A randomized, double-blind study of two combined and two progestogen-only oral contraceptives. Double-blind controlled trial of progesterone substitution in threatened abortion. A multicenter comparative trial of triphasic and monophasic, low-dose combined oral contraceptives. Clinical performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women: a comparative study. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. Combined contraceptive ring versus combined oral contraceptive (30-μg ethinylestradiol and 3-mg drospirenone). Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding. Low-dose oral contraceptive to re-induce menstrual bleeding in amenorrheic women on DMPA treatment: a randomized clinical trial. Clinical comparison of two low-dose oral contraceptives, Minulet and Mercilon, in women over 30 years of age. A comparative study of two low-dose combined oral contraceptives: results from a multicenter trial. Comparison of four continuously administered progestogen plus oestradiol combinations for climacteric complaints. Second-trimester pregnancy termination: comparison of three different methods. Comparative acceptability of combined and progestin-only injectable contraceptives in Kenya. Experience with two different medicated intrauterine devices: a comparative study of the Progestasert and Nova-T. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. Administration of progestogens to hasten pituitary desensitization after the use of gonadotropin-releasing hormone agonist in in vitro fertilization--a prospective randomized study. Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: a randomized comparative dose-ranging study. Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova. Comparative phase III clinical trial of two injectable contraceptive preparations, depot-medroxyprogesterone acetate and Cyclofem, in Vietnamese women. Efficacy and tolerability of vaginal progesterone capsules (Utrogest 200) compared with progesterone gel (Crinone 8%) for luteal phase support during assisted reproduction. Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or intravaginal prostaglandin E2 suppositories: a randomized trial. Long-interval treatment regimen with a desogestrel-containing oral contraceptive. A randomized prospective study comparing pregnancy rates after clomiphene citrate and human menopausal gonadotropin before intrauterine insemination.
A randomized double-blind study of two combined oral contraceptives and two progestogen-only oral contraceptives was conducted using the same protocol at WHO Collaborating Centres for Clinical Research in Human Reproduction in Bombay and Ljubljana of the 518 women admitted to the trial, 123 received mestranol 50 micrograms + norethisterone 1mg (MES 50 + NET 1); 137 received ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (EE 30 + LNG 150); 130 received norethisterone 350 micrograms/NET 350); and 128 received levonorgestrel 30 micrograms (LNG 30). At one year, between 52.6 and 61.0 percent of those recruited had discontinued oral contraceptive use for all reasons, and by two years, between 70.5 and 76.5 percent had discontinued the treatment. These rates did not differ between the four treatment groups. However, discontinuation rates for all medical reasons at one and two years, and at two years pregnancy rates and discontinuation rates for bleeding disturbances, were significantly lower in the EE/LNG preparation. The groups receiving the MES/NET, LNG and NET had similar pregnancy rates, discontinuation rates for all medical reasons and all bleeding disturbances. There were two ectopic pregnancies among the 22 pregnancies in the progestogen-only groups. Discontinuation because of headache, dizziness and other central nervous system symptoms were significantly more common in those receiving MES/NET compared to EE/LNG. In contrast, discontinuation for gastro-intestinal disturbances were significantly higher in the EE/LNG combined preparation. Bleeding disturbances in the first few cycles tended to be higher in NET than in the LNG group. The data suggest that greater consideration be given to the benefits and risks of including progestogen-only oral contraceptives in the family planning programmes of some countries. Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) A comparative multicenter clinical trial of two combined oral contraceptives (OCs) was conducted at clinics located in the Sudan, Sri Lanka, Chile, the Dominican Republic and Ecuador. The trial was designed to determine if there were differences in efficacy, safety and acceptability between a triphasic and a low-dose monophasic OC. This report includes analysis of 1088 women. At each center, subjects were randomly allocated to one of the two OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. There were two accidental pregnancies attributed to user failure reported during the study period; one in the triphasic group and one in the monophasic group. Adverse experiences were mainly minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding. Both OCs were safe and effective. This 1-year randomized study was carried out at family-planning clinics of two university hospitals to compare the safety and acceptability of a levonorgestrel-releasing intrauterine system (LNG IUS) and oral contraceptives (OCs) in young nulliparous women. The study population consisted of 200 women aged 18-25 years seeking contraception. Ninety-four women entered the LNG IUS group and 99 entered the OC group. Continuation rates, reasons leading to discontinuation, adverse events, menstrual questionnaires, subjective well-being and sexual behavior were evaluated. Nineteen women (20%) in the LNG IUS group discontinued the study during the 1-year observation period, and 27 discontinued (27%) in the OC group. The most common reason (31%) for discontinuation in the IUS group was pain. In the OC group, hormonal side effects were the predominant medical reason for study termination. The safety and acceptability of the LNG IUS for contraception was observed to be as good as with OCs, with a high continuation rate. Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients.
