This was a single center, double blind, crossover study designed to assess the effects in 27 eligible women (18–40 years old, surgically sterilized with regular menstrual cycles) of meloxicam, 15 or 30 mg/day, administered orally for five consecutive days during the late follicular phase, starting when the leading follicle reached 18 mm diameter. Volunteers underwent two treatment cycles separated by one resting cycle, with randomization to dose sequence. Main outcomes were follicular rupture; serum LH, progesterone and estradiol (E₂) levels; and incidence of adverse events.

Twenty-two volunteers completed the study. There were no differences between meloxicam doses in menstrual cycle length. Dysfunctional ovulation was observed in 11/22 (50%) cycles treated with 15 mg/day and 20/22 (90.9%) cycles with 30 mg/day (P = 0.0068). All women had normal luteal phase progesterone levels; mean maximal values ± SEM were 42 ± 4.1 and 46.8 ± 2.6 nmol/l for 15 and 30 mg/day groups, respectively. There were no serious adverse events, and no changes in LH and E₂ levels or in cycle length.

Meloxicam 30 mg given for five consecutive days in the late follicular phase is safe, effective and may be an alternative form of emergency contraception.

Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case–control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Åsberg Depression Rating Scale (MADRS-S).

Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1–24 versus 5.0, 0–28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0–5 versus 0, 0–2, P < 0.001), worry (1.5, 0–4 versus 0, 0–6, P = 0.004), phobias (1, 0–4 versus 0, 0–3, P < 0.001), and pain (1, 0–3 versus 0, 0–2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0–27 versus 5.5, 0–24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls.

Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.

To assess the effect of CFTR on human sperm fertilizing capacity, we examined sperm capacitation and the acrosome reaction using chlortetracycline staining, analyzed sperm hyperactivation by computer-assisted semen analysis (CASA), measured intracellular cAMP levels using ElA and evaluated sperm penetration of zona-free hamster eggs assay in fertile men. The percentage of spermatozoa expressing CFTR from fertile, healthy and infertile men (mainly teratospermic, asthenoteratospermic, asthenospermic and oligospermic) was conducted by indirect immunofluorescence staining.

Progesterone significantly facilitated human sperm capacitation and ZP3 triggered the acrosome reaction, both were significantly inhibited by CFTR inhibitor-172 (CFTRinh-172; 10 nM–1 µM) in a dose-dependent manner. The presence of 100 nM CFTRinh-172 markedly depressed intracellular cAMP levels, sperm hyperactivation and sperm penetration of zona-free hamster eggs. In addition, the percentage of spermatozoa expressing CFTR in the fertile men was significantly higher than healthy and infertile men categories (P < 0.01).

CFTR is essential for human sperm fertilizing capacity and the impairment of CFTR expression in spermatozoa is correlated with a reduction of sperm quality. These results suggest that defective expression of CFTR in human sperm may lead to the reduction of sperm fertilizing capacity.

The first embryo transfers performed by five trainees were monitored by the cumulative summation test for learning curve (LC-CUSUM), a statistical tool designed to indicate when a process has reached a predefined level of performance. The main outcome measure was a positive hCG test. A 40% pregnancy rate (PR) per transfer was chosen to define adequate performance and a PR of 20% was considered inadequate. After the learning phase, standard CUSUM were implemented to ensure that performance was maintained. The same CUSUM parameters were also applied to monitor 241 consecutive embryo transfers performed by a senior gynaecologist.

Between 11 and 99 embryo transfers were necessary for the trainees to reach the predefined level of performance. Simple and intuitive graphical representations of the LCs were generated. CUSUM tests confirmed that performance was maintained after the learning phase. The PR of the senior gynaecologist was 42.7% and the CUSUM showed that performance remained adequate throughout the 241 procedures.

This study provides an exportable model for a quantitative monitoring of the LC of embryo transfer as well as a reference curve for continuous monitoring of performance in embryo transfer. The length of the LC of embryo transfer is highly variable, justifying a tailored training to learn this procedure.

We conducted a cross-sectional study with telephone interviews using a semi-structured questionnaire with Health Secretariats' authorities from the 26 States, the Federal District, 26 Municipal state capitals and another 16 cities with more than 500 000 inhabitants. Also, directors of 26 referral centres and teaching hospitals provide ART procedures supported by the state or university teaching hospitals.

Authorities from 24/26 State Secretariats and the Federal District, from 39/42 cities and 26 directors of referral centres and teaching hospitals offering government-funded infertility care and ART were interviewed. In 19/25 states (76%) and 26/39 cities (66.7%), no infertility treatment was available free of charge. The most common reason for lack of services at the state and municipal levels was ‘lack of any political decision to implement them’, followed by ‘lack of human and financial resources’. When ART was available, barriers to access included the fact that patients needed to purchase medication and the more than 1-year waiting list for treatment.

Lack of political commitment results in inequity in the access of low-income couples in Brazil to infertility treatment, including ART.

In a Dutch nationwide database on in vitro fertilization (IVF) treatment from 1983 to 1995, we identified 28 women with a trisomic pregnancy conceived via or within 1 year from IVF treatment. We selected five age-matched controls with a healthy child for each trisomy case. We performed a case–control study to examine whether trisomy cases more often had a history of ovarian surgery and a lower response to ovarian hyperstimulation than controls. Subsequently, cases and controls were followed to compare the incidence of signs of menopause at the end of the study period as self-reported by questionnaire.

Logistic regression analysis showed an association between trisomic pregnancy and a history of ovarian surgery [odds ratio (OR) 3.3; 95% confidence interval (CI): 1.0–10.5; P = 0.04] and between trisomic pregnancy and retrieval of ≤4 oocytes during IVF treatment (OR 4.0; 95% CI: 1.4–11.5; P = 0.01). The adjusted OR for signs of menopause associated with trisomic pregnancy was 5.7 (95% CI: 1.1–29.9; P = 0.04).

