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.     

Comparison between resveratrol and cabergoline in preventing ovarian hyperstimulation syndrome in a rat model

Objective: The aim of this study is to investigate the effects of resveratrol in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline.

Design: Randomized controlled, animal study.

Animal(s): Female Wistar rats.

Material and methods: A rat OHSS model was used to investigate the effects of resveratrol compare with cabergoline administration for preventing OHSS. Body weight, ovary weight, diameter, vascular permeability (VP), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) expression (immunohistochemistry), and serum estradiol (E2) levels were then compared.

Results: The ovarian VEGF concentration was significantly increased in the OHSS Groups (Groups 3–5) compared with the control groups (1 and 2). But vascular permeability, VEGF, and COX-2 expressions were reduced in animals treated with the resveratrol group compared with the cabergoline group (group 5) and the severe OHSS (group 3) group. Blood E2 levels were decreased in group treated with the resveratrol group compared with the cabergoline group (group 5) and severe the OHSS (group 3) group.

Conclusion(s): Our results in a rat model suggest that resveratrol has a beneficial effect on OHSS by reducing the increases in ovarian daimeter, VP, and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of resveratrol.     

Effects of pentoxifylline in the prevention of ovarian hyperstimulation syndrome in a rabbit model

Tumor necrosis factor α (TNF-α) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-α synthesis. The aim of this study was to evaluate whether the use of petoxifylline would prevent the occurrence of OHSS in a rabbit model. Thirteen rabbits were divided into two groups. The first group (n = 6) were given pentoxifylline 15 mg/kg intravenously and the second group (n = 7) were given physiological serum 15 mg/kg before ovulation induction. Ovarian hyperstimulation was induced in rabbits by 200 IU equine chorionic gonadotropin on day 1 and 100 IU human chorionic gonadotropin on day 3. Blood samples were analyzed for TNF-α on days 1, 3 and 5. All animals were autopsied on day 6 to evaluate the ovarian weight, ascites formation and histopathological changes. There was no difference between groups regarding weight gain, ascites formation and plasma TNF-α levels (p > 0.05). Ovarian weight and number of ovulations were significantly lower in the pentoxifylline group than the control group (p < 0.05). Pentoxifylline did not prevent ascites formation despite the observed decrease in ovarian weight and number of ovulations in OHSS in a rabbit model.     

吲哚美辛治疗卵巢过度刺激综合征的实验研究

目的　探讨吲哚美辛 (INDO)治疗卵巢过度刺激综合征 (OHSS)的疗效。方法　未成年Wis tar雌鼠分为对照组、PMSG +hCG组和拮抗剂组 3组。其中PMSG +hCG组和拮抗剂组皮下注射PMSG和hCG ,建立鼠OHSS模型。拮抗剂组围绕注射hCG前后 ,依皮下注射INDO 0 3mg或 3mg。 4 8h后从鼠尾静脉注入亚甲蓝取灌洗腹腔液 ,用分光光度计测定腹腔灌洗液中亚甲蓝含量 ,以了解卵巢和腹膜的通透性 ,称双侧卵巢重量后将卵巢匀浆 ,通过Bligh -Dyer法提取脂质、薄层色层法 (TLC)纯化PAF ,计算卵巢PAF ,并进一步测定血小板的聚集功能。结果　PMSG +hCG组卵巢的总重量、腹腔灌洗液中亚甲蓝的含量和卵巢PAF含量显著高于对照组 ,两组比较 ,差异均有显著性 (P <0 0 5 )。INDO组卵巢重量与PMSG +hCG组比较 ,差异无显著性 (P >0 0 5 )。但0 3mgINDO组卵巢重量与PMSG +hCG组比较降低了 1 2 798%。INDO腹腔灌洗液中亚甲蓝的含量与PMSG +hCG组比较 ,差异无显著性 (P >0 0 5 )。但 0 3mgINDO组腹腔灌洗液中亚甲蓝的含量与PMSG +hCG组比较降低了1 5 72 6 %。 0 3mgINDO组卵巢PAF含量显著低于PMSG +hCG组 ,两组比较差异有显著性 (P <0 0 5 )。结论　在注射hCG后围绕注射hCG前后给予 0 3mgINDO可以在一定程度上降低OHSS鼠卵巢的重量、     

