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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.