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Unlabelled: BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.Methods: A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.Results: A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18-40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) -0.49 nmol/l (-0.55, -0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20-25 µg EE had similar effects on total and free T compared with COCs with 30-35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20-25 µg EE) were found to have less impact on SHBG concentrations.Conclusions: The current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinical implications of suppressed androgen levels during COC use remain to be elucidated. [ABSTRACT FROM AUTHOR]

Background: The Fifth Evian Annual Reproduction (EVAR) Workshop Meeting discussed knowledge regarding contemporary genetics in female reproduction.Methods: Specialist reproductive medicine clinicians and geneticists delivered presentations based on published literature and current research. The content of this report is based on the expert presentations and subsequent group discussions that took place during this Workshop.Results: Numerous ovarian genes with a role in infertility have been identified. Future challenges for genetic screening of patients, such as those with polycystic ovary syndrome, primary ovarian insufficiency or endometriosis, include the identification of high-throughput strategies and how to apply these findings to infertile patients. The identification of high-quality embryos in IVF using objective technologies remains a high priority in order to facilitate single-embryo transfer. Gene expression profiling of cumulus cells surrounding the oocyte, and proteomic and metabolomic approaches in embryo culture media may significantly improve non-invasive embryo quality assessment.Conclusions: The way forward in advancing the knowledge of genes involved in reproduction was considered to be through genome-wide association studies involving large numbers of patients. Establishing international collaboration is required to enable the application of such technologies in sufficient numbers of patients. [ABSTRACT FROM AUTHOR]

BACKGROUND Recent advances in our understanding of the causes of infertility and of assisted reproductive technology (ART) have led to the development of complex diagnostic tools, prognostic models and treatment options. The Third Evian Annual Reproduction (EVAR) Workshop Meeting was held on 26-27 April 2008 to evaluate evidence supporting current approaches to the diagnosis and management of infertility and to identify areas for future research efforts. METHODS Specialist reproductive medicine clinicians and scientists delivered presentations based on published literature and ongoing research on patient work-up, ovarian stimulation and embryo quality assessment during ART. This report is based on the expert presentations and subsequent group discussions and was supplemented with publications from literature searches and the authors' knowledge. RESULTS It was agreed that single embryo transfer (SET) should be used with increasing frequency in cycles of ART. Continued improvements in cryopreservation techniques, which improve pregnancy rates using supernumerary frozen embryos, are expected to augment the global uptake of SET. Adaptation and personalization of fertility therapy may help to optimize efficacy and safety outcomes for individual patients. Prognostic modelling and personalized management strategies based on individual patient characteristics may prove to represent real progress towards improved treatment. However, at present, there is limited good-quality evidence to support the use of these individualized approaches. CONCLUSIONS Greater quality control and standardization of clinical and laboratory evaluations are required to optimize ART practices and improve individual patient outcomes. Well-designed, good-quality studies are required to drive improvements to the diagnosis and management of ART processes. [ABSTRACT FROM AUTHOR]

Background: Recombinant DNA technologies have been used to develop longer-acting therapeutic proteins. One approach is to introduce sequences containing additional glycosylation sites. Using this technique, a new chimeric gene has been developed containing the coding sequences of the FSH beta-subunit and the C-terminal peptide of the hCG beta-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the alpha-subunit and the chimeric FSH beta-subunit produces a new recombinant molecule, named corifollitropin alfa, with a prolonged elimination half-life and enhanced in vivo bioactivity compared with wild-type FSH. Methods: Medline searches by subject and additional searching by hand. Results: Initial studies in pituitary suppressed female volunteers confirmed the extended half-life of the compound. Phase II studies have shown that corifollitropin alfa is able to induce and sustain multi-follicular growth for an entire week in women undergoing ovarian stimulation using GnRH antagonist co-treatment for IVF. Corifollitropin alfa regimens have been developed with dosages of 100 and 150 microg, for patients with body weight 60 kg, respectively. Conclusions: Corifollitropin alfa is the first long-acting hybrid molecule with sustained follicle-stimulating activity developed for the induction of multi-follicular growth along with GnRH antagonist co-treatment for IVF. This new treatment option may be simpler and more convenient for patients compared with conventional long protocols of daily FSH injections in combination with GnRH agonist co-treatment. The safety and efficacy of such regimens is currently being evaluated in large comparative phase III clinical trials. The development of corifollitropin alfa is the first step towards a new generation of recombinant gonadotrophins. [ABSTRACT FROM AUTHOR]

Background: The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation.Methods: PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed.Results: Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH.Conclusions: No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated. [ABSTRACT FROM AUTHOR]

The article outlines the current understanding of implantation in humans and the role the endometrium and embryo play in the process. It also identifies key areas in implantation research and methodology that need to be focused on in the future such as optimizing ovarian stimulation regimens, the timing of human chorionic gonadotrophin injection or the timing of embryo transfer, to help increase implantation rates. Also cited are the strengths and limitations of morphological and immunohistochemistry assessments of endometrial receptivity.

Current ovarian stimulation regimens for IVF are complex and not without risk. Increasing our knowledge of the physiology of follicle development and dominant follicle selection may enable the design of less complex, safer and cheaper ovarian stimulation regimens for IVF. Decremental serum FSH concentrations during the follicular phase of the menstrual cycle are required for single dominant follicle selection. Only the most mature follicle will continue its development due to increased sensitivity for stimulation by FSH. FSH stimulation becomes insufficient for less mature follicles and remaining cohort follicles will therefore go into atresia. The number of days during which FSH is above the threshold for stimulation of follicle development is limited, resulting in a narrow FSH window. More medium sized and large pre-ovulatory follicles and increased oestradiol output can be induced by the administration of small doses of exogenous FSH during the mid- to late follicular phase, preventing the physiological decrease in FSH stimulation. Intervention with decremental serum FSH concentrations in combination with gonadotrophin-releasing hormone (GnRH) antagonists to prevent a premature rise in serum LH may induce ongoing growth of multiple follicles sufficient for IVF. The benefits and risks of these minimal hyperstimulation protocols require further evaluation. [ABSTRACT FROM PUBLISHER]

BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu, and environmental factors may represent important developmental determinants. Environmental and nutritional factors may also modify the downward trajectory of ovarian reserve in adult life. The combination of these early and later life influences has the potential to lead to diminished ovarian reserve, compromising fertility in later reproductive years and altering age at natural menopause. METHODS Literature searches of the ISI Web of Knowledge database were carried out using the main terms 'ovarian reserve' and 'menopause AND age' in conjunction with a range of other terms encompassing a variety of factors with potential effects on ovarian reserve. The various searches were inspected manually and the relevant papers selected for critical analysis and interpretation. RESULTS Evidence was identified supporting the view that elevated prenatal androgens have an adverse effect on the early establishment of ovarian reserve, although the implications for ovarian reserve in the polycystic ovary syndrome (which may also be programmed through prenatal androgen exposure) remain uncertain. Recent evidence is cited suggesting that effects of maternal nutrient restriction on ovarian reserve may also involve changes in prenatal androgen exposure. A general rationale is developed through examination of evidence which emphasizes the roles of the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve modulation. Because of their similarity to the natural ligands, many environmental compounds have the ability to bind to these receptors (albeit at lower affinities) and thereby have the potential to influence either the initial setting of ovarian reserve during development or the trajectory of ovarian reserve during adult life. For example, exposure to compounds in cigarette smoke may accelerate loss of ovarian reserve in smokers leading to diminished ovarian reserve, earlier age at last child and earlier menopause. Socioenocomic factors are clearly associated with age at natural menopause, with correlations with economic status and education level. However, such effects in western societies are in general small, and the underlying mechanisms remain unclear. CONCLUSIONS Exposure to many environmental compounds, particularly to those that leach from plastics and other synthetic materials, is commonplace in modern societies to the extent that many are found at measurable concentrations in body fluids within most of the population. Relating fluid levels of individual compounds to parameters reflecting ovarian reserve in selected populations appears to be an effective way forward and, indeed, some early-stage findings do show some cause for concern. There is a pressing need for the development of practical advice enabling women to minimize their intake of AHR/ER ligands, perhaps through dietary/cosmetic choices or improved food packaging.

Background: Increasing age and post-menopausal status are associated with decreasing androgen concentrations in females. Women with premature loss of ovarian function, such as primary ovarian insufficiency (POI) or iatrogenic menopause may be at increased risk for diminished testosterone levels at a relatively young age. Differentiation between a hypoandrogenic or normoandrogenic state in women with premature loss of ovarian function is problematic due to trueness and precision problems using various testosterone assays. The current meta-analysis was conducted to evaluate current literature reporting serum total testosterone concentrations under these conditions, including stratification for various testosterone assays., Methods: A systematic review and meta-analysis of controlled observational studies were performed. The electronic databases of Pubmed, Embase and the Cochrane Library were systematically searched until October 2011 for comparative studies on total testosterone concentrations in women with spontaneous POI or iatrogenic menopause compared with controls. The literature search, data extraction and critical appraisal, using the Newcastle-Ottawa Scale, were performed by two independent investigators. The effect measure was the weighted mean difference (WMD) with 95% confidence interval (95% CI) in a random effects model., Results: A total of 206 articles for spontaneous POI and 1358 for iatrogenic menopause were reviewed, of which 9 and 17 papers, respectively, were selected for final analysis. Both groups demonstrated significantly lower total testosterone concentrations compared with controls [WMD (95% CI) -0.38 (-0.55 to -0.22) nmol/l, and -0.29 (-0.39 to -0.18) nmol/l, respectively], but with substantial between-study heterogeneity. Subgroup analysis for assay type was statistically significant for spontaneous POI only. Sensitivity analyses of high-quality studies did not change the results, and resulted in a substantial decrease in heterogeneity in spontaneous POI studies., Conclusions: The current meta-analysis demonstrates that total testosterone concentrations are decreased in women with spontaneous POI or iatrogenic menopause. The potential implications of hypoandrogenism in these women remain to be elucidated.

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.

Background: Anti-Mullerian hormone (AMH) is a marker of ovarian reserve status and represents a good predictor of ovarian response to ovarian hyperstimulation. The aim of this study was to assess the accuracy of AMH and antral follicle count (AFC) as predictors of an excessive response in IVF/ICSI treatment., Methods: A systematic review and meta-analysis of the existing literature was performed. Studies were included if 2 × 2 tables for the outcome excessive response in IVF patients in relation to AMH/AFC could be constructed. Using a bivariate meta-analytic model, both summary point estimates for sensitivity and specificity were calculated, as well as summary ROC curves. Clinical value was analysed by calculating post-test probabilities of excessive response at optimal cut-off levels, as well as the corresponding abnormal test rates., Results: Nine studies reporting on AMH and five reporting on AFC were found. Summary estimates of sensitivity and specificity for AMH were 82 and 76%, respectively, and 82 and 80%, respectively, for AFC. Comparison of the summary estimates and ROC curves for AMH and AFC showed no statistical difference. Abnormal test rates for AMH and AFC amounted to ∼14 and 16%, respectively, at cut-off levels where test performance is optimal [likelihood ratio for a positive result (LR + ) > 8], with a post-test probability of ± 70%., Conclusions: Both AMH and AFC are accurate predictors of excessive response to ovarian hyperstimulation. Moreover, both tests appear to have clinical value. This opens ways to explore the potential of individualized FSH dose regimens based on ovarian reserve testing.

Background: Mild ovarian stimulation for in vitro fertilization (IVF) aims to achieve cost-effective, patient-friendly regimens which optimize the balance between outcomes and risks of treatment., Methods: Pubmed and Medline were searched up to end of January 2008 for papers on ovarian stimulation protocols for IVF. Additionally, references to related studies were selected wherever possible., Results: Studies show that mild interference with the decrease in follicle-stimulating hormone levels in the mid-follicular phase was sufficient to override the selection of a single dominant follicle. Gonadotrophin-releasing hormone antagonists compared with agonists reduce length and dosage of gonadotrophin treatment without a significant reduction in the probability of live birth (OR 0.86, 95% CI 0.72-1.02). Mild ovarian stimulation may be achieved with limited gonadotrophins or with alternatives such as anti-estrogens or aromatase inhibitors. Another option is luteinizing hormone or human chorionic gonadotrophin administration during the late follicular phase. Studies regarding these approaches are discussed individually; small sample size of single studies along with heterogeneity in patient inclusion criteria as well as outcomes analysed does not allow a meta-analysis to be performed. Additionally, the implications of mild ovarian stimulation for embryo quality, endometrial receptivity, cost and the psychological impact of IVF treatment are discussed., Conclusions: Evidence in favour of mild ovarian stimulation for IVF is accumulating in recent literature. However, further, sufficiently powered prospective studies applying novel mild treatment regimens are required and structured reporting of the incidence and severity of complications, the number of treatment days, medication used, cost, patient discomfort and number of patient drop-outs in studies on IVF is encouraged.

Background: Endometriosis has a strong genetic component, and numerous genetic studies have been reported., Methods: We have systematically reviewed these studies and included 114 in our final selection., Results: We found no consistent evidence linking endometriosis with specific polymorphisms in genes encoding inflammatory mediators, proteins involved in sex steroid metabolism, vascular function and tissue remodelling. Although a number of polymorphisms have been associated with endometriosis in selected populations, the associations have not been independently confirmed, either because only single studies were carried out on these markers/genes or because other studies reported no association. The most solid evidence linking specific polymorphisms to endometriosis came from studies investigating glutathione-S-transferase, a phase II detoxification enzyme. Carriage of the GSTT1 null deletion variant showed consistent association with endometriosis with a 29% increased risk; however, it cannot be excluded that this result was due to publication bias, and this association should be independently confirmed in large-scale, well-designed case-control studies., Conclusions: The evidence of an association between genetic polymorphisms and endometriosis is weak. Carriage of the GSTT1 null deletion may moderately increase the risk of this disease. We suggest that the methodology of association studies should be improved in order to identify and validate associations in endometriosis.

Background: Milder ovarian stimulation protocols for in vitro fertilization (IVF) are being developed to minimize adverse effects. Mild stimulation regimens result in a decreased number of oocytes at retrieval. After conventional ovarian stimulation for IVF, a low number of oocytes are believed to represent poor ovarian reserve resulting in reduced success rates. Recent studies suggest that a similar response following mild stimulation is associated with better outcomes., Methods: This review investigates whether the retrieval of a low number of oocytes following mild ovarian stimulation is associated with impaired implantation rates. Three randomized controlled trials comparing the efficacy of the mild ovarian stimulation regimen (involving midfollicular phase initiation of FSH and GnRH co-treatment) for IVF with a conventional long GnRH agonist co-treatment stimulation protocol could be identified by means of a systematic literature search., Results: These studies comprised a total of 592 first treatment cycles. Individual patient data analysis showed that the mild stimulation protocol results in a significant reduction of retrieved oocytes compared with conventional ovarian stimulation (median 6 versus 9, respectively, P < 0.001). Optimal embryo implantation rates were observed with 5 oocytes retrieved following mild stimulation (31%) versus 10 oocytes following conventional stimulation (29%) (P = 0.045)., Conclusions: The optimal number of retrieved oocytes depends on the ovarian stimulation regimen. After mild ovarian stimulation, a modest number of oocytes is associated with optimal implantation rates and does not reflect a poor ovarian response. Therefore, the fear of reducing the number of oocytes retrieved following mild ovarian stimulation appears to be unjustified.

Ovarian stimulation is applied in the clinic to restore mono-ovulatory cycles in anovulatory women (ovulation induction) or to induce the development of multiple dominant follicles for assisted reproduction. Ovarian response is the endocrine and follicular reaction of the ovaries to stimulation. Achieving an appropriate ovarian response to anti-estrogens or exogenous gonadotrophins is central to ovulation induction and ovarian stimulation protocols. However, achieving an adequate response, without cycle cancellation or adverse events related to under- or over-stimulation, is complicated by high intra- and inter-individual variability. To predict each patient's ovarian response to medication for ovarian stimulation and to individualize the starting dose of exogenous gonadotrophin or the need for exogenous luteinizing hormone, various clinical, endocrine, ovarian ultrasonographic and genetic characteristics have been explored. Some of these features have been incorporated into prediction models. In this review, the methodology behind predictive factors and prediction models and their potential clinical applicability across ovulation induction and ovarian stimulation are explored.

Preimplantation genetic aneuploidy screening (PGS) has been performed during the last decade as a way of enhancing embryo selection in patients with an increased incidence of embryonic numerical chromosome abnormalities (advanced maternal age, recurrent miscarriage and recurrent implantation failure). It has been proposed that the replacement of euploid embryos in these patients would result in a higher implantation and pregnancy rate and a reduced miscarriage rate. Additionally, the transfer of fewer embryos could reduce the chances for multiple pregnancies in all IVF patients. Although, to date, multiple studies have addressed this issue, contradictory results have been encountered. As a result, the effectiveness of aneuploidy screening remains to be established. Moreover, child outcome studies documenting the safety of this procedure are needed. The aim of this review is to summarize the available evidence concerning the use of PGS to determine the current value of the technique.

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.

The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.

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.

The late 20th century trend to delay birth of the first child until the age at which female fecundity or reproductive capacity is lower has increased the incidence of age-related infertility. The trend and its consequences have also stimulated interest in the possible factors in the female and the male that may contribute to the decline in fecundity with age; in the means that exist to predict fecundity; and in the consequences for pregnancy and childbirth. In the female, the number of oocytes decreases with age until the menopause. Oocyte quality also diminishes, due in part to increased aneuploidy because of factors such as changes in spindle integrity. Although older male age affects the likelihood of conception, abnormalities in sperm chromosomes and in some components of the semen analysis are less important than the frequency of intercourse. Age is as accurate as any other predictor of conception with assisted reproductive technology. The decline in fecundity becomes clinically relevant when women reach their mid-30s, when even assisted reproduction treatment cannot compensate for the decline in fecundity associated with delaying attempts at conceiving. Pregnancies among women aged >40 years are associated with more non-severe complications, more premature births, more congenital malformations and more interventions at birth.