Use of embryo culture supernatant to improve clinical outcomes in assisted reproductive technology: a systematic review and meta-analysis.

We planned a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the best available evidence regarding the intrauterine instillation of embryo culture supernatant prior to embryo transfer in ART. The outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy; and (iv) miscarriage rates. Five RCTs were considered eligible and available for qualitative synthesis. Due to clinical heterogeneity, results from only two trials were combined for the meta-analysis. The live birth rate (risk ratio [RR], 0.47; 95% confidence interval [CI] 0.22-0.98; one study, 60 participants, low-quality evidence) was found to be significantly lower with intrauterine instillation of embryo culture supernatant compared to no intervention. The clinical pregnancy rate was similar between the embryo culture supernatant group and the control group (RR 1.02 RR, 95% CI 0.77-1.36; two trials, 156 participants, I2 = 0%). To conclude, this review did not find any improvement in clinical pregnancy rate with the intrauterine instillation of embryo culture supernatant prior to embryo transfer compared to no intervention in women undergoing ART and we remain uncertain regarding its effect on live birth rate.

Ovulation triggers in anovulatory women undergoing ovulation induction.

BACKGROUND: Anovulation is a common cause of infertility. Drugs used to treat anovulation include selective oestrogen receptor modulators, aromatase inhibitors and gonadotrophins. Ovulation triggers are used with these drugs, as a surrogate for the hormonal surge seen in spontaneous menstrual cycles, to control the timing of ovulation and the timing of sexual intercourse. Ovulation triggers given without reliable evidence of oocyte maturity could be inappropriately timed; they increase costs, and the need to time intercourse precisely after the ovulation trigger is given adds to psychological stress.This is an update of a Cochrane review first published in Issue 3, 2008, of the Cochrane Database of Systematic Reviews. OBJECTIVES: To determine the benefits and harms of administering an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents in comparison with spontaneous ovulation following ovulation induction. SEARCH METHODS: We updated searches of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO to November 2013. We checked conference proceedings, trial registries and reference lists and contacted researchers. SELECTION CRITERIA: Parallel-group, randomised, controlled trials (RCTs) evaluating the administration of an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents. DATA COLLECTION AND ANALYSIS: We independently assessed trial eligibility and trial quality and extracted data. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and used the random-effects model in meta-analyses when significant heterogeneity was present. We assessed overall quality of the evidence by using the GRADE approach. MAIN RESULTS: No new trials were identified. This review includes two RCTs with low risk of bias that compared urinary human chorionic gonadotrophin (hCG) versus no treatment in anovulatory women receiving clomiphene citrate. Urinary hCG did not result in an increase in live birth rate over no hCG (OR 0.97, 95% CI 0.52 to 1.83; two trials, 305 participants, I(2) = 16%; low-quality evidence), but very serious imprecision around the effect estimate reduces our confidence in the apparent lack of effect of hCG as an ovulation trigger in clomiphene-induced cycles in anovulatory women.Among this review's secondary outcomes, urinary hCG may not increase ovulation rate (OR 0.99, 95% CI 0.36 to 2.77; two trials, 305 participants, I(2) = 55%; low-quality evidence), clinical pregnancy rate (OR 1.02, 95% CI 0.56 to 1.89; two trials, 305 participants, I(2) = 35%; low-quality evidence) or miscarriage rate in pregnant women (OR 1.19, 95% CI 0.17 to 8.23; two trials, 54 participants, I(2) = 0%; low-quality evidence). Multiple pregnancies and preterm deliveries were uncommon, and ovarian hyperstimulation syndrome, adverse events and deaths were not reported as outcomes in either trial. We found no trials evaluating other ovulation triggers. AUTHORS' CONCLUSIONS: Evidence is inadequate to recommend or refute the use of urinary hCG as an ovulation trigger in anovulatory women treated with clomiphene citrate. We found no trials evaluating the use of ovulation triggers in anovulatory women treated with other ovulation-inducing agents.

Predictive factors for pregnancy after intrauterine insemination: A prospective study of factors affecting outcome.

OBJECTIVE: To determine the predictive factors for pregnancy after controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI). DESIGN: Prospective observational study. SETTING: University-level tertiary care center. PATIENTS AND METHODS: 366 patients undergoing 480 stimulated IUI cycles between November 2007 and December 2008. INTERVENTIONS: Ovarian stimulation with gonadotrophins was initiated and a single IUI was performed 36 h after triggering ovulation. MAIN OUTCOME MEASURES: The primary outcome measures were clinical pregnancy and live birth rates. Predictive factors evaluated were female age, duration of infertility, indication for IUI, number of preovulatory follicles, luteinizing hormone level on day of trigger and postwash total motile fraction (TMF). RESULTS: The overall clinical pregnancy rate and live birth rate were 8.75% and 5.83%, respectively. Among the predictive factors evaluated, the duration of infertility (5.36 vs. 6.71 years, P = 0.032) and the TMF (between 10 and 20 million, P = 0.002) significantly influenced the clinical pregnancy rate. CONCLUSION: Our results indicate that COH/IUI is not an effective option in couples with infertility due to a male factor. Prolonged duration of infertility is also associated with decreased success, and should be considered when planning treatment.

Ovulation triggers in anovulatory women undergoing ovulation induction.

BACKGROUND: Anovulation is a common cause for infertility. Drugs used to treat anovulation include selective estrogen receptor modulators, aromatase inhibitors and gonadotrophins. Ovulation triggers are used with these drugs, in order to time intercourse. Ovulation triggers without reliable evidence of oocyte maturity could be inappropriately timed, increase costs and psychological stress. This review evaluates different ovulation triggers used when treating anovulatory women with ovulation inducing agents compared to spontaneous ovulation. OBJECTIVES: To determine the efficacy of administering an ovulation trigger compared to spontaneous ovulation in anovulatory women being treated with ovulation inducing agents. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group Trials Register (August week 1 2007), Cochrane Central Register of Controlled Trials (CENTRAL Cochrane library issue 3 2007) and the electronic databases MEDLINE (1950 July week 4 2007), EMBASE(1980 to week 31 2007) and CINAHL (1982 to August week 1 2007) for studies in all languages. SELECTION CRITERIA: Randomised controlled trials (RCT). DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed quality and extracted data. Disagreement was resolved by discussion with the third author and by contacting trial authors. Categorical data were analysed using relative risks and their 95% confidence intervals. A random effects model was used in the presence of significant heterogeneity. MAIN RESULTS: Two RCTs comparing urinary hCG versus no treatment in anovulatory women receiving clomiphene citrate were identified. Urinary hCG did not result in increases in the primary outcome of live birth rate over no treatment { OR 0.98, 95% CI 0.52 to 1.83}.Among the secondary outcomes, urinary hCG did not increase ovulation rate ( OR 0.95, 95% CI 0.49 to 1.83), clinical pregnancy rate (OR 1.02, 95% CI 0.56 to 1.88), multiple pregnancy rate (OR 0.47, 95% CI 0.05 to 4.59), miscarriage rate( OR 1.18, 95% CI 0.18 to 7.66) and preterm delivery (OR 0.12,95% CI 0.00 to 6.29) compared to no treatment. Trials evaluating other ovulation triggers were not identified. AUTHORS' CONCLUSIONS: There is inadequate evidence to recommend or refute the use of urinary hCG, as an ovulation trigger, in anovulatory women being treated with clomiphene citrate. We did not find trials evaluating the use of ovulation triggers in anovulatory women, being treated with other ovulation inducing agents.