weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up weekly for 3?months for the possible development of any signs and symptoms of OHSS.

Results: None of the participants in group A developed severe OHSS, and only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS was significantly higher (n?=?3, 15%) in group B compared with group A (p?n?=?17, 13.3%) women in group B developed mild to moderate OHSS. The probability of developing severe OHSS was also significantly higher in group B as well (p?=?.031). Pregnancy rate (PR) was significantly higher in group A more than group B (67% versus 39%, respectively), and all were single intrauterine pregnancies (IUP) and all developed after fresh embryo transfer (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases in group B after postponing ET due to significantly severe OHSS developed.

Conclusion: LOD could be considered a good prophylactic measure against OHSS, in addition to improving the total outcome of IVF cycles in women with CCR-PCOS.     

Comparison of montelukast and cabergoline for prevention of ovarian hyperstimulation syndrome: in an experimental rat model

Abstract

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication that can occur during assisted reproductive techniques. The aim of this study is to investigate the effects of the leukotriene receptor antagonist (montelukast) treatment in prevention of OHSS and compare to cabergoline treatment. Twenty-four immature female Wistar rats were assigned to four groups. Group 1 was the control group. In the remaning three groups, OHSS was induced through ovarian stimulation with gonadotropins. No treatment was given to Group 2. Group 3 was administered a low-dose 100?mg/kg cabergoline treatment and Group 4 was received 20?mg/kg montelukast. Body weight, ovarian weight, vasculary permability (VP), peritoneal fluid vascular endothelial growth factor (VEGF) values and VEGF immune-expression were compared between the groups. Both cabergoline and montelukast prevented progression of OHSS compared to the OHSS group. Body weight, ovarian weight, VP, peritoneal fluid VEGF values and VEGF expression were significantly lower in both cabergoline- and montelukast-treated rats than in those not treated OHSS group. In conclusion, montelukast is an effective option for prevention of OHSS, as well as cabergoline. Montelukast may be a new treatment option to prevent and control the OHSS.     

Successful pregnancy complicated by spontaneous,familial, recurrent ovarian hyperstimulation syndrome: report of two cases

Abstract

We here report two cases of spontaneous, familial, recurrent ovarian hyperstimulation syndrome ended in a successful pregnancy. First case was a 26-year-old woman, gravida 3 para 0 and two previous terminations of pregnancy due to spontaneous ovarian hyperstimulation syndrome (OHSS). During her pregnancy, patient was treated with IV fluid therapy, albumin and thromboembolic prophylaxis and required pleural and peritoneal drainage. She was referred to the hospital twice, at 8 and 28 weeks’. At 32 weeks due to worsening of clinical condition, decision was made for a caesarean section. A live, healthy preterm baby of 1950?g was delivered. Second case was a 27-year-old woman, gravida 2 para 0 with one previous termination of pregnancy due to spontaneous OHSS. During her pregnancy patient was treated with IV fluid therapy, albumin, and thromboembolic prophylaxis. She did not require any pleural or peritoneal drainage. She was referred to the hospital twice, at 8 and 30 weeks. At 37 weeks of gestation, due to worsening of clinical condition decision for a caesarean section was made. A live, healthy term baby of 2700?g was delivered. Our experience seems to confirm that management of spontaneous OHSS during pregnancy should be conservative and treatment tailored to severity of symptoms.     

Dopamine agonists in prevention of ovarian hyperstimulation syndrome

The aim of this review is to analyze the efficacy of different dopamine agonists in the prevention of ovarian hyperstimulation syndrome (OHSS). Cabergoline, quinagolide and bromocriptine are the most common dopamine agonists used. There are wide clinical variations among the trials in the starting time (from the day of human chorionic gonadotrophin (hCG) to the day following oocyte retrieval); the duration of the treatment (4–21 days), the dose of cabergoline (0.5?mg or 0.25?mg orally) and in the regimens used. At present, the best known effective regimen is 0.5?mg of cabergoline for 8 days or rectal bromocriptine at a daily dose of 2.5?mg for 16 days. Dopamine agonists have shown significant evidences of their efficacy in the prevention of moderate and early-onset OHSS (9.41%), compared with a placebo (21.45%), which cannot be confirmed for the treatment of late OHSS. It would be advisable to start with the treatment on the day of hCG injection or preferably a few hours earlier. The use of dopamine agonists should be indicated in patients at high risk of OHSS, as well as in patients with a history of previous OHSS even without evident signs of the syndrome.     

Immunological and hemostasiological disorders in women with ovarian hyperstimulation syndrome

Abstract

To assess the markers of destabilization of homeostasis in women with ovarian hyperstimulation syndrome (OHSS), the investigation of the levels of cortisol, markers of renin-angiotensin-aldosterone system, endothelin, proinflammatory cytokines, acute phase proteins, and parameters of hemostasis was performed. Our survey involved 105 women who became pregnant after IVF: 21 women with symptoms of the early moderate and severe OHSS, 28 women with the late moderate and severe OHSS, and 56 pregnant women undergoing IVF without symptoms of OHSS. It was found significant increase of levels of cortisol, interleukins, the number of leucocytes, concentration of fibrinogen and D-dimers in patients with early and late OHSS. The development of late OHSS is associated with the lower level of IL-8 and ceruloplasmin. The OHSS is characterized by leukocytosis, higher level of IL-6, TNF-α, fibrinogen, D-dimers, thus reflecting the homeostasis imbalance. The determination of the level of fibrinogen, D-dimers, leukocytes can be an important screening test of the intensity of the inflammatory process in patients with OHSS.     