Our results suggest that IVF-treated women with a reduced ovarian follicle pool are at increased risk of a trisomic pregnancy, independent of their age. Our findings support the hypothesis that follicle pool size and not chronological age determines a woman's trisomy risk. Since a questionnaire was used, we cannot fully exclude the possibility of selection bias in this study.

To determine if THs are present at the site of fertilization and EED in cattle, we evaluated the presence of the hormones in oviductal and uterine horn tissues. To assess the outcome of free TH supplementation (50 ng/ml of each hormone: triiodothyronine-T₃ and thyroxin-T₄), embryos were followed through standard and TH-supplemented in-vitro procedures, and evaluated for the cleavage rates, blastocyst formation rate and hatching rates. Embryo quality was assessed using TUNEL assay and post-cryopreservation survival was also evaluated.

Although TH levels in in-vitro culture media were found to be ~60% of the administered doses, the TH-treated embryos exhibited significant increases in blastocyst formation and hatching rates (P < 0.05). Embryo quality was significantly improved in the treated groups as demonstrated by greater total cell counts and reduced proportions of apoptotic cells (P < 0.05). Finally, TH supplementation was associated with improved post-cryopreservation viability, defined by blastocyst re-expansion and hatching rates after frozen embryos had been thawed and cultured (P < 0.05).

These findings not only provide a way of optimizing ART efficiency, but also further our understanding of how THs influence embryonic development in mammals.

We assessed the IR [using the homeostasis model assessment (HOMA)] and androgen status of 49 women without PCOS undergoing an ART cycle. This was then related to the treatment cycle outcome.

We found a significant positive correlation between HOMA and BMI, and free androgen index (FAI) and testosterone. The FAI significantly positively correlated with total follicle count after COH. The total follicle count was significantly higher in those with a HOMA >2.5, and HOMA positively correlated with total follicle count in this group of IR women (HOMA > 2.5).

Our results suggest a positive correlation of HOMA-IR levels above a threshold level of 2.5 and a continuous positive correlation of free androgen (FAI) to total ovarian follicle count following COH in the non-PCOS patient.

Endometrial tissue from 12 women with subfertility and advanced endometriosis and 11 healthy controls were taken on days 19–24 of the menstrual cycle and processed into either epoxy resin or paraffin wax. Lectin histochemistry was analysed using light microscopy to quantify the amount of glandular reaction product.

There was a significant (P = 0.011) reduction in DBA binding to endometrium from patients with endometriosis compared with controls, which was not seen with VVA (P = 0.135). Three stage IV biopsies and one stage III biopsy completely failed to bind DBA and, of these, three showed moderate glandular binding of VVA. DBA and VVA binding differed significantly (P= 0.0039) in the endometriosis specimens whereas in controls no significant difference was detected (P = 0.812).

Secretory phase glycosylation in women with advanced endometriosis differs from that in healthy women with a reduction in fucosylated N-acetylgalactosamine sequences bound by DBA. Shorter VVA-binding glycans are not significantly affected. In addition to indicating abnormalities of epithelial differentiation, these findings may be directly relevant to implantation failure, as blastocyst attachment requires a critical interaction with the epithelial glycocalyx.

A retrospective birth cohort study was carried out in which 728 women born during 1973–1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27–34 year; n = 728). Symptoms of PCOS (hyperandrogenism, menstrual dysfunction and polycystic ovaries) were identified by examination and the presence of polycystic ovaries in those that did not consent to the ultrasound were imputed.

The estimated prevalence of PCOS in this birth cohort using the NIH criteria was 8.7 ± 2.0% (with no need for imputation). Under the Rotterdam criteria, the prevalence was 11.9 ± 2.4% which increased to 17.8 ± 2.8% when imputed data were included. Under the AES recommendations, PCOS prevalence was 10.2 ± 2.2%, and 12.0 ± 2.4% with the imputed data. Of the women with PCOS, 68–69% did not have a pre-existing diagnosis.

The Rotterdam and AES prevalence estimates were up to twice that obtained with the NIH criteria in this, as well other prevalence studies. In addition, this study also draws attention to the issue of many women with PCOS in the community remaining undiagnosed.

A cohort study was carried out using the electronic hospital booking records of women delivering in a large Dublin maternity hospital between 2000 and 2007. Logistic regression analyses were performed to measure the associations between maternal factors and optimal FA use.

Of the 61 252 women in the cohort, 85% reported taking FA at some point during the periconceptional period; however, only 28% took FA as recommended. Factors associated with taking the recommended amount of FA included nulliparity [adjusted OR: 1.35 (95% CI: 1.28–1.43)], early booking (<12 weeks) [OR: 1.24 (95% CI: 1.17–1.31)], increasing maternal age (e.g. 30–34 years) [OR: 1.39 (95% CI: 1.30–1.48)], private health care [OR: 4.32 (95% CI: 4.1–4.6)] and fertility treatment [OR: 2.88 (95% CI: 2.44–3.40)]. Factors associated with taking less than recommended or no FA included unplanned pregnancy [OR: 0.08 (0.07–0.08)], lower socio-economic status (e.g. unemployed) [OR: 0.63 (95% CI: 0.55–0.71)], non-Irish nationality [OR: 0.82 (0.74–0.90)] and smokers [OR: 0.51 (95% CI: 0.47–0.55)].

Social, demographic and economic factors have an important influence on the FA uptake. Vulnerable groups who report limited uptake of FA need to be specifically targeted in future Public Health campaigns and further consideration needs to be given to the debate on food fortification in countries where this is currently not available.

We conducted a systematic review and meta-analysis of studies to evaluate the association between non-cavity-distorting intramural fibroids and IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. Study selection and data extraction were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scales were used for quality assessment. Meta-analysis was performed if appropriate.

We identified 19 observational studies comprising 6087 IVF cycles. Meta-analysis of these studies showed a significant decrease in the live birth (RR = 0.79, 95% CI: 0.70–0.88, P < 0.0001) and clinical PRs (RR = 0.85, 95% CI: 0.77–0.94, P = 0.002) in women with non-cavity-distorting intramural fibroids compared with those without fibroids, following IVF treatment.

