Prospective observational study from June 2001 to October 2004. All women classified with PUL had serum hCG levels measured at 0 and 48 h to calculate hCG ratio (hCG 48/hCG 0 h). All women were followed up until final diagnosis: failing PUL, viable and non-viable intrauterine pregnancy (IUP), ectopic pregnancy. Those PULs found to have an IPUV at follow-up transvaginal ultrasound scan (TVS) were included in final analysis.

During the study period, 12 572 consecutive first trimester women were scanned. One thousand and three (8%) women were classified PULs. Three hundred and seventy-nine (37.8%) PULs were confirmed IPUVs at follow-up scan. Complete data from 334 IPUVs were analyzed: 82.6% (276/334) viable IUPs and 17.4% (58/334) non-viable IUPs. Median hCG ratio was greater in viable IUPs [2.32, inter-quartile range (IQR) 1.16–4.77] compared with non-viable IUPs 1.83 (IQR 0.97–4.60). Sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratios of an hCG ratio >2.00 for the prediction of a viable IUP are 77.2%, 95.8%, 86.6%, 90.9%, 15.5, 0.24, respectively. In our population, an hCG ratio >2.00 increases the odds for a viable IUP from 0.42 to 6.46 post-test.

The hCG ratio is significantly higher in those IPUVs which become viable IUPs compared with non-viable IUPs. New cut-offs for the hCG ratio need to be evaluated for the prediction of viability in the IPUV group of PULs.

Prospective screening for trisomy 21 by maternal age, fetal NT, free β-hCG and PAPP-A at 11⁺⁰–13⁺⁶ weeks in singleton pregnancies, including 56 376 normal cases, 395 with trisomy 21, 122 with trisomy 18 and 61 with trisomy 13. Risk algorithms were developed for the calculation of patient-specific risks for each of the three trisomies based on maternal age, NT, FHR, free β-hCG and PAPP-A. Detection (DR) and false positive rates (FPR) were calculated and adjusted according to the maternal age distribution of pregnancies in England and Wales in 2000–2002.

The DR and FPR were 90% and 3%, respectively, for trisomy 21, 91% and 0.2% for trisomy 18 and 87% and 0.2% for trisomy 13. When screen positivity was defined by an FPR of 3% on the risk for trisomy 21 in conjunction with an FPR of 0.2% on the maximum of the risks for trisomies 13 and 18, the overall FPR was 3.1% and the DRs of trisomies 21, 18 and 13 were 91%, 97% and 94%, respectively.

As a side effect of first-trimester screening for trisomy 21, ~95% of trisomy 13 and 18 fetuses can be detected with an 0.1% increase in the FPR.

A total of 466 Day 3 embryos, donated with consent, underwent cryopreservation by either slow freezing in straws or vitrification using the cryoloop. The vitrification procedure did not include dimethyl sulfoxide, but rather employed ethylene glycol and 1,2-propanediol as the cryoprotectants. Survival, embryonic metabolism and subsequent development to the blastocyst were used to determine the efficacy of the two procedures.

Significantly, more embryos survived the vitrification procedure (222/234, 94.8%) than slow freezing (206/232, 88.7%; P < 0.05). Consistent with this observation, pyruvate uptake was significantly greater in the vitrification group, reflecting a higher metabolic rate. Development to the blastocyst was also higher following vitrification (134/222, 60.3%) than following freezing (106/206, 49.5%; P < 0.05). In a separate cohort of 73 patients who had their supernumerary embryos cyropreserved with vitrification, the resulting implantation rate and clinical pregnancy rate were 30 and 49%, respectively.

Analysis of metabolism revealed that vitrification had less impact on the metabolic rate of the embryo than freezing, which was reflected in higher survival rate and subsequent development in vitro. Excellent pregnancy outcomes followed the warming and transfer of vitrified cleavage-stage embryos. These data provide further evidence that vitrification imparts less trauma to cells and is, therefore, a more effective means of cryopreserving the human embryo than conventional slow freezing. Clinicaltrials.gov identifier: NCT00608010.

A computer program was created to analyse zygote images semi-automatically, providing precise morphological measurements. The accuracy of this approach was first validated by comparing zygotes from two different IVF centres with computer-assisted measurements or subjective scoring. Computer-assisted measurement and subjective scoring were then compared for their ability to classify zygotes with high and low implantation probability by using a linear discriminant analysis.

