ergoline and Ovarian-Hyperstimulation-Syndrome

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment.. We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature.. We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events.. Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence.. The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 stu. Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

Topics: Abortion, Spontaneous; Administration, Oral; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Fertilization in Vitro; Humans; Live Birth; Ovarian Hyperstimulation Syndrome; Placebos; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence of moderate to severe OHSS ranges from 0.6% to 5% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intravascular compartment to the third space, resulting in profound intravascular depletion and haemoconcentration.. To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles.. For the update of this review, we searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE (PubMed), CINHAL, PsycINFO, Embase, Google, and clinicaltrials.gov to 6 July 2016.. We included only randomized controlled trials (RCTs) in which coasting was used to prevent OHSS.. Two review authors independently selected trials and extracted data. They resolved disagreements by discussion. They contacted study authors to request additional information or missing data. The intervention comparisons were coasting versus no coasting, coasting versus early unilateral follicular aspiration (EUFA), coasting versus gonadotrophin releasing hormone antagonist (antagonist), coasting versus follicle stimulating hormone administration at the time of hCG trigger (FSH co-trigger), and coasting versus cabergoline. We performed statistical analysis in accordance with Cochrane guidelines. Our primary outcomes were moderate or severe OHSS and live birth.. We included eight RCTs (702 women at high risk of developing OHSS). The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data. Coasting versus no coastingRates of OHSS were lower in the coasting group (OR 0.11, 95% CI 0.05 to 0.24; I² = 0%, two RCTs; 207 women; low-quality evidence), suggesting that if 45% of women developed moderate or severe OHSS without coasting, between 4% and 17% of women would develop it with coasting. There were too few data to determine whether there was a difference between the groups in rates of live birth (OR 0.48, 95% CI 0.14 to 1.62; one RCT; 68 women; very low-quality evidence), clinical pregnancy (OR 0.82, 95% CI 0.46 to 1.44; I² = 0%; two RCTs; 207 women; low-quality evidence), multiple pregnancy (OR 0.31, 95% CI 0.12 to 0.81; one RCT; 139 women; low-quality evidence), or miscarriage (OR 0.85, 95% CI 0.25 to 2.86; I² = 0%; two RCTs; 207 women; very low-quality evidence). Coasting versus EUFAThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 0.98, 95% CI 0.34 to 2.85; I² = 0%; 2 RCTs; 83 women; very low-quality evidence), or clinical pregnancy (OR 0.67, 95% CI 0.25 to 1.79; I² = 0%; 2 RCTs; 83 women; very low-quality evidence); no studies reported live birth, multiple pregnancy, or miscarriage. Coasting versus antagonistOne RCT (190 women) reported this comparison, and no events of OHSS occurred in either arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.74, 95% CI 0.42 to 1.31; one RCT; 190 women; low-quality evidence), or multiple pregnancy rates (OR 1.00, 95% CI 0.43 to 2.32; one RCT; 98 women; very low-quality evidence); the study did not report live birth or miscarriage. Coasting versus FSH co-triggerRates of OHSS were higher in the coasting group (OR 43.74, 95% CI 2.54 to 754.58; one RCT; 102 women; very low-quality evidence), with 15 events in the coasting arm and none in the FSH co-trigger arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.92, 95% CI 0.43 to 2.10; one RCT; 102 women; low-quality evidence). This study did not report data suitable for analysis on live birth, mu. There was low-quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low-quality evidence from a single small study to suggest that using FSH co-trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes.

Topics: Abortion, Spontaneous; Cabergoline; Chorionic Gonadotropin; Ergolines; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Live Birth; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Withholding Treatment

The purpose of this review is to analyze current medical strategies in the prevention\ of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation for in vitro fertilization.\ Owing to contemporary preventive measures of OHSS, the incidence of moderate and severe\ forms of the syndrome varies between 0.18% and 1.40%. Although none of medical strategies is\ completely effective, there is high-quality evidence that replacing human chorionic gonadotropin\ (hCG) by gonadotropin-releasing hormone (GnRH) agonists after GnRH antagonists and moderate-\ quality evidence that GnRH antagonist protocols, dopamine agonists and mild protocols reduce\ the occurrence of OHSS. Among various GnRH agonists, buserelin 0.5 mg, triptorelin 0.2 mg and\ leuprolide acetate (0.5-4 mg) have been mostly utilized. Although GnRH trigger is currently regarded\ as the best tool for OHSS prevention, intensive luteal support with exogenous administration\ of estradiol and progesterone or low-dose hCG on the day of oocyte retrieval or on the day of GnRH\ agonist trigger are required to achieve optimal conception rates due to early luteolysis. Among currently\ available dopamine agonists, cabergoline, quinagolide and bromocriptine are the most common\ drugs that should be used for prevention of both early and late OHSS. Mild stimulation protocols\ offer attractive option in OHSS prevention with satisfactory pregnancy rates.

