A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage. The effect of HCG supplementation after combined GnRH agonist/HMG treatment in an IVF programme. Human chorionic gonadotropin supplementation in recurring pregnancy loss: a controlled trial. Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization. First trimester threatened miscarriage treatment with human chorionic gonadotrophins: a randomised controlled trial. A randomized-controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants. Intravenous albumin versus hydroxyethyl starch for the prevention of ovarian hyperstimulation in an in-vitro fertilization programme: a prospective randomized placebo controlled study. Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial. Calcium supplementation and prevention of pregnancy induced hypertension.
Previous trials of intravenous immunoglobulin (IvIg) treatment of women with recurrent miscarriage (RM) have provided diverging results. This may be due to different inclusion criteria and suboptimal treatment protocols in some trials.
                According to a computer-generated list, 58 women with at least four unexplained miscarriages were randomly assigned to receive infusions of high doses of IvIg or placebo starting as soon as the pregnancy test was positive.
                In the intention-to-treat analysis, a 45% live birth rate was found in both allocation groups. In patients with secondary RM, 50% in the treatment group and 23% in the placebo group had successful pregnancies (P = not significant). When data from the present and a previous placebo-controlled trial of the same treatment were combined, 15/26 (58%) of the patients with secondary RM in the treatment group versus 6/26 (24%) in the placebo group had successful outcomes (P < 0.02). Only 7% of the karyotyped abortuses were abnormal.
                IvIg may improve pregnancy outcome in patients with secondary RM. A new placebo-controlled trial focusing on this subgroup should be conducted to confirm the results. The necessity of luteal-phase supplementation in an IVF programme is of continuing interest. After ovarian stimulation with clomiphene and human menopausal gonadotrophin (HMG), the beneficial effect of supporting the luteal phase has never been scientifically demonstrated. After ovarian stimulation with GnRH agonist/HMG, the luteal phase seems to be inadequate, but in a previous study we did not find evidence to support the need for oral progesterone supplementation. To evaluate the beneficial effect of human chorionic gonadotrophin (HCG) supplementation, we performed a multicentre, double-blind, randomized study with HCG (193 transfers) against placebo (194 transfers). The ongoing pregnancy rate per transfer cycle was significantly better with HCG (18.7 versus 9.3). This is the first truly objective (randomized) study demonstrating the beneficial effect of supporting the luteal phase in an IVF programme. To investigate the efficacy of hCG in the management of recurrent early pregnancy loss.
                A prospective, randomized, controlled trial.
                Miscarriage Clinic, Women's Hospital, Liverpool, United Kingdom.
                Eighty-one women attending the miscarriage clinic with idiopathic recurrent pregnancy loss were randomized to receive hCG supplementation or placebo in early pregnancy.
                The success rate or live birth rate.
                In women with regular menstrual cycles it was found that hCG had no beneficial effect, the pregnancy success rate being 86% in both groups. However, women with oligomenorrhea had a pregnancy success rate of 40% in the placebo group but a statistically significant improvement to 86% if hCG was given.
                Human chorionic gonadotropin can be recommended for idiopathic recurrent pregnancy loss in women with oligomenorrhea. To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients.
                Randomized, prospective analysis.
                Private hospital incorporating an established IVF center.
                Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness.
                Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily.
                A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated.
                With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented.
                After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH. To determine whether administration of exogenous human chorionic gonadotrophin (hCG) treatment improve the pregnancy outcome in first trimester threatened miscarriages.
                A prospective, double blind, randomised, placebo-controlled trial.
                The Early Pregnancy Assessment Unit, Royal Bolton Hospital, Bolton, United Kingdom.
                One hundred and eighty-three women with vaginal bleeding and a viable fetus seen on ultrasound scan (USS) in the first 12 weeks of pregnancy.
                The patients were randomised to receive either hCG or placebo treatment until 14 weeks of gestation.
                The primary objective of the trial was to determine the miscarriage rate in the hCG arm compared from the placebo arm.
