Steven Weyers

The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review

BACKGROUND Although hysteroscopy is frequently used in the management of subfertile women, a systematic review of the evidence on this subject is lacking. METHODS We summarized and appraised the evidence for the benefit yielded by this procedure. Our systematic search was limited to randomized and controlled studies. The QUOROM and MOOSE guidelines were followed. Language restrictions were not applied. RESULTS We identified 30 relevant publications. Hysteroscopic removal of endometrial polyps with a mean diameter of 16 mm detected by ultrasound doubles the pregnancy rate when compared with diagnostic hysteroscopy and polyp biopsy in patients undergoing intrauterine insemination, starting 3 months after the surgical intervention [relative risk (RR) = 2.3; 95% confidence interval (CI): 1.6-3.2]. In patients with one fibroid structure smaller than 4 cm, there was a marginally significant benefit from myomectomy when compared with expectant management (RR = 1.9; 95% CI: 1.0-3.7). Hysteroscopic metroplasty for septate uterus resulted in fewer pregnancies in patients with subfertility when compared with those with recurrent pregnancy loss (RR = 0.7; 95% CI: 0.5-0.9). Randomized controlled studies on hysteroscopic treatment of intrauterine adhesions are lacking. Hysteroscopy in the cycle preceding a subsequent IVF attempt nearly doubles the pregnancy rate in patients with at least two failed IVF attempts compared with starting IVF immediately (RR = 1.7; 95% CI: 1.5-2.0). CONCLUSIONS Scarce evidence on the effectiveness of hysteroscopic surgery in subfertile women with polyps, fibroids, septate uterus or intrauterine adhesions indicates a potential benefit. More randomized controlled trials are needed before widespread use of hysteroscopic surgery in the general subfertile population can be justified.

Long‐Term Evaluation of Cross‐Sex Hormone Treatment in Transsexual Persons

INTRODUCTION Long-term effects and side effects of cross-sex hormone treatment in transsexual persons are not well known. AIM The aim of this study is to describe the effects and side effects of cross-sex hormone therapy in both transsexual men and women. MAIN OUTCOME MEASURES Hormone levels were measured by immunoassays. Physical health was assessed by physical examination and questionnaires on general health and specific side effects, areal bone parameters by dual energy X-ray absorptiometry. METHODS Single center cross-sectional study in 100 transsexual persons post-sex reassignment surgery and on average 10 years on cross-sex hormone therapy. RESULTS Transsexual men did not experience important side effects such as cardiovascular events, hormone-related cancers, or osteoporosis. In contrast, a quarter of the transsexual women had osteoporosis at the lumbar spine and radius. Moreover, 6% of transsexual women experienced a thromboembolic event and another 6% experienced other cardiovascular problems after on average 11.3 hormone treatment years. None of the transsexual women experienced a hormone-related cancer during treatment. CONCLUSION Cross-sex hormone treatment appears to be safe in transsexual men. On the other hand, a substantial number of transsexual women suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management.

Penile reconstruction: is the radial forearm flap really the standard technique?

Background: The ideal goals in penile reconstruction are well described, but the multitude of flaps used for phalloplasty only demonstrates that none of these techniques is considered ideal. Still, the radial forearm flap is the most frequently used flap and universally considered as the standard technique. Methods: In this article, the authors describe the largest series to date of 287 radial forearm phalloplasties performed by the same surgical team. Many different outcome parameters have been described separately in previously published articles, but the main purpose of this review is to critically evaluate to what degree this supposed standard technique has been able to meet the ideal goals in penile reconstruction. Results: Outcome parameters such as number of procedures, complications, aesthetic outcome, tactile and erogenous sensation, voiding, donor-site morbidity, scrotoplasty, and sexual intercourse are assessed. Conclusions: In the absence of prospective randomized studies, it is not possible to prove whether the radial forearm flap truly is the standard technique in penile reconstruction. However, this large study demonstrates that the radial forearm phalloplasty is a very reliable technique for the creation, mostly in two stages, of a normal-appearing penis and scrotum, always allowing the patient to void while standing and in most cases also to experience sexual satisfaction. The relative disadvantages of this technique are the rather high number of initial fistulas, the residual scar on the forearm, and the potential long-term urologic complications. Despite the lack of actual data to support this statement, the authors feel strongly that a multidisciplinary approach with close cooperation between the reconstructive/plastic surgeon and the urologist is an absolute requisite for obtaining the best possible results.