Zygote images coming from the two IVF centres were analysed with the software, resulting in a series of precise measurements of 24 variables. Using subjective scoring, the cytoplasmic halo was the only feature which was significantly different between the two IVF centres. Computer-assisted measurements revealed significant differences between centres in PN centring, PN proximity, cytoplasmic halo and features related to nucleolar precursor bodies distribution. The zygote classification error achieved with the computer-assisted measurements (0.363) was slightly inferior to that of the subjective ones (0.393).

A precise and objective characterization of the morphology of human PN zygotes can be achieved by the use of an advanced image analysis tool. This computer-assisted analysis allows for a better morphological characterization of human zygotes and can be used for classification.

Using protein-array technology, we analysed the protein profile corresponding to 24 h conditioned media of blastocysts that implanted versus those that did not implant. A statistical approach was followed to compare each of these media versus a medium in the absence of blastocysts (control medium). In addition, a gene ontology functional analysis—including those proteins showing a statistical difference among conditions—was performed, and a network with the predicted functional partners and corresponding relationships was obtained.

The soluble TNF receptor 1 and IL-10 increased significantly and MSP-, SCF, CXCL13, TRAILR3 and MIP-1β decreased significantly when the protein profile of the blastocyst culture medium was compared with the control medium. CXCL13 (BLC) and granulocyte-macrophage colony-stimulating factor was also decreased significantly in the implanted blastocyst media compared with that in media from the non-implanted counterparts with a similar morphology. None of the proteins included in the array was increased significantly in the implanted blastocyst-conditioned media.

The differences identified in the protein profile of the culture media in the presence of implanted versus non-implanted blastocysts can be considered a new non-invasive approach in the search for new tools to diagnose blastocyst viability.

Fluid was collected from 132 individual FFs that were the source of oocytes subsequently fertilized and transferred. In each, a bead-based multiplex sandwich immunoassay (Luminex) was used to measure 28 cytokines and chemokines simultaneously.

Significantly higher levels of interleukin (IL-2) and interferon (IFN-) were detected in FF for embryos that underwent early cleavage. IL-12 was significantly higher in FF corresponding to highly fragmented embryos and the chemokine CCL5 was significantly higher in FF related to the best quality (Top) embryos. The level of granulocyte colony-stimulating factor (G-CSF) in individual FF samples was correlated with the implantation potential of the corresponding embryo. The area under the receiver operating characteristics curve, which distinguished the embryos that definitely led to delivery from those that did not, was 0.84 (0.75–0.90) (P = 0.0001) for FF G-CSF. FF G-CSF was significantly lower in patients older than 36 years compared with those <30-year old. When the FF G-CSF was 20 pg/ml or higher, the ratio between Top and non-Top embryos was significantly higher than for the group with FF G-CSF below 20 pg/ml (45 versus 20.45%, P = 0.007).

Individual FF composition is related to the development of the corresponding in vitro generated embryo and its potential of implantation. Individual FF G-CSF may provide a non-invasive biomarker of implantation that needs to be evaluated together with in vitro observation to select the oocyte, and hence the embryo, to transfer.

This study was performed retrospectively. IVM was performed on 113 polycystic ovary syndrome patients (n = 120 cycles). Oocyte collection was performed either 35 h (Group 1; n = 76) or 38 h (Group 2; n = 44) after 10 000 IU of hCG priming. Following oocyte retrieval, oocyte maturity was assessed and the remaining immature oocytes were cultured in IVM medium up to Day 2.

The number of in vivo matured oocytes collected was significantly higher in Group 2 (13.6%, 114/840 versus 7.3%, 96/1312 in Group 1) (P < 0.01); the oocyte maturation rate after Day 1 was significantly higher (P < 0.01) in Group 2 (46.3 versus 36.0% in Group 1); and clinical pregnancy (40.9 versus 25%) and implantation rates (15.6 versus 9.6%) were better in Group 2 than those in Group 1.

The results suggest that extending the period of hCG priming time from 35 to 38 h for immature oocyte retrieval promotes oocyte maturation in vivo and increases the IVM rate of immature oocytes. Therefore, oocyte retrieval after 38 h of hCG priming may improve subsequent pregnancy outcome in cycles programmed for IVM treatment.

