Incidence Of Moderate Ovarian Hyperstimulation Syndrome Research Articles

Comparison of cabergoline versus calcium infusion in ovarian hyperstimulation syndrome prevention: A randomized clinical trial

Abstract Aim To compare effectiveness of calcium infusion (CI) versus oral cabergoline (OC) in lowering the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high risk women undergoing in vitro-fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Patients and methods This trial was conducted at Benha University Hospital and Hawaa specialized infertility center, including 230 women undergoing ICSI, 115 women received intravenous Calcium gluconate starting at ovum pick up (OPU) day and 115 women received OC 0.5 mg starting at the day of OPU outcomes were the overall incidence of OHSS as well as its type and severity, in addition to others pregnancy outcomes data. Results The occurrence of overall OHSS was significantly lower in calcium infusion group (CIG) than in oral cabergoline group (OCG) [16/115 (13.9%) in CIG versus 32/115 (27.8%)] in OCG with difference in proportion percentage point (Δ pp) = −13.9% , at 95%CI of −3.38% to −24.10% (P = 0.009) and absolute risk reduction (ARR) in overall OHSS incidence = 13.9% at 95%CI of 3.38–24.10 and relative risk (RR) = 0.5 at 95% CI of 0.29–0.85 (p = 0.012) and relative risk reduction (RRR) = 50% and number need to treatment (NNT) (Benefit) = 7.18 at 95% CI of 4.12 (Benefit) to 28.05 (Benefit)]. Also the incidence of Moderate OHSS was significantly lower in CIG than OCG [2/115 (1.7 %) vs 10/115 (8.6%), p = 0.01] as well as RR of severe OHSS with CI to OC = 0.25 at 95%CI of 0.02–2.20 and RRR of severe OHSS with CI to OC was 75% as it occurred in 4 cases (3.4%) in OCG versus one case (0.8%) in CIG, where this reduction is of great clinical significant despite it does not reach statistical significance (P = 0.17), at NNT (Benefit) = 38.33 at 95% CI of 87.292 (Harm) to ∞ to 15.716 (Benefit) .Other pregnancy outcomes didn't show any statistically significant differences. Conclusion Calcium infusion is more effective than oral cabergoline intake from OPU day in the reduction of OHSS overall incidence as well as its severity with comparable pregnancy outcomes. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03473613 .

Quinagolide compared with cabergoline in the prevention of ovarian hyperstimulation syndrome

Objective The aim of the present study was to compare quinagolide with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in at-risk patients undergoing in-vitro fertilization (IVF) treatments and to compare the pregnancy rate, the tolerability and the complication rate of the two drugs. Study design A randomized controlled trial. Patients and methods A total of 112 patients undergoing IVF/intracytoplasmic sperm injection long luteal GnRH agonist procedure considered at risk of OHSS were randomized into two groups. Group I patients received quinagolide 75 µg and group II patients received cabergoline 0.5 mg for 8 days starting from the day of human chorionic gonadotrophin injection. Results The total number of patients who developed OHSS in our study was similar in the two groups, with nine (16.1%) patients in the quinagolide group compared with 11 (19.6%) in the cabergoline group (P=0.81). However, the majority of these patients developed only mild OHSS comprising 55.6% in the quinagolide group and 63.6% in the cabergoline group. There was no statistical difference between the two groups regarding the incidence of early OHSS (P=0.77) or late OHSS (P=1.0). Severe/critical grades of OHSS occurred in only 3.6% of the cases in the quinagolide group and 1.8% of the cases in the cabergoline group, whereas the incidence of moderate OHSS was 3.6 and 5.4% in the quinagolide and the cabergoline groups, respectively. Quinagolide was responsible for significantly more nausea (P=0.03) and vomiting (P=0.009) than cabergoline, but there was no statistically significant difference between the two groups regarding other side effects. Conclusion Quinagolide seems to be just as effective as cabergoline in the prevention of OHSS in at-risk patients undergoing IVF treatments.

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case-control study.

To investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle. Cohort case-control study. University Hospital. One hundred twenty-two normally cycling women expected to be normal responders to COS. In 61 patients, CFα (100-150 μg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1-2 embryos were transferred in utero under US guidance on day 2. Number of retrieved cumulus-oocyte complexes (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10 weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate. No cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60% of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing PR/transfer was 36.8% in CF-alfa group and 37.5% in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls. CFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.

Can cabergoline prevent ovarian hyperstimulation syndrome in polycystic ovarian patients undergoing gonadotropin stimulation?

Can cabergoline prevent ovarian hyperstimulation syndrome in polycystic ovarian patients undergoing gonadotropin stimulation?

Severe ovarian hyperstimulation syndrome after letrozole-gonadotropin stimulation: a case report

Ovarian hyperstimulation syndrome (OHSS) results from an exaggerated response to ovulation induction, characterized by a fluid shift from the intravascular space to third space compartments. The incidence of moderate OHSS is approximately 3–6% and severe OHSS occurs in 0.1–3% of treatment cycles [1, 2]. A number of causal mechanisms have been investigated, involving estradiol (E2), human chorionic gonadotropin (hCG), and vascular endothelial growth factor (VEGF). A strong association between E2 concentrations and risk for developing OHSS has been observed consistently [3]. A growing awareness and interest in treatments aimed at fertility preservation (FP) has led many women to pursue urgent oocyte or embryo cryopreservation. Those with estrogen-sensitive cancers often receive adjunctive treatment with letrozole, in efforts to limit exposure to elevated estrogen concentrations that typically result from exogenous gonadotropin stimulation; letrozole inhibits estrogen production by binding competitively to the cytochrome P450 component of the aromatase enzyme. Combination stimulation regimens yield results comparable to those achieved with standard gonadotropin stimulation protocols, but are associated with significantly lower E2 levels [4]. The risk of OHSS for women receiving adjunctive treatment with letrozole generally is considered low, because E2 levels are markedly lower than in cycles stimulated with gonadotropins alone. In fact, no cases of severe OHSS have been reported in a patient receiving combined treatment with letrozole and gonadotropins. Here, we report a case of severe OHSS arising in a woman with breast cancer after stimulation with exogenous gonadotropins, despite treatment with letrozole and having only moderately elevated E2 concentrations.

Physiology and Pathology of Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle-stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). With the administration of hCG, the expression vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. These findings suggest that the syndrome can be prevented by inducing ovulation with LH or gonadotropin-releasing hormone analogs, which prevent VEGF overexpression. Also, coadministration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo ( P = 0.04). Another dopamine agonist, quinagolide, was also effective in nonpregnant patients, but those pregnant did not benefit from dopamine agonist administration. In conclusion, the pathophysiological mechanisms involved in OHSS show that targeting VEGF/VEGFR2 is an effective preventive approach to treat the syndrome. Pharmaco-prevention through dopamine agonists is effective only in nonpregnant high-risk OHSS women. Embryo cryopreservation plus dopamine agonist administration might be the most appropriate way to prevent OHSS in high-risk patients.

Effect of bromocriptine on the severity of ovarian hyperstimulation syndrome and outcome in high responders undergoing assisted reproduction

CONTEXT:Ever since ovarian hyperstimulation syndrome (OHSS) was recognized as a clinical entity, various treatment modalities have been tried to prevent its occurrence and reduce its severity. Many recent studies have evaluated the role of dopamine agonists in reducing the incidence of OHSS.OBJECTIVES:To assess the effectiveness of dopamine agonist bromocriptine in reducing the incidence and severity of OHSS in patients undergoing assisted reproduction and its effect on pregnancy rates.SETTINGS AND DESIGN:It was a prospective study in which patients at high risk of developing OHSS undergoing assisted reproduction were recruited.MATERIALS AND METHODS:The study was carried out from August 2008 to August 2009 in patients undergoing assisted reproduction and included 40 patients at high risk for developing OHSS. Tablet bromocriptine 2.5 mg was prescribed for a period of 16 days starting from day of ovum pick up. Patients were analyzed on the basis of incidence of moderate and severe OHSS, timing of onset of OHSS (early/late), hospitalization rate, pregnancy rates and tolerability of medication and were compared with a historical group of high responders matched for age and BMI.STATISTICAL ANALYSIS:Student’s t test and proportion test were used.RESULTS:There was a significant reduction in the incidence of moderate OHSS (P=0.037), early OHSS (P=0.012) as well as the number of admissions (P=0.030). Average duration of hospitalization was also significantly reduced (P=0.036). In the study group, the incidence of clinically significant OHSS was 17.5% as compared to 40.9% in the control group. No difference was detected between the groups in clinical pregnancy rates (P=0.0054).CONCLUSION:Bromocriptine reduced the incidence and severity of clinically significant OHSS in high risk patients without affecting the pregnancy rates.

Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) typically occurs when ovaries are primed with FSH/LH and subsequently exposed to hCG. The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). A search of the literature was carried out using PubMed and the authors' files. In rodents and humans, the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases during ovarian stimulation. With the administration of hCG, the expression of each rises to a maximum. Expression of VEGF/VEGFR-2 mRNAs correlates with enhanced VP, with both peaking 48 h following an injection of hCG. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. Increased VP may be mediated through adhesion molecules such as VE-cadherin, which is involved in the loosening of endothelial intercellular junctions. These findings regarding the pathophysiology of OHSS suggest that the syndrome can be prevented by inducing ovulation with LH or GnRH analogues, which prevent VEGF overexpression. Also, co-administration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo (P = 0.04). The pathophysiological mechanisms involved in OHSS suggest potential preventive approaches, but larger trials are necessary for evaluating the efficacy and safety of the pharmaco-prevention of OHSS.

Dopamine Agonist Cabergoline Reduces Hemoconcentration and Ascites in Hyperstimulated Women Undergoing Assisted Reproduction

Ovarian hyperstimulation syndrome (OHSS) results from increased vascular permeability (VP) caused by ovarian hypersecretion of vascular endothelial growth factor (VEGF), which activates its receptor-2. In animals, the dopamine receptor 2 agonist cabergoline (Cb2) inactivates VEGF receptor-2 and prevents increased VP. Our objective was to test whether Cb2 reduces VP and prevents OHSS in humans. We conducted a prospective, randomized, double-blind study on oocyte donors at risk of developing OHSS (>20 follicles, >12 mm developed, and >20 oocytes retrieved). Cb2 0.5 mg/d (n = 37) or a placebo (n = 32) was administered from the day of human chorionic gonadotropin (d 0) until d 8. Ascites (a pocket of peritoneal fluid > 9 cm(2) in lithotomy position), hemoconcentration, and serum prolactin were recorded. Pharmacokinetic studies with magnetic resonance employing the transfer constant rate (K(trans), measure of permeability) and the extravascular extracellular space (upsilon(e), marker of cellular leakage) were performed to measure VP objectively. Hematocrit (P < 0.01), hemoglobin (P = 0.003), and ascites (P = 0.005) were significantly lower on d 4 and 6 after treatment with Cb2 as compared with placebo. The incidence of moderate OHSS was 20.0 and 43.8%, respectively (P = 0.04). Magnetic resonance studies showed an increase in VP and extravascular leakage of fluid 5 d after human chorionic gonadotropin injection that was significantly prevented with Cb2 (K(trans) P = 0.04 and upsilon(e) P = 0.001, respectively). Given that Cb2 is a well-established and safe medication, this study provides proof of concept for the use of dopamine agonists in the prevention of OHSS in women undergoing assisted reproduction.

Use of Intramuscular Progesterone versus Intravenous Albumin for the Prevention of Ovarian Hyperstimulation Syndrome

This study was designed to compare the effectiveness of intramuscular progesterone with that of intravenous albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). Ninety-six patients at high risk to develop OHSS (estradiol concentration >9,000 pmol/l on the day of hCG administration and over 20 follicles of a diameter larger than 14 mm observed by transvaginal ultrasonography) and undergoing in vitro fertilization-embryo transfer were enrolled. They were randomly treated with intramuscular progesterone (200 mg/day) or 100 ml of 20% intravenous albumin in order to estimate the difference in the incidence of OHSS. A significant difference in the incidence of moderate OHSS and no cases of severe OHSS were observed between the groups. Our data show the effectiveness in preventing OHSS with high doses of progesterone.