ergoline and Abortion--Spontaneous

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

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

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

Cabergoline is a dopamine agonist used to treat hyperprolactinaemia. Because hyperprolactinaemia is a significant cause of infertility in women, cabergoline and other dopamine agonists are frequently prescribed to reduce prolactin levels and restore normal menses. They are usually discontinued shortly after the patient becomes pregnant. Although cabergoline has been used to treat hyperprolactinaemia since the mid-1990s, safety data related to maternal and foetal exposure to this agent are still limited.. The current prospective, observational study reports on a total of 380 pregnancies. This extends by 154 pregnancies the results of a previously published interim report on the outcomes of 226 pregnancies in women treated with cabergoline up to 1994.. Outcomes examined include the incidence of abortions and premature delivery and the number and types of foetal malformations or abnormalities.. Follow-up data were available for 329 pregnancies, including 258 (78%) deliveries and 71 (22%) abortions. Of the 71 reported abortions, 31 (44%) were voluntary, 30 (42%) were spontaneous miscarriages, and nine (13%) were therapeutic. Of the 258 deliveries, 250 (97%) were live deliveries, four (2%) were stillbirths, and the status of delivery was unknown for the remaining four (2%). Of the 250 live deliveries, 193 (77%) were term deliveries (gestational period > 37 weeks), 45 (18%) were preterm deliveries (gestational period < or = 37 weeks), and 62% of the infants had normal birthweights (i.e. 3-4 kg). Neonatal abnormalities were recorded for 23 (9%) of the infants with no apparent pattern in type or severity.. The results of this study suggest that foetal exposure to cabergoline through early pregnancy does not induce any increase in the risk of miscarriage or foetal malformation.

Topics: Abortion, Spontaneous; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Pregnancy; Pregnancy Outcome; Prospective Studies

Cabergoline, a new ergoline derivative, is a potent prolactin inhibitor. In this review, results are combined from previously published and unpublished blind laboratory and open clinical studies with cabergoline in pseudopregnant, pregnant and lactating bitches, in bitches with normal and prolonged cycles, and in pregnant queens. Dose-response studies in nursing bitches, using puppy weight as an endpoint, revealed that a dose of 5 micrograms/kg/day orally (for 5 days) was the optimal dose with a minimum of side effects. This dose effectively lowered blood prolactin concentrations in pregnant bitches and was partly luteolytic during the 1st half of gestation, and fully luteolytic during the 2nd half of gestation. Consequently, pregnancies were terminated in the 2nd half of pregnancy in the bitch, and in the queen. Treatment successes with pseudopregnancy and true and false lactation, including cases of eclampsia, were greater than 90%. The same level of success was seen in bitches with prolonged cycles (anoestrus). A 7-10-day treatment period resulted almost uniformly in oestrus, and restored fertility in greater than 80% of all bitches mated. Cycles were occasionally shortened in bitches treated for false lactation. Attempts to shorten cycles routinely in beagle bitches, in a commercial breeding operation, with a dose of 5 micrograms/kg/day for 14 days during months 4, 5 or 6 of the cycle were unsuccessful.

Topics: Abortion, Spontaneous; Animals; Birth Weight; Cabergoline; Cats; Dogs; Dose-Response Relationship, Drug; Ergolines; Estrus; Female; Lactation; Pregnancy; Pregnancy, Animal; Progesterone; Prolactin; Pseudopregnancy

The natural history of prolactin-secreting adenomas is not known. For this reason, optimal therapy for women harboring these adenomas who desire to conceive is also unknown. Argument can be found to favor surgical excision, radiation therapy, prolactin-suppressing chemotherapy, and clinical observation. In a large series of women with prolactin-secreting pituitary adenomas, 21 have conceived and delivered healthy infants, all of whom had ergocryptine-induced prolactin suppression as the sole form of therapy. Endocrinologic, neurologic, biochemical, and radiologic assessment failed to demonstrate any obvious growth of the pituitary adenoma, except for slight enlargement of the sella turcica in one patient who delivered twins. The failure to demonstrate any worsening of the clinical state may reflect the fact that no large tumors were included in this series, only small but definite microadenomas found on sellar tomography. All of the various modalities of therapy must be considered with each patient, but this series suggests that ergocryptine treatment with careful clinical follow-up is relatively safe in patients with small pituitary tumors.

Topics: Abortion, Spontaneous; Adenoma; Adult; Ergolines; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactin

Electrical activity of the rat uterus was recorded for 1 h daily on days 2--9 of pregnancy with 6 electrodes chronically implanted in the left uterine horn. In 10 untreated and 7 ergocornine treated rats, activity decreased in frequency and intensity during the first days of pregnancy. After day 3 activity was present in only about 30% of electrodes as compared to 85% on day 2. Abortion was induced by ergocornine injected on day 5. In these rats the frequency of bursts increased on days 8 and 9. During the peak of activity the majority of bursts spread in the cervical direction.

Topics: Abortion, Spontaneous; Animals; Electrodes, Implanted; Ergolines; Female; Pregnancy; Pregnancy, Animal; Rats; Uterine Contraction

Topics: Abortion, Habitual; Abortion, Spontaneous; Anilides; Animals; Cyproheptadine; Ergolines; Female; Fetus; Methysergide; Monoamine Oxidase Inhibitors; Pargyline; Pregnancy; Rats; Serotonin; Serotonin Antagonists; Sodium Chloride

Topics: Abortion, Spontaneous; Animals; Corpus Luteum; Enzyme Induction; Ergolines; Ergot Alkaloids; Estrus; Female; Histocytochemistry; Hydroxysteroid Dehydrogenases; Ovary; Pituitary Gland; Pregnancy; Progesterone; Prolactin; Rats; Sheep