                The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS.
                We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial.
                The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
                One hundred nonobese primary infertile anovulatory women with PCOS participated.
                We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each.
                The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates.
                The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).
                Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women. A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered. To compare the adverse effects, cycle control, and metabolic effects of NuvaRing and a combined oral contraceptive (COC).
                Women seeking contraception received NuvaRing (n = 300) or a COC (n = 300) for 12 cycles in a randomized, open-label trial.
                The total number of women with adverse effects did not differ significantly between the 2 groups. Leucorrhea, vaginitis, decreased libido, and ring-related problems were more common with NuvaRing, whereas weight increase, acne, and emotional lability were more common with the COC. Breakthrough bleeding occurred in 11.3% of women receiving NuvaRing and in 14.7% of women receiving the COC; 2.1% and 2.9% of women, respectively, had no withdrawal bleeding. Differences in blood pressure, blood sugar levels, lipid profile, liver enzyme activity, and anticoagulant activity were not statistically significant, with the exception of low-density lipoprotein levels measured at 6 and 12 months, which were significantly lower in the NuvaRing group than in the COC group.
                NuvaRing is a good alternative to a COC. It is associated with a slightly reduced incidence of breakthrough bleeding and there were no clinically relevant adverse effects or changes in blood pressure, blood sugar levels, lipid profile, or anticoagulant activity when compared with the COC.
                Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis.
                Meta-analysis.
                Cohort and case-control studies assessing risk of venous thromboembolism among women using oral contraceptives before October 1995.
                Pooled adjusted odds ratios calculated by a general variance based random effects method. When possible, two by two tables were extracted and combined by the Mantel-Haenszel method.
                The overall adjusted odds ratio for third versus second generation oral contraceptives was 1.7 (95% confidence interval 1.4 to 2.0; seven studies). Similar risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Among first time users, the odds ratio for third versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with 2.0 (1.4 to 2.7; five studies) for longer term users. The odds ratio was 1.3 (1.0 to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in other studies. Differences in age and certainty of diagnosis of venous thrombosis did not affect the results.
                This meta-analysis supports the view that third generation oral contraceptives are associated with an increased risk of venous thrombosis compared with second generation oral contraceptives. The increase cannot be explained by several potential biases. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS.
                CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19-49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%).
                Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (-11% points, 95% CI -19 to -2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1-18).
                The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72. Depot medroxy progesterone acetate (DMPA) is one of the most reliable contraceptive methods with a failure rate less than 0.3 percent. It is injected every three months and Although it has many advantages over many other hormonal contraceptives, But a major disadvantage of it is bleeding disorders which comprise most of the discontinuance reasons. Our Aim was to study bleeding complications of DMPA when used as a contraceptive in Ardabil district and clinical trial of LD and Ethynil oestradiol in controlling these complications.
                All the 917 women who referred to ardabil's health centers for having a DMPA injection for the first time, were entered into a longitudinal study. Those complaining of menstrual cessation were entered into a double blinded randomized clinical trial. Data were collected by means of 9 questionnaires 7 of them used for descriptive and 2 for clinical trial study. Data was analyzed by SPSS statistical package.
                Those DMPA users with a cesarean section history had a higher chance of bleeding complications. Four hundred forty-four of the 917 women receiving the injection discontinued using it before the end of the study period. The main reason for discontinuation (in 70%) was irregular menstrual bleedings and menstrual cessation. In the clinical trial of women with bleeding cessation, 70% of those receiving the LD-OC pill experienced menstrual bleedings again, compared with only 22.7% in the placebo group. The discontinuation rate in the drug group was lower than in the placebo group as well (p < 0.05).
