In cytometric analysis, the percentage of CCR5-positive unfixed spermatozoa varied from ~10 to ~60%, and it significantly decreased after 5 h capacitation. The percentage of CCR5-positive spermatozoa was increased to more than 90% following fixation and permeabilization, suggesting the existence of large intracellular pools of the receptor. Immunocytochemistry showed positive staining in the anterior region of the sperm head. In ejaculates from male partner of 102 infertile couples, the CCR5 expression rate significantly correlated with sperm count, total sperm number and forward motility, but not with sperm morphology. In stepwise analysis, only forward motility entered into the model; however, this explained only ~8% of the variability in CCR5 expression. Interquartile analysis showed significant differences between the first and fourth quartiles of CCR5 expression for all semen parameters, except morphology.

The percentage of CCR5-positive spermatozoa may vary under conditions associated with changes in membrane architecture and spermatozoa showed large intracellular pools of CCR5. A lower expression of CCR5 in asthenozoospermia seems to be suggested; however, it would only partially contribute to the inter-individual variability in the CCR5 expression. A genetic basis can be hypothesized to explain the variability.

In order to explore this issue further, a cohort of Day 5 single embryo transfers was analysed prospectively for embryological and clinical outcome. All transferred embryos resulted from 8-cell embryos on Day 3, from which subsequently either one cell (group I, n = 182) or two cells (group II, n = 259) were removed, or on which no invasion by means of embryo biopsy was performed (group III, control group, n = 702).

Blastocyst formation was significantly better in group III compared with group II, and similar to group I. Group I and group II did not differ in Day 3 nor in Day 5 embryo development. The overall live birth rate was significantly higher in group I (37.4%, CI 29.0–47.4%) than in group II (22.4%, CI 17.0–28.9%), and comparable to the reference ICSI population (35.0%, CI 30.8–39.7%).

The clinical outcome of 1-cell biopsy was significantly better than that of 2-cell biopsy, even when adjusted for availability of genetically transferable embryos.

Mouse blastocysts were cultured from zygote stage in vitro with and without recombinant mouse GM-CSF (rmGM-CSF), and in vivo developed blastocysts were flushed from Csf2 null mutant and wild-type mice. The effect of GM-CSF on blastocyst expression of stress response and apoptosis genes was evaluated by microarray, qPCR and immunochemistry.

Microarray analysis of the gene transcription profile showed suppression of stress response and apoptosis gene pathways in blastocysts exposed to rmGM-CSF in vitro. qPCR analysis confirmed that rmGM-CSF inhibited expression of heat shock protein (HSP) and apoptosis pathway genes Cbl, Hspa5, Hsp90aa1, Hsp90ab1 and Gas5 in in vitro blastocysts. Immunocytochemical analysis of HSP 1 (HSPA1A/1B; HSP70), BAX, BCL2 and TRP53 (p53) in in vitro blastocysts showed that HSPA1A/1B and BCL2 proteins were less abundant when embryos were cultured with rmGM-CSF. BAX and TRP53 were unchanged at the protein level, but Bax mRNA expression was reduced after GM-CSF treatment. In in vivo developed blastocysts, Csf2 null mutation caused elevated expression of Hsph1 but not other stress response genes.

We conclude that GM-CSF inhibits the cellular stress response and apoptosis pathways to facilitate embryo growth and survival, and the protective effects of GM-CSF are particularly evident in in vitro culture media, whereas in vivo other cytokines can partly compensate for absence of GM-CSF.

The study population, drawn from the two last cycles of the National Survey of Family Growth, consists of women aged 15–24 (n = 2543 in 1995, n = 2157 in 2002). We examined trends in use of ‘contraceptive services’ and ‘other reproductive health services for preventive care’ and tested for changes in the patterns of use of these services over time. Logistic regression models were used to further clarify the factors associated with the use of the two types of services in 2002.

Results show no difference in the overall use of reproductive health services in the past year but did reveal changes in the type of service sought. Use of services for contraception increased by 10 percentage points (39.3% in 1995 to 49.7% in 2002, P < 0.001), although the use of other services remained stable (53.2% in 1995, 50.2% in 2002, P = 0.14). The patterns of use varied over time, exhibiting growing social disparities. In 2002, the use of contraceptive services depended on women's age, number of partners, personal and mother's level of education, and menstrual problems. The use of other reproductive health services for preventive care varied across women's socio-economic background.

