Background: Persistent postherniotomy pain (PPP) affects everyday activities in 5-10% of patients. Identification of predisposing factors may help to identify the risk groups and guide anesthetic or surgical procedures in reducing risk for PPP. Methods: A prospective study was conducted in 464 patients undergoing open or laparoscopic transabdominal preperitoneal elective groin hernia repair. Primary outcome was identification of risk factors for substantial pain-related functional impairment at 6 months postoperatively assessed by the validated Activity Assessment Scale (AAS). Data on potential risk factors for PPP were collected preoperatively (pain from the groin hernia, preoperative AAS score, pain from other body regions, and psychometric assessment). Pain scores were collected on days 7 and 30 postoperatively. Sensory functions including pain response to tonic heat stimulation were assessed by quantitative sensory testing preoperatively and 6 months postoperatively to assess nerve damage. Results: Four hundred sixty-four patients were included, whereof 442 were examined at 6 months (95.3% follow-up). Fifty-five patients (12.4%) had "moderate/severe" PPP at 6 months. Logistic regression analysis identified four risk factors for PPP: preoperative AAS score, preoperative pain to tonic heat stimulation, 30-day postoperative pain intensity, and sensory dysfunction in the groin at 6 months (nerve damage) (all P < 0.03). A risk prediction model of only preoperative factors and choice of surgical technique revealed increased preoperative AAS score, increased preoperative pain to heat stimulation, and open surgery to increase the risk for PPP (all P < 0.02). Conclusion: PPP is related to both patient and surgical factors. Patients with a high preoperative AAS score and high pain response to a standardized heat stimulus may preferably be treated using an operative technique with lowest risk for nerve damage.

What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)? Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception. Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown. A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed. Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin. Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71–0.91), PTB (aOR 0.84, 95% CI 0.76–0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66–0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62–0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27–1.55), LGA (aOR 1.45, 95% CI 1.27–1.64), macrosomia (aOR 1.58, 95% CI 1.39–1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07–2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13–1.43), very LBW (aOR 1.69, 95% CI 1.33–2.15), PTB (aOR 1.49, 95% CI 1.35–1.63), VPTB (aOR 2.68, 95% CI 2.24–3.22), SGA (aOR 1.18, 95% CI 1.03–1.35), LGA (aOR 1.29, 95% CI 1.15–1.45), macrosomia (aOR 1.29, 95% CI 1.15–1.45) and perinatal (aOR 1.39, 95% CI 1.03–1.87) neonatal (aOR 1.87, 95% CI 1.23–2.84) and infant mortality (aOR 1.92, 95% CI 1.36–2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04). As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility. Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature. No conflict of interest was reported. The study was supported by grants from the ALF agreement at the Sahlgrenska University Hospital, Gothenburg, Sweden. The European Society for Human Reproduction and Embryology (ESHRE), the University of Copenhagen, Denmark, and the Danish Agency for Science, Technology and Innovation have also supported the project. The CoNARTaS group has received travel and meeting funding from the Nordic Society of Obstetrics and Gynecology (NFOG).

What is the prevalence in a normal population of polycystic ovary syndrome (PCOS) according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone (AMH)? The prevalence of PCOS was 16.6% according to the Rotterdam criteria. When replacing the criterion for polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 and 8.5%, respectively. The Rotterdam criteria state that two out of the following three criteria should be present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (AFC ≥ 12 and/or ovarian volume >10 ml). However, with the advances in sonography, the relevance of the AFC threshold in the definition of polycystic ovaries has been challenged, and AMH has been proposed as a marker of polycystic ovaries in PCOS. From 2008 to 2010, a prospective, cross-sectional study was performed including 863 women aged 20–40 years and employed at Copenhagen University Hospital, Rigshospitalet, Denmark. We studied a subgroup of 447 women with a mean (±SD) age of 33.5 (±4.0) years who were all non-users of hormonal contraception. Data on menstrual cycle disorder and the presence of hirsutism were obtained. On cycle Days 2–5, or on a random day in the case of oligo- or amenorrhoea, sonographic and endocrine parameters were measured. The prevalence of PCOS was 16.6% according to the Rotterdam criteria. PCOS prevalence significantly decreased with age from 33.3% in women < 30 years to 14.7% in women aged 30–34 years, and 10.2% in women ≥ 35 years (P < 0.001). In total, 53.5% fulfilled the criterion for polycystic ovaries with a significant age-related decrease from 69.0% in women < 30 years to 55.8% in women aged 30–34 years, and 42.8% in women ≥ 35 years (P < 0.001). AMH or age-adjusted AMH Z-score was found to be a reliable marker of polycystic ovaries in women with PCOS according to the Rotterdam criteria [area under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990–0.999] and AUC 0.992 (95% CI: 0.987–0.998), respectively], and an AMH cut-off value of 18 pmol/l and AMH Z-score of −0.2 showed the best compromise between sensitivity (91.8 and 90.4%, respectively) and specificity (98.1 and 97.9%, respectively). In total, AFC > 19 or AMH > 35 occurred in 17.7 and 23.0%, respectively. The occurrence of AFC > 19 or AMH > 35 in the age groups < 30, 30–34 and ≥ 35 years was 31.0 and 35.7%, 18.8 and 21.3%, and 9.6 and 18.7%, respectively. When replacing the Rotterdam criterion for polycystic ovaries by AFC > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 or 8.5%, respectively, and in the age groups < 30, 30–34 and ≥ 35 years, the prevalences were 17.9 and 22.6%, 3.6 and 5.6%, and 3.6 and 4.8%, respectively. The participants of the study were all health-care workers, which may be a source of selection bias. Furthermore, the exclusion of hormonal contraceptive users from the study population may have biased the results, potentially excluding women with symptoms of PCOS. AMH may be used as a marker of polycystic ovaries in PCOS. However, future studies are needed to validate AMH threshold levels, and AMH Z-score may be appropriate to adjust for the age-related decline in the AFC. None. Not applicable.

