Low-to-moderate alcohol consumption and success in fertility treatment: a Danish cohort study.

STUDY QUESTION: Does female weekly alcohol intake and binge drinking impact the chance of a successful fertility treatment? SUMMARY ANSWER: Low-to-moderate weekly alcohol drinking and binge drinking were not associated with the chance of achieving a clinical pregnancy or a live birth among women and couples undergoing medically assisted reproduction (MAR) treatments. WHAT IS KNOWN ALREADY: Alcohol consumption is common among women of reproductive age, even though health authorities advise women trying to conceive to abstain from drinking. A growing number of couples struggle with infertility, but it is unknown whether low-to-moderate levels of alcohol consumption and alcohol binge drinking impair success in fertility treatment. STUDY DESIGN, SIZE, DURATION: Cohort study with prospectively collected exposure information including 1708 women and potential partners undergoing fertility treatment at the public fertility clinic, Aarhus University Hospital, 1 January 2010 to 31 August 2015. In total, data on 1511 intrauterine insemination (IUI) cycles, 2870 in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and 1355 frozen embryo transfer cycles. PARTTICIPANTS/MATERIALS, SETTING, METHODS: Exposure to weekly average alcohol intake was assessed from questionnaires completed by participants before the start of treatment. Outcome measures are the achievement of a clinical pregnancy and live birth in consecutive treatment cycles in the Danish national health registries, enabling complete follow-up. A modified Poisson regression with robust standard errors was used to evaluate associations between a weekly average alcohol intake and MAR outcomes, adjusting for female age, body mass index, cigarette smoking, coffee consumption, chronic diseases, level of education, and cycle number. When evaluating the association between binge drinking in the month prior to baseline and MAR outcomes the analyses were further adjusted for average weekly alcohol consumption. MAIN RESULTS AND THE ROLE OF CHANCE: Low-to-moderate average weekly alcohol intake was not statistically significantly associated with the chance of achieving a clinical pregnancy or a live birth following IUI or IVF/ICSI treatment cycles. Compared to women abstaining from alcohol, the adjusted relative risks for achieving a live birth among those reporting 1-2, 3-7, and >7 drinks per week were 1.00 (95% CI 0.66; 1.53), 1.20 (0.76; 1.91), and 1.48 (0.56; 3.93), respectively, among women initiating IUI treatments. Among those initiating IVF/ICSI treatments, the chance for achieving a live birth among those reporting 1-2, 3-7, and >7 drinks per week were 1.00 (0.83; 1.21), 0.95 (0.75; 1.20), and 0.89 (0.53; 1.51), respectively. The chance of achieving a live birth in the first IUI or IVF/ICSI treatment cycle was unrelated to the number of binge drinking episodes in the month preceding baseline. LIMITATIONS, REASONS FOR CAUTION: The risk of non-differential exposure misclassification, confounding, or chance cannot be ruled out. In addition, due to the low number of women reporting an intake of >7 drinks/week, the potential effect of high alcohol consumption should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Although it remains unsettled if and how alcohol affects female reproduction, our results indicate that is not necessary to abstain from alcohol when striving for a successful outcome following fertility treatment. STUDY FUNDING/COMPETING INTEREST(S): J.L. is supported by a fully financed Ph.D. scholarship from Aarhus University and has received funds from the A.P. Møller foundation. The funding sources had no involvement in the conduct of the article. Dr Kesmodel reports personal fees from MSD and Ferring Pharmaceuticals outside the submitted work. All other authors have no conflicts of interest to declare and all have completed the ICMJE disclosure form. TRIAL REGISTRATION NUMBER: Not relevant.

Childhood growth of singletons conceived following in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis.

BACKGROUND: Assisted reproductive techniques are associated with an increased risk of adverse pregnancy outcomes, including low birthweight and intrauterine growth restriction. Yet, the long-term follow-up on the growth of these children is limited. OBJECTIVE: To systematically review the literature on post-neonatal height and weight among children conceived following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, compared with that of children born after spontaneous conception. SEARCH STRATEGY: A systematic computerised literature search using the online databases PubMed, Embase, and Scopus. SELECTION CRITERIA: Cohort or case-control studies with an exposed group of singletons conceived following IVF or ICSI along with a control group of spontaneously conceived singletons. DATA COLLECTION AND ANALYSIS: Studies were reviewed by at least two authors. Meta-analyses were conducted using Cochrane Review Manager. The quality of the studies was assessed with the Newcastle-Ottawa Scale. MAIN RESULTS: Twenty studies were included, with 13 of these eligible for meta-analyses. The meta-analyses compared 3972 children born after IVF/ICSI with 11 012 spontaneously conceived children and revealed no statistically significant difference in child weight [mean difference (MD) in weight of -160 g; 95% confidence interval (95% CI) -360, 3]. When stratifying by age of child at follow-up, we found a significant lower weight in children aged 0-4 years conceived following IVF/ICSI treatment (MD -180 g; 95% CI -320, -4), but this was no longer significant in children from 5 years of age (MD -160 g; 95% CI -580, 260). The pooled analysis revealed no statistically significant difference in childhood height. CONCLUSIONS: In vitro fertilisation/ICSI was not associated with long-term weight and height. TWEETABLE ABSTRACT: Children born following IVF/ICSI do not have impaired long-term weight or height compared with spontaneously conceived children.

Cladding defects in hollow core fibers for surface mode suppression and improved birefringence.

We demonstrate a novel polarization maintaining hollow-core photonic bandgap fiber geometry that reduces the impact of surface modes on fiber transmission. The cladding structure is modified with a row of partially collapsed holes to strip away unwanted surface modes. A theoretical investigation of the surface mode stripping is presented and compared to the measured performance of four 7-cells core fibers that were drawn with different collapse ratio of the defects. The varying pressure along the defect row in the cladding during drawing introduces an ellipticity of the core. This, combined with the presence of antiresonant features on the core wall, makes the fibers birefringent, with excellent polarization maintaining properties.

Age of menarche and time to pregnancy.

STUDY QUESTION: Is age of menarche (AOM) associated with subfecundity and/or infertility in adulthood? STUDY ANSWER: A late onset of menarche was associated with a slightly increased risk of subfecundity and infertility. WHAT IS KNOWN ALREADY: Abnormal age at onset of menarche is a risk factor for several diseases later in life, but the effect on infertility is unknown. STUDY DESIGN, SIZE AND DURATION: A cohort study of  73 107 pregnant Danish women enrolled in the Danish National Birth Cohort (DNBC) between 1996 and 2002 with self-reported data on AOM and waiting time to pregnancy (TTP). PARTICIPANTS/MATERIALS, SETTING AND METHODS: Information on AOM and TTP was collected through a computer-assisted telephone interview scheduled in pregnancy Week 12. We estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression with TTP categorized as subfecundity (TTP ≥6 months) and infertility (TTP >12 months). Multiple imputation was performed to account for missing data. MAIN RESULTS AND THE ROLE OF CHANCE: We found trends towards higher odds of subfecundity and infertility with increasing age of menarche, using 13 years as the starting point. Among women reaching menarche at 15 years, the odds for subfecundity were 1.09 (95% CI: 1.03-1.15), and 1.17 (95% CI: 1.09-1.25) for women reaching menarche later than 15 years compared with the reference group of girls reaching menarche at 13 years. Additionally, women reaching menarche older than 15 years had an OR of infertility of 1.18 (95% CI: 1.08-1.29). Women younger than 11 years at menarche had lower odds of subfecundity. The results were generally attenuated when adjusting for women's age of pregnancy, but the significant positive trend of higher OR for subfecundity persisted, as did the higher OR for subfecundity among women experiencing menarche older than 15 years. LIMITATIONS, REASONS FOR CAUTION: We used retrospectively collected self-reported information on AOM and TTP. Information on male factors was limited in this cohort. We only included pregnant women and have therefore no data on women with untreated and unsuccessfully treated infertility, limiting the generalizability to women who became pregnant. WIDER IMPLICATION OF THE FINDINGS: This study indicates that the onset of menarche at 15 years or later is associated with subfecundity and infertility. STUDY FUNDING/COMPETING INTERESTS: The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the DNBC. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the DNBC is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation. This specific study was supported by a scholarship from the Ministry of Science and Innovation. No conflict of interest declared.

Moderate alcohol intake and menstrual cycle characteristics.

STUDY QUESTION: Does moderate alcohol intake affect menstrual cycle characteristics among women in the Danish population? SUMMARY ANSWER: Levels of alcohol exposure as seen in this study do not substantially affect the menstrual cycle. WHAT IS KNOWN ALREADY: Animal studies indicate alcohol-induced disruptions of the reproductive system, but previous epidemiological studies addressing the possible association between alcohol intake and the menstrual cycle are sparse. STUDY DESIGN, SIZE, DURATION: A cross-sectional study with retrospectively collected data including 82 146 pregnant Danish women in the Danish National Birth Cohort (DNBC) enrolled during the years 1996-2002. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on weekly alcohol consumption and menstrual cycle characteristics before pregnancy was obtained through a computer-assisted telephone interview in pregnancy Week 12-16. The associations between weekly alcohol consumption and menstrual cycle irregularity (≥7 days difference between cycles) and length (short cycle: ≤24 days, long cycle: ≥32 days) were analysed using logistic regression with weekly alcohol intake categorized into abstainers (0 drinks per week), low (0.5-2.0 drinks per week), moderate (2.5-14.0 drinks per week) and high (14.0-86.5 drinks per week). Estimates are given as adjusted odds ratios with 95% confidence intervals. MAIN RESULTS AND THE ROLE OF CHANCE: The overall participation rate was 60% of the women invited. We found that a high weekly alcohol consumption was not associated with menstrual cycle disturbances. We observed higher odds of irregular and short cycles among abstainers when compared with women with a low weekly alcohol consumption, but found no trend of more cycle disturbances with higher alcohol consumption. LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include a risk of selection bias due to the moderate participation rate and the use of retrospective information on alcohol exposure and menstrual cycle characteristics before getting pregnant. The higher odds of irregular and short cycles among abstainers may reflect other health problems in these women rather than an actual effect of alcohol on the menstrual cycle. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to women who manage to conceive and women who do not use oral contraceptives within 2 months before getting pregnant. This study suggests that the menstrual cycle is not substantially affected by higher alcohol consumption among the participating women. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the DNBC. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the DNBC is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation. No conflict of interest declared.

Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study.

STUDY QUESTION: Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? SUMMARY ANSWER: The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. WHAT IS KNOWN ALREADY: PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. STUDY DESIGN, SIZE, DURATION: A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine). LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.

Stress induced birefringence in hybrid TIR/PBG guiding solid photonic crystal fibers.

We report on two types of polarization maintaining solid photonic crystal fibers that guide light by a combination of a photonic bandgap and total internal reflection. Group and phase birefringence are studied experimentally and numerically for stress-applying parts made from B-doped and F-doped silica. The stress field originating from Ge-doped cladding rods is shown to interfere with the stress field from the B-doped and F-doped rods. Since the differential expansion coefficients of B-doped and F-doped silica have opposite signs this interference is either destructive or constructive. Consequently, we found that the fiber with F-doped stress applying parts has the highest modal phase birefringence, and polarization cross talk is characterized by an h-parameter below 310(-5) m(-1).

167 W, power scalable ytterbium-doped photonic bandgap fiber amplifier at 1178 nm.

An ytterbium-doped photonic bandgap fiber amplifier operating at the long wavelength edge of the ytterbium gain band is investigated for high power amplification. The spectral filtering effect of the photonic bandgap efficiently suppresses amplified spontaneous emission at the conventional ytterbium gain wavelengths and thus enables high power amplification at 1178 nm. A record output power of 167 W, a slope efficiency of 61% and 15 dB saturated gain at 1178 nm have been demonstrated using the ytterbium-doped photonic bandgap fiber.

High-power Yb-doped photonic bandgap fiber amplifier at 1150-1200 nm.

Ytterbium-doped solid-core photonic bandgap fiber amplifiers operating at the long-wavelength edge of the ytterbium gain band are reported. The low-loss bandgap transmission window is formed in the very low gain region, whilst outside the bandgap, large attenuation inhibits the exponential growth of amplified spontaneous emission in the huge-gain 1030-1100 nm region. Hence parasitic-lasing-free, high-power amplification with a marked efficiency is enabled. A 32 W output at 1156 nm with a 66% slope efficiency and 30 W output at 1178 nm with a 58% slope efficiency were successfully obtained. To our knowledge, these are the highest output powers generating from active photonic bandgap fibers, as well as from ytterbium-doped fiber lasers at these wavelengths.

7-cell core hollow-core photonic crystal fibers with low loss in the spectral region around 2 microm.

Several 7 cell core hollow-core photonic crystal fibers with bandgaps in the spectral range of 1.4 microm to 2.3 microm have been fabricated. The transmission loss follows the approximately lambda(-3) dependency previously reported, with a minimum measured loss of 9.5 dB/km at 1.99 microm. One fiber with a transmission loss of 26 dB/km at 2.3 microm is reported, which is significantly lower than the transmission loss of solid silica fibers at this wavelength.

Amplification and ASE suppression in a polarization-maintaining ytterbium-doped all-solid photonic bandgap fibre.

We demonstrate suppression of amplified spontaneous emission at the conventional ytterbium gain wavelengths around 1030 nm in a cladding-pumped polarization-maintaining ytterbium-doped all-solid photonic crystal fibre. The fibre works through combined index and bandgap guiding. Furthermore, we show that the peak of the amplified spontaneous emission can be shifted towards longer wavelengths by rescaling the fibre dimensions. Thereby one can obtain lasing or amplification at longer wavelengths (1100 nm - 1200 nm) as the amount of amplification in the fibre is shown to scale with the power of the amplified spontaneous emission.

[Laparoscopic herniotomy in recurrent inguinal hernia]. / Laparoskopisk herniotomi ved recidiv af lyskebrok.

We present a material of 103 patients with a total of 105 recurrent inguinal hernias operated by transabdominal laparoscopic repair. Nine patients developed seromas. One was reoperated due to ileus and one had the mesh removed because of persistent pain in the groin. Following a median observation of 12 months (range 4-48 months) 102 patients were examined and two new recurrences were detected corresponding to 1.9% (95% confidence limits 0.2-6.7%).