A retrospective study has been conducted in our center for the past 10 years (1996–2005). Fifty-two patients experiencing a primary post-partum hemorrhage who were resistant to medical treatment underwent uterine artery embolization and/or hysterectomy. In case of arterial embolization, a follow-up of all the patients was realized, focusing on the preservation of fertility.

Six (11.5%) patients underwent hysterectomy straightaway and 46 (88.5%) arterial embolization in the first instance including 35 arterial embolizations after Cesarean section. Embolization was successful among 41 patients (89.1%) and hysterectomy was performed on the 5 (10.9%) others. Overall, 11/24 398 women suffered from a definitive loss of fertility after post-partum hemorrhage. Fertility was studied at least 1 year after the delivery. All patients had a return of normal menses. Sixteen of 41 women (39%) wanted another child and 100% succeeded. Nineteen pregnancies, including two twin pregnancy and one early spontaneous abortion were observed.

Embolization is a safe and effective non-surgical method to resolve post-partum hemorrhage and should be regarded as gold standard in a hemodynamically stable patient. Furthermore, subsequent fertility is not impaired by the procedure.

This prospective pilot study, included 29 women with symptomatic, surgically diagnosed endometriosis (Group 1) and 27 healthy, fertile, symptom-free women without endometriosis (Group 2, confirmed by laparoscopy). Seventeen women in Group 1 and 15 women in Group 2 had endometrial biopsies taken on Day 21 ± 2 of the cycle. A further 12 women in each group were biopsied on Day 26 ± 2. Telomerase and estrogen receptor beta (ERβ) expression was evaluated by immunohistochemistry. Mean TL was determined by quantitative PCR.

The endometria of fertile healthy women showed either weak or no telomerase immunoreactivity throughout the luteal phase. Immunostaining for telomerase was significantly increased during the implantation window and the premenstrual endometria of women with endometriosis (P < 0.0001). This was associated with a loss of stromal and vascular ERβ immunostaining (P < 0.05). The mean TL were significantly longer in endometria of women with endometriosis during the implantation window (P = 0.005), indicating the biological relevance of our novel finding of telomerase in benign endometrium. There was positive correlation of the circulating estradiol with peripheral blood TL in women.

We speculate that aberrant endometrial expression of telomerase mediates alterations in cell fate that enhance proliferation, contributing to the pathogenesis of endometriosis.

A prospective, longitudinal study of a systematically recruited consecutive cohort of women who had conceived with ART in Melbourne, Australia, in 2001 was investigated using telephone interviews and self-report questionnaires. The experience of birth was explored 3 months post-partum.

One hundred and sixty-six women who had conceived through ART participated. Compared with other Australian women, participants were more likely to have a Caesarean birth (51% versus 25%, P < 0.0001). Women who had a Caesarean birth were less likely to report having had an active say about the management of the birth (P < 0.01) and to have held their baby at birth (P < 0.0001) and more likely to report disappointment with the birth event (P < 0.0001), severe post-natal pain (P = 0.02) and needing a lot of help or advice with infant feeding (P = 0.001) than those who had a vaginal birth.

After ART, there are highly elevated rates of operative birth which appear to influence early post-natal adjustment.

Uterine decidua was collected from women (18–45 years) undergoing surgical termination of pregnancy (n = 7), surgical management of spontaneous abortion (n = 6) and tubal pregnancy (n = 10). Using quantitative RT–PCR and immunohistochemistry, mRNA and protein expression patterns of SLPI and elafin were compared.

Relative SLPI mRNA expression was significantly higher in decidua of women with tubal pregnancy (12.37 ± 2.66) compared with spontaneous abortion (5.09 ± 2.22, P < 0.0185). There was no difference demonstrated in elafin mRNA expression. SLPI and elafin protein expression were demonstrated in the decidual leukocyte populations and epithelium. There was no obvious qualitative difference in levels of SLPI and elafin protein expression or their distribution in the uterine decidua of women with termination of pregnancy, spontaneous abortion or tubal pregnancy.

Herein we demonstrate novel differences in gene expression of uterine decidua of tubal pregnancy compared with spontaneous abortion thereby contributing further to current knowledge of mechanisms involved in extrauterine implantation. The altered expression of SLPI may be a consequence of, or predispose to, tubal pregnancy.

A total of 115 subjects aged <40 years with follicle-stimulating hormone (FSH) levels <12 IU/l underwent transvaginal ultrasound in the early follicular phase of the menstrual cycle and after 14 days of down-regulation using gonadotrophin-releasing hormone agonists. 3D power Doppler was used to quantify ovarian volume, AFC and ovarian blood flow. The relationship between these ultrasound variables and treatment outcome was evaluated using multiple regression analysis.

Although a significant decrease in the ovarian volume (P < 0.05) and flow index (FI; P < 0.01) was demonstrated after pituitary desensitization, no differences were seen in the AFC. The total AFC, regardless of whether this was measured before or after down-regulation, was a significantly better predictor of the number of oocytes retrieved (P < 0.001) and poor ovarian response (P < 0.05) than age, FSH, ovarian volume and vascular indices although pre-treatment ovarian volume (P < 0.05) and FI (P < 0.05) were also predictive of the number of oocytes retrieved.

Pituitary desensitization results in a significant reduction in ovarian volume and vascularity, but has no effect on the AFC. AFC is the single best predictor of ovarian response regardless of whether the assessment is performed before or after down-regulation.

Co-culture models were established to evaluate the secretion of human RANTES and MIP-1. The effects of a dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and estrogen on the invasion of endometrial stromal cells (ESC) were also examined by using an invasion assay, and the translation and proteolytic activity of matrix metalloproteinase (MMP)-9 and MMP-2 in ESC were determined by western blot and zymography, respectively.

Our results showed that the combination of 17β-estradiol and TCDD increased the secretion of RANTES and MIP-1, promoted the invasiveness of ESC and increased the expression of MMP-2 and MMP-9 in ESC. Anti-RANTES, anti-MIP-1 neutralizing antibody or antibody against their receptors could effectively inhibit the invasiveness of ESC and the expression of MMP-2 and MMP-9.

The combination of 17β-estradiol with TCDD may facilitate the onset of endometriosis and contribute to its development by increasing the invasion of ESC mediated by CC-motif chemokines.

A prospective cohort study included all couples eligible for IVF or ICSI treatment, registered in a national waiting list in The Netherlands. The cumulative probability of treatment-free ongoing pregnancy on the IVF waiting list was assessed and the predictive effect of female age, duration of infertility, primary or secondary infertility and diagnostic category was estimated using Cox regression.

We included 5962 couples on the waiting list. The cumulative probability of treatment-free ongoing pregnancy was 9% at 12 months. In multivariable Cox regression, hazard ratios were: 0.95 (P < 0.001) per year of the woman’s age, 0.85 (P < 0.001) per year of duration of infertility, 0.71 (P = 0.005) for primary versus secondary infertility. Diagnostic category showed hazard ratios of 0.7, 1.6, 1.2, 1.7 and 2.6 for endometriosis, male factor, hormonal, immunological and unexplained infertility, respectively, compared with ‘tubal infertility’ (P < 0.001). The 12-months predicted probabilities ranged from 0% to 25%.

The chance of an ongoing pregnancy without treatment while waiting for an IVF or ICSI is below 10% but may be as high as 25% within 1 year for selected patient groups. Timing of IVF should take predictive factors into consideration.

Birthweight, distribution of birthweight, z-score, LBW (<2500 g), gestation and percentage preterm (<37 weeks) for singleton births >19 weeks gestation, conceived by ART or non-ART treatments (ovulation induction and artificial insemination) between 1978 and 2005 were analysed for one large Australian clinic.

For first births, the mean birthweight was significantly (P < 0.005) lower, and LBW and preterm birth more frequent for GIFT (mean = 3133 g, SD = 549, n = 109, LBW = 10.9% and preterm = 10.0%), IVF (3166, 676, 1615, 11.7, 12.5) and ICSI (3206, 697, 1472, 11.5, 11.9) than for FET (3352, 615, 2383, 6.5, 9.2) and non-ART conceptions (3341, 634, 940, 7.1, 8.6). Regression modelling showed ART treatment before 1993 and fresh embryo transfer were negatively related to birthweight after including other covariates: gestation, male sex, parity, birth defects, Caesarean section, perinatal death and socio-economic status.

Birthweights were lower and LBW rates higher after GIFT or fresh embryo transfer than after FET. Results for FET were similar to those for non-ART conceptions. This suggests IVF and ICSI laboratory procedures affecting the embryos are not causal but other factors operating in the woman, perhaps associated with oocyte collection itself, which affect endometrial receptivity, implantation or early pregnancy, may be responsible for LBW with ART.

This is a retrospective population-based study of 36 412 initiated first autologous fresh cycles conducted in Australian clinics during 2002–2005. Pregnancy and live delivery rates per initiated cycle were determined for each age.

The overall live delivery rate per initiated cycle was 20.4% with the highest success rate in women aged between 22 and 36 years. Male factor only infertility had a higher live delivery rate (22.0%) than female factor only infertility (19.2%). Advancing woman's age was associated with a decline in success rate. For women ≥30 years, each additional 1 year in age was associated with an 11% (99% CI: 10–12%) reduction in the chance of achieving pregnancy and a 13% (99% CI: 12–14%) reduction in the chance of a live delivery. If women aged 35 years or older would have had their first autologous fresh treatment 1 year earlier, 15% extra live deliveries would be expected.

This study suggested that women aged 35 years or older should be encouraged to seek early fertility assessment and treatment where clinically indicated.

Women selected for IVF–ICSI cycles who previously underwent bilateral endometriomas cystectomy were matched (1:2) for age and study period with patients who did not undergo prior ovarian surgery.

Sixty-eight cases and 136 controls were recruited. Women operated on for bilateral endometriotic ovarian cysts had a higher withdrawal rate for poor response (P < 0.001). In these patients, despite the use of higher doses of gonadotrophins, the number of follicles (P = 0.006), oocytes retrieved (P = 0.024) and embryos obtained (P = 0.024) were significantly lower. The clinical pregnancy rate per started cycle in cases and controls was 7% and 19% (P = 0.037) and the delivery rate per started cycle was 4% and 17%, respectively (P = 0.013).

IVF outcome is significantly impaired in women operated on for bilateral ovarian endometriomas.

Y chromosome deletion mapping and quantitative PCR analysis of the DAZ-gene copy number, supplemented with haplogroup typing in deleted patients, were performed, in combination with clinical assessments in 264 fathers and their sons conceived by assisted reproduction techniques (ART), and in 168 fertile men with normal sperm concentration.

In the ART fathers group, a complete AZFc deletion was detected in 0.4% (1/264). AZFc rearrangements/polymorphisms were found in 6.8% (18/264; 95% CI: 4.4–10.5), which was significantly more frequent (P = 0.021) than in the controls (3/168; 1.8%, 95% CI: 0.6–5.1). All deletions were transmitted to the sons, without any clinical symptoms in early childhood. In the fathers, there was no significant correlation between the DAZ copy number and the severity of spermatogenic failure.

AZFc rearrangements/polymorphisms are transmitted to sons and may represent a risk factor for decreased testis function and male subfertility, which needs confirmation in further studies in larger cohorts. However, deletions of two DAZ gene copies are compatible with normal spermatogenesis and fertility.

Protein localization of TGFβ family members was examined in secretory phase human endometrium and first trimester decidua by immunohistochemistry. mRNA expression was examined in HESC. Activin inhibitors (Activin-M108A/SB431542) with differing specificities for the other TGFβ members under consideration were applied during HESC decidualization in vitro. The secretion levels of potential TGFβ superfamily members were measured during decidualization, and recombinant proteins added to examine their effect.

This study has identified BMP2, BMP4, BMP7, GDF5, GDF8 and GDF11 but not Nodal in secretory phase human endometrium, but only BMP2, GDF5 and TGFβ1 protein were detected in decidual cells. All ligands except Nodal were expressed by cultured HESC. Both inhibitors significantly reduced decidualization validating the role of activin, but potentially also other TGFβ members, during decidualization. BMP2 and TGFβ1 secretion increased during HESC decidualisation and exogenous administration of these proteins significantly enhanced decidualization in vitro.

Like activin, BMP2 and TGFβ1 are likely to be involved in HESC decidualization. This is the first study to identify and localize BMP4, BMP7, GDF5, GDF8 and GDF11 in secretory phase human endometrium. Understanding the factors critical for the implantation process is needed for improving fertility and pregnancy outcomes.

Aneuploidy was examined in ejaculate sperm from 27 men: 8 carriers of chromosomal rearrangements with severe oligoasthenoteratozoospermia (OAT) or severe teratozoospermia; 10 chromosomally normal men with similarly abnormal semen parameters; and 9 proven fertile men with normal semen parameters. Fluorescence in situ hybridization was used to examine aneuploidy for chromosomes 13, 18, 21, X and Y.

We observed evidence of an ICE in three of the eight carriers of chromosomal rearrangements. However, men who were chromosomally normal but had severe OAT more frequently displayed increased disomy rates. Although autosomal disomy rates were only modestly increased in some of these men, increased XY disomy ranged from slight to extreme (up to a 100-fold increase).

Despite their similar semen parameters, infertile men with normal karyotypes displayed more frequent increases in sperm aneuploidy, particularly involving the sex chromosomes, than infertile men who were carriers of chromosomal rearrangements. The difference in the magnitude and type of sperm aneuploidy between the two infertile groups is likely related to the different causes of infertility.

A total of 333 patients scheduled for in vitro fertilization (IVF) with SET were included in the study. Embryos were selected for transfer by morphological criteria on Days 2 and 3 of in vitro culture, and left over culture media samples were analyzed by NIR spectroscopy.

The NIR spectral analysis produced unique metabolomic profiles that correlated to an embryo's reproductive potential. Resulting relative viability scores between positive and negative pregnancy outcomes were statistically significant (P < 0.03). A logistic regression of factors correlated to pregnancy outcomes showed that maternal age, percent fragmentation and relative viability scores all demonstrated a relationship. The extent of the correlation was determined by accuracy computation, where the accuracy of assessing viable embryos on Day 3 by metabolomic profiling was 53.6% and the accuracy of the morphological selection was 38.5%. In addition, the positive predictive value of metabolomic profiling was 0.365 and the negative predictive value was 0.830.

NIR metabolomic profiling of spent embryo culture media was able to distinguish viable embryos from non-viable embryos for reproduction.

In a Swedish study, 62 adult women with CAH, aged 18–63 years, and 62 age-matched controls were followed-up. Medical records, including those concerning pregnancies and deliveries, were examined and the 21-hydroxylase genotype of patients was noted. All women answered a questionnaire concerning sexual and reproductive health including health of the children.

Pregnancy and delivery rates were significantly lower in women with CAH (P < 0.001, P < 0.0056, respectively), and the severity of the 21-hydroxylase-mutation correlated with the reduced number of children born. More women with salt-wasting CAH were single and had not attempted pregnancy. Pregnancies were normal except for a significantly increased incidence of gestational diabetes in CAH patients (P < 0.0024). The children had normal birthweight and no malformations were observed. A later follow-up of the children showed a normal intellectual and social development. The sex ratio of the offspring differed significantly, with 25% boys in the CAH group compared with 56% among controls (P < 0.016). CAH women had more gynaecological morbidity during menopause.

Pregnancy and delivery rates are reduced in women with CAH mainly due to psychosocial reasons. The outcome of children did not differ from controls. The unexpected sex ratio in children born to mothers with CAH warrants further research.

The average nuclear positions of fluorescence in-situ hybridization signals for three centromeric probes (for chromosomes X, Y and 18) were compared in normoozoospermic men and in men with compromised semen parameters.

In controls, the centromeres of chromosomes X, Y and 18 all occupied a central nuclear location. In infertile men the sex chromosomes appeared more likely to be distributed in a pattern not distinguishable from a random model.

Our findings cast doubt on the reliability of centromeric probes for aneuploidy screening. The analysis of chromosome position in sperm heads should be further investigated for the screening of infertile men.

We performed a retrospective population-based study of 2339 ART cycles conducted in Australia, 2002–2004 to women aged ≥45 years. The cost-outcome study was performed on fresh autologous treatment cycles.

There were 1101 fresh autologous cycles initiated in women aged ≥45, with a pregnancy rate of 1.9 per 100 initiated cycles. There were 21 women who achieved a clinical pregnancy with 15 (71%) ending in early pregnancy loss and 6 in live singleton births. The live birth rate following fresh autologous initiated cycles was 0.5% [95% confidence interval (CI): 0.1–1.0%]. Fresh donor recipients had an higher live birth rate of 19.1% (95% CI: 15.1–23.2) (odds ratio 43.2; 95% CI: 18.6–100.3) compared with women having fresh autologous cycles. The average cost of a live birth following fresh autologous cycles was 753 107.

The success rate of fresh autologous treatment for women aged ≥45 years was <1%. The very high cost of a live birth reflects a treatment failure rate of >99%. The ART profession should counsel patients of the reality of the technology before the patients consent to treatment.

Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium. MEIS1 expression was confirmed during the human menstrual cycle by RT–PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation. To assess the importance of maternal Meis1 expression in a mouse model, the uteri of Day 2 pregnant mice were injected with Meis1 over-expression or small interfering RNA (siRNA) constructs. Blocking Meis1 expression by siRNA before implantation significantly reduced average implantation rates (P = 0.00001). Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin β3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006). Manipulating Meis1 expression before implantation also dramatically affected the number of pinopodes, uterine endometrial epithelial projections that develop at the time of endometrial receptivity.

The results suggest that in mouse, meis1 contributes to regulating endometrial development during the menstrual cycle and establishing the conditions necessary for implantation.

Normal human umbilical vein endothelial cells, immortalized first trimester extravillous trophoblast cells (HTR8/SVneo) and first trimester placental villi explants (8–14 weeks) were used for culture under normoxia (20% O₂) or hypoxia (1% O₂). Culture media were collected for the measurement of cytokines by enzyme-linked immunosorbent assay. Total RNA was extracted for RT-PCR analysis.

Under hypoxia, villous trophoblast expressed higher levels of VEGF, VEGFR-1, sVEGFR-1 and VEGFR-2 mRNAs (P < 0.001), and secreted more VEGF and sVEGFR-1 proteins (P < 0.05). In contrast, PlGF mRNA and protein were decreased in 1% O₂ (P < 0.001), whereas endoglin (Eng) was not modulated. Additionally, sVEGFR-1 directly abolished VEGF/PlGF-induced angiogenesis in the rat aortic ring assay.

Our results support the hypotheses that, in pre-eclampsia, (i) overproduction of VEGF family factors by pre-eclamptic placenta is a consequence of induced hypoxia; (ii) overproduction of sVEGFR-1 by hypoxic villous trophoblast accounts for maternal free VEGF depletion; (iii) low circulating level of free PlGF is not only related to sVEGFR-1 overproduction, but also to hypoxia-induced mRNA down-regulation; (iv) Eng is not modulated by hypoxia.

Prospective cohort study. Real and expected cumulative delivery rates are descriptive. The reproductive outcome per cycle was compared with that of a control group of patients with X-linked recessive disorders. The comparative analysis of ovarian stimulation parameters in the study group versus the control group was carried out using both bivariate (crude) and multivariate (linear regression) analysis.

Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The real cumulative delivery rate (max 6 cycles) overall was 46%. The expected overall cumulative delivery rate was 72%. Multivariate analysis did not show a significant difference in total dose of gonadotrophins used for ovarian stimulation between Group A (in which the female partner was affected) and a control group.

This study shows that ICSI and PGD for DM1 offer good reproductive outcome, both in cumulative terms and per treatment cycle. There is no evidence of impaired gonadal function in female DM1 patients.

A literature search covering MEDLINE, EMBASE, CENTRAL, meeting proceedings and reference lists of published articles was performed to identify relevant RCTs. Data were extracted for meta-analysis yielding pooled relative risks (RR) and 95% confidence intervals (CI). Sensitivity analyses by including studies with pseudo-randomization or unclear method of randomization were also performed (n=1141 patients in total).

Four RCTs (n=587 patients) were eligible for inclusion. No statistically significant differences were present between patients who received a combination of progesterone and estrogen for luteal support when compared with those who received only progesterone, in terms of positive hCG rate (RR: 1.02, 95% CI: 0.87–1.19), clinical pregnancy rate (RR: 0.94, 95% CI: 0.78–1.13) and live birth rate (RR: 0.96, 95% CI: 0.77–1.21) per woman randomized. These results did not materially differ in the sensitivity analyses performed.

The currently available evidence suggests that the addition of estrogen to progesterone for luteal phase support does not increase the probability of pregnancy in IVF. However, there is an obvious need for further RCTs that will assess, with more confidence, the effect of estrogen addition to progesterone during the luteal phase on the probability of pregnancy.

Semen samples from 77 male partners of infertile couples were evaluated. Each sample was analysed both before and after semen preparation by conventional microscopical procedures and by flow cytometry (FC). A multiparameter FC analysis to assess simultaneously sperm concentration, sperm viability, sperm apoptosis, CD45 positive (leukocyte) and CD95 (Fas) positive cell concentration was carried out. A further 10 samples were studied by indirect immunofluorescence to confirm results.

The mean concentration of CD95 positive cells was very low (<1%), with no significant difference between normozoospermic and non-normozoospermic men. There was no correlation between apoptotic sperm and CD95 positive cell concentration. A linear correlation was found between CD95 positive cell and leukocyte (CD45 positive) concentration (r = 0.9946, P < 0.0001). CD95 mean fluorescence intensity of leukocytes was 10-fold greater than that of sperm and of isotypic control. Both incubation with activating anti-Fas antibody and betulinic acid induced apoptosis in leukocytes. Incubation with betulinic acid, but not with activating anti-Fas antibody, induced apoptosis in sperm. Pre-incubation with neutralizing anti-Fas antibody suppressed CD95 expression on leukocytes, whereas it did not change sperm CD95 peak fluorescence.

There is no detectable quantity of Fas on human ejaculated sperm.

A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which five or less oocytes were retrieved, using ≥300 IU of gonadotrophins/day. Patients were randomized by computer-generated list and treated by either the flare-up GnRH agonist protocol (n = 90) or a flexible GnRH antagonist protocol (n = 180).

Ongoing pregnancy rate, the primary outcome measure, was significantly higher in the antagonist group compared with the agonist group (12.2 versus 4.4%, P < 0.048; difference 7.8%, 95% CI: 0.2 to 14.0). Estradiol levels on the day of hCG administration were lower in the antagonist protocol [median (interquartile range): 572 (325–839) versus 727 (439–1029) pg/ml, P = 0.018]. Clinical and biochemical pregnancy rates, fertilization and implantation rates, as well as the number of oocytes retrieved, the number of mature oocytes present, the stimulation period and the gonadotrophin dosage were not significantly different between the two groups compared.

The flexible GnRH antagonist protocol is associated with significantly higher ongoing pregnancy rates compared with the flare-up GnRH agonist protocol in poor responders (www.clinicaltrials.gov; NCT00417066).

We conducted a Monte–Carlo simulation for the reproductive history of 100 000 women based on the fertility and socio-demographic characteristics of the 1968 birth cohort in France. Declines in fecundability of various amplitudes have been implemented, as well as increases in the distribution of age at initiation of pregnancy attempts.

A decline in fecundability by 15% implied a decrease in fertility by 4%, and an increase in the proportion of couples eligible for infertility treatments by 73%. An increase in the mean age at initiation of first pregnancy attempt by 2.5 years from 25 years entailed a decrease by 5% in fertility and an increase by 32% in the proportion of couples eligible for infertility treatments.

A relatively important decrease in fecundability and an increase by 2.5 years in age at first pregnancy attempt are likely to have only a limited impact on fertility. However, they may have a large impact on the proportion of involuntarily infertile couples, likely to resort to assisted reproduction techniques.

Three hundred and sixteen patients were prospectively enrolled to enter their first IVF/ICSI-cycle. Age, FSH-, inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses.

A total of 132 oocyte retrievals were performed. A calculated cut-off level ≤1.26 ng/ml AMH alone detected poor responders (≤4 oocytes) with a sensitivity of 97%, and there was a 98% correct prediction of normal response in COH if levels were above this threshold. With levels <0.5 ng/ml, a correct prediction of very poor response (≤2 oocytes) was possible in 88% of cases. Levels of AMH ≥0.5 ng/ml were not significantly correlated with clinical pregnancy rates.

AMH is a predictor of ovarian response and suitable for screening. Levels ≤1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count. Measurement of AMH supports clinical decisions, but alone it is not a suitable predictor of IVF success.

The study population included 2329 twin pregnancies (4658 twins) and 147 655 singletons delivered in the Northeast of England during 1998–2002. Data were obtained from the population-based Northern Multiple Pregnancy Register and Northern Congenital Abnormality Survey.

The rate of congenital anomalies in twins was 405.8 per 10 000 twins versus 238.2 per 10 000 singletons [rate ratios (RR) = 1.7, 95% confidence interval (CI) 1.5–2.0]. In twins with known chorionicity (84.8% of all twins), the prevalence of congenital anomalies in monochorionic (MC) twins (633.6 per 10 000) was nearly twice that in dichorionic (343.7 per 10 000; RR = 1.8, 95% CI 1.3–2.5). There was an increased rate of congenital anomalies in twin compared with singleton pregnancies for all major types of anomalies, except chromosomal abnormalities.

This study using high quality, population-based data on multiple pregnancies and congenital anomalies found that twins, particularly MC twins, have a higher risk of congenital anomalies than singletons.

We used a register-based cohort study including all ongoing clinical pregnancies achieved by IVF/ICSI in 1995–2000 in Denmark. Data on fertility treatment, pregnancy and pregnancy outcome together with data on cytogenic testing and the use of triple test were retrieved from national statutory registers. Data on the invasive testing rate among the general Danish population were retrieved from the same national registers.

In this 6 year period, 8531 ART pregnancies were recorded representing an unselected national ART population (6122 IVF, 2087 ICSI and 322 ‘IVFICSI’). The number of prenatal invasive procedures was relatively low, 16.3%, and the uptake of second trimester serum screening was very low, 7.4%. The invasive testing rate, corrected for advanced maternal age distribution, was lower in the study population than in the general population. The rate of karyotype aberrations detected by prenatal testing was 2.7% (43/1586), whereas the overall rate of pre- and post-natally detected aberrations was 0.6% (62/9625). Chromosome aberrations were more common in the ICSI-treated group compared with the IVF-treated group [1.3% (30/2297) versus 0.5% (32/6957), P < 0.0001]. This was also the case if only prenatally diagnosed chromosome aberrations were compared [4.3% (24/556) versus 1.9% (19/975), respectively, P < 0.01].

ART pregnancies represent a group of high-risk pregnancies with regard to chromosomal aberrations, but nevertheless their uptake of prenatal testing was low. ICSI pregnancies compared with IVF pregnancies had a higher rate of chromosomal abnormalities, even though the average maternal age was lower.

RT–PCR, western blotting and immunostaining were used to study the expression of the four DAZ genes and the autosomal DAZL gene in human testes and in tissue culture cells.

RNA transcripts of all four DAZ genes were found in the testis, but at much lower levels than that of the DAZL transcripts. Expression in cultured somatic cells showed that DAZ transcripts encoding multiple DAZ repeats were translated inefficiently. No DAZ proteins could be unambiguously identified on western blots when the testicular samples from three patients without the DAZ genes were used as negative controls. Nonetheless, low levels of DAZ were detected in the cytoplasm of spermatogonia by immunostaining.

The expression of DAZ proteins in adult human testes is restricted to the spermatogonia and suggests a premeiotic role.

We compared E-cadherin immunohistochemistry levels on cross-sections of Fallopian tubes in 11 spontaneous (antegrade) versus 13 post-IVF (retrograde) TP. The intensity of immunoreactivity was scored in a semi-qualitative blinded manner.

The semi-quantitative intensity score in IVF tubal samples was more than double that observed in spontaneous TP (16.9 versus 7.3, respectively, P < 0.0005). E-cadherin showed the most intense immunostaining in cytotrophoblast cells of chorionic villi in ectopic TP post-IVF compared with negative or weak staining in spontaneous ectopic TP.

E-cadherin can serve as a marker of implantation. Differential expression of this adhesion molecule in TP post-IVF, when compared with natural conception, may reflect a different mechanism of embryo implantation. Moreover, the observation that E-cadherin is mostly expressed in trophoblasts, and not in the tubal wall, suggests that the preimplantation embryo may actively participate in locating a suitable implantation site.

There were 27 non-obese women with PCOS and 30 healthy, age- and body mass index (BMI) matched controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, fasting glucose, insulin and other hormones (gonadotrophins, androgens) and total l-carnitine levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance.

The women with PCOS had significantly higher serum dehydroepiandrosterone sulfate, total testosterone, free androgen index (FAI), luteinizing hormone (LH), low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, fasting insulin levels and HOMA-IR measurement and LH/FSH ratios than healthy women. However, total l-carnitine and sex hormone-binding globulin (SHBG) levels were significantly lower in women with PCOS. l-Carnitine level was negatively correlated with FAI, but positively correlated with SHBG. Multiple regression analysis revealed that SHBG was a strong predictor of serum total l-carnitine level.

Decreased total l-carnitine levels may be associated with hyperandrogenism and/or insulin resistance in non-obese women with PCOS. Long-term studies are needed to evaluate carnitine metabolism in PCOS, especially with regard to the molecular basis.

Study cycles included the last cycle, of each patient undergoing ART at Brigham and Women's Hospital from January 1998 to December 2004, that resulted either in a pregnancy with a monochorionic pair (n = 41) or a pregnancy without a monochorionic pair at 12 weeks (n = 2460). We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to identify factors significantly associated with a monochorionic pair.

Independent predictors of a monochorionic pair were assisted hatching (OR 2.23, 95% CI 1.06–4.67), ICSI (OR 2.42, 95% CI 1.22–4.83) and Day 5 embryo transfer (OR 2.48, 95% CI 1.62–3.80). The effects of ICSI and Day 5 transfer were amplified when cycles involved both interventions.

ICSI and Day 5 embryo transfer synergistically increase the risk of monochorionic placentation. Patients undergoing these procedures should be counselled regarding these increased risks.

DCI levels and the release of insulin and DCI-IPG during an oral glucose tolerance test (AUCs) were assessed in 27 Greek PCOS and 10 normal Greek women.

PCOS women were heavier than controls (BMI = 28.4 versus 23.7 kg/m², P = 0.05) with higher waist-to-hip ratios (WHR = 0.78 versus 0.71, P = 0.009) and increased free testosterone (P = 0.048) and AUC_insulin (P = 0.04). In PCOS women, incremental AUC_DCI-IPG was significantly decreased by 59% (2158 versus 5276%·min, P = 0.01), even after correction for BMI and WHR. Finally, increased uCl_DCI (r = 0.35, P = 0.04) and decreased AUC_DCI-IPG (r = 0.46, P = 0.004) were significantly associated with hyperinsulinemia in all women together, even after correction for BMI and WHR (Ps = 0.02 and 0.007), and regardless of PCOS status.

Greek women, with or without PCOS, display increased uCl_DCI and decreased AUC_DCI-IPG in association with higher insulin levels but independent of adiposity. Increased clearance of inositols might reduce tissue availability of DCI and decrease the release of DCI-IPG mediator, which could contribute to insulin resistance and compensatory hyperinsulinemia in Greek women, as previously described in American women.

We investigated hospital admissions during the first 3 years of life for all singleton children born in Western Australia between 1994 and 2000 [1328 ART, 162 350 spontaneously conceived (SC)].

ART infants had a significantly longer birth admission and were four times more likely to be admitted to neonatal intensive care units (NICU) than SC infants. ART children had a 60% greater risk of one or more admissions in their first year and an equal risk of admission in their second and third years. Their length of stay in hospital was longer in each age period. Maternal, infant and socio-economic confounders accounted for most of the increased admission risk in the first year. However, after adjustment, a 20% increase in the risk of admission to NICU (P < 0.05) and admission to hospital during the first year (P < 0.05) remained.

Couples undertaking ART should be aware that ART infants are more likely to be admitted to a NICU, to be hospitalized in the first year of life and to stay in hospital longer than other children.

Daily bloodsampling and ultrasound monitoring in the follicular phase was performed in 22 patients with elevated basal FSH levels (identified in screening) and in 16 controls during one menstrual cycle and for 5 days of the next cycle.

Eleven patients showed elevated basal FSH levels in the study cycle (‘High, High’; H,H group) whereas 11 had normalized basal FSH levels (‘High, Low’; H,L group). Anti-Müllerian hormone (AMH) was lower in both groups. In the H,H group, FSH was higher in all phases of the cycle and both inhibin A and B were lower during the EFP. In the H,L group, FSH was also higher than in controls in the EFP and the late luteal phase and inhibin A was higher in the periovulatory phase. ‘Normalization’ of Day 3 FSH in women with previously elevated FSH was associated with normalization of inhibin B levels in the preceding luteal phase.

The endocrine cycle profile in younger subfertile patients with consistently elevated basal FSH resembles that in published data from older women and also reflects a low ovarian reserve. Normalization of FSH in association with normal inhibin B suggests a temporary increase of the available cohort.

Data on all women treated in Finland from 1996–1998 for infertility either with IVF (n = 9175) or ovulation induction (OI, n = 10 254) and the age-matched controls of IVF women were linked to the Abortion and Hospital Discharge Registers for the period 1969–2000.

A notable proportion of IVF women (12%) and OI women (11%) had previous induced abortion(s). Practically all abortions were for social or age reasons. Most IVF women (72% of n = 1099) had their most recent abortion more than 10 years previous to fertility treatment, but more recently among OI women (45% of n = 1123 of the most recent abortions were in the preceding 10 years). Many IVF- and OI women were young and single at the time of the most recent abortion. At the time of IVF treatment most women were aged over 30 and married; OI women were also frequently married, but 42% of them were aged younger than 30.

At different points in their life, women may rely on opposite fertility regulation strategies. Health care professionals providing IVF need to consider the possibility of a previous abortion. Young women need information on the possibility of future infertility in later age.

Using a case–control study of 59 cases with hypospadias and 286 controls, we examined the association of hypospadias with the following polymorphisms: PvuII and XbaI in ESR1, and 2681-4A>G in ESR2.

For the cases, we found a negative association with the G allele containing variants of ESR1 XbaI (OR = 0.52, P < 0.05), and a negative association with the G allele containing variants of ESR2 2681-4A>G (OR = 0.59, P < 0.05). For the cases, we also identified a negative association with the CG haplotype, and a positive association with the CA haplotype, defined by ESR1 PvuII and XbaI (P < 0.05).

These findings suggest that the G allele containing variants of ESR1 XbaI and the G allele containing variants of ESR2 2681-4A>G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk.

Serum uric acid levels were measured in 40 polycystic ovary syndrome (PCOS) patients and 40 non-hyperandrogenic women matched for BMI and grade of obesity, and were followed-up in 34 PCOS patients who were randomized to an oral contraceptive containing 35 mg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane³⁵ Diario) or metformin (850 mg twice daily) for 24 weeks.

There were no statistically significant differences in uric acid levels between PCOS and non-hyperandrogenic control women. Considering all PCOS and non-hyperandrogenic control women as a whole, obese women showed higher uric acid concentrations than lean and overweight women, and the main determinant of serum uric acid level was the BMI. In PCOS women, Diane³⁵ Diario treatment was related with a decrease in uric acid levels (P = 0.018), whereas no changes were observed with metformin.

Obesity is the main determinant of serum uric acid concentrations in PCOS patients, yet amelioration of androgen excess with an antiandrogenic contraceptive pill results in a significant decrease in these levels, an effect that is not observed with metformin. ClinicalTrials.gov NLM Identifier: NCT00428311.

A Google search for the keyword ‘infertility’ was performed and 107 relevant websites were identified and categorized by type. Websites were assessed for credibility, accuracy and ease of navigation using predefined criteria.

The total scores for all types of websites were low, particularly in the accuracy category. Websites affiliated to the UK National Health Service (NHS) scored higher than those affiliated to private fertility clinics and other clinics providing non-conventional fertility treatment. Specifically, NHS websites were more likely to report success rates (92.9% versus 60% and 0%, P ≤ 0.05) and display information about their sources of funding (85.7% versus 15% and 14.8%, P ≤ 0.0001).

Internet resources available to infertile patients are variable. Differences in the quality of infertility information exist between the different types of websites.

A decision-analytic model was constructed to estimate the relative cost-effectiveness of the copper intrauterine device (IUD), the levonorgestrel intrauterine system (LNG-IUS), the etonogestrel subdermal implant and the depot medroxyprogesterone acetate injection (DMPA). Comparisons with the combined oral contraceptive pill (COC) and female sterilization were also performed. Effectiveness data were derived from a systematic literature review. Costs were based on UK national sources and expert opinion.

LARC methods dominated COC (i.e. they were more effective and less costly). Female sterilization dominated LARC methods beyond 5 years of contraceptive protection. DMPA and LNG-IUS were the least cost-effective LARC methods. The incremental cost-effectiveness ratio of implant (most effective LARC method) versus IUD (cheapest LARC method) was £13 206 per unintended pregnancy averted for 1 year of use and decreased until implant dominated IUD in 15 years. Discontinuation was a key determinant of the cost-effectiveness of LARC methods.

LARC methods are cost-effective from the British NHS perspective. Practices improving user satisfaction and continuation of LARC method use should be identified and promoted.

One hundred and fifty-one patients with WHO Group II anovulatory infertility failing to ovulate or conceive on clomiphene citrate underwent ovarian stimulation with FSH-only preparations following a low-dose step-up protocol. The individual FSH threshold dose was defined as the FSH dose when meeting the human chorionic gonadotrophin criteria (one follicle ≥17 mm, or 2–3 follicles ≥15 mm). The influence of demographics, physical characteristics, obstetric and infertility and menstrual cycle history, ovarian ultrasonography, endocrine parameters and type of gonadotrophin preparation on the FSH threshold dose was assessed through multiple regression analysis.

In the univariate analysis, age, body mass index (BMI), failure to ovulate with clomiphene citrate, menstrual cycle history (amenorrhea, oligomenorrhea or anovulatory cycles of 21–35 days), mean ovarian volume, LH/FSH ratio, testosterone and free androgen index were significant (P < 0.05) predictors of FSH threshold dose. In the multivariate analysis, menstrual cycle history, mean ovarian volume and BMI remained significant (P < 0.001).

The individual FSH threshold dose for ovulation induction in anovulatory women can be predicted based on three variables easily determined in clinical practice: menstrual cycle history, mean ovarian volume and BMI. A FSH dosage nomogram was constructed based on these parameters.

Peripheral blood leukocytes (PBL) from antisperm antibody-positive immunoinfertile and vasectomized men were activated with human sperm antigens in vitro, and the complementary DNA prepared and PCR-amplified using primers based on all the variable regions of heavy and light chains of immunoglobulins. The scFv repertoire was cloned into pCANTAB5E vector to create a human scFv antibody library.

Panning of the library against specific sperm antigens yielded several clones, and the four strongest reactive were selected for further analysis. These clones had novel sequences with unique complementarity-determining regions. ScFv antibodies were expressed, purified and analyzed for human sperm reactivity and effect on human sperm function. AFA-1 and FAB-7 scFv antibodies both reacted with fertilization antigen-1 antigen, but against different epitopes. YLP20 antibody reacted with the expected human sperm protein of 48 ± 5 kDa. The fourth antibody, AS16, reacted with an 18 kDa sperm protein and seems to be a human homologue of the mouse monoclonal recombinant antisperm antibody that causes sperm agglutination. All these antibodies inhibited human sperm function.

This is the first study to report the use of phage display technology to obtain antisperm scFv antibodies of defined antigen specificity. These antibodies will find clinical applications in the development of novel immunocontraceptives, and specific diagnostics for immunoinfertility.