                Treating menstrual cessation caused by DMPA with LDs, improves the complication and decreases the discontinuance rate. A comparative study of two low-dose oral contraceptives, gestodene (GES) 75 mcg/ethinyl oestradiol (EE) 30 mcg and desogestrel (DES) 150 mcg/EE 20 mcg, was conducted in women over 30 years of age. This randomised, open-label study was organised in Denmark, Italy, New Zealand and United Kingdom. A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles. The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline. However, the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment. The mean age (+/- SD) was 35 +/- 4 years in the GES/EE group and 35 +/- 5 years in the DES/EE group. The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group, data for 2796 cycles. There were no pregnancies on medication with either preparation. The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6. Irregular bleeding between withdrawal bleeds occurred in 10% of GES/EE and 18.5% of DES/EE cycles. Absence of all bleeding was reported in 29 (1%) and 63 (2%) cycles, respectively. The incidence of missed pills was low in both groups (11% of cycles). No significant differences were observed in cycle length or withdrawal bleeding episode length. Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE. However, for both preparations, the mean intensity was close to light bleeding. No clinically significant differences were noted in weight, blood pressure, Papanicolaou smears or laboratory data. Sixty-eight (13.5%) subjects in the GES/EE group and 64 (12.8%) in the DES/EE group discontinued before the end of the study. Among them, 37 (7%) and 40 (8%) in the respective groups withdrew because of adverse reactions. There was no difference between groups in terms of primary reasons for withdrawal. The most frequently reported complaints that led to discontinuation in both groups were headache, nausea and metrorrhagia. Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group. These results show excellent cycle control, efficacy and very low rate of side effects with both GES/EE and DES/EE. These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause. A comparative multicenter clinical trial of two low-dose combined oral contraceptives (OCs) was conducted in Malaysia, Egypt, Thailand, and Mexico. Efficacy, safety and acceptability were investigated in women taking either a norgestrel-based (NG) OC or a norethindrone acetate-based (NA) OC. This paper includes analysis of 892 women, all of whom were at least 42 days but within 26 weeks postpartum and randomly allocated to one of the above OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Baseline sociodemographic characteristics were similar for both groups, as well as compliance. There were nine unintended pregnancies reported; eight of these occurring in the NA group. Adverse experiences were minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. The group taking the NG-based OC had significantly (p < .05) fewer menstrual-related complaints. Discontinuations due to menstrual problems were significantly more common among NA users (primarily amenorrhea). Discontinuations in the NG group were primarily for other personal reasons, e.g. unable to return to the clinic. There was also a significant difference between the two groups for the 11-month gross cumulative life table discontinuation rates due to menstrual problems (p < .01); the NA group had the higher rate. Sixty women with climacteric complaints who had not menstruated for at least 1 year were randomly allocated to receive one of four hormonal replacement regimens. All four formulations were administered daily and continuously and each contained 2 mg of micronized oestradiol-17 beta in combination with either norethisterone acetate 1 mg (group A) or 0.5 mg (group B) or megestrol acetate 5 mg (group C) or 2.5 mg (group D). The clinical efficacy was the same although the alleviation of vasomotor symptoms was somewhat slower in those women receiving preparation A. The endometrium was atrophied in nearly all biopsies. Irregular uterine bleeding was almost entirely confined to the earlier phase of the study and was substantially less with the formulation containing 1 mg norethisterone acetate. It is concluded that a continuous oestradiol-progestogen combination can be used for long-term treatment of climacteric complaints in postmenopausal women and that after 4 months the clinical efficacy is the same irrespective of the type and dose of progestogen administered. The object of this study was to compare intravaginal misoprostol and dinoprostone (prostaglandin E2) for second-trimester pregnancy termination, and to examine the role of the nitric oxide donor, glyceryl trinitrate, as a possible alternative to prostaglandins to induce cervical ripening in second-trimester pregnancy termination. This was a randomised clinical trial. The trial involved pregnant women between 13 and 28 weeks' gestation admitted with clear medical or obstetric indications for pregnancy termination, and was carried out in the department of obstetrics and gynecology, Assiut University Hospital, Egypt. Patients were classified into Group A, where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms; Group B, where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg; and Group C, where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg. Twenty-four hours after the start of induction, the rate of complete abortion in the three groups was 100%, 66.67% and 0%, respectively. The rate of complete abortion was 100% in the nitric oxide (glyceryl trinitrate)-induced group after introducing a complementary procedure. The induction-abortion interval was significantly shorter, the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone. A higher rate of side effects occurred with the misoprostol-induced group (74%) compared with the other two groups (46.6% and 0%). Misoprostol is a cheap, effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects. Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered. Glyceryl trinitrate is an effective drug for cervical ripening (softening) but it has no role in the stimulation of uterine contractions. We compared 12-month continuation rates, menstrual bleeding patterns and other aspects of acceptability between users of Cyclofem and users of Depo-Provera.