The presence of non-cavity-distorting intramural fibroids is associated with adverse pregnancy outcomes in women undergoing IVF treatment.

For this study, 38 premenopausal women with histologically diagnosed ovarian endometrioma or peritoneal endometriosis and 24 women without endometriosis were selected. Biopsy samples from eutopic endometrium were used for immunohistochemical staining to detect synaptophysin (SYN) and neuron-specific enolase (NSE) expression in women with and without endometriosis.

There were substantially more NE cells of eutopic endometrium stained with SYN and NSE in women with endometriosis than in those without endometriosis (3.8 ± 1.8 versus 0.5 ± 0.7/mm², P < 0.001, and 2.8 ± 2.1 versus 0.4 ± 0.6/mm², respectively, P < 0.001). These cells were scattered in the epithelium of endometrial glands. At all stages of the menstrual cycle, the densities of NE cells stained with SYN and NSE were greater in women with endometriosis than in those without endometriosis (P < 0.05).

These results suggest that NE cells in eutopic endometrium probably play some role in the pathogenesis or symptoms of endometriosis.

We conducted an occupational cohort study to examine the effect of occupational exposure to BPA on the risk of male sexual dysfunction. Current workers from BPA-exposed and control factories were recruited. The exposed workers were exposed to very high BPA levels in their workplace. Male sexual function was ascertained through in-person interviews using a standard male sexual function inventory.

BPA-exposed workers had consistently higher risk of male sexual dysfunction across all domains of male sexual function than the unexposed workers. After controlling for matching variables and potential confounders, exposed workers had a significantly increased risk of reduced sexual desire [odds ratios (OR) = 3.9, 95% confidence interval: 1.8–8.6), erectile difficulty (OR = 4.5, 95% CI 2.1–9.8), ejaculation difficulty (OR = 7.1, 95% CI 2.9–17.6), and reduced satisfaction with sex life (OR = 3.9, 95% CI 2.3–6.6). A dose–response relationship was observed with an increasing level of cumulative BPA exposure associated with a higher risk of sexual dysfunction. Furthermore, compared with the unexposed workers, BPA-exposed workers reported significantly higher frequencies of reduced sexual function within 1 year of employment in the BPA-exposed factories.

Our findings provide the first evidence that exposure to BPA in the workplace could have an adverse effect on male sexual dysfunction.

Levonorgestrel-loaded polylactic acid microspheres (LNG-microspheres) were prepared by using an oil-in-water emulsification–solvent evaporation method. Rabbits with experimental endometriosis were randomized to treatment with local pseudo-pregnancy therapy, local blank microspheres, systemic pseudo-pregnancy therapy, ovariectomy or the control. Local pseudo-pregnancy was induced by injection of LNG-microspheres directly into endometrial cysts. Compared with the systemic pseudo-pregnancy group, significantly higher intra-cystic drug levels were maintained for at least 6 months with much lower serum levels in the local pseudo-pregnancy group (P < 0.01). The high intra-cystic levonorgestrel simulated a state of potent pregnancy, which induced size reductions and endometrial atrophy comparable to those of ovariectomy. Moreover, major metabolic parameters and ovarian function were not disturbed by local pseudo-pregnancy therapy.

Induction of a local pseudo-pregnancy could achieve therapeutic efficacy comparable to that of ovariectomy without provoking any marked side effects in a rabbit endometriosis model. Thus it may be a preferable option for patients with endometriosis.

CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19–49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%).

Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (–11% points, 95% CI –19 to –2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1–18).

The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72.

This retrospective cohort study compared the prevalence of antepartum haemorrhage (APH), placenta praevia (PP), placental abruption (PA) and primary post-partum haemorrhage (PPH) in women with singleton births between 1991 and 2004 in Victoria Australia: 6730 after IVF/ICSI, 24 619 from the general population, 779 after gamete intrafallopian transfer (GIFT) and 2167 non-ART conceptions in infertile patients. Risk factors for haemorrhages in the IVF/ICSI group were examined by logistic regression.

The IVF/ICSI group had more APH: 6.7 versus 3.6% (adjusted OR 2.0; 95% CI 1.8–2.3), PP: 2.6 versus 1.1% (2.3; 1.9–2.9), PA: 0.9 versus 0.4% (2.1; 1.4–3.0) and PPH: 11.1 versus 7.9% (1.3; 1.2–1.4) than the general population. APH, PP and PA were as frequent in the GIFT group as in the IVF/ICSI group, but were less frequent in the non-ART group. Within the IVF/ICSI group, fresh compared with frozen thawed embryo transfers (FET) was associated with more frequent APH (1.5; 1.2–1.8) and PA (2.1; 1.2–3.7) and the odds ratio increased with number of oocytes collected (1.02; 1.00–1.04). Endometriosis patients had more PP (1.7; 1.2–2.4) and PPH (1.3; 1.1–1.6) than those without endometriosis. FET in artificial cycles was associated with increased PPH (1.8; 1.3–2.6) compared with FET in natural cycles.

Obstetric haemorrhages are more frequent with singleton births after IVF, ICSI and GIFT. The exploratory analysis of factors in the IVF/ICSI group, showing associations with fresh embryo transfers in stimulated cycles, endometriosis and hormone treatments, suggests that events around the time of implantation may be responsible and that suboptimal endometrial function is the critical mechanism.

CS (1–30 µM) and plasminogen (precursor of plasmin) were added to the culture media of human endometrial stromal cells and incubated for 24 h. Culture media were collected for analysis of plasmin and MMP-2, -3 and -9 enzyme activities using fluorescence assays. Plasmin and MMP-3 activities were significantly reduced by CS in a dose-dependent manner (P < 0.001). Western blot analysis of the culture media revealed that CS inhibited the conversion by plasmin of MMP-3 from the precursor form to the active form. Fluorescence assay using a common substrate of MMP-2 and MMP-9 showed that enzymatic activity remains at ~50%, even at 30 µM CS. Gelatin zymography demonstrated that CS inhibited the activation of MMP-9 but not MMP-2 from the precursor, suggesting that the activation of MMP-2 may be independent of plasmin.

CS inhibits not only plasmin activity but also MMP activities indirectly by inhibiting the plasmin-mediated process. These findings suggest that CS may be an important regulator of proteolysis during trophoblast invasion.

Infertile women enrolled in an IVF programme were included in this study. Serum T and 4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH.

The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone.

Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

A prospective study of 57 premenopausal PCOS patients and 60 age- and weight-matched control women, with a history of no or minimal alcohol consumption was conducted. Anthropometric variables, biochemical and hormonal parameters were determined and NAFLD was evaluated by abdominal ultrasonography and biochemical testing, after excluding causes of secondary liver disease. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and free androgen index (FAI) was calculated.

PCOS patients had an increased prevalence of HS [21/57 patients (36.8%) versus 12/60 controls (20.0%), P < 0.05] and abnormal (≥40 IU/l) serum aminotransferase levels [13/57 patients (22.8%) versus 2/60 controls (3.3%), P < 0.01] than controls. All patients and controls with metabolic syndrome had HS. Factors associated with HS were PCOS diagnosis, older age, increased BMI, waist circumference (WC), HOMA-IR and FAI values and decreased high-density lipid cholesterol and sex hormone binding globulin levels. PCOS patients had an OR of 3.55 (95% CI: 1.02–5.35) for HS versus controls, after adjustment for age, BMI and WC.

NAFLD is common in PCOS patients and increased androgen bioavailability may be implicated, in combination with metabolic abnormalities. Liver evaluation is proposed in PCOS patients, especially in those with metabolic syndrome.

In a retrospective study, we analysed a large body of data from women, 20–40 years of age, undergoing IVF/ICSI treatment between 1995 and 2008. We defined ovarian function using five variables: basal FSH level, estradiol (E2) level on the day of HCG administration, dose of gonadotrophins used for ovarian stimulation, number of retrieved oocytes and dose of gonadotrophins per oocyte. Controlling simultaneously for temporal changes in patient age and stimulation protocol, we applied generalized additive models to describe the temporal trends.

During the study period the mean age of the study population increased by 2.7 years. Whereas the basal FSH and gonadotrophin dose did not change over time, the E2 level and oocyte retrieval declined, and the dose of FSH per oocyte increased during the study period.

The results are indicative of a small, but detectable decrease in ovarian function over a period of 14 years, which is not causally related to the ageing population.

The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing.

There was no significant difference in the allele distribution of the ER- gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8–28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4–21.6%).

These findings suggest that the ER- gene polymorphisms may be associated with idiopathic POF.

Parents of prepubertal boys with diagnoses at highest risk for treatment-related gonadal damage were offered the option of testicular cryopreservation. Half of the biopsy was frozen for the subject's potential future use and the remainder used for research. Data on negative intraoperative and/or 7 day post-operative sequelae of testicular biopsies were assessed. Two to four weeks later, parents were asked to complete a questionnaire on factors influencing their decision to have the biopsy or not.

Since January 2008, 24 boys have met the eligibility criteria but three required immediate treatment and were excluded. Sixteen of 21 families (76%) consented to testicular biopsy, indicating the prospective acceptability of this option to parents of boys aged 3 months to 14 years; 14 underwent the procedure without any negative intra- or post-operative sequelae. Although the time at diagnosis is stressful, families can give thoughtful consideration to this option. Factors such as religion, finance, ethics and the experimental nature of cryopreservation did not play a major role in decision-making.

Parents of prepubertal boys with cancer are willing to pursue testicular tissue cryopreservation at diagnosis, and testicular biopsy caused no acute adverse effects.

Mixed (qualitative and quantitative) methods were used to identify weaknesses, strengths and needs in fertility care. Four focus groups with 21 infertile patients were used for documenting care aspects relevant to patients. The fully transcribed qualitative results were analysed and converted into a 124-item questionnaire, to investigate whether these aspects were regarded as weaknesses, strengths or needs in fertility care. The questionnaire was distributed to 369 eligible couples attending 13 Dutch fertility clinics. Descriptive statistics were used to determine the quantity of the weaknesses, strengths and needs.

Overall, 286 women (78%) and 280 men (76%) completed the questionnaire. Patients experienced many weaknesses in fertility care, mostly regarding emotional support and continuity of care. Respect and autonomy and partner involvement were considered strengths in current care. Furthermore, women expressed their need for more doctors' continuity during their treatment, and couples strongly desired to have free access to their own medical record. The questionnaire's internal consistency and construct validity were sufficient.

Infertile couples experience strengths, but also many weaknesses and needs in current fertility care. Lack of patient centredness seems to be a major cause herein. Using mixed methods is a sensitive means for identifying these weaknesses and needs.

In order to validate the effectiveness of oocyte vitrification a non-inferiority trial was started on sibling metaphase II (MII) oocytes. To demonstrate the non-inferiority based on an absolute difference of 17% in the fertilization rate per sibling oocyte, a minimum of 222 oocytes were required. After oocyte denudation, MII oocytes with normal morphology were randomly allocated to fresh ICSI insemination or to vitrification procedure. If pregnancy was not obtained a subsequent ICSI cycle was performed with warmed oocytes of the same cohort. In both groups, three oocytes were inseminated per cycle by ICSI procedure. Primary end-points were fertilization rates calculated per warmed and per injected oocytes. Secondary end-points were zygote and embryo morphology.

A total of 244 oocytes were involved in this study. Of the 120 fresh sibling oocytes inseminated, 100 were fertilized (83.3%). Survival rate of sibling vitrified oocytes was 96.8% (120/124 oocytes). Fertilization rate after ICSI was 76.6% (95/124) per warmed oocyte and 79.2% (95/120) per survived/inseminated oocyte. No statistical difference in fertilization rates was observed between the two groups when calculated per sibling oocytes (absolute difference –6.73%; OR: 0.65; 95% CI = 0.33–1.29; P = 0.20) and per inseminated oocyte (absolute difference –4.17%; OR: 0.76; 95% CI = 0.37–1.53; P = 0.50). Embryo development was also similar in both treatment groups up till Day 2. The percentage of excellent quality embryos was 52.0% (52/100) in the fresh group and 51.6% (49/95) in the vitrification group (absolute difference –0.43%; OR: 0.98; 95% CI = 0.53–1.79; P = 0.9). The mean age of the 40 patients included in this study was 35.5 ± 4.8 years (range 26–42). Fifteen clinical pregnancies were obtained in the vitrification cycles of 39 embryo transfers performed (37.5% per cycle, 38.5% per embryo transfer), with an implantation rate of 20.2% (19/94). Three spontaneous miscarriages occurred (20%). Twelve pregnancies are ongoing (30.0% per cycle, 30.8% per embryo transfer) beyond 12 weeks of gestation.