Serum leptin concentrations in patients with severe ovarian hyperstimulation syndrome during in vitro fertilization-embryo transfer treatment

OBJECTIVE: To investigate the changes in serum leptin concentration in the conception cycle of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study of 66 IVF-ET cycles between May 2000 and June 2002. SETTING: Infertility outpatient clinic at a Japanese medical school. PATIENT(S): Infertile patients undergoing IVF-ET cycles at the infertility outpatient clinic were divided into three groups consisting of group 1 (conception-cycle patients with severe OHSS, n = 9), and group 2 (conception cycle, non-OHSS, n = 28), and group 3 (nonconception cycle, non-OHSS, n = 29). INTERVENTION(S): Blood samples were collected at five different periods. Period I, on the first day of ovarian stimulation with FSH; period II, at hCG administration before oocyte retrieval; period III, 7 days after oocyte retrieval; period IV, 14 days after oocyte retrieval; and period V, 21 days after oocyte retrieval. MAIN OUTCOME MEASURE(S): Serum leptin concentration. RESULT(S): The serum leptin concentration was low in the OHSS group compared with that of the non-OHSS groups in all serum samples, with significant levels at periods III (vs. groups 2 and 3; P<.05) and IV (vs. group 3; P<.01). A twofold increase of leptin concentration from period I to period II (P<.05) was observed in all groups. CONCLUSION(S): The change pattern in serum leptin concentration might provide a great contribution to the pathophysiology development of OHSS patients during assisted reproductive treatment.     

Gonadotroph adenoma causing ovarian hyperstimulation syndrome in a premenopausal woman

Introduction: Gonadotroph adenomas occur commonly in middle-aged adults without any specific endocrinological symptoms. To date, only 30 cases of gonadotropinoma causing ovarian hyperstimulation syndrome in pre-menopausal women have been reported.

Case report: A 37-year old woman with pituitary macroadenoma and hyperprolactinaemia was admitted to the Department of Endocrinology, Diabetology and Isotope Therapy. She presented with recurrent ovarian cysts, menstrual disturbances, headaches, visual impairment and galactorrhea. Her endocrine profile showed normal values of FSH, elevated concentrations of estradiol and suppressed LH levels. Transsphenoidal resection of the tumor tissue resulted in normalization of the hormone values and improvement in the clinical picture.

Conclusions: Gonadotroph adenomas should be considered in the differential diagnosis in premenopausal women with OHSS.     

Oocyte quality in patients with severe ovarian hyperstimulation syndrome: a self-controlled clinical study

OBJECTIVE: To investigate the oocyte quality in patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Self-controlled clinical study. SETTING: University teaching hospital. PATIENT(S): Twenty-two patients from our assisted reproductive technology (ART) program who developed severe OHSS during their first controlled ovarian hyperstimulation for IVF or intracytoplasmic sperm injection (ICSI) (OHSS cycles) during a period of 10 years and had a second ART attempt performed in our center in which OHSS did not develop (control cycles). INTERVENTION(S): IVF and ICSI. MAIN OUTCOME MEASURE(S): Oocyte yield and quality, fertilization rate, embryo yield and quality, implantation rate, and pregnancy rate. RESULT(S): The total number of oocytes retrieved and the mean number of metaphase II oocytes were significantly higher in patients with OHSS than in control cycles. Fertilization rates were similar in both groups of ART cycles, and thus the number of viable embryos were significantly higher in OHSS cycles. Implantation and pregnancy rates were similar in OHSS and control cycles. Oocyte and embryo yield and quality were similar in early and late OHSS. Oocyte yield and quality, embryological outcome, and implantation and pregnancy rates were similar in patients with and without polycystic ovarian syndrome (PCOS) both in cycles developing OHSS and control cycles. CONCLUSION(S): Oocyte quality is not compromised in severe OHSS cycles irrespective of whether patients had or did not have PCOS.     

Postparacentesis bilateral massive vulvar edema in a patient with severe ovarian hyperstimulation syndrome

OBJECTIVE: To report a case of bilateral massive vulvar edema following lower abdominal paracentesis in a patient with ovarian hyperstimulation syndrome. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S): A 32-year-old woman with primary infertility. Intervention(S): The patient underwent ovarian stimulation with leuprolide acetate, highly purified FSH, and hCG. Because of the development of severe ovarian hyperstimulation syndrome, bilateral paracentesis through the lower abdominal quadrants was performed. MAIN OUTCOME MEASURE(S): Treatment of ovarian hyperstimulation syndrome. RESULT(S): Development of bilateral massive vulvar edema 24 hours after lower abdominal paracentesis. CONCLUSION: This case report suggests that lower abdominal paracentesis could be the cause of vulvar edema development in ovarian hyperstimulation syndrome, probably due to a fistulous tract created between the peritoneal cavity and the subcutaneous tissues.