A randomized placebo-controlled trial was designed with 21 women with severe pain and a rectovaginal nodule of at least 1 cm. After 1 month of observation, three infusions of infliximab (5 mg/kg) or placebo were given. Surgery was performed 3 months later and follow-up continued for 6 months. The primary end-point was pain (dysmenorrhea, deep dyspareunia and non-menstrual pain) rated at each visit by the clinician and on a daily basis by the patient who in addition scored pain by visual analog pain scale and analgesia intake. Secondary end-points included the volume of the endometriotic nodule, pelvic tenderness and the visual appearance of endometriotic lesions at laparoscopy.

Pain severity decreased during the treatment by 30% in both the placebo (P < 0.001) and infliximab groups (P < 0.001). However, no effect of infliximab was observed for any of the outcome measures. After surgery, pain scores decreased in both groups to less than 20% of the initial value.

Infliximab appears not to affect pain associated with deep endometriosis. Treatment is associated with an important placebo effect. After surgery, pain decreases to less than 20%. Trials registration number ClinicalTrials.gov: NCT00604864.

An adenomyosis animal model was established using Institute for Cancer Research, Swiss-derived (ICR) mice, grafted with a single pituitary gland (n = 30). Four months after grafting, IUCDs with three different quantities of danazol were prepared and used to treat the ICR mice with adenomyosis. After 2 months of treatment with a danazol-loaded IUCD, the number of adenomyosis nodules and the hematoxylin-eosin staining scores were measured and compared with mice given daily oral danazol and controls (no adenomyosis).

As the danazol dose increased, the nodule number decreased reaching significance at a dose of 2.0 mg per 20 g body weight (P = 0.002). When compared with oral administration, the plasma danazol concentrations with IUCD delivery were low and stable.

These results suggest that an IUCD loaded with an appropriate dose of danazol may be an effective treatment for adenomyosis and that human trials are warranted.

Using polymorphic DNA markers, we compared the alleles of seven moles with those of the normal co-fetuses and deduced the number of oocytes and spermatozoa represented in each twin pregnancy.

The genomes of all seven moles were androgenetic diploid; six moles were homozygous in all loci analyzed and one mole was heterozygous in several loci. In one homozygous mole, the paternal alleles were identical to those of the normal co-fetus in 13 non-linked informative microsatellite loci, indicating the involvement of one spermatozoon only, and thus of one oocyte only. Duplications of the paternal genome followed by abnormal cell division can explain this observation. In six moles, the paternal alleles were different from those of the normal co-fetus suggesting involvement of two (or more) spermatozoa. Overfertilization of one oocyte followed by abnormal cell division is a possibility.

It is possible that twin pregnancies comprising a diploid mole and a normal co-fetus most often derive from one single oocyte fertilized with one or more spermatozoa. This can explain why diploid moles are far more frequent than triploid moles in twin pregnancies.

We performed explorative, semi-structured, in-depth interviews, based on two theoretical models. The interviews were performed among 19 Dutch IVF professionals and 20 patients who had just undergone IVF or were on the waiting list for IVF. The interviews were fully transcribed and two researchers independently scored the factors according to the models.

We identified a wide variety of factors, potentially influencing eSET use: 37 with the professionals and 26 among the patients. Examples of factors mentioned by both patients and professionals were: uncertainty about the eSET technique, couples' lack of knowledge about essential eSET aspects, absence of a reimbursement system which favours eSET, inadequate options to select couples suitable for eSET and inferior cryopreservation success rates.

This study demonstrates that both IVF professionals and patients identify numerous factors preventing eSET use in clinical practice. To estimate the impact of these factors identified, a quantitative confirmation and assessment of the magnitude of the effect is necessary.

A decision analytic model was created to simulate treatment. Outcome probabilities were derived from peer-reviewed literature and the Society for Assisted Reproductive Technologies database. Procedural costs were derived from a sampling of high-volume IVF centers and the Medicare Resource Based Relative Value Scale. Indirect costs of complications, lost productivity and multiple gestation pregnancies were considered. Sensitivity analyses were performed.

Vasectomy reversal was more cost-effective than either MESA or TESE under all probability conditions. In 1999, vasectomy reversal demonstrated superior cost-effectiveness to TESE and MESA ($19 633 versus $45 637 and $48 055, respectively, equivalent to $25 321 versus $58 858 and $61 977 in 2005 dollars). In 2005, vasectomy reversal ($20 903) remained the most cost-effective treatment over TESE ($54 797) and MESA ($56 861). The cost-effectiveness of all treatments improved over projections by inflation. The relative cost-effectiveness of the therapies was unchanged over time.