Our results indicate that oocyte vitrification procedure followed by ICSI is not inferior to fresh insemination procedure, with regard to fertilization and embryo developmental rates. Moreover, ongoing clinical pregnancy is compatible with this procedure, even with a restricted number of oocytes available for insemination. The promising clinical results obtained, in a population of infertile patients, need to be confirmed on a larger scale.

Clinical Trials Registration number: iSRCTN60158641.

Digit ratios were determined in 98 women diagnosed with PCOS by the 2003 international consensus guidelines and in 51 women with regular menstrual cycles, no clinical or biochemical signs of hyperandrogenism and normal ovarian morphology. Women with PCOS were categorized into four clinical phenotypes (i.e. Frank, Non-PCO, Ovulatory and Mild) and 2D:4D among groups were compared by Tukey–Kramer multiple comparisons tests.

Left (P = 0.77) and right (P = 0.68) hand 2D:4D were similar among the four clinical phenotypes and no phenotype of PCOS demonstrated a 2D:4D that differed from controls (Left Hand, P = 0.44 and Right Hand, P = 0.75).

Women with PCOS do not demonstrate finger length patterns that are consistent with increased prenatal androgen exposure. These findings do not preclude a role for prenatal androgens in the development of PCOS; however, low 2D:4D are not a characteristic of PCOS.

All new subfertile couples (n = 1391) that were referred to our fertility clinic by their general practitioner between January 2002 and December 2006 were included. Fertility care was provided according to the national Dutch fertility guidelines. Data on diagnosis, treatment, mode of conception and pregnancy outcome were documented. If follow-up data were missing, couples were contacted. Cumulative pregnancy curves were constructed for the whole cohort and per diagnostic group.

As per December 2008 the overall ongoing pregnancy rate was 72.0% (n = 1001). Almost half of the pregnancies were conceived spontaneously (45.6%), 19.2% after ovulation induction (OI), 14.0% after intrauterine insemination (IUI) and 21.2% after IVF. A quarter (n = 349) of couples received IVF treatment, which was successful in 60% of cases. IVF had the largest contribution to ongoing pregnancies in patients with ‘tubal factor’, ‘endometriosis’ and ‘male factor’ (45, 45 and 37%, respectively) while in couples with ‘unexplained subfertility’ and ‘ovulation disorders’ the contribution to ongoing pregnancies of IVF was limited (13 and 4.5%, respectively).

In a cohort of subfertile couples, most pregnancies were conceived spontaneously. The contribution of IVF to ongoing pregnancy rates was comparable to those of OI and IUI. Compared with the pre-IVF era, couples with ‘endometriosis’, ‘tubal factor’ and ‘male subfertility’ have benefited most from its introduction.

Women with PCOS, 18–35 years (n = 23), and normal ovulatory controls, 18–35 years (n = 10) were recruited for study. Dose–responses were assessed over 24 h following intravenous administration of 0 (saline), 37.5, 75 and 150 IU of recombinant human FSH (r-hFSH) in PCOS and normal women. In addition, E₂ and Inh B responses to 150 IU of r-hFSH were assessed at baseline and 4, 6 and 8 weeks following suppression of ovarian steroidogenesis by a long-acting GnRH agonist in PCOS women.

In PCOS women and normal controls, serum Inh B and E₂ exhibit similar and simultaneous dose-responsiveness to FSH stimulation. During recovery from ovarian suppression, basal and stimulated Inh B release appear to be restored earlier than that of E₂ in PCOS women.

These findings are consistent with the notion that, in PCOS women, the level of ovarian follicle activity largely determines the earlier release of Inh B compared with E₂.

Using a cross-sectional design, a convenience sample of 121 individuals with infertility completed a background questionnaire, the Posttraumatic Growth Inventory and the Social Support Questionnaire.

While individuals reported moderate PTG, moderate availability of, and high satisfaction with social support, there was no significant association between the variables. Infertility-related variables emerged as central to explaining PTG with those with non-female related diagnoses and unexplained diagnoses demonstrating lower PTG than others (t = 2.96, t = 3.6, respectively, P ≤ 0.05). Additionally, live birth deliveries was positively associated with PTG (r² = 0.22, P ≤ 0.02), and those who engaged in clergy counseling had higher PTG than those who did not (t = 2.34, P ≤ 0.02). Determinants were unexplained infertility (lower PTG) and number of live birth deliveries (higher PTG).

In spite of limitations related to the convenience sampling, correlational design and subjective self-report nature of the data, findings suggest that individuals who suffer from infertility can experience personal growth. Further research will help identify correlates and provide guidance for mental health practitioners on counseling infertility patients to promote growth.

Data on 6946 IVF or ICSI singleton pregnancies were linked to perinatal outcomes obtained from population-based data sets on births and birth defects occurring between 1991 and 2004 in Victoria, Australia. These were compared with 20 838 outcomes for singleton births in the same population, conceived without IVF or ICSI. Birth defects were classified according to pathogenesis.

Overall, birth defects were increased after IVF or ICSI [adjusted odds ratio (OR) 1.36; 95% CI: 1.19–1.55] relative to controls. There was no strong evidence of risk differences between IVF and ICSI or between fresh and thawed embryo transfer. However, a specific group, blastogenesis birth defects, were markedly increased [adjusted OR 2.80, 95% CI: 1.63–4.81], with the increase relative to the controls being significant for fresh embryo transfer (adjusted OR 3.65; 95% CI: 2.02–6.59) but not for thawed embryo transfer (adjusted OR 1.60; 95% CI: 0.69–3.69).

