Cabergoline reduces the early onset of ovarian hyperstimulation syndrome: a prospective randomized study. Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction. [Cabergoline for inhibition of lactation]. Cabergoline versus bromocriptine in suppression of lactation after cesarean delivery. Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline. Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo-controlled study. Oral cabergoline. Single-dose inhibition of puerperal lactation. A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS. Termination of early human pregnancy with RU 486 (mifepristone) and the prostaglandin analogue sulprostone: a multi-centre, randomized comparison between two treatment regimens.
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. 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. Despite advances in prevention inhibition of lactation, only administration of estrogens or these combined with androgens show variable effectiveness and are indirectly associated with high percentage for lactation rebound, thrombosis, or pulmonary embolism or both of the later during puerperium; in addition, bromocriptine, also used indirectly for inhibition of lactation, is associated with lactation, rebound in 18-40%. Cabergolin is a new ergoline with efficient and durable prolactin reducer effect with fewer adverse effects.
                Which will the smallest cabergolin dosage be to inhibit lactation?
                To demonstrate clinical effectiveness with smallest cabergolina dosage in lactation inhibition.
                We carried on a the Service Clinical test on patients hospitalization with an indication to inhibit lactation as the Hospital of Gynecology and Obstetrics, Infantil Maternal Institute of the State of Mexico (IMIEM). The study was done 80 patients to who we administered oral 0.5 mg cabergoline to 40 patients and another group of 40 whom we administered 1.0 mg of cabergoline orally at random and blinded by means of out-patient consultation. We studied correlation between dose and inhibition of lactation as well as presence of adverse effects.
                In the group of patients to whom administered 0.5 mg, we found 65% (n = 26) with lactation inhibition; adverse effects in this group appeared in 32.5% (n = 13) the second group with a dose of 1.0 mg; 95% with adverse effects in 25% P < 0.001.
                Inhibition of lactation with unique dose of 1.0 has satisfactory clinical effectiveness, this being the smaller dose to inhibit lactation at a suitable percentage. We evaluated the efficacy of cabergoline, a new ergoline derivative, in blocking puerperal lactation in a group of women delivered by cesarean section. In a single-blind controlled trial 36 women were randomly allocated to treatment with cabergoline 1 mg in a single dose p.o. (n = 18) or bromocriptine 5 mg/day p.o. for 14 days (n = 18). Treatment was started about 50 h after delivery. Clinical assessment of breast signs and determination of serum prolactin were performed just before treatment and at 3, 5, 7 and 14 days. In the cabergoline-treated group milk secretion was inhibited in 17 women (94.4%). Maximum decrease of serum prolactin was -89.7% at 5 days, and the prolactin-lowering effect of cabergoline was still present at 14 days. In the bromocriptine group milk secretion was inhibited in 16 women (88.9%). Maximum prolactin decrease (-86.9%) was reached at 3 days. Persistent side effects were comparable in the two groups. This study demonstrates that a single oral dose of 1 mg cabergoline is as effective in suppressing puerperal lactation as a full treatment with bromocriptine, even in women delivered by cesarean section. To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug. To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS).
                A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS.
                Specialized assisted reproduction unit.
                Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration.
                After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval.
                Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles.
                Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates.
                Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach. Cabergoline, a new dopaminergic drug with a long-lasting prolactin inhibitory effect, was investigated at different single oral doses administered to puerperas who wished to inhibit their lactation. The study was prospective, randomized and double blind and included 140 puerperas divided into three groups of 40 women each treated with cabergoline and one group of 20 women who received a placebo. The tested doses were 1.0, 0.75 and 0.5 mg, administered orally within 24 hours after delivery. Prolactin levels were measured immediately before drug administration and then after 6 and 12 hours as well as on days 2, 3, 4, 5 and 14 after delivery. At those times the subjects were examined for milk secretion, breast engorgement, pain and possible side effects. In cases of symptoms requiring treatment, an additional 1 mg of cabergoline was administered. Complete inhibition of lactation up to day 14 was obtained in 90.2% of the women given 1 mg, 62.5% of those given 0.75 mg, 45% of those given 0.5 mg and 20% of those given a placebo. Four subjects experienced mild and transient side effects. This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group. A multi-centre, randomized trial was conducted to compare the efficacy and side-effects of two combination regimens of the antiprogestin RU 486 and the intramuscular PGE2 analogue sulprostone for termination of early pregnancy (amenorrhoea up to 49 days). Women in the 3-day group (n = 125) received 25 mg RU 486 twice daily for 3 days plus a single injection of 0.25 mg sulprostone in the morning of the third day of antiprogestin treatment. In the 4-day group (n = 126), RU 486 was given for 4 days and the sulprostone injection in the morning of the fourth day. Treatment outcome in the two groups was similar. Overall, 88.8% had a complete abortion, 6.8% an incomplete abortion and 2.4% were treatment failures; in the remaining 2% treatment outcome could not be determined. Only three of the six women with treatment failure still had detectable fetal heart activity when the pregnancy was terminated by vacuum aspiration two weeks after the start of treatment. Five of the 17 interventions for incomplete abortion were carried out as emergency procedures because of heavy bleeding; two of these five women were given a blood transfusion. The majority of the curettages (10/17) were performed in one centre. If the data from this centre and the women with undetermined treatment outcome were excluded, the rates for complete abortion, incomplete abortion and treatment failure in the remaining six centres were 93.6, 3.7 and 2.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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.