Neurotrophins (BDNF and NGF) in follicular fluid of women with different infertility diagnoses.

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±0.3years) of age. The median concentrations of BDNF and NGF in the follicular fluid was 19.4pg/ml and 344.6ng/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.

Clinical outcomes in relation to the daily dose of recombinant follicle-stimulating hormone for ovarian stimulation in in vitro fertilization in presumed normal responders younger than 39 years: a meta-analysis.

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.

A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

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.

A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.

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.

A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency.

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.

Levels of environmental contaminants in human follicular fluid, serum, and seminal plasma of couples undergoing in vitro fertilization.

Environmental chemicals are thought to adversely affect human reproductive function, however there are no studies that have explored the association between failed fertilization and exposure of both partners to environmental contaminants. Therefore, we collected blood and follicular fluid from the female partner and seminal plasma from the male partner of 21 couples attending an in vitro fertilization (IVF) program, in order to determine the extent of the existence of environmental chemicals in these fluids. Any relationship to the outcome of IVF was also considered. Sera and fluids were analysed for a variety of contaminants, including polychlorinated biphenyls, pesticides, cotinine, and the steroids progesterone and estradiol. Of the couples examined, 18 had fertilizations, three of whom became pregnant. There were no fertilizations in three other couples. The contaminants most frequently found in follicular fluid, more than 50% of the samples tested, were p,p'-DDE, mirex, hexachloroethane, 1,2,4-trichlorobenzene, PCB 49, PCB 153, and PCB 180. Cadmium was detected in eight of 21 (38.1%) samples of follicular fluid whereas cotinine was detected in 18 (85.7%). Residue levels of p,p'-DDE, endosulfan I, PCB 99, PCB 138, PCB 153, PCB 180 were quantified in more than 50% of the sera samples examined. Seminal plasma was relatively free of pollutants with mirex being the most frequently detected contaminant found in seven of 21 (33.3%) samples. Mirex could not be detected in the seminal plasma of the husbands whose partner's oocytes failed to fertilize whereas significant levels of mirex were found in the seminal plasma of all couples who had a pregnancy. Cadmium was also found in the follicular fluid of these pregnant subjects. No relationship was found between follicular fluid cotinine in pregnant and non-pregnant subjects. Where identical contaminants were found in both sera and follicular fluids, the levels were about twofold higher in serum and were positively correlated in both fluids. Fertilization was negatively correlated with serum and follicular fluid p,p'-DDE whereas pregnancy was positively correlated with follicular fluid PCB 49. These data reveal that more than 50% of the population of women attending a fertility program have had exposure to environmental chemicals sufficient to produce detectable concentrations in their serum and ovarian follicular fluid. Of the chemical contaminants detected in the serum and follicular fluid of these women, p,p'-DDE was the most frequently detected, had the highest residue levels, and was associated with failed fertilization.

Funding in vitro fertilization treatment for persistent subfertility: the pain and the politics.

OBJECTIVE: To consider the arguments for and against funding for in vitro fertilization (IVF) and to explore potential avenues for policy change. DESIGN: Narrative literature review, policy analysis. SETTING: University Department of Obstetrics and Gynecology. PATIENT(S): Sub-fertile women and men. INTERVENTION(S): Fertility treatments, in particular IVF. RESULT(S): The two main arguments used against funding for IVF are that [1] subfertility is a social, not a medical problem, and therefore its treatment is not medically indicated or necessary, and [2] the clinical effectiveness of IVF is unproven. These and other major arguments are critiqued. CONCLUSION(S): Dismissing IVF as medically unnecessary seems premature because medical necessity has not been operationally defined. Demonstrating IVF effectiveness through a randomized trial has not been done but is feasible: a multicenter trial is currently underway in Canada. Dealing with the concern that subfertility treatment challenges the role of women in society, as well as with questions of cost-effectiveness, are more difficult challenges that deserve further debate. The potential for unethical uses and broader social implications of IVF add to its dubious status and provide a convenient rationale for refusing to pay. However, none of these concerns is unique to IVF: many currently covered health services are susceptible to the same criticisms. For all services, judgments of eligibility for coverage should be consistent and transparent and should explicitly separate the issues of cost from other factors.

Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis.

OBJECTIVE: To compare dinoprostone 10 mg controlled-release vaginal insert with other forms of vaginal or cervical prostaglandin for cervical ripening. DATA SOURCES: Literature search strategy included review of the Cochrane database of randomized trials, on-line searching of MEDLINE, hand searching of bibliographies, and contact with authors of relevant reports. METHODS OF STUDY SELECTION: Randomized trials were included if they compared a dinoprostone slow-release vaginal insert with an alternative vaginal or cervical prostaglandin for cervical ripening and labor induction in women at term with singleton gestations. Primary end points were delivery by 24 hours postinsertion, uterine hypertonus with fetal heart change, and cesarean delivery rate. Study inclusion, validity assessment, and data extraction were carried out independently by two reviewers, and cross-checked for consistency. Data were combined when appropriate, using the Mantel-Haenszel fixed-effects method. Statistical heterogeneity was assessed using chi-square statistics. TABULATION, INTEGRATION, AND RESULTS: Nine relevant trials were identified, seven comparing the dinoprostone 10 mg vaginal insert with dinoprostone gel and two with misoprostol. Five trials reported adequate methods for randomization concealment. None were double blind. The likelihood of delivery by 24 hours was similar with the vaginal insert and alternatives: common odds ratio (OR) 0.80 (95% confidence interval [CI] 0.56, 1.15). Uterine hypertonus with change in fetal heart and cesarean delivery rate were also similar: common OR 1.19 (95% CI 0.56, 2.54) and 0.78 (95% CI 0.56, 1.08), respectively. The secondary end points of mean time to delivery and delivery by 12 hours appeared to favor misoprostol-dinoprostone gel. However, data for these end points were heterogeneous and their combination is therefore of limited value and potentially misleading. CONCLUSION: No clinically significant differences were identified between the vaginal insert and alternatives used for cervical ripening at term.

Randomized trial of a "stage-of-change" oriented smoking cessation intervention in infertile and pregnant women.

OBJECTIVE: To assess a "stage-of-change" oriented smoking cessation intervention for infertile and pregnant women, compared with standard of care. DESIGN: Randomized controlled trial. SETTING: Three university teaching hospitals in Hamilton, Ontario, Canada. PATIENT(S): Infertile women at their first visit to a tertiary referral infertility clinic (n = 94) and new patients seeking pre-natal care (n = 110) who had smoked >/= 3 cigarettes in the past six months. INTERVENTION(S): A three to five minute scripted intervention and booklet specific to the woman's "stage-of-change" in the smoking continuum, versus standard of care. Exhaled carbon-monoxide (CO) monitoring was used to validate exposure in both groups. MAIN OUTCOME MEASURE(S): Delta "stage-of-change" and rate of maintained cessation at 12 months post follow-up. RESULT(S): Intervention and control were similarly effective for infertile women: the rate of maintained cessation rose significantly from 4% to 24% over twelve months, with a mean delta "stage-of-change" 0.28. In prenatal women, neither approach was effective. Maintained cessation did not significantly change from 0 to 12 months (19% to 18%). Mean delta "stage-of-change" declined by -0.62. CONCLUSION(S): For infertile women, basic information describing the impact of smoking on fertility, along with exhaled CO monitoring and a more intensive intervention were both highly effective. In pregnant women neither approach was beneficial, with some evidence of post-partum relapse.

20 years of medical surveillance on exposure to allergenic and non-allergenic platinum compounds: the importance of chemical speciation.

OBJECTIVES: Chloroplatinates are potent allergens but other soluble platinum compounds such as tetraammine platinum dichloride (TPC) do not provoke reactions in subjects who are sensitive to chloroplatinates. TPC has been used in the manufacture of autocatalysts for 20 years. This study analyses 20 year data on exposure to soluble platinum compounds and medical surveillance to confirm that TPC is not allergenic. METHODS: Workers in three distinct operations were exposed to soluble platinum compounds as chloroplatinates, chloroplatinates with TPC, or to TPC alone. Results of personal air sampling for soluble platinum compounds were compared together with the results of medical surveillance. RESULTS: The levels of exposure to soluble platinum compounds in each operation were comparable but the incidence of allergy was significantly different. In a subgroup of workers consistently exposed to chemical processes in each operation, the cumulative chance of being sensitised after 5 years of exposure was estimated as 51% for chloroplatinate exposure, 33% for mixed exposure, and 0% for TPC alone. The differences in sensitisation rates could not be explained by age, sex, and atopy. Nor could they be explained by the increased frequency of smoking in the workers with chloroplatinate exposure, despite the markedly higher risk of sensitisation in smokers. The differences could only be explained by the chemical stability of TPC. CONCLUSIONS: This study shows that the soluble platinum compound TPC is not allergenic under normal industrial conditions. Characterisation of the chemical compound (speciation) is essential to prevent stringent exposure limits being imposed for all soluble compounds on a generic basis.

A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility.

This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility.

The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta-analysis.

A systematic review was conducted to evaluate the effectiveness of intrauterine insemination (IUI) with or without ovarian stimulation using gonadotrophin in the treatment of persistent infertility. Relevant randomized controlled trials were identified by a diverse strategy including a hand search of 43 core journals from 1966 to the present. Two approaches to meta-analysis were used to summarize data. First, using a standard Mantel-Haenszel approach, eight trials comparing FSH/IUI with FSH/timed intercourse for unexplained infertility were combined. The common odds ratio for pregnancy was 2.37 [95% confidence interval (CI), 1.43, 3.90], suggesting a significant improvement with IUI following ovulation induction in this patient group. Although the data were statistically homogeneous, clinically important heterogeneity was present. Second, across all diagnostic groups, the independent effects of treatment with follicle stimulating hormone (FSH), clomiphene citrate, IUI, as well as the diagnoses of male factor and endometriosis were assessed using stepwise logistic regression. Based on 5214 cycles reported in 22 trials, the odds ratio for pregnancy associated with FSH use was 2.35 (95% CI, 1.87, 2.94) for IUI, 2.82 (95% CI, 2.18, 3.66) for male factor, 0.48 (95% CI, 0.37, 0.61), and for endometriosis 0.45 (95% CI, 0.27, 0.76). This summary of the best available evidence may prove useful in counselling couples who are considering FSH and/or IUI therapy.

Does cigarette smoking impair natural or assisted fecundity?

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 literature review and meta-analysis.

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.

[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.

Delayed-type hypersensitivity to human gonadotropin: case report.

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.

Pharmacological interventions for the induction of ovulation.

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.

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.