Our findings suggest that there is a specific risk of blastogenesis birth defects arising very early in pregnancy after IVF or ICSI and that this risk may be lower with use of frozen-thawed embryo transfer.

To compare the inter- and intra-cycle stability of AFC and AMH, we used age-adjusted intra-class correlation coefficients (ICCs). To measure inter-cycle stability across a number of up to four menstrual cycles, we used data, prospectively collected for the purpose of an other study, from 77 regularly cycling, infertile women aged 24–40 years. AMH and AFC values were measured on cycle day 3. To study intra-cycle variability, we used data from a prospective cohort study of 44 regularly cycling volunteers, aged 25–46 years and measured AMH and assessed the AFC (2–10 mm) every 1–3 cycle days.

Between menstrual cycles, AFC and AMH varied between 0 and 25 follicles (median 10), and 0.3 and 27.1 ng/ml (median 4.64). The difference in age-adjusted ICC between AMH [ICC, 0.89 (95% CI, 0.84–0.94)] and AFC [ICC, 0.71 (95% CI, 0.63–0.77)] was 0.18 (95% CI, 0.12–0.27). For the intra-cycle variation, 0–43 antral follicles (median 7) were counted per volunteer. The difference in age-adjusted ICC between AMH [ICC, 0.87 (95% CI, 0.82–0.91)] and AFC [ICC, 0.69 (95% CI, 0.46–0.82)] was 0.18 (95% CI, 0.034–0.42).

Serum AMH demonstrated less individual intra- and inter-cycle variation than AFCs and may therefore be considered a more reliable and robust means of assessing ovarian reserve in subfertile women.

Age- and BMI-matched groups of endurance athletes with menstrual disturbance (OAM, n = 9) and regularly cycling athletes (RM, n = 8) and sedentary controls (CTRL, n = 8) were examined, and hormone levels measured, before and after 8 months of treatment with a low-dose combined OC (30 µg ethinyl estradiol + 150 µg levonorgestrel).

Before OC treatment, the diurnal profile of insulin was lower (P < 0.01) and levels of IGFBP-1 (P < 0.05) and cortisol (P < 0.05) were higher in OAM athletes than in CTRL, whereas GH secretion was higher than in RM athletes (P < 0.05). After treatment, diurnal secretions of these hormones were similar between groups with an increase of IGFBP-1 in the regularly menstruating subjects only (P < 0.001). OC treatment increased body fat mass in OAM athletes (P < 0.01 versus baseline). The change in total fat mass correlated positively with pretreatment diurnal levels of GH (r_s = 0.67, P < 0.01) and cortisol (r_s = 0.64, P < 0.01).

OC treatment in endurance athletes with menstrual disturbance increases body fat mass and results in diurnal levels of insulin, IGFBP-1, GH and cortisol that are comparable to those in regularly menstruating subjects. These results suggest that OCs improve metabolic balance in OAM athletes.

In this study, 27 families headed by single heterosexual mothers (solo mothers) and 20 families headed by lesbian mothers were compared with 36 two-parent heterosexual families as the child entered adulthood. Data were obtained from mothers and their young adult children by standardized interviews and questionnaires.

The female-headed families were found to be similar to the traditional families on a range of measures of quality of parenting and young adults’ psychological adjustment. Where differences were identified between family types, these pointed to more positive family relationships and greater psychological wellbeing among young adults raised in female-headed homes.

The findings of this study show that children raised by solo heterosexual mothers or lesbian mothers from infancy continue to function well as they enter adulthood. The findings are of relevance to the UK Human Fertilisation and Embryology (2008) Act.

KITL signaling studies were conducted by differentiating human embryonic stem cells (hESCs) on KITL wild-type, hetero- or homozygous knockout feeders for 10 days, and the effects of BMP signaling was determined by differentiation in the presence of BMP4 or its antagonist, Noggin. The formation of germ-like cells was ascertained by immunocytochemistry, flow cytometry and quantitative RT–PCR for germ cell markers.

The loss of KITL in enrichment and differentiation cultures resulted in significant down-regulation of germ cell genes and a 70.5% decrease in germ-like (DDX4+ POU5F1+) cells, indicating that KITL is involved in human germ cell development. Moreover, endogenous BMP signaling caused germ-like (DDX4+ POU5F1+) cell differentiation, and the inhibition of this pathway caused a significant decrease in germ cell gene expression and in the number of DDX4+ POU5F1+ cells. Further, we demonstrated that eliminating feeders but maintaining their secreted extracellular matrix is sufficient to sustain the increased numbers of DDX4+ POU5F1+ cells in culture. However, this resulted in decreased germ cell gene expression.

From these studies, we establish that KITL and BMP4 germ cell signaling affects in vitro formation of hESC derived germ-like cells and we suggest that they may play an important role in normal human germ cell development.

We prospectively collected IVF and ICSI treatment data from 11 out of 13 IVF centres in the Netherlands, between 2002 and 2004. Adjustment for sampling variation was made using a random effects model. A prognostic index for subfertility-related factors was used to adjust for differences in patient mix. The remaining variability between centres was split into random variation and true differences.

The crude 1-year ongoing pregnancy chance per centre differed by nearly a factor 3 between centres, with hazard ratios (HRs) of 0.48 (95% CI: 0.34–0.69) to 1.34 (95% CI: 1.18–1.51) compared with the mean 1-year ongoing pregnancy chance of all centres. After accounting for sampling variation, the difference shrank since HRs became 0.66 (95% CI: 0.51–0.85) to 1.28 (95% CI: 1.13–1.44). After adjustment for patient mix, the difference narrowed somewhat further to HRs of 0.74 (95% CI: 0.57–0.94) to 1.33 (95% CI: 1.20–1.48) and 17% of the variation between centres could be explained by patient mix. The 1-year cumulative ongoing pregnancy rate in the two most extreme centres was 36% and 55%.