Everolimus,an mTOR pathway inhibitor,is highly successful on ovarian hyperstimulation syndrome by reducing ovarian weight and progesterone levels: a preclinical experimental randomized controlled study

Abstract

The usefulness of various pathways inhibitors, Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), Infliximab, a monoclonal antibody which blocks the tumor necrosis factor-a (TNF-a), Erlotinib, a tyrosine protein kinase inhibitor of the epidermal growth factor receptor (EGFR), Metformin, an activator of AMP-activated protein kinase enzyme (AMPK) and vascular permeability reducers were explored in an ovarian hyperstimulation syndrome (OHSS) rat model. Sixty-three female Wistar rats were randomly divided in seven groups. The control group received saline, while the OHSS group received recombinant -- follicle-stimulating hormone (rec-FSH) for four consecutive days. The other five groups received rec-FSH for 4?d and Everolimus daily, Infliximab once, Erlotinib daily, Metformin daily and Vitamin C daily, respectively. All groups received human chorionic gonadotropin (hCG) at the fifth day. The efficacy of Everolimus administration for various intervals was also explored. Significantly reduced ovarian weight was observed in the Everolimus group (rec-FSH?+?hCG?+?mTOR inhibitor) compared to the OHSS group (p?<?0.001). The Everolimus group also showed the lowest progesterone (PRG) concentration (p?=?0.007). The Erlotinib group (rec-FSH?+?hCG?+?EGFR inhibitor) presented with the lowest graafian follicle number, while the Everolimus group was characterized by the lowest corpus luteum number. The vascular permeability and the estradiol levels did not differ between groups. Finally, the Everolimus intra-comparison showed no difference in all measured outcomes. Studying the different pathways linked to vascular endothelial growth factor (VEGF) pathway, we conclude that targeting mTOR pathways is beneficial for reducing ovarian weight and PRG levels in an OHSS animal model.     

The combination of Everolimus with Verapamil reduces ovarian weight and vascular permeability on ovarian hyperstimulation syndrome: a preclinical experimental randomized controlled study

The efficacy of pathways inhibition and the combined effect of Everolimus (mTOR inhibitor) and Verapamil (CYP3A inhibitor) in ovarian hyperstimulation syndrome (OHSS) need to be tested. Therefore, the impact of a leucotriene receptor antagonist, an anticoagulant, a GnRH antagonist as well as Everolimus plus Verapamil (at various doses and days of administration) on an OHSS rat model was tested. Sixty three female Wistar rats were randomly divided into seven groups. The control group received saline, while the OHSS group received rec-FSH for four consecutive days. The other five groups received rec-FSH for four days and Montelukast daily, Heparin daily, GnRH antagonist daily, Everolimus plus Verapamil in the last two days (half days group) and Everolimus plus Verapamil (half dose group) daily, respectively. All groups received also hCG at the fifth day. Significantly reduced ovarian weight was observed in the Everolimus plus Verapamil groups (half days and half-dose groups) and the Montelukast group compared to the OHSS group (p?=?0.001 and p?=?0.001, respectively). The vascular permeability was significantly reduced in the Everolimus plus Verapamil group (half dose group) and the GnRH antagonist group compared to the OHSS group (p?p?=?0.011, respectively). However, estradiol and progesterone levels did not differ significantly between the groups. Studying the inhibition of different pathways, we concluded that the co-administration of Everolimus and Verapamil (at half dose) is beneficial for reducing ovarian weight and vascular permeability in an OHSS animal model.     

The Role of Intravenous Immunoglobulin in the Prevention of Severe Ovarian Hyperstimulation Syndrome

Purpose: The role of intravenous immunoglobulin (IVIG) in the prevention of severe ovarian hyperstimulation syndrome (OHSS) was evaluated. Methods: Ovarian hyperstimulation was induced in eight rabbits using human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) after pretreatment with IVIG (IVIG group) or bovine serum albumin (BSA group). Main outcome measures included (1) signs of OHSS, such as the degree of ascites formation and the increase in body weight; and (2) the degree of ovarian stimulation as reflected by serum sex-steroid hormone levels. Results: A significantly lower ascites response and a tendency toward a decreased change in body weight were observed in the IVIG group compared to the BSA group. Serum estradiol, progesterone, total protein, and ovarian weights were not statistically different between the two groups. Conclusions: IVIG prevented severe OHSS in a rabbit model, whereas BSA did not. Further studies are justified in an attempt to clarify the role of the immune system and IVIG in the pathophysiology and prevention of severe OHSS.     