Vasectomy reversal appears more cost-effective than percutaneous TESE and MESA for treatment of obstructive azoospermia when the impact of indirect costs is considered. The absolute cost-effectiveness of all therapies improved over time. These results may be tailored with institution-specific data to allow more individualized results.

The incidence of drop-out from IVF treatment and factors related to drop-out were studied in a cohort of IVF patients aged <38 years embarking on IVF treatment either with a mild or a standard treatment strategy for a planned maximum number of treatment cycles.

Of the 384 couples studied, 17% dropped out of IVF treatment. The physical or psychological burden of treatment was the most frequent cause of drop-out (28%). The application of a mild treatment strategy (mild ovarian stimulation along with the transfer of a single embryo) significantly reduced the chance of drop-out (hazard ratio (HR) 0.55; 95% confidence interval (CI), 0.31–0.96). When a mild IVF strategy was employed, the association between the baseline anxiety score and drop-out was reduced by >50%. The presence of severe male subfertility (HR 4.80; 95% CI, 1.63–14.13) and the failure to achieve embryo transfer (odds ratio 0.41; 95% CI, 0.24–0.72) were also related to drop-out.

Reducing drop-out rate is crucial to further improve the efficacy and cost-effectiveness of IVF treatment. An important factor determining the risk of drop-out is the burden of the treatment strategy. The application of a mild treatment strategy and managing patient’s expectations might reduce drop-out rates.

Participants were 1090 consecutive women and men, 545 couples, attending a fertility clinic in Sweden during a two-year period. The Primary Care Evaluation of Mental Disorders (PRIME-MD), based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV), was used as the diagnostic tool for evaluating mood and anxiety disorders.

Overall, 862 (79.1%) subjects filled in the PRIME-MD patient questionnaire. Any psychiatric diagnosis was present in 30.8% of females and in 10.2% of males in the study sample. Any mood disorder was present in 26.2% of females and 9.2% of males. Major depression was the most common mood disorder, prevalent in 10.9% of females and 5.1% of males. Any anxiety disorder was encountered in 14.8% of females and 4.9% males. Only 21% of the subjects with a psychiatric disorder according to DSM-IV received some form of treatment.

Mood disorders are common in both women and men undergoing IVF treatment. The majority of subjects with a psychiatric disorder were undiagnosed and untreated.

Standardized questionnaires assessing quality-of-life (36-item short-form health survey, SF-36), depressiveness (Beck Depression Inventory), emotional distress (Symptom Check List 90, SCL-90-R), sexual satisfaction and self-worth (visual analogue scales), and a questionnaire on the desire for a child (FKW) were administered at the outpatient endocrine clinic to consecutive PCOS patients.

Questionnaires from 115 PCOS patients were analysed. The majority (76.1%) worried about remaining childless in the future, and 51.3% reported a current wish to conceive. 23.9% of patients had scores indicating mild to moderate depression, and 25.2% had scores indicating clinically relevant depression. Furthermore, all quality-of-life scores were significantly lower compared with normative data (P < 0.001). Unexpectedly, comparisons of patients with a current unfulfilled desire to conceive to those with no present wish for a child revealed no discernable impact on depressive symptoms, quality-of-life or emotional distress. Reduced sexual satisfaction and self-worth were largely determined by partnership status and not infertility. However for PCOS patients who wished to conceive, the wish for a child was a significantly greater priority when compared with normative data from infertile patients.

PCOS represents a major risk factor for psychosocial and emotional problems, but at least in this sample of PCOS patients, infertility does not appear to constitute a primary determinant of psychological problems.

A group of 30 women, scheduled for surgical treatment of leiomyomas, were randomized to either 50 mg mifepristone or placebo every other day, for 3 months. Fine needle aspiration biopsies were obtained at baseline and after 3 months. Immunocytochemical analysis of Ki-67 was performed to reflect breast epithelial cell proliferation. Samples from 14 women were included in the final analyses.

The Ki-67 index was significantly reduced after mifepristone treatment compared with baseline (P = 0.012). Furthermore, less individual variation in the Ki-67 index was seen in the mifepristone group. Treatment with mifepristone did not affect cortisol levels, whereas an increase in serum testosterone was noted. Breast symptoms like soreness and swelling were reduced, whereas the incidence of flushes increased.

The ability of mifepristone to block breast epithelial cell proliferation in premenopausal women may prove beneficial when used for contraceptive purposes or for other gynaecological indications. Future studies should address a possible antiproliferative effect in the post-menopausal breast tissue during hormone replacement therapy. Our results implicate a possible protective effect of mifepristone on the breast epithelium. ClinicalTrials.gov NCT00579475.

In Experiment 1, IVF embryos from young (7–10 weeks) mice were cultured in medium supplemented with an oxidizing agent, hypoxanthine/xanthine oxidase, in the presence and absence of erythrocytes. In Experiment 2, the development of embryos derived from young and ageing (40–50 weeks) female mice was assessed in the presence and absence of erythrocytes.

In Experiment 1, the presence of hypoxanthine/xanthine oxidase significantly inhibited embryo development (P < 0.0001). Erythrocyte supplementation clearly overcame the detrimental effects in a dose-related manner. In Experiment 2, in the absence of erythrocytes, developmental competence was significantly lower in embryos from ageing females than in those from young females (P < 0.01). However, in ageing females, the supplementation of erythrocytes significantly promoted the development of embryos to the blastocyst stage (51.1% versus 77.3%; P < 0.01).

Supplementation with erythrocytes can counteract the negative effect of maternal ageing on embryo development and blastocyst formation.

The HEL-75 gene was amplified by PCR, and its structure and function were predicted and analyzed with bioinformatics tools. Polyclonal serum was raised against recombinant HEL (rHEL)-75 protein. The gene expression pattern was analyzed with RT–PCR and immunofluorescent staining. Finally, the antimicrobial activity and function during fertilization of HEL-75 were analyzed using a colony-forming unit assay and IVF, respectively.

The human HEL-75 gene is located on chromosome 20p13 and encodes a 95 amino acid protein with a predicted N-terminal signal peptide of 22 amino acids. The protein has six conserved cysteine residues, characteristic of members of the β-defensin superfamily, as well as several potential post-translational modification sites. At the transcriptional level, HEL-75 was expressed in the epididymis and lung, but only in the epididymis at the translational level. Immunofluorescent staining showed that HEL-75 protein bound spermatozoa in the epididymis. RHEL-75 protein could kill Escherichia coli in vitro in a dose- and time-dependent fashion. However, no effect was observed on sperm motility nor fertilization when spermatozoa were blocked with anti-rHEL-75 polyclonal serum.

HEL-75 is a new β-defensin expressed in the epididymis and on sperm; it may play an important role in host defense.

Leydig cell production of mRNA and protein for interferons (IFNs) and of three antiviral proteins—2'5' oligoadenylate synthetase (2'5'OAS), double-stranded RNA-activated protein kinase (PKR) and MxA—was investigated, in the absence or presence of mumps virus or viral stimuli including poly I:C, a mimetic of RNA viruses replication product.

Stimulated or not, human Leydig cells appeared unable to produce routinely detectable IFNs , β and . Although the level of PKR remained unchanged after stimulation, the expression of 2'5'OAS and MxA was enhanced following either mumps virus or poly I:C exposure (P < 0.05 versus control).

Overall, our results demonstrate that mumps virus replication in human Leydig cells is not associated with a specific inhibition of IFNs or 2'5'OAS, MxA and PKR production and that these cells display relatively weak endogenous antiviral abilities, as opposed to their rat counterparts.

We compared the expression of ezrin and phospho-ezrin in normal endometrium from women without endometriosis with their expression in eutopic and ectopic endometrial tissues from women with endometriosis, using immunohistochemistry and western blot analysis. Paired eutopic and ectopic endometrial tissue samples from women with endometriosis (n = 13) and normal endometrium from women without endometriosis (n = 12) were collected. Invasive potential of ESCs from each of these samples was compared using Matrigel membrane invasion assay.

Eutopic and ectopic endometrial tissues from women with endometriosis have higher ezrin and phospho-ezrin levels as confirmed by immunohistochemistry and western blot analysis (P < 0.05). The Matrigel membrane invasion assay revealed that ectopic ESCs have more invasive characteristics, more protrusions and higher ezrin staining than normal ESCs (P < 0.05).

Ezrin can be a potential marker for endometrial cell invasion and may play a role in the pathogenesis of endometriosis.

In 35 women with PCOS (17 lean, lean PCOS and 18 obese, obese PCOS) and 25 control women (9 lean, lean controls and 16 obese, obese controls), β-cell function was evaluated by the first-phase insulin response after intravenous glucose, acute insulin response to glucose (AIRg); insulin sensitivity, determined as insulin sensitivity index (ISI), was evaluated by the euglycemic hyperinsulinemic clamp. Indirect calorimetry was used for the assessment of glucose and lipid oxidation. Body composition was estimated by dual X-ray absorptiometry scan.

When adjusted for obesity, PCOS was associated with higher 2-h glucose levels (P < 0.05), higher trunk/periphery fat ratio (P < 0.001), lower ISI (P < 0.001), lower insulin-stimulated glucose oxidation (GOX 2) (P < 0.05) and lower non-oxidative glucose metabolism (P < 0.05), but a normal AIRg compared with control women. Lean women with PCOS had lower ISI (P < 0.001), GOX-2 (P < 0.05) and higher trunk/periphery fat ratio (P < 0.05) than lean control women. In obese women with PCOS, ISI was reduced with 25% compared with obese control women, whereas trunk/peripheral fat ratio did not differ. AIRg was increased in obese groups compared with lean groups (P < 0.05), but was, in all groups, appropriate for the ambient action of insulin.

PCOS is associated with a low ISI, which in lean women with PCOS may partly be explained by higher trunk/peripheral fat ratio. AIRg was amplified by obesity, but was, in all groups, appropriate for prevailing insulin sensitivity, suggesting a normal β-cell adaptation.

Follicular fluid was aspirated from 4–8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS (n = 11) and those with regular ovulatory cycles (n = 8). Follicular AMH was compared in the two groups. Serum samples were analysed for AMH and endocrine profile.

Follicular fluid AMH levels were significantly higher (P < 0.0001) in women with anovulatory PCOS (median: 466.2 ng/ml) compared with normal-ovulatory controls (median: 78.0 ng/ml). Mean follicular fluid AMH levels in PCOS patients were 60 times higher than in the serum. Moreover, there was a significant correlation between the follicular fluid and serum concentrations of AMH in the PCOS group (r = 0.86; P = 0.007) but not in controls.

Highly elevated AMH in follicular fluid from PCOS patients in contrast to age-matched normal controls suggests that increased circulating concentrations of AMH are partly due to the increased production of AMH by individual follicles and not simply attributable to the increased number of small antral follicles. This suggests an intrinsic abnormality in the ovarian follicles themselves in PCOS, which could contribute to disordered folliculogenesis.

Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients.

Metformin significantly reduced testosterone (1.56 ± 0.52 after 6 months versus 2.98 ± 1.00 at baseline) and 17-hydroxyprogesterone (0.03 ± 0.01 versus 0.06 ± 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 ± 0.68 versus 3.2 ± 0.41 and 5.2 ± 0.6 versus 3.76 ± 0.5 mm, respectively), thus documenting an improved endothelial function.

Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.

At age 31, a postal questionnaire including questions about hirsutism and oligo-amenorrhea was sent to all women from the population-based Northern Finland Birth Cohort 1966 (total n = 5889). Of these, 4535 (79.5%) answered the questionnaire, 1103 reported hirsutism and/or oligo/amenorrhea (symptomatic women) and 3420 were non-symptomatic. The fecundability ratio (FR) was defined as the probability of conception of a clinically detectable pregnancy within 12 months.

The overall pregnancy (77.7% versus 75.6%) and spontaneous abortion (19.3% versus 18.6%) rates did not differ between the two groups and the risk of spontaneous abortion was not associated with body mass index (BMI), waist-to-hip ratio (WHR) or waist circumference. Symptomatic women had suffered more often from infertility than non-symptomatic women (19.4% versus 11.1%, P < 0.01). Oligo-amenorrhea and/or hirsutism (FR = 0.74, P < 0.001) and obesity (FR = 0.68, P = 0.002) were both independently associated with decreased fecundability, but symptomatic women had become pregnant and had one or two successful deliveries as often as non-symptomatic women.

Women with self-reported oligo-amenorrhea and/or hirsutism had lower fecundability and suffered more often from infertility, but had at least one delivery as often as non-symptomatic women, and did not exhibit an increased risk of spontaneous abortion.

A cross-sectional survey collected information on socio-demographic and basic reproductive characteristics of HIV-infected women in Europe. A total of 403 women participated; 121 were pregnant.