Topics: Aminoquinolines; Bromocriptine; Buserelin; Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Estradiol; Estrogens; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Triptorelin Pamoate

Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33% in its mild form and 3% to 8% in its moderate or severe form. These numbers might even be higher for high-risk women such as those with polycystic ovaries or a high oocyte yield from ovum pickup.. The objective of this overview is to identify and summarise all evidence from Cochrane systematic reviews on interventions for prevention or treatment of moderate, severe and overall OHSS in couples with subfertility who are undergoing ART cycles.. Published Cochrane systematic reviews reporting on moderate, severe or overall OHSS as an outcome in ART cycles were eligible for inclusion in this overview. We also identified Cochrane submitted protocols and title registrations for future inclusion in the overview. The evidence is current to 12 December 2016. We identified reviews, protocols and titles by searching the Cochrane Gynaecology and Fertility Group Database of Systematic Reviews and Archie (the Cochrane information management system) in July 2016 on the effectiveness of interventions for outcomes of moderate, severe and overall OHSS. We undertook in duplicate selection of systematic reviews, data extraction and quality assessment. We used the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the quality of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables.. We included a total of 27 reviews in this overview. The reviews were generally of high quality according to AMSTAR ratings, and included studies provided evidence that ranged from very low to high in quality. Ten reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Metformin treatment before and during an ART cycle for women with PCOS (moderate-quality evidence).• Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence).• GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence).• Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence).• Intravenous fluids (plasma expanders) around the time of hCG administration or oocyte pickup in ART cycles (very low-quality evidence).• Progesterone for luteal phase support in ART cycles (low-quality evidence).• Coasting (withholding gonadotrophins) - a promising intervention that needs to be researched further for reduction of OHSS.On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of embryo cryopreservation.. Currently, 27 reviews in the Cochrane Library were conducted to report on or to try to report on OHSS in ART cycles. We identified four review protocols but no new registered titles that can potentially be included in this overview in the future. This overview provides the most up-to-date evidence on prevention of OHSS in ART cycles from all currently published Cochrane reviews on ART. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise other outcomes such as pregnancy or live birth rate. Review results, however, are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.

Topics: Cabergoline; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Metformin; Ovarian Hyperstimulation Syndrome; Pregnancy; Progesterone; Reproductive Techniques, Assisted; Review Literature as Topic

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. The dopamine agonist cabergoline was introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. As cabergoline seemed to be effective in preventing OHSS, other types of dopamine agonists, such as quinagolide and bromocriptine, have since been studied in ART to prevent OHSS.. To assess the effectiveness and safety of dopamine agonists in preventing OHSS in high-risk women undergoing ART treatment.. We searched several databases from inception to August 2016 (Cochrane Gynaecology and Fertility Specialised Register of trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Clinicaltrials.gov and the World Health Organization International Trials Registry Platform (ICTRP)) for randomised controlled trials (RCTs) assessing the effect of dopamine agonist in preventing OHSS. We handsearched the reference lists of relevant studies.. We considered RCTs which compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in high-risk women for inclusion. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment.. Two authors independently screened titles, abstracts and full texts of publications, selected studies, extracted data and assessed risk of bias. We resolved any disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. In addition, we graded the overall quality of the evidence using GRADE criteria.. The search identified 14 new RCTs since the last published version of this review, resulting in 16 included RCTs involving 2091 high-risk women for this updated review. They evaluated three types of dopamine agonists: cabergoline, quinagolide and bromocriptine.When compared with placebo or no intervention, dopamine agonists seemed effective in the prevention of moderate or severe OHSS (OR 0.27, 95% CI 0.19 to 0.39; 1022 participants; 8 studies; I. Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence). If a fresh embryo transfer is performed, the use of dopamine agonists does not affect the pregnancy outcome (live birth rate, clinical pregnancy rate and miscarriage rate) (very low to moderate quality evidence). However, dopamine agonists might increase the risk of adverse events, such as gastrointestinal symptoms. Further research should focus on dose-finding, comparisons with other effective treatments and consideration of combination treatments. Therefore, large, well-designed and well-executed RCTs that involve more clinical endpoints (e.g., live birth rate) are necessary to further evaluate the role of dopamine agonists in OHSS prevention.

Topics: Abortion, Spontaneous; Administration, Oral; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted

To evaluate the efficacy and safety of using cabergoline for reducing the risk of ovarian hyperstimulation syndrome (OHSS).. Systematic review and meta-analysis of randomized clinical trials (RCTs).. Women submitted to controlled ovarian stimulation (COS) for assisted reproduction.. Cabergoline.. Fertility centers.. Moderate-severe OHSS, live birth, clinical pregnancy, number of retrieved oocytes, miscarriage, congenital abnormalities. Comparisons were performed with the use of risk ratios (RRs) or mean differences (MDs) and their respective 95% confidence intervals (CIs).. Eight RCTs were considered to be eligible; data from seven studies could be extracted and included in the meta-analysis. Cabergoline reduces the risk of moderate-severe OHSS (RR 0.38, 95% CI 0.29-0.51, 7 studies, 858 women) and probably has no clinically relevant negative impact on clinical pregnancy (RR 1.02, 95% CI 0.78-1.34, 4 studies, 561 women) or on the number of retrieved oocytes (MD 1.15, 95% CI -0.76 to 3.07, 5 studies, 628 women). However, our estimates were imprecise for distinguishing between substantial harm, no effect, and substantial benefit considering live birth (RR 1.03, 95% CI 0.71-1.48, 1 study, 200 women), and miscarriage (RR 0.69, 95% CI 0.27 to 1.76, 3 studies, 194 pregnant women). No studies reported congenital abnormalities.. Cabergoline reduces the occurrence of moderate-severe OHSS. Cabergoline is unlikely to have a clinically relevant negative impact on clinical pregnancy or on the number of retrieved oocytes. However, we are still uncertain of its impact on live birth, miscarriage, and congenital abnormalities.

Topics: Cabergoline; Ergolines; Female; Humans; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted

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.

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction

One of the most serious complications of assisted reproduction techniques is ovarian hyperstimulation syndrome (OHSS). OHSS not only increases morbidity and mortality in IFV cycles, but also causes significant other problems, as cancelled in vitro fertilization (IVF) cycles, prolonged hospitalization, causing emotional and sociofinancial consequences. Several treatments for OHSS have been proposed and among these Cabergoline (Cb2). Despite the above-mentioned beneficial effect, Cb2 has not been widely used in everyday's clinical practice. With our study, we try to review all studies with strong evidence examining Cb2 use for OHSS prevention.

