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BACKGROUND: Although observational studies suggest that IVF is more effective than no treatment for women with Fallopian tube patency, this has not been tested rigorously in a randomized controlled trial (RCT). METHODS: Eligible consenting couples planning their first treatment cycle in five Canadian fertility clinics received either IVF, within 90 days of randomization, or a period of 90 days with no treatment. Random allocation was stratified by female age and sperm quality, and administered using numbered, opaque, sealed envelopes. Follow‐up assessed live birth and associated morbidity. RESULTS: Sixty‐eight couples were randomized to a first cycle of IVF and 71 couples had 3 months without treatment. The live birth rates were 20/68 (29%) and 1/71 (1%), respectively. The single delivery in the untreated group was of twins, as were six of the 20 IVF deliveries (30%). An average of 2.0 embryos were transferred and no triplet pregnancies resulted. The relative likelihood of delivery after allocation to IVF was 20.9‐fold higher than after allocation to no treatment [95% confidence interval (CI) 2.8–155]. The presence of abnormal sperm did not reduce this likelihood. Treating four women (95% CI 3–6) with one cycle of IVF is required to achieve a single additional birth. CONCLUSIONS: This study provides a valid and up‐to‐date comparison for policy makers and patients as they make choices around IVF, accurately measuring and confirming a major benefit from treatment. [ABSTRACT FROM AUTHOR]

The inhalation of hazardous concentrations of fresh brown cadmium oxide fume that can occur in a confined space or with inadequate ventilation may give rise to acute pulmonary damage which may be fatal after a single exposure. A Special Short Exposure Limit (SSEL) is given for this fume. Long term exposure to cadmium dust or fume may give rise to shortness of breath, due to permanent lung damage, or to kidney damage characterised by renal tubular dysfunction. Current knowledge about the toxic effects of cadmium that have been observed in cadmium exposed workers is reviewed in the light of the actions of cadmium on the mammalian body. Recommendations are made for the type and frequency of medical surveillance on workers exposed to cadmium as well as for the techniques for measuring exposure. A hygiene standard is recommended of 0.05 mg cadmium/m for the respirable fraction of all cadmium compounds and, for that portion of tha total dust sample which is soluble in 0.1 N hydrochloric acid, the level shall not exceed 0.2 mg cadmium/m. [ABSTRACT FROM PUBLISHER]

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are intra-ovarian signalling peptides that are important in follicle development and oocyte maturation. In the ovary, neurotrophin expression is regulated by gonadotrophins. Therefore, this study postulates that aetiology of infertility will affect follicular-fluid BDNF and NGF concentrations. follicular fluid from the first follicle aspirated from 190 infertile women attending a university-affiliated fertility programme (McMaster University and ONE Fertility, Burlington, Ontario) was collected between February 2004 and November 2010. The relationship between follicular-fluid BDNF and NGF concentration and age, day-3 FSH and peak serum oestradiol concentrations and antral follicle count was determined. Participants were aged between 24 and 44 years (mean ± SEM, 35.2 ± 0.3 years) of age. The median concentrations of BDNF and NGF in the follicular fluid was 19.4 pg/ml and 344.6 ng/ml, respectively. The concentrations of BDNF and NGF were significantly related (P = 0.028) but only the BDNF concentration was significantly higher (P < 0.05) in women with unexplained infertility compared with other causes of infertility. It is concluded that, apart from unexplained infertility, the underlying cause of infertility did not affect ovarian output of BDNF and NGF in response to ovulation induction. [ABSTRACT FROM AUTHOR]

Background: The optimal ovarian stimulation dose to obtain the best balance between the probability of pregnancy and the risk of complications, while maximizing cost-effectiveness of in vitro fertilization (IVF) treatment, is yet to be established., Methods: A systematic search of the electronic databases PubMed, EMBASE and Cochrane library, from 1984 until October 2009 for randomized controlled trials comparing different doses of recombinant FSH in IVF, was performed., Results: Ten studies (totaling 1952 IVF cycles) were included in the present meta-analysis, comprising patients younger than 39 years with regular menstrual cycle, normal basal FSH levels and two normal ovaries. Comparison was made between studies using a daily dose of 100 versus 200 IU recFSH, and between 150 versus 200 IU recFSH or higher. Although oocyte yield was greater in the >200 IU/day dose group, pregnancy rates were similar compared with lower dose groups. The risk of insufficient response to ovarian stimulation was greatest in the 100 IU/day dose group. The risk of developing ovarian hyperstimulation syndrome was greater in the >200 IU/day dose group. The number of embryos available for cryopreservation was lowest in the 100 IU/day group, but similar comparing the 150 IU/day and the >200 IU/day dose groups., Conclusions: This meta-analysis suggests that the optimal daily recFSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy and embryo cryopreservation rates. Furthermore, the wide spread adherence to this optimal dose will allow for a considerable reduction in IVF costs and complications.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.