Only a minor part of the differences in pregnancy chance between IVF centres is explained by patient mix. Further research is needed to elucidate the causes of the remaining differences.

We examined the association between anthropometric factors and TTP among 1651 Danish women participating in an internet-based prospective cohort study of pregnancy planners (2007–2008). We categorized body mass index (BMI = kg/m²) as underweight (<20), normal weight (20–24), overweight (25–29), obese (30–34) and very obese (≥35). We used discrete-time Cox regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CI), controlling for potential confounders.

We found longer TTPs for overweight (FR = 0.83, 95% CI = 0.70–1.00), obese (FR = 0.75, 95% CI = 0.58–0.97), and very obese (FR = 0.61, 95% CI = 0.42–0.88) women, compared with normal weight women. After further control for waist circumference, FRs for overweight, obese, and very obese women were 0.72 (95% CI = 0.58–0.90), 0.60 (95% CI = 0.42–0.85) and 0.48 (95% CI = 0.31–0.74), respectively. Underweight was associated with reduced fecundability among nulliparous women (FR = 0.82, 95% CI = 0.63–1.06) and increased fecundability among parous women (FR = 1.61, 95% CI = 1.08–2.39). Male BMI was not materially associated with TTP after control for female BMI. Compared with women who maintained a stable weight since age 17 (–5 to 4 kg), women who gained ≥15 kg had longer TTPs (FR = 0.72, 95% CI = 0.59–0.88) after adjustment for BMI at age 17. Associations of waist circumference and waist-to-hip ratio with TTP depended on adjustment for female BMI: null associations were observed before adjustment for BMI and weakly positive associations were observed after adjustment for BMI.

Our results confirm previous studies showing reduced fertility in overweight and obese women. The association between underweight and fecundability varied by parity.

We previously identified an orphan guanylyl cyclase receptor (mouse GC-G) highly enriched in mouse testis and involved in sperm activation. By using a comparative genomic approach, we found the homologue gene in human (hGC-G) composed of 21 exons, spanning a minimum of 48 kb on chromosome 10q25. Real-time RT–PCR analysis revealed hGC-G mRNA selectively expressed in testis but with low or no expression in all other tissues examined. Compared with mGC-G, the hGC-G transcript contains three 1-bp deletions and two in-frame termination codons, which results in a short putative receptor-like polypeptide. Western blot analysis with an anti-hGC-G-specific antibody confirmed the protein expression of hGC-G in human sperm lysate. Flow cytometry and confocal immunofluorescence analysis demonstrated the localization of hGC-G protein on the acrosome cap and equatorial segment of mature human sperm. In addition, an integrin-binding Arg-Gly-Asp (RGD) motif was found in the extracellular domain of hGC-G. Pre-incubation of the hGC-G RGD peptide with zona pellucida-free oocytes greatly decreased the binding of human sperm to hamster oocytes, which suggests a role for hGC-G role in sperm–oocyte interaction.

hGC-G is a novel surface protein on human sperm and potentially mediates sperm–oocyte interaction through its RGD-containing motif.

Meiotic progression was analyzed following pairing-synapsis and recombination progress. A total of 7119 oocytes were studied and analyzed. The proteins used to evaluate meiotic progression were: REC8, SYCP1, SYCP3 and MLH1, studied by immunofluorescence. Four different sample disaggregating methods were used, two enzymatic (trypsin and collagenase + hyaluronidase) and two mechanical (puncture and ovarian fragments). Two different culture media were used, control media and stem cell factor (SCF)-supplemented media. The oocytes were studied at initial time T0, and then at T7, T14 and T21 days after culture.

The mechanical methods increased the total number of oocytes found at the different times of culture and decreased the number of degenerated oocytes. Independently of the disaggregation method used, oocytes cultured with SCF-supplemented media showed a higher proportion of viable oocytes and fewer degenerated cells at all culture timepoints. No evidence of abnormal homologous chromosome synapsis was observed. Meiotic recombination was only observed in oocytes mechanically disaggregated and cultured with supplemented media.

The oocytes obtained by mechanical disaggregating methods and cultured with SCF-supplemented media are able to follow pairing-synapsis and recombination, comparable to oocytes in vivo. The culture conditions described herein confirm the methodology as a standardized and reproducible method.

In the present study, we analyse the frequency of chromosome imbalances in a series of metaphase I (MI; n = 44) and metaphase II (MII; n = 103) oocytes from 140 young donors (aged from 18 to 35 years, mean age 26.6) after hormone-induced superovulation. The aneuploidy frequency found in MII oocytes was 12.6%, and both whole-chromosome non-disjunction (1.94%) and premature separation of sister chromatids (PSSC) (12.6%) have been found. The chromosomes involved have been identified by multiplex fluorescent in situ hybridization (FISH). Achiasmate chromosomes have been identified in MI oocytes (9.1%), with most of them corresponding to chromosome 16 (6.8%). For this reason, the meiotic recombination pattern of chromosome 16 has been analysed in prophase I oocytes (n = 81) by immunofluorescence staining against MLH1 protein and subsequent FISH with specific probes. Our results show a percentage of oocytes with non-crossover bivalent 16 (2.5%) and a high percentage of bivalents 16 with a single exchange (19.8%).

In the present study, we report the finding of a considerable frequency of aneuploidy in oocytes from young donors, with the frequency of PSSC being higher than the frequency of whole-chromosome non-disjunction. In addition, we report vulnerable patterns of meiotic recombination in chromosome 16 that may be at risk of leading to a non-disjunction event. This gives new data on the susceptibility of the control population to conceive a trisomic 16 embryo.

Data were drawn from the Millennium Cohort Study. Interviews captured sociodemographic, behavioural and pregnancy information. Developmental assessments conducted at age three included the British Ability Scales II Naming Vocabulary (BAS-NV) instrument. We compared ART infants (born after IVF or ICSI) to four comparison groups: a ‘matched’ group; a ‘subfertile’ group (time to conception >12 months); a ‘fertile’ group (time to conception <12 months); and an ‘any spontaneous conceptions’ group. Linear regression provided estimates of the difference in mean BAS-NV scores in the ART and comparison groups; both unadjusted estimates and those adjusted for confounding and mediating factors are presented.