Topics: Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Evidence-Based Medicine; Female; Fertility Agents, Female; Gene Expression Regulation; Humans; Ovarian Hyperstimulation Syndrome; Ovary; Phosphorylation; Protein Processing, Post-Translational; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Ovarian hyperstimulation syndrome (OHSS) is a complication resulting from administration of human chorionic gonadotrophin (hCG) in assisted reproduction technology (ART) treatment. Most case are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Recently, the dopamine agonist cabergoline has been introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS who are undergoing ART treatment.. To assess the effectiveness and safety of cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing ART treatment.. Major medical databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and PsycINFO) were systematically searched for randomised controlled trials (RCTs) assessing the effect of cabergoline in preventing OHSS. Databases were searched up to September 2011. Registers of clinical trials, abstracts of scientific meetings and reference lists of included studies were searched. No language restrictions were applied.. RCTs which compared cabergoline with placebo, no treatment or another intervention for preventing OHSS in high-risk women were considered for inclusion. Primary outcome measures included incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment.. Two authors independently screened titles, abstracts and the full text of publications; extracted data; and assessed risk of bias. Any disagreements were resolved by consensus. Pooled results were reported as odds ratio (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method.. Only two trials involving 230 women met the inclusion criteria. Both studies had a moderate risk of bias. Oral cabergoline, 0.5 mg daily, was given as an intervention and compared with a matched placebo. A statistically significant reduction in OHSS was observed in the cabergoline treated group (OR 0.40, 95% CI 0.20 to 0.77; 2 RCTs, 230 women) with a number needed to treat (NTT) of 7. There was a statistically significant difference in the incidence of moderate OHSS, favouring cabergoline (OR 0.38, 95% CI 0.19 to 0.78; 2 RCTs, 230 women) but not in severe OHSS (OR 0.77, 95% CI 0.24 to 2.45; 2 RCTs, 230 women). There was no significant difference in the clinical pregnancy rate (OR 0.94, 95% CI 0.56 to 1.59; 2 RCTs, 230 women), miscarriage rate (OR 0.31, 95% CI 0.03 to 3.07; 1 RCT, 163 women) or any other adverse effects of the treatment (OR 2.07, 95% CI 0.56 to 7.70; 1 RCT, 67 women). However, no data on multiple pregnancy rate or live birth rate were reported in either trial.. Cabergoline appears to reduce the risk of OHSS in high-risk women, especially for moderate OHSS. The use of cabergoline does not affect the pregnancy outcome (clinical pregnancy rate, miscarriage rate), nor is there an increased risk of adverse events. Further research should consider the risk of administering cabergoline and the comparison between cabergoline and established treatments (such as intravenous albumin and coasting). Large, well-designed and well-executed RCTs that involve more clinical endpoints are necessary to further evaluate the role of cabergoline in OHSS prevention.

Topics: Abortion, Spontaneous; Administration, Oral; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication associated with ovarian stimulation. Despite the numerous breakthroughs that have been made in other areas of assisted reproduction technology, it is only in recent years that the understanding of OHSS has advanced sufficiently to develop treatment options aimed at reducing the incidence and effects of OHSS. However, suitable predictors and tests with which to identify susceptible patients remain unreliable, although anti-Müllerian hormone is currently a good risk-factor candidate. More progress has been made with the prevention of OHSS, and physicians now have a wide range of treatment options, including coasting, re-initiation of gonadotrophin-releasing hormone (GnRH) antagonist and induction of a luteinizing hormone flare-up using GnRH agonist. Recently, vascular endothelial growth factor (VEGF) has been identified as a key player in the vascular permeability that is associated with OHSS. The use of the dopamine agonist cabergoline has been found to reduce the effects of VEGF-mediated vascular permeability without compromising implantation and pregnancy rates. Together, these treatments will complement the ongoing progress with other procedures such as in-vitro maturation and oocyte vitrification, and enable physicians to improve the prediction and prevention of OHSS.

Topics: Cabergoline; Clinical Protocols; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Randomized Controlled Trials as Topic

To assess the efficacy of coasting alone, cabergoline alone, or combining both interventions for preventing ovarian hyperstimulation syndrome (OHSS) among high-risk patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles.. The present randomized controlled trial was conducted at the IVF unit of a university hospital in Cairo between October 28, 2013, and July 31, 2015. Patients undergoing IVF/ICSI considered at risk of OHSS were randomly allocated to coasting, cabergoline, or combined coasting and cabergoline. The primary outcome was the rate and degree of symptomatically assessed OHSS. Data were analyzed on a per-protocol basis.. There were 100 patients recruited to each group. The occurrence of early OHSS was lowest in the combination group compared with the other groups (P=0.002).. Combining coasting and cabergoline was associated with a lower OHSS rate compared with either therapy alone. CLINICALTRIALS.GOV: NCT01984320.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic

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.. 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.. 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 < .001). Another (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.. 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.

Topics: Adult; Cabergoline; Chemoprevention; Clomiphene; Drug Resistance; Ergolines; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gynecologic Surgical Procedures; Hormone Antagonists; Humans; Infertility, Female; Laparoscopy; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Secondary Prevention; Treatment Failure

To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS).. In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels.. The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues.. Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

Topics: Animals; Cabergoline; Capillary Permeability; Chorionic Gonadotropin; Ergolines; Eye Proteins; Female; Gonadotropins, Equine; Humans; Letrozole; Nerve Growth Factors; Nitriles; Ovarian Hyperstimulation Syndrome; Ovary; Pregnancy; Prospective Studies; Rats; Rats, Wistar; Serpins; Triazoles; Vascular Endothelial Growth Factor A

The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS.. Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation.. The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups.. GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS.. Clinical trial.gov ( NCT02461875 ).