This meta-analysis was conducted to compare outcomes of conventional IVF in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. Studies in which PCOS patients undergoing IVF were compared with a matched--no male factor--control group were considered for this review. A definition consistent with the Rotterdam consensus criteria of PCOS was required, and all patients within a given study had to be treated with the same ovarian stimulation protocol. Information regarding patient characteristics and pregnancy outcome was also required. Nine out of 290 identified studies reporting data on 458 PCOS patients (793 cycles) and 694 matched controls (1116 cycles) fulfilled these inclusion criteria. PCOS patients demonstrated a significantly reduced chance of oocyte retrieval per started cycle, odds ratio (OR) = 0.5 [95% confidence interval (CI) = 0.2-1.0]. However, no difference was observed in chance of embryo transfer per oocyte retrieval between the groups (OR = 0.7, 95% CI = 0.4-1.3). Significantly more oocytes per retrieval were obtained in PCOS patients compared with controls [random effects estimate 3.4 [95% (CI) = 1.7-5.1)]. The number of oocytes fertilized did not differ significantly between PCOS patients and controls, weighted mean difference (WMD) 0.1 oocytes (95% CI = 21.4-1.6). No significant difference was observed in the clinical pregnancy rates per started cycle, OR = 1.0 (95% CI = 0.8-1.3). The incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported. This meta-analysis demonstrates an increased cancellation rate, but more oocytes retrieved per retrieval and a lower fertilization rate in PCOS undergoing IVF. Overall, PCOS and control patients achieved similar pregnancy and live birth rates per cycle.

Objectives: To assess the effects of female and male smoking on natural and assisted fecundity., Design: A systematic review of published studies was conducted, identifying reports using on-line and hand search techniques., Included Studies: Potentially relevant articles were screened for inclusion based on the following criteria: comparative study (cohort or case control) with clinical pregnancy or live birth reported among smokers and nonsmokers., Exposure: Cigarette smoking., Main Outcome Measures: Time to conceive; conceptions per subject or per cycle; spontaneous abortion rate., Results: Thirteen relevant studies of natural conception were identified. All but one demonstrated a negative association between smoking and fecundity (odds ratio [OR] for conception or live birth 0.33 to 1.0). Seven studies of IVF-GIFT yielded a common odds ratio for conception of 0.57 (95% confidence interval 0.42 to 0.78). Seven studies evaluating spontaneous abortion suggested a small increased risk among female smokers (OR 0.83 to 1.8). Twenty-one studies assessing smoking in men demonstrated no consistent effect on sperm quality. None of the four studies evaluating fertility in male smokers demonstrated significant impairment., Conclusion: This body of literature suggests a small but clinically significant detrimental effect of female smoking on both time to conception and spontaneous abortion risk. Variability between studies, particularly in terms of adjustment for confounding factors, undermines the strength of these conclusions. However, the consistent dose-response effect in both the spontaneous conception and abortion literature and a return to normal fecundity among exsmokers suggest a causal association. The effect of male smoking on fecundity is probably far less significant.

Systematic error or bias in a review is hard to avoid when the review is executed without a clearly defined research question and methodology. The methods of systematic review and meta-analysis are designed to address these and other sources of bias with the goal of producing the most valid and precise estimate of effect or risk possible. The guiding principle is the a priori establishment of a protocol which details the research question, study inclusion criteria, and methods for quantitatively combining data to provide an overall estimate of effect or risk. Randomized clinical trials generally provide the least biased estimates of treatment effect and are therefore more suitable for meta-analysis. The strengths and weaknesses of this approach are discussed in detail. Finally, a description of the goals and structure of the Cochrane Collaboration is included.

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.

Objective: To investigate adverse reactions to hMG preparations in two women in IVF programs., Design: Two case reports with skin tests for delayed hypersensitivity (DH) to hMG and a biopsy of one delayed reaction., Setting: Allergy and infertility clinics in university medical center., Patients: Two affected patents with a history of local reactions to the injected hMG, one of whom also had fever, and nine control subjects., Interventions: Skin tests and biopsy., Main Outcome Measures: Delayed hypersensitivity skin response to hMG in affected patients indicated by timing and biopsy results. Negative skin test with the purified hFSH, which was also used in treatment with no adverse effects., Conclusion: Use of the purified preparation avoids DH reaction.

Ovulation induction is the most common medical intervention for the treatment of infertility. Clomifene is generally the first treatment choice for patients with amenorrhoea, unless there is profound hypothalamic deficiency. When clomifene fails to induce ovulation, menotropins (human menopausal gonadotrophin) or gonadotrophin-releasing hormone (GnRH) are effective, most notably in WHO group 1. In this condition associated with low estrogen and gonadotrophin levels, the aggregate of reported pregnancy rates is 25% per cycle. In hyperprolactinaemic anovulation bromocriptine reduces prolactin levels and thereby restores normal cyclicity. In all of the above conditions, the pharmacological agent addresses a specific defect in an explicit manner. WHO group 2 ovulatory disorders arise from hyperandrogenicity and other conditions that respond less predictably to gonadotrophin therapy. In women with WHO group 2 disorders, the aggregate of reported pregnancy rates is 8%. Ovulation induction is also used in ovulatory infertile women to generate multiple follicles and increase the likelihood of fertilisation. The aggregate of pregnancy rates in clomifene trials was 7% per cycle, and 6% in gonadotrophin trials. Gonadotrophin therapy is more effective, however, in association with assisted reproduction techniques. The contrasting treatment success in discrete disorders (25% per cycle) and heterogeneous disorders such as WHO group 2 and persistent infertility (6 to 8% per cycle) underlines the need for research to discover specific causal mechanisms and identify explicit new pharmacological interventions.