                Of the 183 cases, 87 were randomised to treatment with hCG while 96 were randomised to receive a placebo. Forty-seven (25%) did not comply with the study protocol. The mean [SD] gestational age at presentation was 7 [1.33] weeks. The mean [SD] age of women in study was 27 [5] years in the placebo and 28 [5] in the hCG group. The mean body mass index (kg/m(2)) was 25 [5] in the study. The number of patients actively bleeding per vaginum at presentation was 85 (93%) in placebo group and 79 (96%) in the hCG group. The median number of hCG or placebo injections for both groups was 7. Ten women (11%) in the placebo group proceeded to have a complete miscarriage, as did 10 women (12%) in the hCG group, relative risk (RR) [95% confidence interval (CI)] of 1.1 (0.63-1.6).
                Our study showed no evidence of a difference in the outcome of threatened miscarriages when treated with hCG in the first trimester, this may be because our study sample size was small and follow up was suboptimal. A large, randomised, multicentre trial is still needed to establish the usefulness of hCG treatment in cases of threatened miscarriage. Extremely low birth weight (ELBW) infants are at risk for hypotension. Abnormal adrenal function may play a role in the pathogenesis of hypotension, and therefore, the administration of hydrocortisone (HC) may be an effective treatment for hypotension in some infants. However, the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied. We conducted a randomized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants.
                Infants were assigned to receive either HC or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors (VP) was standardized based on an a priori protocol.
                A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the HC group 25% received VP at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the HC group received VP compared to 39% of the placebo group (p<0.05).
                Prophylactic treatment with HC reduces the incidence of hypotension, defined by treatment with VP, among ELBW infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established. A prospective randomized placebo controlled clinical trial was carried out on 250 patients (cycles) considered at risk of developing OHSS in an IVF programme. Criteria for inclusion were: estradiol value of more than 3000 pg/ml or the presence of more than 20 follicles on the day of hCG administration. Patients were randomized by using a random table to receive either 20% human albumin 50 ml (n: 82); 6% hydroxyethyl starch (200/0.5) 500 ml (n: 85) or a placebo of 500 ml 0.9% NaCl solution (n: 83) over 30 min during oocyte collection. Groups were similar with respect to patients' age, estradiol levels on hCG day, body mass index, number of oocytes retrieved, number of embryos transferred and pregnancies (P>0.05). There was no severe OHSS in patients who received albumin and HES while four patients who received placebo developed severe OHSS. On the other hand moderate OHSS was encountered in four patients in the albumin group; five patients receiving HES; and 12 patients receiving placebo. There was a statistically significant difference in the incidence of moderate, severe and overall OHSS among groups (P values of <0.05, <0.05, and <0.01, respectively). Both HES and albumin significantly reduced the incidence of moderate, severe and overall incidence of OHSS. It is concluded that hydroxyethyl starch is a cheaper and safer alternative to Human Albumin in OHSS prevention. Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.
                Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.
                The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).
                Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified. In a randomized controlled trial 201 healthy nulliparous women were randomly allocated by means of a computer generated randomization list. From 20 weeks of gestation until delivery they received either 2 g of oral elemental calcium (n = 103) per day or an identical placebo (n = 98). Eleven women (5.47%) were lost to follow-up after randomization. The study groups were very similar at the time of randomization; with respect to several clinical and demographic variables. Treatment compliance was very similar in both groups as was determined by pill count. The rate of pregnancy induced hypertension was lower in the calcium group than in the placebo group 8.24%; vs 29.03%; (RR = 0.28; 95% CI 0.14-0.59). The incidence of gestational hypertension was 6.18% in the calcium group and 17.20% in the placebo group (RR = 0.28; 95% CI 0.08-0.80), and the incidence of preeclampsia was 2.06% in the calcium group and 11.82% in the placebo group (RR = 0.13; 95% CI 0.01-0.64). In conclusion calcium supplementation given in pregnancy to nulliparous women reduces the incidence of pregnancy induced hypertension.
The evidence supporting hCG supplementation to prevent RM remains equivocal. A well-designed randomised controlled trial of adequate power and methodological quality is required to determine whether hCG is beneficial in RM.