This study demonstrates increasing social differentials in the use of reproductive health services for preventive care among young women in the USA between 1995 and 2002, a finding which calls for careful monitoring in the context of limited resources.

Endometrial biopsies, with immunohistochemical nerve fibre detection using protein gene product 9.5 as marker, taken from 99 consecutive women presenting with pelvic pain and/or infertility undergoing diagnostic laparoscopy by experienced gynaecologic laparoscopists, were compared with surgical diagnosis.

In women with laparoscopic diagnosis of endometriosis (n = 64) the mean nerve fibre density in the functional layer of the endometrial biopsy was 2.7 nerve fibres per mm² (±3.5 SD). Only one woman with endometriosis had no detectable nerve fibres. Six women had endometrial nerve fibres but no active endometriosis seen at laparoscopy. The specificity and sensitivity were 83 and 98%, respectively, positive predictive value was 91% and negative predictive value was 96%. Nerve fibre density did not differ between different menstrual cycle phases. Women with endometriosis and pain symptoms had significantly higher nerve fibre density in comparison with women with infertility but no pain (2.3 and 0.8 nerve fibre per mm², respectively, P = 0.005).

Endometrial biopsy, with detection of nerve fibres, provided a reliability of diagnosis of endometriosis which is close to the accuracy of laparoscopic assessment by experienced gynaecological laparoscopists.

This study was registered with the Australian Clinical Trials Registry (ACTR) 00082242 (registered: 12/12/2007). The study was approved by the Ethics Review Committee (RPAH Zone) of the Sydney South West Area Health Service (Protocol number X05-0345) and The University of Sydney Human Research Ethics Committee (Ref. No. 10761) and all women gave their informed consent for participation.

Secretory phase endometrium samples (n = 40), obtained from women with laparoscopically/histologically confirmed minimal–mild endometriosis (n = 20) and from women with a normal pelvis (n = 20) were selected from the biobank at the Leuven University Fertility Centre. Immunohistochemistry was performed to localize neural markers for sensory C, A, adrenergic and cholinergic nerve fibres in the functional layer of the endometrium. Sections were immunostained with anti-human protein gene product 9.5 (PGP9.5), anti-neurofilament protein, anti-substance P (SP), anti-vasoactive intestinal peptide (VIP), anti-neuropeptide Y and anti-calcitonine gene-related polypeptide. Statistical analysis was done using the Mann–Whitney U-test, receiver operator characteristic analysis, stepwise logistic regression and least-squares support vector machines.

The density of small nerve fibres was ~14 times higher in endometrium from patients with minimal–mild endometriosis (1.96 ± 2.73) when compared with women with a normal pelvis (0.14 ± 0.46, P < 0.0001).

The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal–mild endometriosis with 95% sensitivity, 100% specificity and 97.5% accuracy. To confirm our findings, prospective studies are required.

This prospective, open-label, non-randomized trial included 82 women with pain symptoms caused by rectovaginal endometriosis. Patients received either a combination of letrozole and norethisterone acetate (group L) or norethisterone acetate alone (group N) for 6 months. Changes in pain symptoms during treatment and in the 12 months of follow-up were evaluated. Side effects of each treatment protocol were recorded.

Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (P < 0.001 versus baseline by 3 months) in both study groups. At both 3- and 6-month assessment, the intensity of chronic pelvic pain (P < 0.001, P = 0.002, respectively) and deep dyspareunia (P < 0.001, P = 0.005, respectively) was significantly lower in group L than group N. At completion of treatment, 63.4% of women in group N were satisfied with treatment compared with 56.1% in group L (P = 0.49). Pain symptoms recurred after the completion of treatment; at 6-month follow-up no difference was observed in the intensity of pain symptoms between the groups. Adverse effects were more frequent in group L than in group N (P = 0.02).

The combination drug regimen was more effective in reducing pain and deep dyspareunia than norethisterone acetate; however, letrozole caused a higher incidence of adverse effects, cost more and did not improve patients' satisfaction or influence recurrence of pain.

In May 2005, we introduced a ‘post-operative OC recommendation’ for patients treated with laparoscopic excision of endometrioma. That is, at the time of the operation, we provided each patient with information about OC, known and possible benefits and risks and let her decide whether to take OC. A retrospective cohort study included 87 patients who underwent a laparoscopy after May 2005. The endometrioma recurrence rate at 24 months was compared between those who used OC for the entire follow-up period OC (n = 34) and all of the others (n = 53). We also performed logistic regression analysis to identify variables associated with recurrence. A before–after study included another 224 patients who underwent a laparoscopy before May 2005 and compared the recurrence rate before and after introduction of the ‘post-operative OC recommendation’.

The recurrence rate in those who used OC for the entire period was significantly lower than in the ‘others’ group (2.9 versus 35.8%, relative risk 0.082, 95% CI 0.012–0.58, P < 0.001). Post-operative OC was determined as an independent variable associated with lower recurrence (OR 0.054, 95% CI 0.007–0.429, P < 0.001). The overall recurrence rate in patients who underwent laparoscopy after the introduction of the ‘post-operative OC recommendation’ was significantly lower than that in patients who received laparoscopy before the introduction (18.6 versus 33.1%, relative risk 0.56, 95% CI 0.32–0.97, P < 0.05).

Post-operative OC use reduces the risk of ovarian endometrioma recurrence after laparoscopic excision. This information will help in appropriate planning of pre- and post-operative management.

This study linked two data sets: Taiwan's birth certificate registry and its National Health Insurance Research Data set. A total of 5627 mothers with uterine leiomyoma and 28 135 unaffected mothers were included for analysis. After adjusting for mother and infant characteristics and monthly family income, log-binominal regression and multivariate regression analyses were conducted to examine the risks of preterm birth, SGA and lower birthweight among mothers with uterine leiomyoma and unaffected mothers.

Women with uterine leiomyoma had a significantly higher percentage of preterm births (10.98 versus 7.78%, P < 0.001) and SGA infants (19.00 versus 17.28%, P = 0.002) than unaffected mothers. The mean birthweights for mothers with and without uterine leiomyoma were 3083 and 3172 g, respectively (P < 0.001). Log-binominal regression models show that the adjusted risk ratios of preterm births and SGA infants for mothers with uterine leiomyoma were 1.32 (95% CI 1.19–1.46) and 1.16 (95% CI 1.08–1.26), respectively, compared with unaffected mothers. After finally adjusting for gestational age and other covariates, a multivariate regression analysis revealed that women with uterine leiomyoma had, on average, a 14.7 g lower birthweight than unaffected mothers (P = 0.022).

We concluded that after adjusting for potential confounders, women with uterine leiomyoma experience a small yet significant increased risk of preterm and SGA infants. We suggest that clinicians intensively monitor women with uterine leiomyoma during pregnancy.

This cohort study includes all patients undergoing TLH for benign pathologies between January 1993 and June 2007 in Cochin university hospital (Paris). Demographic and surgical data were analysed. A comparison between overweight and obese patients versus non-obese patients and multivariate analyses were performed.

Of 1460 patients undergoing TLH, 101 patients (6.9%) had a BMI of 30 or higher and 338 (23.2%) were overweight. After adjustment with respect to the patients’ characteristics and past history (age, parity, past history of laparotomies, previous Cesarean section, menopausal status), no significant difference was found whether in terms of intra-operative (haemorrhage, transfusion, thrombosis, ureter, bladder or bowel injuries) or post-operative complications (hyperthermia, infections, fistula). Concerning the intra- and post-operative characteristics of these patients, only a significantly longer operating time was noted in the case of obesity (RR = 1.80; CI 95%: 1.16–2.81).

In our experience, provided that the operating technique is meticulous, the intra- and post-operative complications are not increased in the case of obesity, although the operating time is longer.

In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 µg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol.

The study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): –3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus–oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15).

Corifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800.

This study evaluated whether or not adopting an eSET strategy instead of a DET strategy lowers the probability of having at least one live-born infant in good prognosis couples. Seven hundred and twenty-six couples were divided into two groups. The retrospective arm of the study was undertaken on the first group of couples (n = 483, DET group) and the prospective arm performed on the second group of couples (n = 243, SET group). In these specific populations, the probability of a woman having at least one live-born infant and the probability that one embryo utilized leads to a child were the main outcome measures.

The probability of a woman having at least one live-born infant was 60.5% in the DET group compared with 60.8% in the SET group. The probability of a live-born child per embryo utilized was not significantly different between the SET and the DET groups, 18.9% and 17.6%, respectively. In addition, the cumulative multiple live birth rate was significantly lower in the SET compared with the DET group.