Are singletons born after frozen embryo transfer (FET) at increased risk of being born large for gestational age (LGA) and if so, is this caused by intrinsic maternal factors or related to the freezing/thawing procedures? Singletons after FET have an increased risk of being born LGA. This cannot solely be explained by intrinsic maternal factors as it was also observed in sibling pairs, where the sibling conceived after FET had an increased risk of LGA compared with the sibling born after Fresh embryo transfer. FET singletons have a higher mean birthweight than singletons born after transfer of fresh embryos, and FET singletons may be at an increased risk of being born LGA. The national register–based controlled cohort study involves two populations of FET singletons. The first population (A: total FET cohort) consisted of all FET singletons (n = 896) compared with singletons born after Fresh embryo transfer (Fresh) (n = 9480) and also with that born after natural conception (NC; n = 4510) in Denmark from 1997 to 2006. The second population (B: Sibling FET cohort) included all sibling pairs, where one singleton was born after FET and the consecutive sibling born after Fresh embryo transfer or vice versa from 1994 to 2008 (n = 666). The sibling cohort included n = 550 children with the sibling combination first child Fresh/second child FET and n = 116 children with the combination first child FET/second child Fresh. Main outcome measures were LGA defined as birthweight of >2 SD from the population mean (z-score >2) according to Marsáls curves. Macrosomia was defined as birthweight of >4500 g. Crude and adjusted odds ratios (AORs) of LGA and macrosomia were calculated for FET versus Fresh and versus NC singletons in the total FET cohort. Similarly, AOR was calculated for FET versus Fresh in the sibling cohort. Adjustments were made for maternal age, parity, child sex, year of birth and birth order in the sibling analyses. Meta-analyses were performed by pooling our data with the previously published cohort studies on LGA and macrosomia. The AORs of LGA (z-score >2) and macrosomia in FET singletons versus singletons conceived after Fresh embryo transfer were 1.34 [95% confidence interval (95% CI) 0.98–1.80] and 1.91 (95% CI 1.40–2.62), respectively. The corresponding risks for FET versus NC singletons were 1.41 (95% CI 1.01–1.98) for LGA and 1.67 (95% CI 1.18–2.37) for macrosomia. The increased risk of LGA and macrosomia in FET singletons was confirmed in the sibling cohort also after adjustment for birth order. Hence, the increased risk of LGA in FET singletons cannot solely be explained by being the second born or by intrinsic maternal factors, but may also partly be related to freezing/thawing procedures per se. In the meta-analysis, the summary effects of LGA and macrosomia in FET versus singletons conceived after Fresh embryo transfer were AOR 1.54 (95% CI 1.31–1.81) and AOR 1.64 (95% CI 1.26–2.12), respectively. The corresponding figures for FET versus NC singletons were for LGA AOR 1.32 (95% CI 1.07–1.61) and macrosomia AOR 1.41 (95% CI 1.11–1.80), respectively. Adjustment for body mass index as a possible confounder was not possible. The size of the FET/Fresh sibling cohort was limited; however, the complete sibling cohort was sufficiently powered to explore the risk of LGA. A bias is very unlikely as data coding was based on national registers. Our findings are consistent with the previous Nordic studies and thus can be generalized to the Nordic countries. The causes for LGA in FET singletons should be further explored. No external funding was used for this project. None of the authors have any conflict of interest to declare.

Studies suggest that bipolar disorder is associated with increased risk of developing dementia^1,2 and that the risk increases with every new affective episode.³ On the other hand, it has been suggested that lithium may have neuroprotective abilities and may reduce the risk of developing dementia because lithium inhibits glycogen synthase kinase 3, which is a key enzyme in the metabolism of amyloid precursor protein and in the phosphorylation of the tau protein involved in the pathogenesis of Alzheimer disease.^4-6 However, the association between lithium consumption and dementia has been investigated in only 2 human studies. One study suggested an increasing risk of dementia with increasing numbers of lithium prescriptions,⁷ whereas the other study found that patients receiving long-term lithium therapy had decreased prevalence of Alzheimer disease compared with patients not receiving recent lithium therapy.⁸ Findings from both studies were hampered by the inclusion of low numbers of patients taking lithium, including 87 and 114 patients, respectively.