                The life-table method was used to calculate quarterly continuation rates. In all, 360 Kenyan women were randomly assigned to one of the two contraceptives. User-satisfaction questionnaires were administered at 6 and 12 months or at discontinuation, whichever occurred first.
                The 1-year continuation rate was 75.4% for Depo-Provera users versus 56.5% for Cyclofem users (p<.001). Main reasons for discontinuation included difficulty making clinic visits (45.1% for Cyclofem vs. 40% for Depo-Provera), menstrual changes (14.1% vs. 12.5%) and nonmenstrual problems (15.5% vs. 12.5%). None of the Depo-Provera users and 8.5% of the Cyclofem users claimed frequency of visits as the main reason for discontinuation. In all, 70.6% of the Depo-Provera users were amenorrheic after 12 months, as were 20.8% of the Cyclofem users.
                The 1-year continuation rate was higher for Depo-Provera than for Cyclofem. There was no important difference in discontinuation rates because of menstrual problems; the difference mainly reflected the frequency of visits required. A comparative study of the Progestasert (UPS) and the Nova-T in 326 randomly selected women was carried out. The observation period was 1 year. The over-all continuation rates for the two types of intrauterine devices (IUDs) were similar. The expulsion rate for the Nova-T (9.2%) was considerably higher (P = 0.001) than that for the UPS (1.2%). Medical removals for bleeding/pain were more frequent (P = 0.028) for the UPS (15.4%) as compared with the Nova-T (6.1%). The pregnancy rate for the UPS (Pearl index = 4.8) was insignificantly higher than that for the Nova-T (Pearl index = 2.8). Two of the pregnancies in the UPS group were ectopic. No significant changes in the reactive immunoglobulins (IgA, IgG, or IgM) were observed in either of the groups. Our results indicate that neither of these two IUDs is preferable to the already existing medicated IUDs, such as the Copper T or the Copper 7. This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol.
                This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years.
                Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG.
                A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC. To assess the effect of administration of adjuvant IM progestogen to patients undergoing IVF who were not pituitary desensitized after 14 days of GnRH agonist (GnRH-a) administration.
                Prospective randomized study.
                A tertiary referral center for assisted conception.
                Forty-nine patients undergoing 51 IVF treatment cycles.
                Patients in whom the endometrial thickness was > 5 mm or who had an ovarian cyst > 15 mm after 14 days of GnRH-a administration were recruited if the serum E2 concentration was > 27.24 pg/mL (> 100 pmol/L). Patients in group 1 (n = 22) received a single IM injection of 100 mg P whereas patients in group 2 (n = 29) did not. Patients in both groups continued to receive SC GnRH-a 500 micrograms/d and had serum E2 levels measured every 3 days until the concentrations were < or = 100 pmol/L.
                The number of days of GnRH-a administration from recruitment until serum E2 concentration measured < or = 100 pmol/L, number of cycles with withdrawal bleeding, number of days from recruitment to withdrawal bleeding, total dose of hMG used, number of follicles > 14 mm, number of oocytes, number of embryos, and pregnancy rates per cycle commenced and per ET.