In the unadjusted analyses, ART children gained significantly better BAS-NV test results than did the comparison group children. When converted to an estimate of developmental age gap, ART children were 2.5, 2.7, 3.6 and 4.5 months ahead of the ‘matched’, ‘subfertile’, ‘fertile’ and ‘spontaneous conception’ children, respectively. After adjusting for confounding and mediating factors, the differences were reduced, and were not statistically significant.

ART is not associated with poorer cognitive development at 3 years. We have highlighted methodological considerations for researchers planning to study the effect of infertility and ART on childhood outcomes.

This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded.

Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle.

In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Luteal-phase blood samples from women with RM (n = 104) and controls (n = 33) were analysed by four-colour flow cytometry. NK cells were analysed as a percentage of lymphocytes, total NK concentration, CD56^Dim subtype concentration and percentage, activated CD69⁺CD56^Dim subtype concentration and percentage and CD56^+Bright:CD56^+Dim subtype ratio. Women with RM were analysed in two subgroups: those positive in ≥1 RM screening tests (karyotype, uterine, antiphospholipid syndrome, thrombophilia) (n = 48) and those who had negative screening tests (n = 56).

Women with RM had significantly higher NK percentage (P < 0.001), and significantly lower CD56^+Bright:CD56^+Dim ratio (P < 0.05) than controls. NK percentage was the only significantly higher variable in the RM screening test negative subgroup (P < 0.01). A ROC analysis (AUC = 0.71) found that an NK percentage >18% was highly specific for women with RM (97.0%), and defined 12.5% of women with RM as having high NK percentage, compared with 2.9% of controls.

Women with RM have altered peripheral blood NK parameters. NK cells as a percentage of lymphocytes best discriminated RM and control populations. Women with RM and high NK levels may have an immunological disorder.

Testis material was donated for research by four men undergoing bilateral castration as part of prostate cancer treatment. Testicular cells were cultured using StemPro medium. Colonies that appeared sharp edged and compact were collected and subcultured under hES-specific conditions. Molecular characterization of these colonies was performed using RT–PCR and immunohistochemistry. (Epi)genetic stability was tested using bisulphite sequencing and karyotype analysis. Directed differentiation protocols in vitro were performed to investigate the potency of these cells and the cells were injected into immunocompromised mice to investigate their tumorigenicity.

In testicular cell cultures from all four men, sharp-edged and compact colonies appeared between 3 and 8 weeks. Subcultured cells from these colonies showed alkaline phosphatase activity and expressed hES cell-specific genes (Pou5f1, Sox2, Cripto1, Dnmt3b), proteins and carbohydrate antigens (POU5F1, NANOG, SOX2 and TRA-1-60, TRA-1-81, SSEA4). These ES-like cells were able to differentiate in vitro into derivatives of all three germ layers including neural, epithelial, osteogenic, myogenic, adipocyte and pancreatic lineages. The pancreatic beta cells were able to produce insulin in response to glucose and osteogenic-differentiated cells showed deposition of phosphate and calcium, demonstrating their functional capacity. Although we observed small areas with differentiated cell types of human origin, we never observed extensive teratomas upon injection of testis-derived ES-like cells into immunocompromised mice.

Multipotent cells can be established from adult human testis. Their easy accessibility and ethical acceptability as well as their non-tumorigenic and autogenic nature make these cells an attractive alternative to human ES cells for future stem cell therapies.

In this study, we used an anti-eppin antibody to clarify the effect of eppin on human sperm functions during fertilization. Immunofluorescence studies were performed on ejaculated human spermatozoa in uncapacitated, capacitated and ionophore-treated states. Human spermatozoa were incubated in the presence or absence of anti-eppin antibody under capacitating conditions and with A23187. The effects of the antibody were evaluated on sperm motility, protein phosphotyrosine content and free intracellular calcium.

Immunofluorescence results demonstrated that eppin is located on the acrosome and tail. After the acrosome reaction eppin is found on the equatorial segment and tail. We found that blocking eppin with antibodies significantly inhibited the human sperm acrosome reaction induced by A23187 in a dose-dependent manner. Finally, fluo-3 analysis demonstrated that the A23187-induced elevation of sperm intracellular calcium concentration was markedly reduced after incubation with anti-eppin antibody. However, the tyrosine phosphorylation of sperm proteins did not change.

These results demonstrate that eppin can modulate intracellular calcium concentrations and subsequently affect the calcium ionophore A23187-induced acrosome reaction.

A prospective cohort study was undertaken from 1992 until 2005, using the same approach as for the follow-up of IVF and ICSI children conceived in the same centre. Questionnaires were sent to physicians and parents at conception and at delivery. Children were examined at 2 months of age by trained clinical geneticists whenever possible.

Data collected on 581 post-PGD/PGS children showed that term, birthweight and major malformation rates were not statistically different from that of 2889 ICSI children, with overall rates of major malformation among these post-PGD/PGS and ICSI children being 2.13 and 3.38%, respectively (odds ratio [OR]: 0.62; exact 95% confidence limits [95% CL]: 0.31–1.15). However, the overall perinatal death rate was significantly higher among post-PGD/PGS children compared with ICSI children (4.64 versus 1.87%; OR: 2.56; 95% CL: 1.54–4.18). When stratified for multiple births, perinatal death rates among PGD/PGS singleton and ICSI singleton children were similar (1.03 versus 1.30%; OR: 0.83; 95% CL: 0.28–2.44), but significantly more perinatal deaths were seen in post-PGD/PGS multiple pregnancies compared with ICSI multiple pregnancies (11.73 versus 2.54%; OR: 5.09; 95% CL: 2.80–9.90). The overall misdiagnosis rate was below 1%.

Embryo biopsy does not add risk factors to the health of singleton children born after PGD or PGS. The perinatal death rate in multiple pregnancies is such that both caution and long-term follow-up are required.