Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals.

The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for GI.

Predictive Pattern Classification Can Distinguish Gender Identity Subtypes from Behavior and Brain Imaging.

The exact neurobiological underpinnings of gender identity (i.e., the subjective perception of oneself belonging to a certain gender) still remain unknown. Combining both resting-state functional connectivity and behavioral data, we examined gender identity in cisgender and transgender persons using a data-driven machine learning strategy. Intrinsic functional connectivity and questionnaire data were obtained from cisgender (men/women) and transgender (trans men/trans women) individuals. Machine learning algorithms reliably detected gender identity with high prediction accuracy in each of the four groups based on connectivity signatures alone. The four normative gender groups were classified with accuracies ranging from 48% to 62% (exceeding chance level at 25%). These connectivity-based classification accuracies exceeded those obtained from a widely established behavioral instrument for gender identity. Using canonical correlation analyses, functional brain measurements and questionnaire data were then integrated to delineate nine canonical vectors (i.e., brain-gender axes), providing a multilevel window into the conventional sex dichotomy. Our dimensional gender perspective captures four distinguishable brain phenotypes for gender identity, advocating a biologically grounded reconceptualization of gender dimorphism. We hope to pave the way towards objective, data-driven diagnostic markers for gender identity and transgender, taking into account neurobiological and behavioral differences in an integrative modeling approach.

Male-to-female gender dysphoria: Gender-specific differences in resting-state networks.

INTRODUCTION: Recent research found gender-related differences in resting-state functional connectivity (rs-FC) measured by functional magnetic resonance imaging (fMRI). To the best of our knowledge, there are no studies examining the differences in rs-FC between men, women, and individuals who report a discrepancy between their anatomical sex and their gender identity, i.e. gender dysphoria (GD). METHODS: To address this important issue, we present the first fMRI study systematically investigating the differences in typical resting-state networks (RSNs) and hormonal treatment effects in 26 male-to-female GD individuals (MtFs) compared with 19 men and 20 women. RESULTS: Differences between male and female control groups were found only in the auditory RSN, whereas differences between both control groups and MtFs were found in the auditory and fronto-parietal RSNs, including both primary sensory areas (e.g. calcarine gyrus) and higher order cognitive areas such as the middle and posterior cingulate and dorsomedial prefrontal cortex. Overall, differences in MtFs compared with men and women were more pronounced before cross-sex hormonal treatment. Interestingly, rs-FC between MtFs and women did not differ significantly after treatment. When comparing hormonally untreated and treated MtFs, we found differences in connectivity of the calcarine gyrus and thalamus in the context of the auditory network, as well as the inferior frontal gyrus in context of the fronto-parietal network. CONCLUSION: Our results provide first evidence that MtFs exhibit patterns of rs-FC which are different from both their assigned and their aspired gender, indicating an intermediate position between the two sexes. We suggest that the present study constitutes a starting point for future research designed to clarify whether the brains of individuals with GD are more similar to their assigned or their aspired gender.

Association of high fetuin-B concentrations in serum with fertilization rate in IVF: a cross-sectional pilot study.

STUDY QUESTION: Is serum fetuin-B associated with the fertilization rate in in vitro fertilization (IVF)? SUMMARY ANSWER: Serum fetuin-B increased during IVF cycles when oocytes could be fertilized while remained unchanged in fertilization failure. WHAT IS KNOWN ALREADY: Fetuin-B deficiency in mice causes premature zona pellucida hardening mediated by the zona protease ovastacin. Thus fetuin-B deficiency renders females infertile. STUDY DESIGN, SIZE, DURATION: We determined the human serum fetuin-B reference range, studying longitudinally, over the course of one month, five male and seven female volunteers without hormone treatment and four female volunteers on varying hormonal contraception. We sampled blood and determined serum fetuin-B, luteinizing hormone (LH), estradiol (E2) and progesterone (P4). In addition, we determined serum fetuin-B and estradiol in eight women undergoing intracytoplasmatic sperm injection (ICSI, nine ICSI cycles) and 19 women undergoing IVF (21 IVF cycles) after ovarian stimulation with recombinant human follicular stimulating hormone (rFSH) and/or a combined medication of FSH and LH. At least three blood samples were analyzed in each cycle. We compared serum fetuin-B and follicular fluid fetuin-B in nine patients by measuring follicular fetuin-B in pooled follicular fluid, and in fluid obtained from individual follicles. Samples were drawn from January 2012 to March 2014. PARTICIPANTS/MATERIALS, SETTING, METHOD: All volunteers and patients gave informed consent. Fetuin-B was measured employing a commercial sandwich enzyme-linked immunosorbent assay. Serum fetuin-B was determined as duplicates in 5 male (34 ± 14.6 years) and 11 female volunteers (29.4 ± 4.1 years) as well as in female volunteers on hormonal contraception (30.0 ± 6.5 years). The duplicate standard deviation was 4.0 ± 2.3%. The contraceptive drugs were mono or combined preparations containing 0-0.03 mg ethinyl estradiol, and 0.15-3.0 mg of various progestins. In addition, serum fetuin-B was determined as triplicates in 27 female patients undergoing conventional IVF (19) or ICSI (8). The triplicate standard deviation was 3.3 ± 1.8%. IVF was declared as 'successful', if at least one oocyte was fertilized, and 'unsuccessful', if no oocyte could be fertilized. Patient age was 34.4 ± 4.4 years in successful IVF, and 35.4 ± 3.3 years in unsuccessful IVF. Serum and follicular fluid of patients undergoing controlled ovarian hyperstimulation were analyzed. Serum was drawn at the day of follicle aspiration. MAIN RESULTS AND THE ROLE OF CHANCE: Serum fetuin-B and follicular fluid fetuin-B were not significantly different in six out of nine patients suggesting, in principle, free exchange of fetuin-B between serum and follicular fluid. Thus serum fetuin-B may be used as a proxy of follicular fluid fetuin-B. Serum fetuin-B increased during successful IVF cycles (n = 15, P < 0.0001), but did not change in unsuccessful IVF cycles (n = 6, P = 0.118) despite increased estradiol levels (P = 0.0019 and P = 0.0254, respectively). LIMITATIONS, REASONS FOR CAUTION: The female volunteers self-reported their respective hormone medication. Medication was verified by serum estradiol, LH and progesterone measurements. For oocyte harvesting, the vaginal wall was punctured once only to minimize co-morbidity. Low grade cross-contamination of individual follicular fluid aspirates and contamination of the follicular fluid with small amounts of blood were inevitable. Samples were routinely checked for the presence of hemoglobin that would suggest blood contamination. Only samples containing <250 erythrocyte equivalents/µl were used for analysis. WIDER IMPLICATIONS OF THE FINDING: Serum fetuin-B may be used as a marker to predict the fertilization success in IVF. Fetuin-B levels attained during IVF stimulation may help to make an informed decision whether oocytes should be fertilized by IVF or by ICSI to overcome the zona pellucida as a barrier. STUDY FUNDING/COMPETING INTERESTS: The research was supported by a grant from Deutsche Forschungsgemeinschaft and by the START program of the Medical Faculty of RWTH Aachen University. J.F., E.D., J.N., B.R. and W.J.-D. declare that they are named inventors on the RWTH Aachen University patent application EP 13157317.2, 'Use of fetuin-B for culture of oocytes', applied for by RWTH Aachen University.

More than just two sexes: the neural correlates of voice gender perception in gender dysphoria.

Gender dysphoria (also known as "transsexualism") is characterized as a discrepancy between anatomical sex and gender identity. Research points towards neurobiological influences. Due to the sexually dimorphic characteristics of the human voice, voice gender perception provides a biologically relevant function, e.g. in the context of mating selection. There is evidence for a better recognition of voices of the opposite sex and a differentiation of the sexes in its underlying functional cerebral correlates, namely the prefrontal and middle temporal areas. This fMRI study investigated the neural correlates of voice gender perception in 32 male-to-female gender dysphoric individuals (MtFs) compared to 20 non-gender dysphoric men and 19 non-gender dysphoric women. Participants indicated the sex of 240 voice stimuli modified in semitone steps in the direction to the other gender. Compared to men and women, MtFs showed differences in a neural network including the medial prefrontal gyrus, the insula, and the precuneus when responding to male vs. female voices. With increased voice morphing men recruited more prefrontal areas compared to women and MtFs, while MtFs revealed a pattern more similar to women. On a behavioral and neuronal level, our results support the feeling of MtFs reporting they cannot identify with their assigned sex.

Women with one ovary in assisted reproduction technologies: a review of the literature.

BACKGROUND: A number of patients who have undergone assisted reproductive technology (ART) have only one ovary. PURPOSE: This article reviews the clinical implications of the absence of an ovary on the reproductive potential and the outcome in ART cycle. DATA SOURCES: MEDLINE, Pubmed, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews from the 1980s through April 2010. STUDY SELECTION: Randomized, controlled trials; systematic reviews of trials; and observational studies; all restricted to English-language articles. DATA SYNTHESIS: This review includes 58 articles. Women with a single ovary did not, in general, respond as well to ovulation induction treatment than women with two ovaries in ART cycles. It appears however, that once women with a single ovary achieve the stage of embryo transfer, they can be reassured that their chances of having a child are the same as women with two ovaries. Whether the right or left ovary responds better to superovulation is a question which remains unanswered in the literature. LIMITATIONS: The authors could not address all management questions, and excluded non-English-language literature.

Fertility sparing in cancer patients.

Infertility can arise as a consequence of treatment of oncological conditions. As cancer survival rates continue to improve, many women will face infertility after successful treatment of their malignant diseases. This review summarizes the current state of different fertility preservation options in these patients. This review will discuss the premature ovarian failure and other adverse reproductive outcomes in female patients who receive chemotherapy and radiation. In addition, cancer-specific fertility preservation methods are presented. Embryo cryopreservation is a well established technique to preserve fertility. However, it requires delaying cancer treatment for two to six weeks and a partner or willingness to use donor sperm. When these criteria cannot be met, more experimental options include oocyte cryopreservation for later IVF and ovarian tissue cryopreservation. In-vitro maturation is a promising technology and can be applied in combination with oocyte or ovarian tissue cryopreservation. Ovarian transposition remains the standard option for women undergoing pelvic radiation. Lastly, the efficacy of GnRH analoga in ovarian protection during chemotherapy has still not been proved. As fertility preservation choices include both established and experimental methods, a highly individualized approach is required in the management of patients looking for fertility preservation options.

Estrogen receptor alpha and progesterone receptor A and B concentration and localization in the lower uterine segment in term parturition.

OBJECTIVE: To determine the localization and concentrations of estrogen receptor alpha and progesterone receptors A and B in the lower uterine segment during term parturition. METHODS: Biopsies were taken from 70 patients during nonelective cesarean delivery. The patients were at different stages of cervical dilatation (<2 cm, 2-3.9 cm, 4-6 cm, >6 cm) and different duration of labor (< or =6 hours, >6-12 hours, >12 hours). The receptor concentrations were determined with solid phase immunoassays, and their localization was investigated immunohistochemically. RESULTS: Estrogen receptor alpha concentration decreased significantly from 2.12 fmol/mg protein at less than 2 cm dilatation to 1.08 fmol/mg (4-6 cm) but tended to increase at greater than 6 cm. Progesterone receptor A and B concentration was 84.7 fmol/mg at less than 2 cm dilatation, decreased significantly to 36.6 fmol/mg (2-3.9 cm), and increased again with further dilation. Concentrations of both receptors did not depend on duration of labor. By immunohistochemistry only progesterone receptor A and B was found to be expressed by endothelial and smooth muscle cells of the vessels, stromal fibroblasts, smooth muscle cells in the myometrium, and glandular epithelial cells. Regardless of the extent of cervical dilatation, expression of progesterone receptors A and B was marked. CONCLUSION: A decrease in estrogen receptor alpha and progesterone receptor A and B concentration in the early phase of first stage labor may play a role in cervical dilation at term.