Topics: Adult; Antineoplastic Agents; Cabergoline; Chorionic Gonadotropin; Ergolines; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Incidence; Outcome Assessment, Health Care; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Young Adult

Cabergoline, a dopamine receptor-2 agonist, is suggested to prevent ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. The aim of this study was to evaluate the influence of different timing of cabergoline administration on clinical outcome among patients at risk of developing OHSS. Among infertile women undergoing IVF treatment at risk of developing OHSS, 206 were enrolled in this study. The subjects were randomly allocated into two groups, i.e. the study group (n=100) receiving cabergoline beginning on the day of human chorionic gonadotrophin (HCG) injection and the control group (n=100) receiving cabergoline starting on the day of oocyte retrieval. Oocyte metaphase-II rate, fertilization rate, clinical outcome and incidence of severe OHSS were compared between the two groups. There were no significant differences in oocyte metaphase-II rate (0.86 ± 0.16 versus 0.85 ± 0.15) or fertilization rate (0.79 ± 0.22 versus 0.76 ± 0.20) or in the incidence of OHSS between two groups. Similarly, there were no significant differences in implantation or clinical pregnancy rate between the two groups. Cabergoline can be administered as soon as HCG injection to prevent early OHSS, without adverse effects on oocyte maturation, fertilization rate and clinical outcome.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Pregnancy; Treatment Outcome

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.

Topics: Adult; Anti-Mullerian Hormone; Cabergoline; Cellular Microenvironment; Cohort Studies; Ergolines; Female; Fertilization in Vitro; Follicular Fluid; Hepatocyte Growth Factor; Humans; Inhibins; Insulin-Like Growth Factor I; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Risk Factors; Young Adult

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.. 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 0.5mg cabergoline administration for 8 days, starting on the day of hCG administration.. 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%).. 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.

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Hydroxyethyl Starch Derivatives; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Plasma Substitutes; Pregnancy; Pregnancy Rate; Prospective Studies; Secondary Prevention; Triptorelin Pamoate

To compare the efficacy of cabergoline (Cb2) and intravenous human albumin (HA) in the prevention of ovarian hyperstimulation syndrome.. In this randomized controlled trial study, 138 women who were at high risk for developing OHSS were randomly allocated into two groups. In Group one, 20 gr of HA 20% was infused over 1 h. Group two received 0.5 mg per day of Cb2 orally for 7 days, starting on oocyte pickup day. All patients were visited seven and 14 days after oocyte retrieval to determine early clinical or ultrasound evidence of OHSS.. Moderate OHSS was observed in 33 versus 14 cases in the HA and Cb2 groups, respectively, which was significantly different. The number of severe OHSS cases in the HA group was significantly higher than in the Cb2 group (P < 0.001).. Prophylactic oral low dose cabergoline was more effective and less costly than intravenous human albumin in the prevention of OHSS in high-risk patients.

Topics: Adult; Cabergoline; Dopamine Agents; Ergolines; Female; Fertilization in Vitro; Humans; Incidence; Infertility; Infusions, Intravenous; Iran; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Risk Factors; Serum Albumin; Serum Albumin, Human; Severity of Illness Index; Sperm Injections, Intracytoplasmic; Young Adult

This novel study describes an effective outpatient treatment for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms.. 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.. 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.. GnRH antagonists seem to be an effective outpatient treatment with rapid onset activity and minimal side effects for the management of early OHSS.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovarian Hyperstimulation Syndrome; Pilot Projects; Young Adult

Dopamine agonists were proposed as a preventive strategy for severe ovarian. The aim of this randomized controlled study is to evaluate the role of dopamine agonist at lower doses (0.25mg) as a preventive strategy of severe hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment cycles.. Two hundred women at risk to develop OHSS undergoing IVF/ICSI treatment cycle were included; the study group received 0.25mg of cabergoline for 8 days from the day of HCG administration versus no treatment for the prevention of OHSS. Reduction of the incidence OHSS was the primary outcome.. The overall incidence of OHSS was significantly reduced, almost 50%, in cabergoline group in comparison with control group (RR: 0.5, 95% CI: 0.29-0.83), with absolute risk reduction following cabergoline administration 11% (ARR: 0.11, 95% CI: 1.09-20.91). The corresponding number needed to treat (NNT) was 9.. Prophylactic treatment with the dopamine agonist, cabergoline, at lower doses (0.25mg) reduces the incidence of OHSS in women at high risk undergoing IVF/ICSI treatment.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Pregnancy; Sperm Injections, Intracytoplasmic

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.

Topics: Adult; Albumins; Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Estradiol; Female; Fertilization in Vitro; Humans; Oocytes; Ovarian Hyperstimulation Syndrome; Prospective Studies; Risk; Sperm Injections, Intracytoplasmic; Treatment Outcome

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.