In this observational study, using appropriate cryopreservation techniques, the chance of delivering a live baby, per utilized embryo, in an elective SET strategy is as good as that for DET.

We report a retrospective study in a university tertiary care center. Multivariate analysis and logistic regression were used to identify predictive factors of pregnancy in a series of 450 OD FTET cycles in 198 infertile women between January 1992 and December 2006.

The mean (±SD) recipient age was 35.7 (±4.5). Impaired ovarian function was the main indication for OD. The mean ± SD (range) number of embryos transferred was 1.65 ± 0.5 (1–3). Overall clinical pregnancy, implantation and delivery rates were 30, 18 and 23%, respectively. After univariate analysis, pregnancy rates were significantly higher in recipients under 35 years, in women with a body mass index (BMI) <30 kg/m², in women with an endometrial thickness of ≥8 mm, in amenorrheic women and in women not receiving pituitary down-regulation before endometrial preparation. Using multivariate analysis, the BMI, endometrial thickness and the use of pituitary down-regulation were independent predictors of pregnancy, regardless of age.

This study supports that endometrial thickness of <8 mm, obesity and the use of GnRH analogue pituitary down-regulation before endometrial priming negatively impact pregnancy rates, independently of the recipient's age.

Effect of MICA on the susceptibility to C. trachomatis infection and its association with tubal pathology were investigated in 214 infertile women recruited during the period from 2004 to 2007. Subjects were tested for C. trachomatis antibodies, and were further divided into two groups: those with (n = 42) and without (n = 59) tubal pathology based on laparoscopy results. The relationship between prevalence of C. trachomatis, tubal pathology and MICA allele polymorphisms was analysed.

Women with tubal infertility more often had antibodies to C. trachomatis [66.7 versus 39.1%; odds ratio (OR): 3.12, 95% CI: 1.68–5.78, P = 0.004] than infertile women without tubal pathology. Moreover, allele 008 had a highly negative correlation with C. trachomatis infection (P_c = 0.0036, OR: 2.14), while other allele polymorphisms showed no significant association with the disease. No statistically significant differences were found in the MICA allele frequencies of C. trachomatis-positive women with or without tubal pathology.

The association of a specific MICA allele with C. trachomatis IgG antibodies among women with infertility suggests that the MICA locus might modify host susceptibility to C. trachomatis infection.

A postal questionnaire survey of a random population-based sample of women aged 31–50 years was performed in the Grampian region of Scotland. Questions addressed the following areas: pregnancy history, length of time taken to become pregnant each time, whether medical advice had been sought and self-reported exposure to factors associated with infertility.

Among 4466 women who responded, 400 (9.0%) [95% CI 8.1, 9.8] had chosen not to have children. Of the remaining 4066 women, 3283 (80.7%) [95% CI 79.5, 82.0] reported no difficulties in having children and the remaining 783 (19.3%) [95% CI 18.1, 20.5] had experienced infertility, defined as having difficulty in becoming pregnant for more than 12 months and/or seeking medical advice. In total 398 (9.8%) [95% CI 8.9, 10.7] women had primary infertility, 285 (7.0%) [95% CI 6.2, 7.8] had secondary infertility, 100 (2.5%) [95% CI 2.0, 2.9] had primary as well as secondary infertility. A total of 342 (68.7%) and 208 (73.0%) women with primary and secondary infertility, respectively, sought medical advice and 202 (59.1%) and 118 (56.7%) women in each group subsequently conceived. History of pelvic surgery, Chlamydial infection, endometriosis, chemotherapy, long-term health problems and obesity were associated with infertility. In comparison with a similar survey of women aged 46–50 from the same geographical area, the prevalence of both primary infertility (>24 months) [70/1081, (6.5%) versus 68/710 (9.6%) P = 0.02] and secondary infertility [29/1081 (2.7%) versus 40/710 (5.6%) P = 0.002] were significantly lower.

Nearly one in five women attempting conception sampled in this study experienced infertility, although over half of them eventually conceived. Fertility problems were associated with endometriosis, Chlamydia trachomatis infection and pelvic surgery, as well as obesity, chemotherapy and some long-term chronic medical conditions. There is no evidence of an increase in the prevalence of infertility in this population over the past 20 years.

A survey was conducted among the centres for reproductive medicine that are allowed to handle oocytes and create embryos (B-centres). Data were collected on the nationality of patients and the type of treatment for which they attended during the period 2000–2007.

Sixteen of 18 centres responded to the questionnaire. The flow of foreign patients has stabilized since 2006 at approximately 2100 patients per year. The majority of foreign nationals seeking treatment in Belgium were French women for sperm donation. The next highest group was patients entering the country to obtain ICSI with ejaculated sperm.

There are clear indications that numerous movements are motivated by the wish to evade legal restrictions in one's home country, either because the technology is prohibited or because the patients have characteristics, which exclude them from treatment in their own countries.

In this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development.

The NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups.

We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4–18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.

We analysed a consecutive cohort of 1391 couples, referred to our secondary care hospital between January 2002 and December 2006. Discontinuation rates were studied at six stages. Stage I: immediately after first visit, Stage II: during diagnostic workup, Stage III: after finishing diagnostic workup but before treatment, Stage IV: during or after non-IVF treatment, Stage V: during IVF, Stage VI: after at least 3 cycles of IVF. Reasons to discontinue and spontaneous pregnancy rates after discontinuation were secondary outcomes.

In our cohort 319 couples dropped out of fertility care, 76.8%, [95% confidence interval (CI): 72.2–81.4] on their own initiative and 23.2% (95% CI: 18.6–27.8) on doctor's advice. Percentage (95% CI) of couples discontinuing per stage were: Stage I 6.0% (3.4–8.6), Stage II 3.4% (1.5–5.5), Stage III 35.7% (30.5–41.0), Stage IV 23.5% (18.9–28.2), Stage V 17.9% (13.7–22.1) and Stage VI 13.5% (9.7–17.2). Main reasons for dropout (%, 95% CI) were ‘emotional distress’ (22.3%, 17.7–26.8), ‘poor prognosis’ (18.8%, 14.5–23.1) and ‘reject treatment’ (17.2%, 13.1–21.4). The spontaneous ongoing pregnancy rate after discontinuation was 10% (6.7–13.3).

About half of the couples stopped before any fertility treatment was started and one-third stopped after at least one IVF cycle. The main reasons for withdrawal were emotional distress and poor prognosis. This insight may help to improve quality of patient care by making care more responsive to the needs and expectations of subfertile couples.

A total of 406 women participated in this study (mean age = 22, SD = 2.9). There were 211 participants in the gain condition and 195 in the loss condition.

An analysis of covariance found a main effect for framing (F(1, 402) = 6.3; P < 0.01) after controlling for existing attitudes towards oocyte donation and pre-message intentions to donate. Specifically, participants in the gain-framed condition were significantly more likely to report higher post-message intentions to donate oocytes than participants in the loss condition. However, the framing effect was only observed with British populations and not with women from South East Asia. Further, structural equation modelling analyses revealed lower levels of ‘perceived behavioural control’ (β = –0.420, P < 0.03) and positive attitudes towards ‘the importance of genetic ties between parent and child’ (β = 0.70, P < 0.001) were direct predictors of post-message intentions in the gain (but not loss) frame condition.

Findings obtained from this study indicate that oocyte donation campaigns should consider using gain-framed messages in recruitment appeals and message frames should be matched to the target populations’ perceived level of behavioural control.

The instrument was an author-constructed questionnaire completed online on the Donor Sibling Registry website. Questions assessed women's accounts of medical complications, contact with the infertility clinic through which they had provided ova, and information exchange or contact with people conceived from their ova.

Responses were received from 49.1% of the 287 donors with valid e-mail addresses. The 155 respondents completed the survey an average of 9.4 years after their first donation. Reported medical complications included ovarian hypersensitivity syndrome (30.3%) and infertility (9.6%). Subsequent to ova donation, 2.6% of women reported that they had been contacted by the IVF clinic for medical updates. On the questionnaire, 34.2% of women reported that medical changes they thought would interest donor children; half said that they had attempted to report these changes to the clinic with variable results. Many, who did not report such information, did not realize they could or should. Donors said that they frequently had not sought information about pregnancy outcomes because of confusion about the definition of ‘anonymity’ or ‘confidentiality’.

US-based IVF clinics need to give clearer guidelines to anonymous oocyte donors about follow-up information exchange. Additional long-term studies are needed to ascertain oocyte donors' risks of infertility or cancer.

Human ESCs were differentiated as embryoid bodies (EBs) in vitro. Gene and protein marker expression profiles of EBs in different periods of culture were analysed by quantitative polymerase chain reaction (Q-PCR) and immunolocalization to monitor germ cell development. Secretion of hormones involved in germ cell maturation was measured, to detect the existence of a germ cell niche within EBs.

Q-PCR revealed gene expression profiles consistent with PGC formation and germ cell development. A small population of post-meiotic spermatid cells were identified using sperm-specific antibodies (Protamine 1 and 1.97). Although gene expression profiles characteristic of oocyte development and follicle-like structures were detected, a committed oocyte with extra-cellular zona pellucida was not recognized with zona pellucida-specific monoclonal antibody.

hESCs can form PGCs and post-meiotic spermatids in vitro, however, there remains doubt about oocyte development. Levels of steroid hormones produced by EBs were significant when compared with known values for a similar quantity of human testis, suggesting that hESC may intrinsically create a favourable hormonal niche for spermatogenesis.

DSCs were isolated from human term decidua. The expression of B7-H1/B7-DC and HLA-DR and their alteration following IFN- and/or TNF- stimulation were assessed. DSCs with or without IFN- pretreatment were co-cultured with allogenic CD4⁺ T cells. The effect of PD-1:B7-H1/B7-DC and T cell receptor (TCR):HLA-DR interactions on T cell cytokine production was evaluated by adding blocking antibodies.

DSCs constitutively expressed B7-H1 and B7-DC, as well as small amounts of HLA-DR. Exogenous IFN- and TNF- up-regulated the B7-H1/-DC expression on DSCs, whereas HLA-DR expression was increased only by IFN-. IFN- pretreatment of DSCs stimulated T cell cytokine production through HLA-DR up-regulation. B7-H1 blockade on DSCs strongly enhanced T cell cytokine production (IFN-, TNF- and IL-2), whereas B7-DC blockade had similar but more modest effects. Blockade of both B7-H1 and B7-DC resulted in additive effects.

Our findings support the categorization of human DSCs as non-professional APCs and suggest that PD-1 ligands on DSCs, together with major histocompatibility complex class II, may play a crucial role in the regulation of decidual CD4⁺ T cell cytokine production. This helps to maintain a balanced cytokine milieu at the feto-maternal interface.

Ectopic ESCs were obtained from ovarian chocolate cysts in patients undergoing laparoscopic surgery (n = 22). Eutopic ESCs were isolated from endometrial tissue of cyclic premenopausal women undergoing hysterectomy for fibroids (n = 22). Purified stromal cells were studied in vitro. The number of surviving cells and activation of caspases were assessed by WST-8 assay and immunoblotting. Expression of inhibitor of apoptosis proteins (IAP) family members: cIAP1 (birc2), cIAP2 (birc3), XIAP (birc4), survivin (birc5) were examined using cDNA array and real-time RT–PCR. Effects of gene silencing by small inhibitor RNAs (siRNA) were examined by WST-8-assay, Annexin-V staining and immunoblotting.

After staurosporine (SS) treatment, 55% of eutopic ESCs survived versus 70% of ectopic ESCs. Procaspase-3 or -7 was more intensely activated by SS treatment in eutopic than in ectopic ESCs (P < 0.01). mRNAs for IAP-family genes, such as cIAP-1, XIAP and survivin, were highly expressed in ectopic ESCs before SS treatment. The fold induction of survivin expression after SS treatment was higher in ectopic than eutopic ESCs (2.8 ± 0.27 versus 0.69 ± 0.07, respectively). Survivin gene silencing in SS-treated ectopic ESCs led to an increase of apoptotic cells (P < 0.05, versus control siRNA).

We demonstrated that survivin plays a critical role in susceptibility of ESCs to apoptosis. Our results indicate that a survivin inhibitor may be effective as a novel treatment for endometriosis.

Expression levels of HOXA-10 mRNA and protein in endometrium were measured during the mid-secretory phase. This study utilized laser capture microdissection, real-time RT–PCR and immunohistochemistry.

HOXA-10 mRNA and protein expression levels in endometrial stromal cells were significantly lower in infertile patients with different types of endometriosis (deep infiltrating endometriosis, ovarian endometriosis and superficial peritoneal endometriosis), with uterine myoma, and unexplained infertility patients as compared with healthy fertile controls. HOXA-10 mRNA expression levels of microdissected glandular epithelial cells were significantly lower than those of microdissected stromal cells, without significant differences among the different groups. No protein expression was detected in glandular epithelial cells. The percentage of patients with altered protein expression of HOXA-10 in stromal cells were significantly higher in patients with only superficial peritoneal endometriosis (100%, 20/20, P < 0.05) compared with the other infertile groups (deep infiltrating endometriosis: 72.7%, 16/22; ovarian endometriosis: 70.0%, 14/20; uterine myoma: 68.8%, 11/16; unexplained infertility: 55.6%, 5/9).

The present findings suggested that altered expression of HOXA-10 in endometrial stromal cells during the window of implantation may be one of the potential molecular mechanisms of infertility in infertile patients, particularly in patients with only superficial peritoneal endometriosis. One of the underlying causes of infertility in patients with only superficial endometriosis may be altered expression of HOXA-10 in endometrial stromal cells.

Thirteen normal (control), 11 early-treated and 6 late-treated PA adult female monkeys had serum AMH levels measured at random times of the menstrual cycle or anovulatory period. Using some of the same animals, basal serum AMH, gonadotrophins and steroids were also measured in six normal, five early-treated and three late-treated PA female monkeys undergoing FSH therapy for IVF during late-reproductive life (>17 years); serum AMH also was measured on day of HCG administration and at oocyte retrieval.

Serum AMH levels in early-treated PA females declined with age to levels that were significantly lower than those of normal (P ≤ 0.05) and late-treated PA females (P ≤ 0.025) by late-reproductive life. Serum AMH levels positively predicted numbers of total/mature oocytes retrieved, with early-treated PA females having the lowest serum AMH levels, fewest oocytes retrieved and lowest percentage of females with fertilized oocytes that cleaved.

Based on these animals, early PA appears to program an exaggerated decline in ovarian reserve with age, suggesting that epigenetically induced hormonal factors during fetal development may influence the cohort size of ovarian follicles after birth.

A population-based health survey (HUNT 1) was conducted during 1984–1986 in Nord-Trøndelag county, Norway, with follow-up from 1995 to 1997 (HUNT 2). The study included 3887 women, <45 years old in HUNT 2. PA was assessed by baseline questionnaire, and fertility and parity by questionnaire at follow-up. Data focused on overall occurrence of infertility in the population (without biological confirmation).

Increased frequency, duration and intensity of PA were associated with increased subfertility, and frequency of PA was associated with voluntary childlessness (P < 0.01). After adjusting for age, parity, smoking, and marital status, women who were active on most days were 3.2 times more likely to have fertility problems than inactive women. Exercising to exhaustion was associated with 2.3 times the odds of fertility problems versus low intensity. Women with highest intensity of PA at baseline had the lowest frequency of continuing nulliparity and highest frequency of having three or more children during follow-up (P < 0.05). Sensitivity analysis including body mass index as confounder did not alter the results. No associations were found between lower activity levels and fertility or parity.

Increased risk of infertility was only found for the small group of women reporting the highest levels of intensity and frequency of PA. Awareness of the possible risks of infertility should be highlighted among non-athletic women who exercise vigorously.

In this population-based cohort study, we included 1 209 151 singleton pregnancies reported to the Medical Birth Registry of Norway between 1984 and 2006 and compared the risk of breech presentation in 8229 ART pregnancies with that in spontaneously conceived pregnancies. Risk ratios (RR), adjusted for maternal age, parity, gestational length and year of birth, were estimated using binominal regression, and we describe differences and time trends in obstetric management for breech and cephalic presentations after ART compared with management of spontaneously conceived pregnancies.

Breech presentation occurred nearly 50% more often in ART singleton pregnancies than in spontaneously conceived singletons [crude RR: 1.48, 95% confidence interval (CI): 1.34–1.64], but after adjustment for potentially confounding factors, the difference was fully attenuated (RR: 0.97, 95% CI: 0.88–1.07). The most important contributors to the attenuation were parity and length of gestation. In general, Caesarean sections and induced deliveries were more likely in ART pregnancies, but over the study period, the proportion of Caesarean sections in ART pregnancies gradually approached that of spontaneously conceived pregnancies.

