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15.07.2003

Newsletter Nr. 22

Gonal-F: 150 or 225 IU per day for ovarian stunmulation in IVF. Maternal and paternal alcohol consumption and IVF. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia Selective COX 2 inhibition in preterm labor 1. Gonal-F: 150 or 225 IU per day for ovarian stimulation in IVF To compare fixed daily doses of the recombinant FSH (rFSH) Gonal-F (150 IU vs. 225 IU) for ovarian stimulation in IVF-ET one hundred twenty-four women aged 23-41 years participated in the study. Exclusion criteria were as follows: FSH of >10 IU/L, polycystic ovarian syndrome, one ovary or previous ovarian surgery, previous poor response to ovarian stimulation, or ovarian hyperstimulation syndrome (OHSS).The patients were randomized to commence 150 IU or 225 IU of Gonal-F per day without dose alterations during treatment. More oocytes were retrieved in women aged ≤32 years in the 225-IU compared with the 150-IU group (11.8 +/- 8.0 vs. 7.0 +/- 5.8). In older women (≥33 years), the number of oocytes retrieved in the two groups were similar. No significant differences were found for fertilization rate, number of embryos formed and cryopreserved, and pregnancy rates between the two groups. The total rFSH dose used was higher in the 225-IU group (2,595.0 +/- 510.0 vs. 1,897.5 +/- 457.5 IU). The cancellation rate due to insufficient ovarian response was higher in the 150-IU group (15.0% vs. 3.3%). All cases of ovarian hyperstimulation syndrome (n = 4) occurred in the 225-IU group.Two hundred twenty-five IU is more effective than 150 IU in younger women but requires a higher total dose of Gonal-F. The use of 225 IU in older women did not result in a higher oocyte yield, suggesting that 225 IU of rFSH does not compensate for the age-related decline in the number of follicles available for stimulation. Reference Yong PY, Brett S, Baird DT, Thong KJ. A prospective randomized clinical trial comparing 150 IU and 225 IU of recombinant follicle-stimulating hormone (Gonal-F*) in a fixed-dose regimen for controlled ovarian stimulation in in vitro fertilization treatment. Fertil Steril. 2003 Feb;79(2):308-15. TOP 2. Maternal and paternal alcohol consumption and IVF The multicenter prospective study was undertaken to determine whether the amount and timing of female and male alcohol use during IVF and GIFT affect reproductive endpoints. Two hundred twenty-one couples with female infertility were included. Endpoints of the study were egg retrieval, transfer, fertilization, pregnancy, miscarriage, live birth, and multiple gestations. Female alcohol consumption was associated with: (1) a 13% decrease in the number of eggs aspirated (adjusted 95% confidence interval [CI]: -2% to -23%, for one additional drink per day, 1 year before the IVF or GIFT attempt); (2) an increase in risk of not achieving pregnancy by 2.86 times (0.99-8.24, 1 month prior); and (3) an increase in risk of miscarriage by 2.21 times (1.09-4.49, 1 week before the procedure).For men, one additional drink per day increased the risk of not achieving a live birth by 2.28 (1.08-4.80) to 8.32 (1.82-37.97) times, depending on the time period; beer also affected live births (ORs = 5.49-45.64). This outcome may be due partially to increased risk of miscarriage by 2.70 to 38.04 times for men who drank Reference Klonoff-Cohen H, Lam-Kruglick P, Gonzalez C. Effects of maternal and paternal alcohol consumption on the success rates of in vitro fertilization and gamete intrafallopian transfer. Fertil Steril. 2003 Feb;79(2):330-9. TOP 3. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. The objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia. An unblinded, multicenter trial was conducted in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure. Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001). Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia. Reference Belfort MA, Anthony J, Saade GR, Allen JC Jr; Nimodipine Study Group. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003 Jan 23;348(4):304-11. TOP 4. Selective COX 2 inhibition in preterm labor The safety of celecoxib, a selective cyclo-oxygenase-2 inhibitor, was compared with the safety of the nonselective cyclo-oxygenase inhibitor indomethacin, when it was administered for treatment of preterm labor. In a randomized, double-blind, placebo-controlled trial, 24 pregnant women in preterm labor at 24 to 34 weeks of gestation received either indomethacin or celecoxib for 48 hours. Clinical assessment, fetal sonography, and Doppler blood flow studies of the fetal ductus arteriosus were performed daily. Mean maximum ductal flow velocity was significantly elevated over baseline (82.9 +/- 4.6 cm/s vs 111.14 +/- 14.3 cm/s; P =.02) after 24 hours of indomethacin, but not celecoxib. Both medications were associated with a transient decrease in amniotic fluid volume, with a greater effect by indomethacin. The medications were equally effective in the maintenance of tocolysis. There were no significant maternal or neonatal adverse events. Thus, in this initial evaluation, the safety of short-term celecoxib in women with preterm labor was superior to that of indomethacin. Reference Stika CS, Gross GA, Leguizamon G, Gerber S, Levy R, Mathur A, Bernhard LM, Nelson DM, Sadovsky Y. A prospective randomized safety trial of celecoxib for treatment of preterm labor. Am J Obstet Gynecol. 2002 Sep;187(3):653-60 TOP

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