                There were no significant differences in all the above parameters except in the mean number of days from recruitment to onset of withdrawal bleeding, which were 5.33 +/- 0.7 (mean +/- SEM) and 8.62 +/- 1.26 days in groups 1 and 2, respectively. The pregnancy rate per ET was higher in group 1 (38.88%) when compared with group 2 (19.04%). However, this difference was not statistically significant.
                Adjuvant administration of a single IM injection of progestogen hastens the onset of withdrawal bleeding in patients who are not pituitary desensitized after 2 weeks of administration of SC GnRH-a. It does not appear to affect the length of time the serum E2 concentrations take to reach basal levels or to alter the ovarian responsiveness to exogenous gonadotropins. We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E(2)) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study.
                440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E(2)V+2.5 mg MPA; 1 mg E(2)V+5 mg MPA; or 2 mg of E(2)+1 mg NETA. After the first 6 months, the E(2)V dose was increased to 2 mg in both E(2)V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits.
                Significantly fewer bleeding days were experienced in the first 3 months by women taking E(2)V/MPA compared with women taking E(2)/NETA. When the dose of E(2)V was increased in the E(2)V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E(2)/NETA group compared with either of the E(2)V/MPA groups. The overall continuation rates ranged from 70 to 86%.
                These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E(2)V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT. In a prospective randomized study, the effect of two ovulation induction regimens on implantation rate of frozen/thawed pronucleate ova was investigated. Patients received either human menopausal gonadotrophin (HMG) or clomiphene/HMG. Ovulation induction was done on an individual basis using ultrasound and plasma 17 beta-oestradiol concentrations. Ovulation was induced with human chorionic gonadotrophin (HCG) when the leading follicle reached a diameter of 18 mm. Pronucleate ova had been frozen using the slow-freezing method of Lassalle et al. (1985) (Fertil. Steril., 44, 645-651) and were thawed in synchrony with the age of the endometrium. Both groups of patients were comparable for age, indication for in-vitro fertilization, pre-ovulatory 17 beta-oestradiol concentration, number of large follicles and number and quality of embryos transferred. The only difference found was that HCG was administered 1 day earlier in the HMG group compared to the clomiphene/HMG group (P < 0.01). Using univariate analysis, the pregnancy rate was higher in patients stimulated with HMG alone compared to those stimulated with clomiphene/HMG (27 versus 15% respectively; P < 0.03), when HCG was administered later in the menstrual cycle (P < 0.01) and when more and better quality embryos were transferred (P < 0.01). Using multivariate regression analysis, the influence of the stimulation on pregnancy rate was even more pronounced (P < 0.01) when the day of HCG administration and the number and quality embryos transferred were taken into account. Therefore, we conclude that HMG alone increases pregnancy rate compared to clomiphene/HMG during replacement cycles of frozen/thawed pronucleate ova. These data suggest that HMG results in a better endometrium receptivity for embryos.(ABSTRACT TRUNCATED AT 250 WORDS) A multicenter clinical trial was conducted in Viet Nam, comparing two injectable contraceptive preparations: the three-monthly injectable depot-medroxyprogesterone acetate (DMPA) and the once-a-month injectable Cyclofem. A total of 600 volunteers were randomized to the two treatment groups and followed for one year. No pregnancy occurred during the trial. Approximately one quarter of the women in each group discontinued early from the trial. In the DMPA group, this was mostly because of amenorrhea and vaginal bleeding irregularities. In the Cyclofem group, an equal number discontinued because of menstrual problems and personal reasons. These personal reasons are probably related to the inconvenience of having to return to the clinic for injection on a monthly basis. Thus, Vietnamese women experience less side effects with Cyclofem than with DMPA, and once Cyclofem is made more widely available and is more accessible, it may better meet their needs than does DMPA. To demonstrate the comparative efficacy and tolerability of capsules containing 200 mg of P (Utrogest 200) or Crinone 8% gel for luteal phase and early pregnancy support during assisted reproduction techniques (ART).
                Prospective, multicenter, randomized, controlled, open, parallel-group Phase III trial.
                Seventeen German IVF centers.
                Four hundred thirty women who underwent their first IVF or intracytoplasmic sperm injection cycle were randomized after successful transfer of two or three embryos from July 1999 through September 2001.
                Patients vaginally applied capsules containing 200 mg of P (Utrogest 200) three times per day or containing Crinone 8% gel twice per day. Therapy was started in the evening of the ET day and continued up to 10 weeks in pregnant women. If the pregnancy test proved to be negative, application was stopped.
                Ongoing pregnancy rate at the end of the study (12th week of gestation). Secondary outcomes were rate of implantation and abortion, number and reasons of withdrawals, as well as adverse events, assessment of tolerability, and acceptance.
                There were no relevant differences in demographic and other characteristics between the two groups. Ongoing pregnancy rates were 25.2% in the Utrogest 200 group and 22.2% in the Crinone 8% group when patients were analyzed who normally completed the trial. In the Utrogest 200 vs. the Crinone 8% group, the implantation rate (14.7% vs. 11.9%) and abortion rate (18.2% vs. 19.1%) were not statistically different. The rate of withdrawals at the individual visits also did not differ between treatment groups. Tolerability of both drugs was good, and very few study drug-related adverse events were observed in both groups.
                The luteal phase support in ART cycles with Utrogest 200 capsules (three times per day) or Crinone 8% gel (two times per day) by the vaginal route resulted in similar outcomes with respect to implantation, ongoing pregnancy, and abortion rates. The two recommended regimens of P supplementation in ART proved to be equivalent and safe. To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M-PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects.
                Fifty-one women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2 intravaginal suppositories for second-trimester abortion. Efficacy and side effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis with Fisher exact test, and survival analysis.
                The mean times to rupture of membranes, delivery of fetus, and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories. The cumulative abortion rate after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2 alpha group. Although there were few differences in side effects, the 15M-PGF2 alpha group had significantly fewer headaches, fevers, and chills.
                Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion. A randomized multicenter study was performed in order to investigate the acceptance of a low-dose OC (30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel), using a 9 weeks on and 1 week off schedule (prolonged regimen, n = 198), compared to a traditional 3 weeks on, 1 week off schedule (standard regimen, n = 96). Haemoglobin and blood pressure remained the same in both groups during the study. No significant differences were found in body weight changes between the two groups. There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with standard regimen, but both breakthrough bleeding and spotting decreased during the trial. Irregular bleeding was significantly less in women who were already using OC, compared to "new starters." No serious side effects occurred. Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen, while there were significantly more women who stopped the trial because of headache in the group with standard regimen. After completing 12 months, or after premature withdrawal from the study, each women completed a questionnaire. Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC. To determine whether hMG offers an advantage over clomiphene citrate (CC) in achieving pregnancy after IUI with husband's sperm.
                Randomized prospective trial.
                Infertility patients in a university teaching hospital.
                Fifty-eight women under 39 years old undergoing ovulation induction before IUI.
                The women were assigned randomly to one of two treatment groups. Patients in group I (CCHH) received CC for the first two cycles and hMG for the last two cycles. Patients in group II (HHCC) received hMG for the first two cycles and CC for the last two cycles.
                Cycle fecundity rates for the two treatment modalities were compared statistically with use of life-table analysis.
                Of the 174 cycles studied, overall cycle fecundity rate was 11.11 (9 of 81 cycles) in the CCHH group and 10.75 (10 of 93 cycles) in the HHCC group. The difference was not statistically significant. The cycle fecundity rate was 14.44% (13 of 90 cycles) for cycles with CC and 7.14% (6 of 84) with hMG. The difference was not statistically significant.
                These data suggest that CC is an effective alternative to hMG in the population examined.
Women using COCs containing second-generation progestogens may be less likely to discontinue than those using COCs containing first-generation progestogens. Based on one small double-blind trial, third-generation progestogens may be preferable to second-generation preparations with regard to bleeding patterns but further evidence is needed. Without blinding as to treatment group, comparisons between the various "generations" of progestogens used in COCs cannot be made. Until this widespread methodological flaw is overcome in better trials conducted according to CONSORT guidelines and internationally accepted definitions, no further conclusions can be drawn.