A double-blind randomised controlled trial of the effects of medroxyprogesterone acetate on bone density of women taking oestrogen replacement therapy.

OBJECTIVE: To assess the effects of medroxyprogesterone acetate on bone density in women who have had a hysterectomy. DESIGN: Randomised, double-blind, placebo-controlled trial of medroxyprogesterone acetate 10 mg, 20 mg or placebo as an adjunct to oestrogen therapy. PARTICIPANTS: One hundred and twenty-three women, aged 18 to 45 years and currently receiving daily oestrogen, who presented at a university-based rheumatology practice. INTERVENTIONS: The women were randomly assigned to receive either medroxyprogesterone acetate 10 mg, 20 mg or placebo daily beginning on day 15 of each month for one year. Forty-one women were randomised into each group. MAIN OUTCOME MEASURE: The primary outcome measurement was the percentage of change from baseline in bone mineral density of the lumbar spine (L2-L4). Secondary outcome measures included differences in femoral neck bone density, cholesterol and triglyceride levels between groups. RESULTS: At one year, change in bone mineral density did not differ between either the treatment or placebo groups. Medroxyprogesterone acetate 20 mg and 10 mg led to statistically significant reductions in very low density lipoprotein cholesterol, total triglycerides, and very low density lipoprotein triglycerides when compared with placebo. Medroxyprogesterone acetate 20 mg also led to a statistically significant reduction in high density lipoprotein cholesterol, high density lipoprotein-2 cholesterol, and high density lipoprotein-2 triglycerides. CONCLUSIONS: Medroxyprogesterone acetate at either dose as an adjunct to oestrogen did not improve bone mineral density at one year when compared with placebo. Medroxyprogesterone acetate 10 mg may not adversely affect lipids. Medroxyprogesterone acetate 20 mg, however, did reduce high density lipoprotein cholesterol and therefore may increase cardiovascular risk.

[A randomized, controlled trial comparing follicle stimulating hormone (FSH) to human menopausal gonadotropin (hMG) in fertilization in vitro]. / Essai contrôlé, randomisé, comparant l'hormone folliculo-stimulante (FSH) à la gonadotrophine ménopausique humaine (hMG) dans la fécondation in vitro.

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2,500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To conduct a systematic overview of available data comparing FSH with hMG in IVF treatment cycles. DESIGN: A meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Search strategies included on-line searching of the National Library of Medicine MEDLINE data base from 1975 to 1993 and hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings. Common odds ratio (OR) and overall absolute treatment effect were calculated after demonstrating homogeneity of treatment effect across all trials. MAIN OUTCOME MEASURES: Clinical pregnancy rates per cycle start, per cycle reaching oocyte retrieval, and per cycle reaching ET. RESULTS: Eight trials met the inclusion criteria. The overall OR in favor of FSH for cycle start, oocyte retrieval, and ET were 1.71, 1.69 and 1.70, respectively, and represented an overall absolute treatment effect of 8.5%, 8.0% and 8.3%, respectively. CONCLUSIONS: This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.

Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome.

Improvements in oocyte culture technique, sperm preparation, oocyte retrieval method and ovarian stimulation regimens have produced higher pregnancy rates with in-vitro fertilization (IVF) treatment. However, because ovarian stimulation is expensive and not without risk, there is increasing interest in the option of using natural cycles for IVF. This study was performed to document the experience and outcome in 240 natural cycles. Cancellation occurred in 28 cycles (12%), and LH surge was observed in 56 (23%), leaving 156 (65%) cycles which progressed to oocyte retrieval. No oocytes were retrieved in 26 cycles. Among the successful oocyte retrievals, the majority yielded one oocyte. There was no evidence of fertilization in 26 cases, and triploid fertilization was observed in 12 cases. Embryos suitable for transfer were available in 92 cycles in which 11 (12%) clinical pregnancies were confirmed. Despite the high failure rate at each step in the process, natural cycles are more cost-effective than stimulated cycles which incur an incremental cost per live birth of $48,000. Natural cycles offer a low-cost alternative that may be more accessible to patients.

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization.

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6)). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action.

OBJECTIVE: To assess whether cigarette smoking in women or men affects the outcomes of IVF-ET and at what functional levels smoking is active. INTERVENTIONS: Demographic and smoking data were collected by questionnaire at the onset of consecutive treatment cycles (n = 462) and at the time of ET. In addition to routine endocrine and clinical data, circulating immunoreactive inhibin, follicular fluid E2 endometrial thickness, and morphology were assessed. Reported exposure to cigarettes was validated using a serum cotinine assay. RESULTS: Serum cotinine level at the onset of treatment correlated strongly with the number of cigarettes reported (r = 0.68). The duration and dose of gonadotropin treatment was greater among active smokers than never smokers: 10.2 versus 9.2 days and 24.7 versus 19.8 ampules, respectively. Fertilization, pregnancy, and abortion rates were similar between groups. Multivariate analyses demonstrated negative correlation between female age, but no such effect was seen with female or male smoking. Sperm concentration was significantly reduced in male smokers (prewash: 108 versus 130 x 10(6); postwash: 17.1 versus 21.6 x 10(6)), although fertilization rate was unaffected (66% versus 62%). Follicular function, assessed using serum inhibin and E2, as well as follicular fluid E2 levels showed no significant difference between active smokers and never smokers. Endometrial thickness and morphology also were similar between groups. CONCLUSIONS: These data suggest that among couples undergoing IVF neither female nor male smoking has a measurable deleterious effect on conception rate. Female age remains a far more potent prognostic factor in the current study. However, when all the published data are combined, a significant deleterious effect of smoking on conception is suggested, with a common odds ratio of 0.540 (95% confidence interval 0.385 to 0.757).

The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN: Meta-analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES: The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS: Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS: This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment.

A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome.

Treatment with low-dose follicle-stimulating hormone (FSH) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome (PCOS), but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin. We undertook a randomized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin (hMG) using a low-dose regimen in 30 women with PCOS. Each subject received a maximum of three cycles of either FSH or hMG. Ovulation occurred in 75% of subjects and in 77% of cycles induced with FSH and in 94% of women, 85% of cycles of those treated with hMG. A single dominant follicle developed in 70% (FSH) and 65% (hMG) of cycles, respectively. Five singleton pregnancies occurred in each group. This study shows that low-dose FSH and hMG are equally successful in inducing ovulation, suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation.