Archimetrosis: the evolution of a disease and its extant presentation : Pathogenesis and pathophysiology of archimetrosis (uterine adenomyosis and endometriosis).

PURPOSE: This article presents a novel concept of the evolution and, thus, the pathogenesis of uterine adenomyosis as well as peritoneal and peripheral endometriosis. Presently, no unifying denomination of this nosological entity exists. METHODS: An extensive search of the literature on primate evolution was performed. This included comparative functional morphology with special focus on the evolution of the birthing process that fundamentally differs between the haplorrhine primates and most of the other eutherian mammals. The data were correlated with the results of own research on the pathophysiology of human archimetrosis and with the extant presentation of the disease. RESULTS: The term Archimetrosis is suggested as a denomination of the nosological entity. Archimetrosis occurs in human females and also in subhuman primates. There are common features in the reproductive process of haplorrhine primates such as spontaneous ovulation and corpus luteum formation, spontaneous decidualization and menstruation. These have fused Müllerian ducts resulting in a uterus simplex. Following a usually singleton pregnancy, the fetus is delivered in the skull position. Some of these features are shared by other mammals, but not in that simultaneous fashion. In haplorrhine primates, with the stratum vasculare, a new myometrial layer has evolved during the time of the Cretaceous-Terrestrial Revolution (KTR) that subserves expulsion of the conceptus and externalization of menstrual debris in non-conceptive cycles. Hypercontractility of this layer has evolved as an advantage with respect to the survival of the mother and the birth of a living child during delivery and may be experienced as primary dysmenorrhea during menstruation. It may result in tissue injury by the sheer power of the contractions and possibly by the associated uterine ischemia. Moreover, the lesions at extra-uterine sites appear to be maintained by biomechanical stress. CONCLUSIONS: Since the pathogenesis of archimetrosis is connected with the evolution of the stratum vasculare, tissue injury and repair (TIAR) turns out to be the most parsimonious explanation for the development of the disease based on clinical, experimental and evolutionary evidence. Furthermore, a careful analysis of the published clinical data suggests that, in the risk population with uterine hypercontractility, the disease develops with a yet to be defined latency phase after the onset of the biomechanical injury. This opens a new avenue of prevention of the disease in potentially affected women that we consider to be primarily highly fertile.

[Evidence-based Facts of non-hormonal treatment of menopausal symptom]. / «Hard Facts¼ bei der nicht-hormonalen Therapie des klimakterischen Syndroms.

Evidence-based Facts of non-hormonal treatment of menopausal symptom Abstract. Menopausal symptoms like hot flushes and night sweats can have a great impact on quality of life. As first line, hormonal therapy with estrogens in combination with progestins is used, and shows beneficial effects on these symptoms. Some women, however, have contraindications against hormonal therapy or do not wish to take hormones at all. In these women, alternative treatments are needed to treat vasomotor symptoms. Pharmacologic substances like antidepressants, anticonvulsants or antihypertensive drugs show a significant reduction of these symptoms in menopausal women. Phytopharmaceutical products may show beneficial effects but study designs often do not fulfil strict scientific criteria. Furthermore, dosage and composition of the products may differ considerably. Best data are available for isoflavons and extracts of cimicifuga racemosa. Other alternative therapies like yoga, exercise, hypnosis and acupuncture showed promising results in small studies and may be recommended individually.

Beta endorphin in serum and follicular fluid of PCOS- and non-PCOS women.

PURPOSE: To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters. METHODS: Fifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol. RESULTS: There was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels. CONCLUSION: Beta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.

Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis: an immunohistochemical study.

BACKGROUND: The roles of the neurotrophins NGF (Neurotrophic growth factor) and BDNF (brain-derived neurotrophic factor) in neuronal growth and development are already known. Meanwhile, the neurotrophin receptors TrkA (tropomyosin related kinase A), TrkB, and p75 are important for determining the fate of cells. In endometriosis, this complex system has not been fully elucidated yet. The aim of this study was to evaluate the expression and location of these neurotrophins and their receptors in peritoneal (PE) and deep infiltrating endometriotic (DIE) tissues and to measure and compare the density of nerve fibers in the disease subtypes. METHODS: PE lesions (n = 20) and DIE lesions (n = 22) were immunostained and analyzed on serial slides with anti-BDNF, -NGF, -TrkA, -TrkB, -p75,-protein gene product 9.5 (PGP9.5, intact nerve fibers) and -tyrosine hydroxylase (TH, sympathetic nerve fibers) antibodies. RESULT: There was an equally high percentage (greater than 75 %) of BDNF-positive immunostaining cells in both PE and DIE. TrkB (major BDNF receptor) and p75 showed a higher percentage of immunostaining cells in DIE compared to in PE in stroma only (p < 0.014, p < 0.027, respectively). Both gland and stroma of DIE lesions had a lower percentage of NGF-positive immunostaining cells compared to those in PE lesions (p < 0.01 and p < 0.01, respectively), but there was no significant reduction in immunostaining of TrkA in DIE lesions. There was no difference in the mean density of nerve fibers stained with PGP9.5 between PE (26.27 ± 17.32) and DIE (28.19 ± 33.15, p = 0.8). When we performed sub-group analysis, the density of nerves was significantly higher in the bowel DIE (mean 57.33 ± 43.9) than in PE (mean 26.27 ± 17.32, p < 0.01) and non-bowel DIE (mean 14.6. ± 8.6 p < 0.002). CONCLUSIONS: While the neurotrophin BDNF is equally present in PE and DIE, its receptors TrkB and p75 are more highly expressed in DIE and may have a potential role in the pathophysiology of DIE, especially in promotion of cell growth. BDNF has a stronger binding affinity than NGF to the p75 receptor, likely inducing sympathetic nerve axonal pruning in DIE, resulting in the lower nerve fiber density seen.

Opiate receptor blockade on human granulosa cells inhibits VEGF release.

The objectives of this study were to determine whether the main opioid receptor (OPRM1) is present on human granulosa cells and if exogenous opiates and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production via OPRM1. Granulosa cells were isolated from women undergoing oocyte retrieval for IVF. Complementary to the primary cells, experiments were conducted using COV434, a well-characterized human granulosa cell line. Identification and localization of opiate receptor subtypes was carried out using Western blot and flow cytometry. The effect of opiate antagonist on granulosa cell VEGF secretion was assessed by enzyme-linked immunosorbent assay. For the first time, the presence of OPRM1 on human granulosa cells is reported. Blocking of opiate signalling using naloxone, a specific OPRM1 antagonist, significantly reduced granulosa cell-derived VEGF levels in both COV434 and granulosa-luteal cells (P < 0.01). The presence of opiate receptors and opiate signalling in granulosa cells suggest a possible role in VEGF production. Targeting this signalling pathway could prove promising as a new clinical option in the prevention and treatment of ovarian hyperstimulation syndrome.

Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects.

PURPOSE: To study the influence of xenotransplantation on follicular recruitment and growth in cryopreserved/thawed human ovarian tissue. METHOD: Two 3-mm pieces of cryopreserved/thawed human ovarian tissue obtained from female cancer patients (n = 11) were xenotransplanted into a subcutaneous neck pouch of 6-week-old ovarectomized SCID mice (n = 33) for 4 (n = 18) and 12 (n = 15) weeks. RESULT: Thirty-two out of 33 mice survived the entire observation periods. Graft recovery rate was 95.58 % (65 of 68 grafts). The percentages of primordial follicles after 4 weeks (P < 0.001) and 12 weeks (P = 0.009) of grafting were significantly lower in comparison to pregraft controls. The percentage of secondary follicle was significantly higher after 4 weeks of grafting (P = 0.018) and after 12 weeks (P = 0.001) of grafting in comparison to pregraft controls. Ki67 immunohistochemistry showed that proliferative follicles were significantly higher after 4 and 12 weeks of grafting compared to pregraft controls (P < 0.001). All follicles analyzed by TUNEL staining appeared healthy after xenotransplantation. The expression level of PTEN was reduced by 2.47-fold after 4 weeks of xenotransplantation, and this result was significant when 2-ΔCt were analyzed (P = 0.042). CONCLUSION: The higher proportion of growing follicles compared to resting follicles observed after xenotransplantation is most likely due to downregulation of PTEN gene expression followed by acceleration of follicular recruitment.

Metformin induces a prompt decrease in LH-stimulated testosterone response in women with PCOS independent of its insulin-sensitizing effects.

BACKGROUND: The use of insulin-sensitizing drugs has been shown to improve both the reproductive and the metabolic aspects of PCOS. However, the mechanisms by which metformin exerts its effects in PCOS are still not completely understood. There is growing evidence of a direct effect of metformin on ovarian steroidogenesis, independent of its effects on insulin sensitivity. METHODS: We evaluated the short-term effects of metformin compared to placebo on basal and LH- stimulated androgen secretion as well as on hormonal and metabolic parameters in 19 women with PCOS during a four-day randomized, double-blinded placebo-controlled clinical trial. In a three month follow-up evaluation, we investigated the longer-term therapeutic effects of metformin on ovulation, metabolic and endocrine parameters. RESULTS: Compared to placebo, 2 days of metformin was associated with a borderline significant reduction in the free androgen index (FAI) (p = 0.05) and with a reduction in the serum concentration of LH-stimulated testosterone (T) (p = 0.03). Following three months of use, a decline in serum T was observed, independent of changes in weight, metabolic parameters, or insulin sensitivity. CONCLUSIONS: In women with PCOS, Metformin induces a prompt decrease in LH-stimulated T secretion after only several days of use. This action precedes the medication's effects on insulin sensitivity or weight loss.

Afamin serum concentrations are associated with insulin resistance and metabolic syndrome in polycystic ovary syndrome.

BACKGROUND: High plasma concentrations of the vitamin E-binding protein afamin have been previously shown to be associated with insulin resistance and metabolic syndrome. We set out to determine whether the concentration of afamin in the serum of women with polycystic ovarian syndrome (PCOS) is elevated in relation to the presence and severity of insulin resistance (IR). METHODS: This cross-sectional study looked at 53 patients with PCOS and 49 non-PCOS patients. IR was diagnosed as a HOMA Index >2.4 and confirmed with a three-hour glucose tolerance test. Serum concentrations of afamin were determined using enzyme-linked immunosorbent assay (ELISA). Clinical characteristics, hormone and metabolic parameters were correlated to afamin concentrations. RESULTS: Serum concentrations of afamin did not differ between women with PCOS and controls. When separated according to the presence of IR a significant difference in median afamin levels was seen between PCOS with IR and PCOS without IR (73.06+/-27.36 mg/L and 64.25+/-17.41 mg/L, p = 0.033). No difference in afamin levels was detected when comparing the few controls with IR and the controls without IR (76.20+/-27.96 mg/L and 60.44+/-21.03 mg/L, p = 0.235). On univariate analyses, afamin serum concentrations significantly correlated with BMI, triglycerides, HOMA Index, and AUC-Insulin. On multivariate linear regression analysis, only triglyceride concentration was seen to be an independent predictor of afamin. Subjects with metabolic syndrome had higher median afamin concentrations than did those without metabolic syndrome (77.43+/-28.60 mg/L and 65.08+/-18.03 mg/L, p = 0.010). CONCLUSIONS: Elevated afamin concentrations are associated with the presence of metabolic syndrome in young women and may potentially serve as an independent predictor for the development of metabolic syndrome in at-risk women, especially those with IR.

Reproductive endocrine health in pubertal females with epilepsy on antiepileptic drugs: time to screen?

OBJECTIVES: Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy. PATIENTS AND METHODS: Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject. RESULTS: Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups. CONCLUSIONS: Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended.

Dynamics of anti-Müllerian hormone during controlled ovarian stimulation.

AIM: To evaluate the dynamics of anti-Müllerian hormone (AMH) during controlled ovarian stimulation (COH) and to correlate changes in AMH to age, estradiol (E2) levels, and the presence of polycystic ovary syndrome (PCOS). METHODS: Data were retrospectively collected from women presenting for COH in the outpatient clinic of a university hospital between January and July 2011. Concentrations of AMH and E2 during COH with gonadotropins for in vitro fertilization (IVF) (n = 68) and clomiphene or low-dose gonadotropin stimulation cycles (n = 27) for intrauterine insemination were evaluated. Percentage change in AMH and E2 from pre-stimulation values was calculated. Dynamics of hormonal changes were analyzed using non-parametric tests. Correlations between changes in AMH and E2 were analyzed with Spearman correlation. RESULTS: During IVF stimulation, AMH declined steadily from pre-stimulation values. No significant change in AMH dynamics was observed during clomiphene or low-dose stimulation cycles. Percentage decline in AMH during IVF stimulation correlated with rise in E2 at all time points. CONCLUSIONS: The observed phenomena contribute to an improved understanding of AMH expression and its role in the follicular development. Our data support the concept that AMH is produced by secondary, preantral and small antral follicles in the early part of stimulation and declines as these follicles are recruited into dominant growing follicles.

Medical management of early pregnancy failure (EPF): a retrospective analysis of a combined protocol of mifepristone and misoprostol used in clinical practice.

PURPOSE: To evaluate the efficacy of a combined protocol of mifepristone and misoprostol in the management of early pregnancy failure (EPF) and the average time to expulsion of tissue and rate of side effects. METHODS: Retrospective chart review of all consecutive women treated with primary medical management for EPF at our institution from 2006 to 2012. RESULTS: 168 patients were included in the present study. The overall success rate, defined as the absence of the need for surgical intervention, was 61 % and did not differ by calendar year. There was no difference in success rate grouped by diagnosis [intrauterine embryonic/fetal demise (IUED/IUFD) vs. anembryonic gestation; p = 0.30] or gestational age (<9 or ≥9 weeks; p = 0.48). The success rate varied significantly according to the required dose of misoprostol, ≤800 or >800 µg (68 vs. 50 %, p = 0.029). Of the possible predictive factors of success, only the dose of misoprostol required was a significant independent negative predictor. Mean and median time to tissue expulsion after the first dose of misoprostol were 8.4 and 5.5 h, respectively. The incidence of side effects was low with no blood transfusions required. CONCLUSIONS: The success rate in this study is markedly below published data. This can possibly be attributed to retrospective study design, allowing for physician subjectivity and patients' wishes in the absence of strict study requirements. The protocol was well tolerated with a paucity of side effects. We make suggestions for enhancing success rates in the clinical setting by optimizing medication protocols, establishing precise treatment guidelines and training physicians in the accurate interpretation of treatment outcomes.

Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations.

The aims of this cross-sectional study were to evaluate the relative agreement of both static and dynamic methods of diagnosing IR in women with polycystic ovary syndrome (PCOS) and to suggest a simple screening method for IR. All participants underwent serial blood draws for hormonal profiling and lipid assessment, a 3 h, 75 g load oral glucose tolerance test (OGTT) with every 15 min measurements of glucose and insulin, and an ACTH stimulation test. The prevalence of IR ranged from 12.2% to 60.5%, depending on the IR index used. Based on largest area under the curve on receiver operating curve (ROC) analyses, the dynamic indices outperformed the static indices with glucose to insulin ratio and fasting insulin (fInsulin) demonstrating the best diagnostic properties. Applying two cut-offs representing fInsulin extremes (<7 and >13 mIU/l, respectively) gave the diagnosis in 70% of the patients with high accuracy. Currently utilized indices for assessing IR give highly variable results in women with PCOS. The most accurate indices based on dynamic testing can be time-consuming and labor-intensive. We suggest the use of fInsulin as a simple screening test, which can reduce the number of OGTTs needed to routinely assess insulin resistance in women with PCOS.

Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic progestins in human plasma.

Co-administration of synthetic progestin containing hormonal contraceptives (HCs) and antiepileptic drugs (AEDs) is a common clinical situation which needs specific considerations due to drug interactions. Several studies have demonstrated that lamotrigine plasma levels are significantly decreased during co-medication with HCs, and that this interaction is associated with increased seizure frequency in most of the cases. Additionally, an increase in contraceptive failure and unintended pregnancy could be observed during co-medication. Hence, monitoring of progestin plasma levels in patients with AED co-medication is of interest. A rapid and reliable online solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (online SPE-LC-MS/MS) method using gradient elution in the LC domain was established and validated for the simultaneous quantitative determination of gestodene, dienogest, drospirenone, etonogestrel, cyproterone acetate, and levonorgestrel in human plasma. The online SPE-LC-MS/MS method covered a quantification concentration range of 5-100 ng/ml for dienogest, 1-100 ng/ml for etonogestrel and 2-100 ng/ml for all other analytes. Stable isotope-labeled internal standards were used for analyte quantification based on selected reaction monitoring experiments. Inter- and intra-assay precision and accuracy were determined from quality control (QC) samples at the lower limits of quantification and at low, medium, and high concentration levels within the calibration range. Inter-assay reproducibility at the QC levels was better than 10% (relative standard deviation, RSD), accuracy at these levels ranged from -3.7% to 11.3%. Total extraction efficiency, tested at three concentrations, ranged from 92.5% to 106.4%. Matrix interferences were excluded by post-column infusion experiments. To prove the applicability of the assay in clinical cohorts, a sample set (n = 298) stemming from study patients under AED/oral HC co-medication was screened for progestin plasma levels. This method has to be considered a research-use-only assay and must not be used for diagnostic or therapeutic purposes, since it did not undergo formal performance evaluation in the sense of the IVD directive (98/79/EG) of the European Community.

An ultra-sensitive online SPE-LC-MS/MS method for the quantification of levonorgestrel released from intrauterine devices.

A selective and sensitive liquid chromatography-tandem mass spectrometry method for the determination of very low levonorgestrel (D-(-)-norgestrel) serum levels such as those found in patients using levonorgestrel-releasing intrauterine devices (IUDs) was developed. To achieve the sub-nanomolar sensitivity needed to measure such serum levels, a diethyl ether extraction sample preparation protocol was applied prior to the online solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) assay. Analyte quantification from the selected reaction monitoring experiments relied on the use of sixfold deuterated norgestrel as internal standard. The final method was linear up to 1.50 ng/ml with a lower limit of quantification (LLOQ) of 0.05 ng/ml. It was found to be precise and accurate with imprecision <8% and bias <6% assessed at three control levels. Total analyte recovery measured in patient pools at three concentration levels was found to exceed 92%. Matrix interferences were excluded by post-column analyte infusion experiments. As a proof of concept, a set of IUD patient serum samples was screened for their levonorgestrel content. A total of 97.5% (n = 94) of the samples did show serum levels exceeding the LLOQ, proving the applicability of the assay in relevant clinical cohorts. This method must not be used for diagnostic or therapeutic purposes, since it did not undergo formal performance evaluation in the sense of the in vitro diagnostic directive (98/79/EG) of the European community.

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020).

Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature. Methods To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions. Recommendations Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to women's individual needs, take account of her personal circumstances, and have few or no side effects.

Bidirectional interaction between oral contraception and lamotrigine in women with epilepsy - Role of progestins.

PURPOSE: To investigate the effects of various progestins in combined oral contraceptives (COCs) on lamotrigine (LTG) serum concentrations and, vice versa, the potential impact of LTG on progestin serum levels during the menstrual cycle. METHODS: Twenty women with epilepsy (WWE) undergoing LTG monotherapy and COC (LTG group; mean ± SD [median; range] age 24.2 ± 4.6 [23.0; 18-37] years) as well as fourteen controls on COC (24.9 ± 5.6 [22.5; 20-39] years) were assessed for eligibility and all agreed to participate in the study and remained for data analyses. RESULTS: LTG levels differed significantly between phases of inactive pill and active pill use (p= 0.004), particularly with drospirenon (p= 0.018) and levonorgestrel (p= 0.068) as progestogen component but not with gestoden (p= 0.593). Furthermore, the LTG group showed significantly lower progestin levels during inactive pill when compared to active pill use with respect to levonorgestrel (p= 0.042) and drospirenon (p= 0.018) but not to gestoden (p= 0.109). Progestin concentrations did not differ between patients and controls (p> 0.05). CONCLUSIONS: The findings suggest that drospirenon and levonorgestrel but not gestoden seem to reduce LTG serum concentrations when being co-administered in WWE which might be of importance concerning seizure risk. Vice versa, no effect of LTG on several progestins could be demonstrated, arguing against a potential loss of contraception safety with LTG.

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe.

Purpose: In the accompanying article, "Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe," we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results: We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion: Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients.