[Desire to have children in the menopausal transition]. / Kinderwunsch in der menopausalen Übergangszeit.

Desire to have children in the menopausal transition Abstract. The menopausal transition is characterized by the loss of ovarian reserve, i. e. the number and quality of oocytes. This impairment results in a quick and massive decline in female fecundity. Ovarian reserve can be determined with the measurement of FSH and AMH in the serum plus the count of the sonographically visible follicles (antral follicle count; AFC). Therapeutically the desire to have children can be fulfilled by using homologous fertility treatments such as monofollicular ovarian stimulation and In Vitro Fertilization. More promising, however, is heterologous egg donation. As a preventive measure Social Egg Freezing is utilized increasingly.

Qualitative and quantitative aspects of sex life in the context of endometriosis: a multicentre case control study.

RESEARCH QUESTION: What are the specific characteristics of sexual activity in women with endometriosis compared with women without endometriosis? DESIGN: Multicentre case control study. Participants were recruited from university hospitals, district hospitals and doctor's offices in Germany, Switzerland and Austria. A total of 565 women with endometriosis were pair-matched to 565 control women by age and ethnic background. Diagnosis of endometriosis was confirmed by histology, and disease stage was classified according to American Society for Reproductive Medicine criteria. Data on sexuality were collected using selected questions from the Brief Index of Sexual Function and the Sexual History Form. RESULTS: Altogether, 69.1% of women with endometriosis and 77.8% of control women engaged in sexual activity during the month before the study period (P < 0.001). Overall, 42.3% of endometriosis-affected women and 30.5% of the control women desired a higher frequency of sexual activity (P < 0.001). Petting, foreplay and vaginal sexual intercourse were reported to be practised less often by women with endometriosis. Frequencies for masturbation, reciprocal masturbation, oral and anal sex were similar in both groups. Dyspareunia was negatively associated with sexual activity (OR 2.42, 95% CI 1.26 to 4.63), whereas chronic pain showed no association with sexual activity (OR 1.35, 95% CI 0.93, 1.96). CONCLUSIONS: Women with endometriosis have lower frequencies of petting, foreplay and vaginal sexual intercourse than control women; this difference has to be attributed, at least in part, to dyspareunia. Potentially pain-free sexual options are used to a limited degree. As endometriosis-affected women desire higher levels of sexual activity, sexual counselling should be included in medical support.

Are WHO Recommendations to Perform 2 Consecutive Semen Analyses for Reliable Diagnosis of Male Infertility Still Valid?

PURPOSE: We evaluated whether a second semen analysis as suggested by the WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction would improve diagnostic reliability in the evaluation of male infertility. MATERIALS AND METHODS: We analyzed a total of 5,132 semen samples from 2,566 men who underwent at least 2 consecutive semen analyses at a university fertility center. Reproducibility and correlation between the first and second analyses were evaluated for sperm concentration, motility and morphology according to the WHO criteria as well as the total motile sperm count. RESULTS: Altogether 51.2% of the second analyses confirmed the initial findings according to WHO criteria and 60% confirmed them when applying total motile sperm count criteria. After finding normozoospermia on the initial analysis 27% of the second semen analyses were pathological. Following a first pathological semen analysis 23% of the second analyses were normal and 77% were pathological. The coefficient of variation ranged from 0.23 to 0.60. The Spearman correlation coefficient was high for sperm concentration (rs = 0.84) and normal morphology (rs = 0.80) but lower for progressive motility (rs = 0.57). The discriminating capacity of each semen parameter to distinguish between men with a normal vs a pathological second semen analysis was rather limited (ROC AUC 0.72 to 0.79). CONCLUSIONS: In accordance with WHO recommendations 2 consecutive semen analysis should be performed.

The use of home remedies and complementary health approaches in endometriosis.

RESEARCH QUESTION: Conventional treatments are often associated with adverse effects and endometriosis pain symptoms may reoccur despite treatment. Consequently, many women use complementary health approaches (CHA) and home remedies (HR) to relieve their pain. The aim of this study was to examine the frequency and the subjectively perceived efficacy of CHA/HR use by women affected by endometriosis. DESIGN: Retrospective evaluation using medical charts and a questionnaire. Women recruited in hospitals and in self-help groups were asked about the use of 'topical heat', 'repose/relaxation', 'movement/massages', 'homeopathy/phytotherapy', 'acupuncture/traditional Chinese medicine (TCM)' and 'kinesiology/physiotherapy'. RESULTS: From a total of 574 women with a confirmed diagnosis of endometriosis, 359 (62.5%) applied some form of CHA/HR. Women suffering from fatiguing disease symptoms more often selected alternative therapies (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.39-7.11, P = 0.006) compared with women without these characteristics. Furthermore, women dissatisfied with healthcare provided by their treating physician, more frequently (OR 2.30, 95% CI 1.19-4.45, P = 0.013) chose the aforementioned alternative strategies. CONCLUSION: As conventional therapies may not be sufficiently effective, women's needs should be closely examined, and individual treatment options should be discussed and initiated by clinicians to provide the best comprehensive treatment possible for endometriosis.

Effect of desogestrel 75 µg on headache frequency and intensity in women with migraine: a prospective controlled trial.

Objective: In contrast with combined hormonal contraception, progestin-only contraception is not associated with an increase in venous thromboembolism or stroke. Women with migraine are at increased risk of ischaemic stroke. Several studies have reported a reduction in migraine frequency and intensity with desogestrel 75 µg, a progestin-only pill. At present the quality of data is limited by retrospective study designs, lack of control groups and small sample sizes. We present the first prospective nonrandomised controlled trial. Methods: A total of 150 women with migraine visiting our clinic for contraceptive counselling were screened. The intervention group comprised women who opted for contraception with desogestrel (n = 98); the control group comprised women who continued their usual contraceptive (n = 36). Participants completed daily diaries for 90 days before the intervention and 180 days after the intervention. Results: In the intervention group, we found improvements in migraine frequency (p < .001), migraine intensity (p < .001) and the number of triptans used (p < .001). These improvements were already significant after 90 days of desogestrel use (p < .001). Disability scores also decreased significantly. No improvement was seen in the nonintervention group. Conclusion: These data demonstrate for the first time in a prospective controlled setting that daily use of the progestin desogestrel is associated with a decrease in migraine frequency, migraine intensity and pain medication use in women with migraine, with and without aura, who had previously been experiencing at least three days of migraine per month. Trial registration: The study is registered in the University of Zürich database ( www.research-projects.uzh.ch/unizh.htm ).

Fatigue - a symptom in endometriosis.

STUDY QUESTION: Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER: Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY: Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION: The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE: Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION: Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF THE FINDINGS: As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue. STUDY FUNDING/COMPETING INTEREST(S): There was no additional funding received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02511626.

Natural and environmental oestrogens induce TGFB1 synthesis in oviduct cells.

Autocrine/paracrine factors generated in response to 17ß-oestradiol (E2), within the oviduct, facilitate early embryo development for implantation. Since transforming growth factor beta 1 (TGFB1) plays a key role in embryo implantation, regulation of its synthesis by E2 may be of biological/pathophysiological relevance. Here, we investigated whether oviduct cells synthesize TGFB1 and whether E2 and environmental oestrogens (EOEs; xenoestrogens and phytoestrogens) modulate its synthesis. Under basal conditions, bovine oviduct cells (OCs; oviduct epithelial cells and oviduct fibroblasts; 1:1 ratio) synthesized TGFB1. E2 concentration-dependent induced TGFB1 levels in OCs and these effects were mimicked by some, but not all EOEs (genistein, biochanin A and 4-hydroxy-2',4',6'-trichlorobiphenyl, 4-hydroxy-2',4',6'-dichlorobiphenyl); moreover, EOEs enhanced (P < 0.05) the stimulatory effects of E2 on TGFB1 synthesis. The OCs expressed oestrogen receptors alpha and beta and aryl hydrocarbon; moreover, co-treatment with ER antagonist ICI182780 blocked the stimulatory effects of E2 and EOEs on TGFB1 synthesis. Treatment with non-permeable E2-BSA failed to induce TGFB1, thereby ruling out the involvement of membrane ERs. Cycloheximide (protein synthesis inhibitor) blocked E2-induced TGFB1 synthesis providing evidence for de novo synthesis. The stimulatory effects of E2 and EOEs, were inhibited (P < 0.05) by MAPK inhibitor (PD98059), whereas intracellular-Ca2+ chelator (BAPTA-AM) and adenylyl cyclase inhibitor (SQ22536) abrogated the effects of E2, but not EOEs, suggesting that post-ER effects of E2 and EOEs involve different pathways. Our results provide the first evidence that in OCs, E2 and EOEs stimulate TGFB1 synthesis via an ER-dependent pathway. Exposure of the oviduct to EOEs may result in continuous/sustained induction of TGFB1 levels in a non-cyclic fashion and may induce deleterious effects on reproduction.

Does Endometriosis Affect Sexual Activity and Satisfaction of the Man Partner? A Comparison of Partners From Women Diagnosed With Endometriosis and Controls.

BACKGROUND: Endometriosis-associated pain and dyspareunia influence female sexuality, but little is known about men's experiences in affected couples. AIM: To investigate how men partners experience sexuality in partnership with women with endometriosis. METHODS: A multi-center case-control study was performed between 2010 and 2015 in Switzerland, Germany, and Austria. 236 Partners of endometriosis patients and 236 partners of age-matched control women without endometriosis with a similar ethnic background were asked to answer selected, relevant questions of the Brief Index of Sexual Functioning and the Global Sexual Functioning questionnaire, as well as some investigator-derived questions. OUTCOMES: We sought to evaluate sexual satisfaction of men partners of endometriosis patients, investigate differences in sexual activities between men partners of women with and without endometriosis, and identify options to improve partnership sexuality in couples affected by endometriosis. RESULTS: Many partners of endometriosis patients reported changes in sexuality (75%). A majority of both groups was (very) satisfied with their sexual relationship (73.8% vs 58.1%, P = .002). Nevertheless, more partners of women diagnosed with endometriosis were not satisfied (P = .002) and their sexual problems more strongly interfered with relationship happiness (P = .001) than in partners of control women. Frequencies of sexual intercourse (P < .001) and all other partnered sexual activities (oral sex, petting) were significantly higher in the control group. The wish for an increased frequency of sexual activity (P = .387) and sexual desire (P = .919) did not differ statistically between both groups. CLINICAL TRANSLATION: There is a need to evaluate qualitative factors that influence sexual satisfaction in endometriosis patients. CONCLUSIONS: This is one of the first studies to investigate male sexuality affected by endometriosis. The meticulous verification of diagnosis and disease stage according to operation reports and histology allows for a high reliability of diagnosis. Our men's response rate of almost 50% is higher compared to other studies. Recruiting men through their woman partner may have caused selection bias. The adjustment to the specific situation in endometriosis by selecting questions from the Brief Index of Sexual Functioning and Global Sexual Functioning and adding investigator-derived questions likely influenced the validity of the questionnaires. Despite the fact that both partners of endometriosis patients and of control women largely reported high sexual satisfaction, there are challenges for some couples that arise in the context of a sexual relationship when one partner has endometriosis. Challenges such as sexuality-related pain or a reduced frequency of sexual activities should be addressed by health care professionals to ameliorate any current difficulties and to prevent the development or aggravation of sexual dysfunction. Hämmerli S, Kohl Schwartz AS, Geraedts K, et al. Does Endometriosis Affect Sexual Activity and Satisfaction of the Man Partner? A Comparison of Partners From Women Diagnosed With Endometriosis and Controls. J Sex Med 2018;15:853-865.

Is there a need for better sexual education of young men? Sexual behaviour and reproductive health in Swiss university students: a questionnaire-based pilot study.

OBJECTIVES: There is evidence that men's perception of contraceptive methods and of their effectiveness and health risks have a major impact on couples contraceptive choices. Engaging men in decision making improves reproductive health outcomes. If they are better informed, men can potentially contribute to more effective use of contraception, thus reducing the rate of sexually transmitted infections and abortion. In Central European countries, few data are available on male contraceptive knowledge and behaviour. METHODS: To collect more data we conducted an anonymous survey among young men studying at Zürich University in Switzerland. A questionnaire was distributed to 1500 male students which included a broad range of items addressing sexual behaviour, condom use and knowledge, and attitudes regarding contraceptive methods. RESULTS: Three hundred and sixty-one questionnaires were eligible for evaluation. Condoms and the combined oral contraceptive pill were the most frequently used methods. However, at last intercourse 15.6% of respondents had not used any method of contraception. Many respondents (37%) had had a one-night stand without protection. Contraceptive methods most regarded as unhealthy for women were the combined oral contraceptive pill, progestin-only methods, intrauterine devices (IUDs) and emergency contraception. Characteristics considered by young men to be important in determining contraceptive method choice were: efficacy, partner satisfaction and no impact on fertility and libido. CONCLUSIONS: Awareness among male Swiss students about contraceptive methods is high, but in-depth knowledge is limited. Myths were expressed about the combined oral contraceptive pill, progestin-only methods, IUDs and the emergency contraceptive pill. High-risk behaviour occurs frequently. The internet was reported to be the most important source of information about contraception.

Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake by Brain Microvascular Endothelial Cells.

We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound 3 H-propranolol and 14 C-warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1-1000 µM) increased the free fraction (fu) of both albumin and alpha-acid glycoprotein bound drugs in a concentration-dependent manner (p < 0.01). Moreover, piperine (10 µM) increased the uptake of 3 H-propranolol and 14 C-warfarin by BMECs (p < 0.01). In conclusion, our findings provide the first evidence that piperine displaces plasma bound drugs from both albumin and alpha-acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs. Copyright © 2017 John Wiley & Sons, Ltd.

Improvement of migraine with change from combined hormonal contraceptives to progestin-only contraception with desogestrel: How strong is the effect of taking women off combined contraceptives?

Migraine is a disabling headache disorder, which affects up to 17% of the female population. Oestrogen withdrawal during the menstrual cycle or the hormone-free interval in users of combined hormonal contraceptives (CHC) plays a pivotal role. Two diary-based studies demonstrated a positive impact of the progestin-only pill (POP) desogestrel 75 µg on the frequency of the migraine attacks and pain intensity. In both studies, CHC users as well as nonusers were included, which makes it difficult to distinguish between the effect of taking women off the CHC and the benefit of the POP itself. With the present study, we compared the therapeutic effect of the POP desogestrel 75 µg on migraine in current CHC users and nonusers. We found a positive influence of desogestrel on migraine not only in women who switched from CHCs to desogestrel, but also in those who had not used hormones over 6 months before starting it. Our findings need to be confirmed in prospectively conducted studies with larger sample size.

Temporal relations in hormone-withdrawal migraines and impact on prevention- a diary-based pilot study in combined hormonal contraceptive users.

BACKGROUND: Menstrually related migraine (MRM) in the hormone-free interval (HFI) of combined hormonal contraceptives (CHC) are according to the ICHD definition also estrogen withdrawal migraines (EWH). MRMs are less responsive to acute medication. Therefore short-term prevention, initiated 1-2 days before onset of the anticipated bleeding and continued for 6 days, is recommended. Such a long prophylactic triptan use might increase the risk for medication overuse headache in women suffering in addition from non-menstrual migraines. In CHC users onset of hormone decline is predictable. It is however unknown, whether the EWHs are rather associated with onset of hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention. METHODS: For this observational diary-based pilot study we collected data from daily conducted headache diaries of CHC users with MRM in at least two of three cycles, visiting our clinic from 2009 to 2015. We analyzed frequency of migraines for each hormone free day, onset of migraine, onset of bleeding and the relation of migraine to onset of bleeding in the 7-day period following estrogen withdrawal. We identified in addition the onset of migraine attacks lasting more than 1 day (episodes). RESULTS: Forty patient charts met the inclusion criteria, what allowed us to analyze 103 cycles. The mean number of migraine days in the HFI was 2.2 ± 1.6. Migraine started typically on days 1-5 and bleeding on days 3-5. In relation to first day of bleeding, migraines started on days -1 to 4. Almost half of the migraine attacks lasted longer than 24 h, despite the use of rescue medication. CONCLUSION: MRM in CHC users starts on bleeding days -1 to 4, what differs from findings in the natural cycle. Referring to the HFI interval migraine started mostly on days 1-5. According to these data, it seems to be reasonable to initiate short-term prevention at the last day of pill use or the first day of the HFI and continue for 5 days.

2-Methoxyestradiol blocks the RhoA/ROCK1 pathway in human aortic smooth muscle cells.

2-Methoxyestradiol (2-ME), a metabolite of estradiol with little affinity for estrogen receptors, inhibits proliferation of vascular smooth muscle cells; however, the molecular mechanisms underlying this effect are incompletely understood. Our previous work shows that 2-ME inhibits initiation (blocks phosphorylation of ERK and Akt) and progression (reduces cyclin expression and increases expression of cyclin inhibitors) of the mitogenic pathway and interferes with mitosis (disrupts tubulin organization). Because the RhoA/ROCK1 pathway (RhoA → ROCK1 → myosin phosphatase targeting subunit → myosin light chain) is involved in cytokinesis, herein we tested the concept that 2-ME also blocks the RhoA/ROCK1 pathway. Because of the potential importance of 2-ME for preventing/treating vascular diseases, experiments were conducted in female human aortic vascular smooth muscle cells. Microarray transcriptional profiling suggested an effect of 2-ME on the RhoA/ROCK1 pathway. Indeed, 2-ME blocked mitogen-induced GTP-bound RhoABC expression and membrane-bound RhoA, suggesting interference with the activation of RhoA. 2-ME also reduced ROCK1 expression, suggesting reduced production of the primary downstream signaling kinase of the RhoA pathway. Moreover, 2-ME inhibited RhoA/ROCK1 pathway downstream signaling, including phosphorylated myosin phosphatase targeting subunit and myosin light chain; the ROCK1 inhibitor H-1152 mimicked these effects of 2-ME; both 2-ME and H-1152 blocked cytokinesis. 2-ME also reduced the expression of tissue factor, yet another downstream signaling component of the RhoA/ROCK1 pathway. We conclude that 2-ME inhibits the pathway RhoA → ROCK1 → myosin phosphatase targeting subunit → myosin light chain, and this likely contributes to the reduced cytokinesis in 2-ME treated HASMCs.

Positive effects of the progestin desogestrel 75 µg on migraine frequency and use of acute medication are sustained over a treatment period of 180 days.

BACKGROUND: Premenopausal migraines frequently are associated with fluctuations of estrogen levels. Both, migraine and combined hormonal contraceptives (CHC) increase the risk of vascular events. Therefore progestagen-only contraceptives (POC) are a safer alternative. A previous short-term study demonstrated a positive impact of the oral POC desogestrel on migraine frequency. To study the effect of the POC desogestrel 75 µg on migraine frequency, intensity, use of acute medication and quality of life in a clinical setting over the period of 180 days. METHODS: Patients' charts were screened for women with migraine, who had decided to use desogestrel for contraception. Charts were included, if routinely conducted headache diaries were complete for 90 days before treatment (baseline) and over a treatment period of 180 days. We also report about starters who stopped treatment early, because of adverse events. Baseline data (day 1-90 before treatment) were compared with first and second treatment period (treatment days 1-90 and days 91-180). Quality of life was evaluated using MIDAS questionnaires. RESULTS: Days with migraine (5.8 vs 3.6), with any kind of headache (9.4 vs 6.6), headache intensity (15.7 vs 10.7), days with severe headache (5.4 vs 2.4) and use of triptans (12.3 vs7.8) were significantly reduced after 180 days. MIDAS score and grade improved significantly. CONCLUSION: Contraception with desogestrel 75 µg resulted in a significantly improved quality of life and a reduction of migraine days over the observation period of 180 days. A clinically meaningful 30% reduction in pain was observed in 25/42 (60%) participants. For counselling reasons it is of importance, that the major reduction in migraine frequency occured during the initial 90 days, however further improvement occurs with longer duration of use. Prospective studies are needed to confirm these results.

Headache frequency and intensity in female migraineurs using desogestrel-only contraception: a retrospective pilot diary study.

BACKGROUND: Migraine seems to be substantially related to hormonal changes. However, migraine, but also the use of combined oral contraceptives (COC), is associated with an increased risk for vascular events. Therefore progestagen-only contraception is an important alternative to combined preparations. Clinical observations and one pilot study demonstrate that the use of desogestrel 75 µg may have a positive impact on migraine. AIM: The aim of this retrospective analysis of prospectively collected headache diaries was to study the effect of desogestrel 75 µg on headache frequency, intensity and use of acute medication in premenopausal women with migraine in a clinical setting. METHODS: Patients' charts were included from women who wanted to use desogestrel 75 µg as a contraceptive and had kept headache diaries over six months (three months pretreatment and three months during treatment). Out of 58 women, 38 women had completed headache diaries for this period. Incomplete diaries ( N = 12), side effects ( N = 5) and loss to follow-up ( N = 3) were the reasons for the exclusion of 20 women. The three months (total of 90 days) before and after initiation of the progestin were compared. RESULTS: Days with migraine (5.2 vs. 3.7), days with all kind of headache (8.3 vs. 6.5) and days with use of any headache medication (5.7 vs. 3.5) were significantly reduced at follow-up after three months. In addition there was a reduction in headache intensity ( P < 0.0001). The reduction in number of days with use of triptans was not significant ( P < 0.14). CONCLUSION: In the 38/58 migraineurs with complete diaries there was a statistically significant decrease in migraine days, headache intensity and medication use. Tension-type headache days decreased but were not significant. Our preliminary data are promising, but should be interpreted cautiously because they were obtained in a small population of women visiting a specialty hormone and migraine clinic. Randomised controlled trials need to be conducted to substantiate our results.

The relevance of age in female human reproduction--current situation in Switzerland and pathophysiological background from a comparative perspective.

During recent years women tend to postpone childbirth to ages when fertility declines. Consequently, an increasing number of women experiences reproductive difficulties and seeks help by assisted reproductive techniques (ART). To investigate the dynamics of age-related fertility in Switzerland we evaluated data from the nationwide FIVNAT-CH statistics on ART as well as from a subsample receiving ART at the Division of Reproductive Endocrinology, University Hospital Zurich. Since 2000 the average age of women receiving ART increased from 34.9 to 36.3 years in Switzerland and since 2006 numbers of annual ART cycles augmented steadily. The percentage of women ≥40 increased from 17.2% in 2007 to 19.6% in 2011. In the Zurich cohort AMH, the number of oocytes retrieved, the number of fertilized oocytes with two pronuclei, the number of embryos with an adequate cell number, clinical pregnancy rates as well as life birth/ongoing pregnancy rates were lower in the age group ≥40 years, especially when compared to 33 year-old women. In the nationwide sample pregnancy rates decreased from about 45% at the age of 30 to less than 3% at the age of 45; delivery rates declined from about 38% to nearly 0%. In the Zurich cohort percentages of clinical pregnancies declined from 46% in women ≤34 years to 21% in women ≥40 years. In the national sample as well as in the Zurich cohort the percentage of miscarriages increased dramatically from 15.4% and 22% in women ≤34 years to 38.6% and 33% in women ≥40 years, respectively. Even in a country with high health standards such as Switzerland fertility is declining with age and ART does not succeed to improve reduced fertility. Rodent and primate models enrich our knowledge on the pathophysiological mechanisms underlying reproductive senescence. As non-infertility specialist physicians as well as the general public are not sufficiently aware of the dramatic reduction of chances for life births in women ≥40 years, medical counseling as well as schools and media should support the distribution of information future parents need for successful family planning.

Desogestrel-only contraception may reduce headache frequency and improve quality of life in women suffering from migraine.

OBJECTIVE: To analyse the effects of a three-month course of progestogen-only contraception with desogestrel 75 µg on disability, headache frequency and headache intensity in migraineurs. MATERIALS AND METHODS: Migraine disability headache questionnaires (MIDAS) were collected from 37 migraineurs during counselling, and at the end of three months treatment with desogestrel. Another ten women initiated but did not complete treatment. They are included in the overall evaluations of the effect of the regimen on migraine status. RESULTS: Desogestrel was associated with significant reductions in headache days and intensity (p < 0.001; p < 0.006), and a significant improvement in quality of life. Days missed at work and days missing leisure activities diminished (p < 0.001; p < 0.001). The MIDAS migraine disability score improved significantly (from 27.4 to 11.1 points) (p < 0.001). While 25 of the 37 women (68%) experienced a decrease of at least one grade, this level of benefit cannot be extrapolated to all initiators. When dropouts are considered, MIDAS grades decrease in 53% (25/47) of the cases. CONCLUSION: The majority of migraineurs experienced a clinically significant reduction in headache frequency and improvement of quality of life with use of desogestrel. Prospective randomised controlled trials are needed to substantiate our results.

Childlessness in Patients with Inflammatory Bowel Disease - Data from the Prospective Multi-center Swiss IBD Cohort Study.

BACKGROUND AND AIMS: Childlessness and infertility represent a frequent and important issue in inflammatory bowel disease (IBD) patients. Nevertheless, until now epidemiological data remains scarce. Therefore, main objectives of this study were to evaluate the rate of childlessness and the cumulative probability of reproduction in female and male IBD patients within the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), a large prospective multicenter nationwide cohort. METHODS: Prospectively collected data of SIBDCS was used, comprising more than 3,300 patients with Crohn's disease (CD) and ulcerative colitis (UC). We analyzed the following groups of patients: 1) female IBD patients aged ≥40 years and diagnosed before age of 30 years with at least one follow-up, 2) female IBD patients who reported actively trying to conceive, with IBD diagnosed <35 years and with age at enrolment <45 years (longitudinal observation), with at least one follow-up, and 3) childless males who actively tried to conceive. RESULTS: A total of 1,412 female patients from the SIBDCS [843 CD, 539 UC, 30 indeterminate colitis (IC)] with available data were included in our analyses. Out of those 184 females (70.1% CD and 29.9 % UC) were aged ≥ 40 years and have been diagnosed with IBD before the age of 30 years. Among these, 184 women 32.1% were childless. The portion of childless females (36.4%) was significantly higher in CD vs. UC (36.4% vs. 21.8%; p=0.026), equaling a relative risk of childlessness of 1.7 in CD vs. UC. and higher than in the Swiss general population (21%). The mean number of children per female patient was 1.32 (median 1, min 0, max 6), per female with CD 1.12 (median 1, min 0, max 4), per female with UC/IC 1.78 (median 2, min 0, max 6; P=0.001). The longitudinal analysis of female IBD patients trying to conceive revealed that one out of two women neither were pregnant nor had born a child five years after first trying to conceive. CONCLUSIONS: The rate of childlessness in females with CD is higher compared to the general Swiss population, whereas it is similar in women with UC. Moreover, the mean number of children is lower in CD than in UC. Females with CD remain more often childless compared to their UC counterparts. Although the exact underlying mechanisms are largely unknown, this discrepancy should alert healthcare professionals treating CD patients to actively address this topic.

Six years after deregulation of emergency contraception in Switzerland: has free access induced changes in the profile of clients attending an emergency pharmacy in Zürich?

OBJECTIVES: Emergency contraception (EC) has been freely accessible in Swiss pharmacies since November 2002. Today some groups are still concerned that free access might result in less use of efficient contraceptive methods, overuse and more risky sexual behaviour. METHODS: Profiles of EC users one and six years after deregulation were analysed with regard to age, contraceptive methods used, reasons for EC use, and last contact with a gynaecologist. Data were collected from a centrally located pharmacy. Written official assessment forms concerning 1500 women (750 in 2004 and 750 in 2009) were analysed. RESULTS: Free access to EC use had no impact on regular contraceptive behaviour. The percentage of pill and condom users was very high (85%). The percentage of EC-users without any contraception (17-18%) was the same over the years. In 2009, condom rupture was reported more frequently (p < 0.001). In addition significantly more women had used EC previously in their history. CONCLUSION: Free access to EC has not resulted in less use of efficient contraceptive methods. In the context of falling abortion rates our results are reassuring. This also applies to adolescents, who mainly used EC as a back-up method and seldom in the context of unprotected intercourse.