The median age was 29 years and 84% (228) of women were born in Europe. Overall 68% (275 of 403) had been pregnant at some time. At the time of the survey, 59% (n = 160) of women had no HIV symptoms; severe symptoms were more frequent among non-pregnant than pregnant respondents (36% (65 of 181) versus 5% (4 of 88)). Of the women, 80% reported being in a long-standing relationship; 39% (74 of 190) reported that they became infected by their current partner and, overall, heterosexual infection was reported as the mode of acquisition in 55% (190 of 344). Maternal well-being, no previous live birth and having an uninfected partner were strongly associated with the likelihood of being pregnant. To assess the problems relating to fertility, pregnant and non-pregnant women were considered separately. Overall, 46% of pregnant women reported not using condoms to protect against infection during pregnancy. Of the 60 pregnant women who planned their pregnancies, 10 reported the need for assistance in conceiving: five monitored their ovulation period and five became pregnant through in vitro fertilization. Of 34 non-pregnant women currently trying for a baby, 15 (44%) had done so for more than 18 months. Overall 25 (27%) of 94 women who planned to become pregnant needed reproductive care.

Our results suggest that these days knowledge of HIV infection neither influences the desire for children nor the decisions regarding pregnancy in HIV-infected women living in Europe.

This population-based retrospective study compared perinatal outcome of twin pregnancies in primiparae aged 35 or older (N = 240) to that of twin pregnancies in primiparae aged 25–29 years (N = 940). Observed outcomes are adjusted for intermediate (mode of conception and hypertension during pregnancy) and confounding variables (level of education). The possible effect of zygosity and chorionicity was tested in a subset of this database, recorded in the East Flanders Prospective Twin Survey (EFPTS).

In twin pregnancies, maternal age of 35 or over is associated with a lower incidence of preterm birth [adjusted odds ratio (AOR) 0.59, 95% confidence interval (CI) 0.44–0.79] and low birthweight (AOR 0.75, 95% CI 0.58–0.98) compared with younger women. Differences in zygosity and chorionicity between both cohorts do not seem to affect the result.

In comparison with primiparae aged 25–29 years, perinatal outcome of twin pregnancies is more favourable in primiparae aged 35 or over.

In order to test the hypothesis that CRISP2 variations contribute to male infertility, we screened coding and flanking intronic regions in 92 infertile men with asthenozoo- and/or teratozoospermia and 176 control men using denaturing HPLC and sequencing. There were 21 polymorphisms identified, including 13 unreported variations. Three SNPs resulted in amino acid substitutions: L59V, M176I and C196R. All were only present in a heterozygous state and found in fertile men. However, the C196R polymorphism was of particular interest as it resulted in the loss of a strictly conserved cysteine involved in intramolecular disulphide bonding. Screening of an additional 637 infertile men identified 23 heterozygous C196R men to give an overall frequency of 3.6%, compared with 3.4% in control men. The functional significance of the C196R polymorphism was defined using a yeast two-hybrid assay. The C196R substitution resulted in the loss of CRISP2–GGN1 binding.

Although none of the many polymorphisms identified herein showed a significant association with male infertility, functional studies suggested that the C196R polymorphism may compromise CRISP2 function.

A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 ± 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia.

Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 ± 1.79 IU/l, n = 423) compared with heterozygotes (2.84 ± 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 ± 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 ± 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups.

The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed.

The haplogrouping was carried out using 12 polymorphic loci on the Y chromosome in 269 non-AZFc-deleted controls with an unknown spermatogenic status and 214 men with a partial AZFc deletion defined by the absence of the sequence-tagged site and sequence family variant loss of the DAZ and CDY1 genes. In the latter group, 57 men had normozoospermia and 157 men had azoo/oligozoospermia. Among these, 122 had a de novo partial AZFc deletion.

Y haplogroup distribution differed significantly between men with a de novo partial AZFc deletion and the control group, and between men with a specific subtype of the partial AZFc deletions and the control group. Further, partial AZFc deletions gave rise to spermatogenesis impairment in some Y haplogroups.

The findings indicate that some monophyletic Y chromosomes may be associated with predisposition to specific subtypes of partial AZFc deletion and adverse effect on spermatogenesis. Although these deletions were not confirmed with gene dosage analysis, the results suggest that Y chromosome background is an important factor that affects partial AZFc deletion formation and its contribution to spermatogenic failure.