Topics: Adult; Ascites; Cabergoline; Dopamine Agonists; Double-Blind Method; Ergolines; Extracellular Space; Female; Fertilization in Vitro; Granulosa Cells; Hematocrit; Hemoglobins; Humans; Image Processing, Computer-Assisted; Luteal Cells; Magnetic Resonance Imaging; Ovarian Hyperstimulation Syndrome; Ovary; Pregnancy; Prospective Studies; Receptors, Dopamine D2; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Treatment Outcome

To assess the effect of cabergoline on endometrial vascular endothelial growth factor receptor-2 (VEGFR-2) immunoexpression in an ovarian hyperstimulation syndrome (OHSS) rat model.. Twenty-one immature female Wistar rats were assigned into three groups: group 1, the control group; group 2, stimulated with gonadotropins to mimic OHSS; and group 3, in which an OHSS protocol was induced and thereafter treated with cabergoline (100 μg/kg/day). Body weight, ovarian volume, corpora lutea numbers, and endometrial VEGFR-2 expression were compared between the groups.. While successful implantation requires a vascularized receptive endometrium, impaired expression of VEGFR-2 and disrupted endometrial angiogenesis due to cabergoline administration may be associated with IVF failure in fresh OHSS cycles. The insignificant decrease in endometrial VEGFR-2 expression observed in this research needs to be investigated by further studies involving additional techniques such as immunoblotting and/or RT-PCR analyses.

Topics: Animals; Cabergoline; Dopamine Agonists; Ergolines; Female; Ovarian Hyperstimulation Syndrome; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

To assess the outcome of using low-dose aspirin, dopamine agonist and triggering ovulation by low dose of HCG in combination with GnRH agonist in fixed GnRH antagonist protocol in patients at risk of OHSS.. This prospective cohort study was conducted on 50 infertile women who were at high risk of OHSS. They received low dose aspirin from first day of stimulation, cabergoline 0.5mg daily from the day of HCG for 8days and low dose of HCG (2500 IU) in combination with GnRH agonist for final oocyte maturation in fixed GnRH antagonist protocol.. The study was conducted on 50 cases and all of them completed the study protocol. The clinical pregnancy rate was 40% (20 cases of 50) and no cases developed severe or critical OHSS. Only 8% (4 cases) developed moderate OHSS.. Combining aspirin, cabergoline, and triggering with low dose of HCG in combination with GnRH agonist produced excellent clinical pregnancy rate, and decreased hospital admissions with severe or critical OHSS.

Topics: Adult; Aspirin; Cabergoline; Chorionic Gonadotropin; Drug Therapy, Combination; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Severity of Illness Index

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.. Randomized controlled, animal study.. Female Wistar rats.. 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.. 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.. 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.

Topics: Animals; Antioxidants; Cabergoline; Disease Models, Animal; Dopamine Agonists; Ergolines; Female; Ovarian Hyperstimulation Syndrome; Ovary; Random Allocation; Rats; Rats, Wistar; Resveratrol; Stilbenes

Ovarian hyperstimulation syndrome is a potentially life-threatening, but preventable iatrogenic complication of in vitro fertilisation treatment. In recent years, new strategies have been developed to minimise the risk of ovarian hyperstimulation syndrome after in vitro fertilisation, including better at-risk patient identification prior to starting treatment, the use of a lower human chorionic gonadotrophin dose or alternative medication instead of human chorionic gonadotrophin to induce final oocyte maturation such as gonadotrophin-releasing hormone agonist and kisspeptin in antagonist cycles, cryopreservation of all embryos and delayed embryo transfer, and the use of oral dopamine agonists after oocyte retrieval. In this article, the advantages and limitations of those new developments are discussed and future directions towards establishment of an ovarian hyperstimulation syndrome-free in vitro fertilisation clinic are explored.

Topics: Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Estradiol; Estrogens; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Leuprolide; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Reproductive Control Agents; Risk Assessment

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 remaining 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.

Topics: Acetates; Animals; Ascitic Fluid; Body Weight; Cabergoline; Capillary Permeability; Chorionic Gonadotropin; Cyclopropanes; Dopamine Agonists; Ergolines; Female; Gonadotropins, Equine; Horses; Humans; Immunohistochemistry; Leukotriene Antagonists; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Quinolines; Rats; Rats, Wistar; Reproductive Control Agents; Sulfides; Vascular Endothelial Growth Factor A

The aim of the study is to investigate the effects of the interleukin-6 (IL-6) blocker tocilizumab in a hyperstimulated rat model and compare it with ranibizumab, a gonadotropin-releasing hormone antagonist (GnRHA), and cabergoline. Forty-seven rats were randomly divided into the following seven groups: Group 1: OHS; Group 2: OHS+ GnRHA; Group 3: OHS + ranibizumab; Group 4: OHS + cabergoline; Group 5: OHS + low-dose tocilizumab (TL); Group 6: OHS + high-dose tocilizumab (TH); Group 7: sham. Ovarian weight was significantly lower only in the ranibizumab group than in the OHS group. Estrogen levels were significantly lower in the GnRHA group than in the OHS and the treatment groups. Progesterone levels were significantly lower in the ranibizumab, cabergoline, and TL groups than in the OHS group. Among the treatment groups, corpus luteum counts were lower than in the OHS group. Corpus luteum counts were lowest in the tocilizumab groups. IL-6 intensity was lower in all treatment groups than in the OHS group. In the ranibizumab group IL-6 intensity was the lowest. The TL group did not significantly differ from the GnRHA and cabergoline groups regarding IL-6 expression. Ovarian VEGF expression was significantly lower in all treatment groups. For the TL, ranibizumab, and cabergoline groups VEGF intensity was similar. Tocilizumab may be a new strategy for preventing ovarian hyperstimulation syndrome by inhibition of IL-6.

Topics: Animals; Antibodies, Monoclonal, Humanized; Cabergoline; Ergolines; Estrogens; Female; Gonadotropin-Releasing Hormone; Interleukin-6; Ovarian Hyperstimulation Syndrome; Ovary; Progesterone; Ranibizumab; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A

To determine the efficacy of montelukast in comparison with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in rats.. An experimental OHSS model was formed in 35 female Wistar rats. Rats (22 days old) were randomized into 5 groups, each containing 7 animals. The control group received no therapy; the mild OHSS group was administered pregnant mare serum gonadotropin (PMSG) 10 IU for 4 days, hCG 10 IU on the 5th day; the severe OHSS group received PMSG 10 IU for 4 days, hCG 30 IU on the 5th day The montelukast group: received montelukast 10 mg/kg/day and the cabergoline group was administered cabergollne 100 microg/kg/day via oral gavage for 6 days (days 22-27), in addition to those of severe OHSS. All groups were sacrificed on 28th day Body weight, ovarian diameter and weight, vascular permeability vascular endothelial growth factor (VEGF), semiquantitative VEGF receptor-1, and VEGF receptor-2 (VEGFR-2) immunohistochemistry were evaluated.. Ovarian diameter and VEGF expression were significantly lower in the montelukast and cabergoline groups than in the severe OHSS group. While montelukast was more effective in limiting vascular permeability in the severe OHSS, cabergoline was superior to montelukast with respect to the limiting effect on increased body weight and VEGFR-2 expression.. The VEGF/VEGFR-2 interaction plays an important role in OHSS pathogenesis. Montelukast limits VEGF expression, and cabergoline reduces both VEGF and VEGFR-2 expressions; they are both effective therapies for the prevention of severe OHSS.

Topics: Acetates; Animals; Cabergoline; Chorionic Gonadotropin; Cyclopropanes; Disease Models, Animal; Dose-Response Relationship, Drug; Ergolines; Female; Ovarian Hyperstimulation Syndrome; Ovary; Quinolines; Random Allocation; Rats; Rats, Wistar; Sulfides

Presentation of seven cases of patients at risk for moderate or severe OHSS, treated with Cabergoline.

Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy

Embryo cryopreservation after triggering oocyte maturation with GnRH agonist (GnRHa) in GnRH antagonist protocols has been proposed to prevent ovarian hyperstimulation syndrome (OHSS). However, a small percentage of patients still developed severe OHSS. The purpose of the study was to investigate the efficacy of preventing OHSS in patients at very high risk when cabergoline was given in addition to elective cryopreservation after GnRHa triggering.. This is a retrospective observational study. The patients were stimulated with GnRH antagonist protocol. When serum E2 concentration was >6,000 pg/ml and there were more than 20 follicles ≥11 mm on the day of final oocyte maturation, GnRHa was used to trigger oocyte maturation. Cabergoline was given to augment the effect of preventing OHSS. The embryos were electively cryopreserved by vitrification and thawed in subsequent cycles. The primary outcome measure was the incidence of severe OHSS. The secondary outcome measure was the clinical pregnancy rate in the first frozen-thawed embryo transfer cycle.. One hundred and ten patients underwent 110 stimulated cycles were included for analysis. No patients developed moderate/severe OHSS. Mean E2 concentration on the day of final oocyte maturation was 7,873 pg/ml, and an average of 22.7 oocytes was obtained from each patient. One hundred and ten thawing cycles were performed, resulting in 69 clinical pregnancies (62.7 %).. Combining cabergoline and embryo cryopreservation after GnRHa triggering in GnRH antagonist protocol could prevent OHSS in patients at very high risk.

Topics: Adult; Cabergoline; Cryopreservation; Embryo Transfer; Ergolines; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Retrospective Studies; Sperm Injections, Intracytoplasmic

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.. 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.. 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.. 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.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Hormones; Humans; Infertility, Female; Leuprolide; Longitudinal Studies; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Young Adult

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.

Topics: Animals; Antibodies, Monoclonal, Humanized; Bevacizumab; Cabergoline; Cell Count; Disease Models, Animal; Drug Evaluation, Preclinical; Ergolines; Female; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Ovum; Rats; Rats, Wistar

We report the management of spontaneous ovarian hyperstimulation syndrome in a 23-year-old patient, diagnosed at 8 gestational weeks, in a context of moderate hypothyroidism. The etiology of spontaneous ovarian hyperstimulation syndrome should seek hypersecretion of glycoprotein hormones (hCG, TSH, FSH and LH) and/or mutation of FSH and LH receptors. It will eliminate an incipient ovarian neoplasia. The laparoscopic exploration can be done if diagnosis doubt persists. A diagnostic algorithm can be proposed.

Topics: Abdominal Pain; Adrenal Cortex Hormones; Adult; Cabergoline; Chorionic Gonadotropin; Ergolines; Female; Fibrinolytic Agents; Follicle Stimulating Hormone; Gestational Age; Graves Disease; Humans; Hypothyroidism; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Complications; Thyroidectomy; Thyrotropin

Topics: Adult; Cabergoline; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome

The dopamine/dopamine receptor 2 (D2/Drd2) pathway modulates vascular endothelial growth factor (VEGF)-dependent vascular permeability and angiogenesis in the ovary. Deregulation of the VEGF/VEGF receptor (VEGFR)-2 pathway leading to increased risk of ovarian hyperstimulation syndrome has been described in the ovary of patients suffering from polycystic ovarian syndrome (PCOS).. The objective of the study was to ascertain whether deregulation of the VEGF/VEGFR-2 might a least be partially due to abnormalities of the D2/Drd2 pathway in PCOS women.. Dated, archived ovaries from PCOs and control group patients as well as human chorionic gonadotropin-stimulated luteinized granulosa cells form PCOS and non-PCOS oocyte patients were used.. The study was conducted at a private research center.. PCOS and nonpolycystic ovarian patients and oocyte patients participated in the study.. Human ovarian sections were stained against the Drd2 antibody. Human chorionic gonadotropin-stimulated luteinized granulosa cells (LGC) were cultured in the presence/absence and the Drd2 agonist cabergoline.. Drd2 and vascularized stained area in the theca layer of antral (< 8 mm) and luteinized follicles was quantified. VEGF, D2, and its related metabolites were measured in the supernatant of cultured LGC by ELISA and HPLC, respectively. VEGFR-2 and Drd2 expressed by LGC was quantified through an In-Cell ELISA.. Decreased Drd2 expression and increased vascularization in the theca layer of antral and luteinized follicles of PCOS ovaries was observed. A lower dopamine production and reduced efficacy of cabergoline in inhibiting VEGF secretion was uncovered in LGC from PCOS.. Decreased dopaminergic tone as well as deregulated Drd2 signaling might explain higher VEGF and vascularization leading to increased ovarian hyperstimulation syndrome risk in PCOS.

Topics: Adult; Cabergoline; Cells, Cultured; Dopamine; Dopamine Agonists; Ergolines; Female; Granulosa Cells; Humans; Luteal Cells; Neovascularization, Physiologic; Oocytes; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Receptors, Dopamine D2; Risk Factors; Signal Transduction; Tissue Banks; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Young Adult

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Estradiol; Female; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Treatment Failure

To compare the efficacy of cabergoline (Cb2) and meloxicam in curbing vascular endothelial growth factor (VEGF) expression and preventing ovarian hyperstimulation syndrome (OHSS).. Randomized controlled, animal study.. Academic facility.. We used a total of 50 immature Wistar female rats randomly to create an experimental OHSS model.. Ten rats each formed the control group and mild OHSS group. The remaining 30 were separated into three equal groups of severe OHSS. Mild and severe OHSS were induced through ovarian stimulation with gonadotropins. One group with severe OHSS was administered a low-dose 100 microg/kg Cb2 therapy; another group with severe OHSS received 600 microg/kg meloxicam. Body weight, vascular permeability (VP), VEGF expression, ovary weight, and diameter were then compared.. The efficacy of Cb2 and meloxicam for preventing OHSS.. Comparison of the severe OHSS groups with the controls and mild OHSS group revealed significant increases in VEGF expression, VP, ovary weight, and diameter. The increase in VEGF expression was demonstrated to be dependent on human chorionic gonadotropin doses. However, low-dose Cb2 and meloxicam therapies were shown to be ineffective in decreasing VEGF expression and VP, ovary weight, and ovary diameter in severe OHSS.. VEGF elevation played a critical part in OHSS pathogenesis, but the therapies administered failed to curb VEGF expression.

Topics: Analysis of Variance; Animals; Biopsy, Needle; Body Weight; Cabergoline; Chorionic Gonadotropin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Ergolines; Female; Immunohistochemistry; Injections, Intramuscular; Meloxicam; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy, Animal; Probability; Random Allocation; Rats; Rats, Wistar; Thiazines; Thiazoles; Vascular Endothelial Growth Factor A

To describe a case of moderate ovarian hyperstimulation syndrome (OHSS) that was treated with high dose cabergoline.. Case report.. Private assisted reproduction center.. A 29-year-old woman who developed early moderate OHSS despite preventive cabergoline administration (0.5 mg/day) following controlled ovarian hyperstimulation for IVF treatment.. Cabergoline dose was increased to 1 mg/day upon diagnosis of OHSS on the second day after oocyte collection and embryo transfer was postponed to the fifth day after oocyte collection.. Resolution of OHSS and achievement of healthy live birth.. OHSS resolved rapidly despite occurrence of pregnancy and patient delivered a healthy boy at term.. The higher cabergoline dose might have prevented an increase in the severity of OHSS and its prolongation following occurrence of pregnancy. Randomized controlled trials assessing the efficacy and safety of different doses and durations of cabergoline administration in both prophylactic and therapeutic settings are required.

Topics: Adult; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Severity of Illness Index; Treatment Outcome

To describe an outpatient treatment protocol for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms with minimal side effects.. Case series.. Midwestern academic reproductive endocrinology division.. Four consecutive patients, diagnosed with OHSS, who presented after oocyte retrieval but before embryo transfer.. All embryos were frozen and each patient was treated with the same dopamine agonist and GnRH antagonist protocol.. Daily weights, days to resolution of clinical symptoms, side effects of the treatment protocol, and whether or not acute care or hospitalization was necessary.. The most rapid weight loss was within the first 5 days of treatment. The average time to resolution of clinical symptoms was 5.75 days. No side effects were reported and no patients required acute care or hospitalization.. Dopamine agonists and GnRH antagonists, when given together at the time of diagnosis of OHSS, appear to work rapidly and effectively to diminish the clinical symptoms of the disease. The potential benefit of finding an outpatient treatment for OHSS with rapid onset and minimal side effects warrants further investigation into this protocol.

Topics: Adult; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Treatment Outcome

Topics: Adenoma; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gonadotropins; Humans; Neovascularization, Pathologic; Ovarian Hyperstimulation Syndrome; Pituitary Neoplasms; Polycystic Ovary Syndrome; Vascular Endothelial Growth Factor A

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Fertilization in Vitro; Humans; Ovarian Hyperstimulation Syndrome; Pregnancy; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A

Ovarian hyperstimulation syndrome (OHSS) is a result of ovarian overexpression of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR2). VEGF/VEGFR2 binding disrupts cellular junctions and increases vascular permeability (VP), a characteristic of OHSS, but enhances angiogenesis, which is a fundamental step in implantation. In animals, the dopamine agonist Cabergoline (Cb2) prevents VP without affecting angiogenesis. In humans, Cb2 averts OHSS, but a possible detrimental effect on angiogenesis and implantation has not been explored. A pilot study was designed to analyze whether or not Cb2 administration, as a procedure for preventing OHSS, affects the outcome of assisted reproduction treatment (ART).. A retrospective study with endpoints of implantation and ongoing/term pregnancy rates. Women (n = 35) at risk of OHSS (20-30 follicles developed and >20 oocytes collected) took a daily oral dose of 0.5 mg Cb2 for 8 days, beginning on the day of hCG. They were matched with controls treated during the same period and who were similar with respect to age, number and quality of the embryos replaced, embryonic stage at transfer and sperm quality.. No difference was detected between the groups in fertilization, implantation or pregnancy rates. A total of 14 ongoing (beyond 32 weeks) or full term pregnancies were registered in each group. No major problem was detected during pregnancy or after delivery in any of these babies.. Administration of Cb2 in order to prevent OHSS is safe and does not appear to affect ART outcome.

Topics: Adult; Cabergoline; Dopamine Agonists; Embryo Implantation; Ergolines; Female; Humans; Ovarian Hyperstimulation Syndrome; Pilot Projects; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted; Retrospective Studies

No specific treatment is available for ovarian hyperstimulation syndrome (OHSS), the most important complication in infertile women treated with gonadotropins. OHSS is caused by increased vascular permeability (VP) through ovarian hypersecretion of vascular endothelial growth factor (VEGF)-activating VEGF receptor 2 (VEGFR-2). We previously demonstrated in an OHSS rodent model that increased VP was prevented by inactivating VEGFR-2 with a receptor antagonist (SU5416). However, due to its toxicity (thromboembolism) and disruption of VEGFR-2-dependent angiogenic processes critical for pregnancy, this kind of compound cannot be used clinically to prevent OHSS. Dopamine receptor 2 (Dp-r2) agonists, used in the treatment of human hyperprolactinemia including pregnancy, inhibit VEGFR-2-dependent VP and angiogenesis when administered at high doses in animal cancer models. To test whether VEGFR-2-dependent VP and angiogenesis could be segregated in a dose-dependent fashion with the Dp-r2 agonist cabergoline, a well-established OHSS rat model supplemented with prolactin was used. A 100 microg/kg low-dose Dp-r2 agonist cabergoline reversed VEGFR-2-dependent VP without affecting luteal angiogenesis through partial inhibition of ovarian VEGFR-2 phosphorylation levels. No luteolytic effects (serum progesterone levels and luteal apoptosis unaffected) were observed. Cabergoline administration also did not affect VEGF/VEGFR-2 ovarian mRNA levels. Results in the animal model and the safe clinical profile of Dp-r2 agonists encouraged us to administer cabergoline to oocyte donors at high risk for developing the syndrome. Prophylactic administration of cabergoline (5-10 microg/kg x d) decreased the occurrence of OHSS from 65% (controls) to 25% (treatment). Therefore, a specific, safe treatment for OHSS is now available.

Topics: Animals; Cabergoline; Capillary Permeability; Corpus Luteum; Disease Models, Animal; Dopamine Agonists; Ergolines; Female; Neovascularization, Physiologic; Ovarian Hyperstimulation Syndrome; Phosphorylation; Rats; Rats, Wistar; Receptors, Dopamine D2; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

To report the effect of cabergoline on ovarian hyperstimulation syndrome associated with gonadotropin-secreting pituitary adenomas.. Case report.. Outpatient practice.. Two women with menstrual irregularity, enlarged ovaries, high E(2), and normal gonadotropin levels.. Cabergoline treatment and transsphenoidal surgery.. Estradiol levels, transvaginal ultrasonography, and pituitary magnetic resonance imaging. Transsphenoidal surgery showed pituitary adenoma staining for LH in both patients.. Cabergoline was effective in reducing E(2) levels and decreasing ovarian size but ineffective in shrinking the pituitary adenomas.. This is the first description of the effectiveness of cabergoline as the primary treatment of spontaneous ovarian hyperstimulation syndrome in patients with gonadotropin-producing pituitary adenomas.

Topics: Adenoma; Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gonadotropins; Humans; Ovarian Hyperstimulation Syndrome; Pituitary Neoplasms

Polycystic ovary syndrome (PCOS) is characterized by abnormal gonadotrophin secretion, in particular an elevated serum concentration of LH, depressed FSH, and an LH/FSH ratio of >or =2. Mild, transient hyperprolactinaemia is frequently associated with PCOS (30% of patients); furthermore, it can be observed during the late follicular and luteal phases of both natural and stimulated cycles. It is suggested that a reduction of the dopamine inhibitory effect might raise both prolactin (PRL) and LH.. We compared ovarian stimulation in two groups of hyperprolactinaemic (hyperPRL)-PCOS patients; one group was treated with cabergoline, reducing PRL plasma concentrations to the range normally observed during ovulation induction. In the untreated hyperPRL-PCOS group, we noted a reduced total number of ampoules of recombinant FSH (P < 0.04), fewer days to reach HCG administration (P < 0.04), and significantly higher peak oestrogen plasma concentrations (P < 0.03) compared with the treated group. By ultrasound examination the same group showed significantly higher ovarian volume and an increased total number of follicles of every size. In untreated hyperPRL-PCOS patients, four cycles out of 65 were cancelled due to mild ovarian hyperstimulation syndrome (OHSS) that occurred during ovulation induction. Only one cycle out of 42 in the patients treated with cabergoline was cancelled. No significant differences in pregnancy rate nor in multiple pregnancy were found.. Our data suggest a dopaminergic control of LH release and support the use of cabergoline in the management of such patients, in order to provide better clinical control of ovarian response and consequently a reduction of the risk of OHSS, with no decrease in pregnancy rate.

Topics: Adult; Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hyperprolactinemia; Infertility, Female; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Recombinant Proteins; Time Factors; Ultrasonography