Increased risk of breech presentation in pregnancies after ART is mediated by lower parity and shorter gestational length. In general, the obstetric management of women with ART pregnancies is gradually approaching the ordinary surveillance of pregnant women.

The authors used data on 41 268 live born singleton boys of mothers who were enrolled into the Danish National Birth Cohort in 1996–2002. During early childhood, 1598 cases of cryptorchidism were identified and 398 of these were orchiopexy verified. Maternal alcohol consumption including number and timing of binge drinking episodes was assessed in two computer-assisted telephone interviews around gestational weeks 17 and 32. Adjusted hazard ratios (HRs) of cryptorchidism were estimated by Cox regression.

Average weekly alcohol consumption as well as frequency of binge drinking at any time during pregnancy was not associated with risk of cryptorchidism. Binge drinking in gestational weeks 7–15 was associated with a slightly increased risk of cryptorchidism with adjusted HRs between 1.03 and 1.66.

Prenatal exposure to alcohol—measured as average intake as well as frequency and timing of binge drinking—was not associated with cryptorchidism. Our findings, however, do not rule out that binge drinking during the suggested male programming window may increase the risk of cryptorchidism.

From nationwide estimates of numbers of live births conceived by IVF (n = 40 330), we estimated the expected numbers of patients with retinoblastoma conceived by IVF in the period 1995–2007. The observed number of retinoblastoma diagnoses in children conceived by IVF was obtained by questionnaires sent to the parents of children with retinoblastoma diagnosed between 1995 and 2005. For non-responders and patients diagnosed after 2005, information was available through the medical files, in which information on fertility treatment has been routinely recorded since 2000. The relative risk (RR) of retinoblastoma among children conceived by IVF was calculated for the total study period (1995–2007) and for the expanded study period (2002–2007).

Of all eligible patients with retinoblastoma (n = 162) diagnosed in the period 1995–2007, seven were conceived by IVF. In the total study period (1995–2007) the risk was significantly elevated [RR = 2.54, 95% confidence interval (CI) = 1.02–5.23]. In the expanded study period (2002–2007), no significantly elevated risk (RR = 1.29, 95% CI = 0.16–4.66) was found.

We found a significantly increased risk of retinoblastoma in children conceived by IVF in the total study period 1995–2007. However, this increased risk was mostly based on the much stronger risk increase observed previously, for 1995–2002. Caution and awareness on the one hand and avoiding unnecessary worries on the other hand are important at this stage of our knowledge.

Informative markers flanking the DMD, IKBKG and NF2 genes were used to construct non-linked haplotypes. Polar bodies 1 (PB1) and 2 (PB2) were biopsied and analyzed to determine allelic association between the mutation and markers in multiplex PCR reactions.

For each family, the first PGD cycle allowed the establishment of linked haplotypes based on homozygous PB1 and PB2 analysis; however, no embryos were available for transfer. Subsequent cycles, when performed, confirmed this linkage. A mutation-free child was born to the family affected with DMD and an ongoing pregnancy (32 weeks) was achieved with the carrier of the IKBKG deletion.

PB analysis for reverse linkage in real-time coupled with the PGD cycle is a powerful tool for diagnosis and linkage between markers and de novo mutations for maternal autosomal dominant or X-linked disorders. Simultaneous amplification of multiple informative markers in conjunction with the mutation allows the building of familial haplotypes and accurate PGD analysis.

A clinic-based case–control study. Seventy-eight patients with non-familial, non-syndromic POF, and 90 controls were recruited to investigate the CAG repeat numbers in exon 1 of the AR gene by PCR and Gene Scan analysis.

The mean CAG repeat length in exon 1 of the AR gene of women with POF was 23.6 ± 3.8, which was significantly higher than controls (20.08 ± 3.45) (P < 0.001). The biallelic mean CAG repeat ranged from 11 to 32 in the control women, compared to 16 to 30 in the POF patients. The 22 CAG repeat allele followed by the 24 CAG repeat allele was found to be at highest frequency (15.38 and 12.8%) in POF cases, although the 19 CAG repeat allele was observed at highest frequency (12.2%) in controls.

The observation suggests that the CAG repeat length is increased in women with POF as compared with controls, and may be pathogenic for POF, at least in a subset of Indian women.