Ovarian hyperstimulation syndrome inhibition by targeting VEGF,COX-2 and Calcium pathways: a preclinical randomized study

Objective: The efficacy of vascular endothelial growth factor (VEGF), COX-2, calcium and aromatase inhibitors in an ovarian hyperstimulation syndrome (OHSS) rat model was tested.

Methods: One hundred and eight female Wistar rats were randomly divided in nine groups. The control group received saline, while the OHSS group received rec-FSH for 4 consecutive days. The other seven groups received rec-FSH (4d) and Bevacizumab twice, Parecoxib daily, Verapamil daily, Parecoxib daily and Bevacizumab twice, Verapamil daily and Bevacizumab twice, Parecoxib and Verapamil daily, Letrozole and Meloxicam daily, respectively. All groups received also hCG at the 5th day.

Results: All intervention groups were characterized by reduced vascular permeability compared to the OHSS group, which in the groups of Verapamil (Calcium inhibition) and Parecoxib?+?Verapamil (COX-2?+?Calcium inhibition) presented significant statistical difference. The Verapamil group showed the lowest corpus luteum formation, while the Parecoxib (COX-2 inhibition), the Parecoxib?+?Verapamil (COX-2?+?Calcium inhibition), the Bevacizumab?+?Parecoxib (VEGF?+?COX-2 inhibition) and the Bevacizumab?+?Verapamil (VEGF?+?Calcium inhibition) groups were also characterized by lower corpus luteum numbers compared to the OHSS group. Furthermore, lower graafian follicle formation was observed in the above groups, while the ovarian weight and the hormonal profile were not significantly affected.

Conclusions: Studying the different check points of the VEGF pathway, we conclude that targeting calcium pathways could be beneficial for the vascular permeability control in an OHSS animal model.     

The effects of resveratrol on ovarian hyperstimulation syndrome in a rat model

Objective

The aim of the present study was to investigate effects of resveratrol (RSV) over ovarian hyperstimulation syndrome (OHSS) in rat model.

Effect of GnRH-antagonist,mifepristone and letrozole on preventing ovarian hyperstimulation syndrome in rat model

Research questionCan luteolysis-targeted drugs, gonadotrophin-releasing hormone antagonist (GnRH-ant), mifepristone and letrozole, administered separately or in combination, prevent the progression of ovarian hyperstimulation syndrome (OHSS) in a rat model?DesignThirty-six female Wistar rats were randomly divided into six groups, including control group (OHSS group, ovarian hyperstimulation-induced OHSS); GnRH-ant group (OHSS with GnRH-ant treatment); mifepristone group (OHSS with mifepristone treatment); letrozole group (OHSS with letrozole treatment); combination group (OHSS with GnRH-ant, mifepristone and letrozole treatment in combination). The main outcomes were the alterations in OHSS-related indices, including ovarian weight, vascular permeability, serum oestradiol and progesterone levels, corpus luteum proportion and diameter, ovarian vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), caspase-3 and cleaved caspase-3 levels.ResultsNo significant difference was found in body weight gain among the six groups. Compared with the control group, the OHSS group showed significant increases in all OHSS-related indices. GnRH-ant treatment showed decreases in vascular permeability, serum oestradiol level, corpus luteum diameter, ovarian VEGF /IL-6 mRNA levels, and increases in ovarian caspase-3 and cleaved caspase-3 levels. Mifepristone treatment demonstrated reduction in serum progesterone level and corpus luteum diameter, and elevation in ovarian caspase-3 and cleaved caspase-3 levels. Letrozole treatment displayed a decline in serum oestradiol level and corpus luteum diameter, and up-regulation in ovarian caspase-3 and cleaved caspase-3 levels. The combination treatment by GnRH-ant, mifepristone and letrozole showed enhanced synergistic effect on reducing OHSS-related indices.ConclusionsGnRH-ant, mifepristone and letrozole are beneficial in preventing the progression of OHSS through different luteolytic mechanisms. Cocktail style treatment shows enhanced synergistic effect on preventing the progression of OHSS.     

Cabergoline administration prevents development of moderate to severe ovarian hyperstimulation syndrome and it contributes to reduction in ovarian volume

PurposeThe aim of this study was to determine the prophylactic effects of cabergoline on ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval.MethodsA total of 187 women underwent controlled ovarian stimulation using gonadotropin releasing hormone (GnRH) agonist long protocol or flexible GnRH antagonist protocol for in vitro fertilization. They responded excessively to ovulation induction, and fresh embryo transfers were canceled. Sixty‐one patients in the intervention group were administered oral cabergoline (0.5 mg) three times after oocyte retrieval (day 0, 2, and 4 following the oocyte retrieval). Ultrasonography and blood examination were performed on the seventh day following oocyte retrieval. The main outcomes measured were the incidence of OHSS, estimated ovarian volumes, ascites, hematocrits, and white blood cell counts.ResultsThe incidence of moderate to severe OHSS was lower after cabergoline administration (9.8 vs. 23.0 %, p = 0.03). The ovarian volumes reduced after intervention (96.2 vs. 145.5 cm³, p = 0.008). The reduction was evident in the patients with agonist long protocol (92.1 vs. 167.5 cm³, p = 0.0005). No significant differences were observed for other factors.ConclusionsCabergoline has a favorable effect on the prevention of moderate to severe OHSS affiliated with ovarian volume reduction.     

Effects of pentoxifylline in the prevention of ovarian hyperstimulation syndrome in a rabbit model.

Tumor necrosis factor alpha (TNF-alpha) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-alpha synthesis. The aim of this study was to evaluate whether the use of pentoxifylline would prevent the occurrence of OHSS in a rabbit model. Thirteen rabbits were divided into two groups. The first group (n = 6) were given pentoxifylline 15 mg/kg intravenously and the second group (n = 7) were given physiological serum 15 mg/kg before ovulation induction. Ovarian hyperstimulation was induced in rabbits by 200 IU equine chorionic gonadotropin on day 1 and 100 IU human chorionic gonadotropin on day 3. Blood samples were analyzed for TNF-alpha on days 1, 3 and 5. All animals were autopsied on day 6 to evaluate the ovarian weight, ascites formation and histopathological changes. There was no difference between groups regarding weight gain, ascites formation and plasma TNF-alpha levels (p < 0.05). Ovarian weight and number of ovulations were significantly lower in the pentoxifylline group than the control group (p < 0.05). Pentoxifylline did not prevent ascites formation despite the observed decrease in ovarian weight and number of ovulations in OHSS in a rabbit model.     

The effect of cabergoline on folicular microenviroment profile in patients with high risk of OHSS

Abstract

The aim of this study to evaluate the effect of cabergoline on follicular microenvironment by measuring follicular fluid (FF) insulin like growth hormone –I (IGF-I), antimullerian hormone (AMH), inhibin B and hepatocyte growth factor (HGF) levels in women with PCOS and high risk of ovarian hyperstimulation syndrome (OHSS). In this prospective cohort study, 41 women with PCOS undergoing controlled ovarian hyperstimulation for assisted reproduction and having the high risk factors for OHSS are included. The women in the study group (n?=?15) received cabergoline for OHSS prevention while the women in the control did not received any medications for OHSS prevention. FF samples were collected during oocyte pick-up procedure for all women were determined using commercially available ELISA kits. Concentrations of FF IGF-I, AMH, inhibin B and HGF were assessed. In the study group FF AMH (2.96?±?1.27 versus 1.91?±?0.64?ng/mL), Inhibin B (1339.47?±?198.56 versus 1200.09?±?133.64?pg/mL), HGF (5623.21?±?2411.09 versus 3787.42?±?2269.89?pg/mL) and IGF-I (298.60?±?37.80 versus 219.90?±?71.40?pg/mL) concentrations were significantly decreased compared with control group. Cabergolin prevents OHSS in high risk patients by disrupting FF hormone microenvironment.     

Vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) immunoreactivities in rat ovaries and uterine tubes after tubal ligation: a controlled immunohistochemical study

Objective To evaluate the effects of tubal ligation on ovarian and tubal tissues by means of immunohistochemical evaluation of two hypoxia related mediators: vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS).

Design Fourteen Sprague-Dawley female rats were divided into two groups: a tubal ligation (Pomeroy technique) was carried out on rats in group 1 (n = 7) whereas those in group 2 served as controls (n = 7). Salpingo-oophorectomy was performed in group 1 during the second oestrous period following tubal ligation. Rats in group 2 were submitted to a salpingo-oophorectomy, as well. VEGF and iNOS immunoreactivities in ovarian and tubal tissues were evaluated by means of immunohistochemistry. Immunohistochemical scores and number of antral follicles were compared.

Results In the ovary, VEGF immunoreactivity was significantly more intense in the granulosa (p = 0.002) and the theca cells (p = 0.001) of rats in group 1 but, in ovarian medulla (p = 0.259) and germinal epithelium (p = 0.209), it was not significantly different from that of rats in group 2. The iNOS immunoreactivity in ovarian granulosa cells (p = 0.073) and germinal epithelial cells (p = 0.805) did not differ between the two groups. The cytoplasmic VEGF (p = 0.001) and iNOS (p = 0.017) immunoreactivities in the uterine tube, were significantly more intense in group 1. However, VEGF immunoreactivity in the lamina propria of the uterine tube (p = 0.209) was of similar intensity in both groups.

Conclusion Tubal ligation may lead to supraphysiological hypoxia as evidenced by increased VEGF and iNOS immunoreactivities in ovarian and tubal tissues.     

Preventing ovarian hyperstimulation syndrome: cabergoline versus coasting

Purpose

The use of cabergoline and coasting are both effective in reducing the risk of ovarian hyperstimulation syndrome (OHSS). Our aim was to compare the effectiveness of cabergoline with coasting to prevent moderate–severe OHSS.

Methods

Fifty-seven consecutive infertile patients (81 cycles) at risk of developing OHSS were enrolled through our computerized IVF database system. Inclusion criteria were: (i) E2 level on the day of human chorionic gonadotrophin (hCG) greater than 3,500 pg/ml; (ii) patients who underwent luteal long GnRH agonist cycle; (iii) patients who used cabergoline for OHSS prevention; (iv) patients who underwent coasting for OHSS prevention. The cabergoline group constituted 17 patients (26 cycles) who started using 0.5 mg oral cabergoline daily for 8 days on the day of hCG, whereas the coasting group constituted 40 patients (55 cycles) who underwent coasting.

Results

Both groups were comparable regarding the women’s mean age, body mass index and duration of infertility. Implantation rate, clinical pregnancy per embryo transfer and miscarriage rates were not different between the two groups. There was no OHSS in the cabergoline group (0 %), whereas there were two OHSS (3.6 %) in the coasting group; however, this difference was not significant.

Conclusions

In conclusion, 0.5 mg daily use of cabergoline for 8 days beginning from hCG administration is a very effective way to reduce moderate–severe OHSS without sacrificing pregnancy rates in patients at risk of developing OHSS.     

Increased risk of ovarian hyperstimulation syndrome following controlled ovarian hyperstimulation in patients with vascular endothelial growth factor +405 cc genotype

Ovarian hyperstimulation syndrome (OHSS) is a serious complication following controlled ovarian hyperstimulation (COH) for in vitro fertilization. OHSS has a range of clinical features from mild abdominal distention to severe thromboembolic events. Several clinical manifestations of OHSS such as ascites and hemoconcentration can be attributed to increased vascular permeability. Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 have been identified as an important signaling system in mediating this increase. There is considerable genetic variation in the VEGF/R2 signaling system. We present the first study to examine if single nucleotide polymorphisms (SNPs) in the genes encoding the VEGF/R2 signaling system are associated with OHSS following COH. Blood samples from 53 OHSS patients and 100 controls were analyzed for six SNPs of interest. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by a multivariate logistic regression model. We found an association between the VEGF +405cc genotype and OHSS (OR 3.4, 95% CI 1.01–11.7). This finding requires confirmation from other patient populations.     

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.     

Cabergoline reduces the early onset of ovarian hyperstimulation syndrome: a prospective randomized study

Prophylactic use of cabergoline has been associated with a decrease in the severity of ovarian hyperstimulation syndrome (OHSS). A prospective randomized study was designed to evaluate the potential of cabergoline to decrease the incidence of OHSS in high-risk patients undergoing assisted reproductive technology treatment; 166 patients with oestradiol concentrations over 4000 pg/ml on the day of human chorionic gonadotrophin (HCG) administration were evaluated. They all received 20 g routine preventive intravenous human albumin on the day of oocyte retrieval. They were then randomized into two groups: group A (n = 83) received 0.5 mg oral cabergoline per day for 3 weeks beginning on the day after oocyte retrieval, and group B (n = 83) received no medication. ‘Early’ OHSS was defined as being when the onset of the syndrome was initiated during the first 9 days after HCG administration, and ‘late’ OHSS was defined as being when the onset of the syndrome was initiated from 10 days after HCG administration. In group A, no patients progressed to ‘early’ OHSS and nine patients (10.8%) developed ‘late’ OHSS; in group B, 12 patients (15.0%) progressed to ‘early’ OHSS and three (3.8%) to ‘late’ OHSS. Although the risk of ‘early’ OHSS decreased significantly (P < 0.001), the risk of ‘late’ onset OHSS did not. The two groups presented no changes in pregnancy, implantation or miscarriages rates.     

Treatment of ovarian hyperstimulation syndrome using gonadotropin releasing hormone antagonist: a pilot study

Objective: This novel study describes an effective outpatient treatment for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms. Study design: A total of twenty-seven infertile women undergoing assisted reproductive technique with early-onset OHSS were enrolled in this non-randomized clinical trial in an academic infertility center. In all patients, after complete desensitization with long-term protocol ovarian stimulation with gonadotropins was commenced. Final oocyte maturation was triggered with human chorionic gonadotrophin. Oocytes were collected 36–38 h later using transvaginal-guided follicle aspiration under general anaesthesia. All embryos were frozen and study group patients received two consecutive doses of GnRH antagonist (Cetrotide) and the control group received daily dose of cabergoline for a week. Results: The research revealed that moderate and severe OHSS, hospitalization or acute care for OHSS and ascites tap were significantly lower in the antagonist (Cetrotide) group. The Patients’ satisfaction with Cetrotide was noticeable. No side effect was reported in either group. Conclusion: GnRH antagonists seem to be an effective outpatient treatment with rapid onset activity and minimal side effects for the management of early OHSS.     

Prevention of ovarian hyperstimulation syndrome in GnRH agonist IVF cycles in moderate risk patients: randomized study comparing hydroxyethyl starch versus cabergoline and hydroxyethyl starch

Objective

To assess whether, in GnRH agonist IVF cycles where there is a risk of ovarian hyperstimulation syndrome (OHSS), the addition of cabergoline to the hydroxyethyl starch (HES) infusion could decrease OHSS incidence and severity.

Materials and methods

Prospective randomized study. The population under study consisted of women undergoing IVF cycles with GnRH agonist protocols, at risk of OHSS (more than 20 follicles observed larger than 12 mm in diameter and/or estradiol levels of 3000–5000 pg/mL). Women received a slow infusion of 500 mL of 6% HES during follicular aspiration alone or combined with 0.5 mg cabergoline administration for 8 days, starting on the day of hCG administration.

Results

The rates of OHSS (both early and late) were very similar in the HES alone group (3.19% (3/94)) and in the HES plus cabergoline group (5.68% (5/88)), as were the rates of severe cases of OHSS (1.06% and 2.27%). Pregnancy rates (PR) were also similar in the two groups (ongoing PR per transfer, 47.56% and 47.50%).

Comments

The co-administration of cabergoline in patients receiving HES due to OHSS risk did not reduce the rate or severity of OHSS in GnRH agonist IVF cycles.