Long-term Assessment of the Physical, Mental, and Sexual Health among Transsexual Women

INTRODUCTION Transsexualism is the most extreme form of gender identity disorder and most transsexuals eventually pursue sex reassignment surgery (SRS). In transsexual women, this comprises removal of the male reproductive organs, creation of a neovagina and clitoris, and often implantation of breast prostheses. Studies have shown good sexual satisfaction after transition. However, long-term follow-up data on physical, mental and sexual functioning are lacking. AIM To gather information on physical, mental, and sexual well-being, health-promoting behavior and satisfaction with gender-related body features of transsexual women who had undergone SRS. METHODS Fifty transsexual women who had undergone SRS >or=6 months earlier were recruited. MAIN OUTCOME MEASURES Self-reported physical and mental health using the Dutch version of the Short-Form-36 (SF-36) Health Survey; sexual functioning using the Dutch version of the Female Sexual Function Index (FSFI). Satisfaction with gender-related bodily features as well as with perceived female appearance; importance of sex, relationship quality, necessity and advisability of gynecological exams, as well as health concerns and feelings of regret concerning transition were scored. RESULTS Compared with reference populations, transsexual women scored good on physical and mental level (SF-36). Gender-related bodily features were shown to be of high value. Appreciation of their appearance as perceived by others, as well as their own satisfaction with their self-image as women obtained a good score (8 and 9, respectively). However, sexual functioning as assessed through FSFI was suboptimal when compared with biological women, especially the sublevels concerning arousal, lubrication, and pain. Superior scores concerning sexual function were obtained in those transsexual women who were in a relationship and in heterosexuals. CONCLUSIONS Transsexual women function well on a physical, emotional, psychological and social level. With respect to sexuality, they suffer from specific difficulties, especially concerning arousal, lubrication, and pain.

Quality of Life and Sexual Health after Sex Reassignment Surgery in Transsexual Men

INTRODUCTION Although sexual health after genital surgery is an important outcome factor for many transsexual persons, little attention has been attributed to this subject. AIMS To provide data on quality of life and sexual health after sex reassignment surgery (SRS) in transsexual men. METHODS A single-center, cross-sectional study in 49 transsexual men (mean age 37 years) after long-term testosterone therapy and on average 8 years after SRS. Ninety-four percent of the participants had phalloplasty. MAIN OUTCOME MEASURES Self-reported physical and mental health using the Dutch version of the Short Form-36 Health Survey; sexual functioning before and after SRS using a newly constructed specific questionnaire. RESULTS Compared with a Dutch reference population of community-dwelling men, transsexual men scored well on self-perceived physical and mental health. The majority reported having been sexually active before hormone treatment, with more than a quarter having been vaginally penetrated frequently before starting hormone therapy. There was a tendency toward less vaginal involvement during hormone therapy and before SRS. Most participants reported an increase in frequency of masturbation, sexual arousal, and ability to achieve orgasm after testosterone treatment and SRS. Almost all participants were able to achieve orgasm during masturbation and sexual intercourse, and the majority reported a change in orgasmic feelings toward a more powerful and shorter orgasm. Surgical satisfaction was high, despite a relatively high complication rate. CONCLUSION Results of the current study indicate transsexual men generally have a good quality of life and experience satisfactory sexual function after SRS.

Reproductive wish in transsexual men

BACKGROUND Hormonal therapy and sex reassignment surgery (SRS) in transsexual persons lead to an irreversible loss of their reproductive potential. The current and future technologies could create the possibility for female-to-male transsexual persons (transsexual men) to have genetically related children. However, little is known about this topic. The aim of this study is to provide information on the reproductive wishes of transsexual men after SRS. METHODS A self-constructed questionnaire was presented to 50 transsexual men in a single-center study. RESULTS The majority (64%) of transsexual men were currently involved in a relationship. Eleven participants (22.0%) reported having children. For eight participants, their female partner was inseminated with donor sperm, whereas three participants gave birth before hormonal therapy and SRS. At the time of interview, more than half of the participants desired to have children (54%). There were 18 participants (37.5%) who reported that they had considered freezing their germ cells, if this technique would have been available previously. Participants without children at the time of investigation expressed this desire more often than participants with children (χ²; test: P= 0.006). CONCLUSIONS Our data reveal that the majority of transsexual men desire to have children. Therefore, more attention should be paid to this topic during the diagnostic phase of transition and to the consequences for genetic parenthood after starting sex reassignment therapy.

Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene.

Background. It is widely assumed that the uterine cavity in non-pregnant women is physiologically sterile, also as a premise to the long-held view that human infants develop in a sterile uterine environment, though likely reflecting under-appraisal of the extent of the human bacterial metacommunity. In an exploratory study, we aimed to investigate the putative presence of a uterine microbiome in a selected series of non-pregnant women through deep sequencing of the V1-2 hypervariable region of the 16S ribosomal RNA (rRNA) gene. Methods. Nineteen women with various reproductive conditions, including subfertility, scheduled for hysteroscopy and not showing uterine anomalies were recruited. Subjects were highly diverse with regard to demographic and medical history and included nulliparous and parous women. Endometrial tissue and mucus harvesting was performed by use of a transcervical device designed to obtain endometrial biopsy, while avoiding cervicovaginal contamination. Bacteria were targeted by use of a barcoded Illumina MiSeq paired-end sequencing method targeting the 16S rRNA gene V1-2 region, yielding an average of 41,194 reads per sample after quality filtering. Taxonomic annotation was pursued by comparison with sequences available through the Ribosomal Database Project and the NCBI database. Results. Out of 183 unique 16S rRNA gene amplicon sequences, 15 phylotypes were present in all samples. In some 90% of the women included, community architecture was fairly similar inasmuch B. xylanisolvens, B. thetaiotaomicron, B. fragilis and an undetermined Pelomonas taxon constituted over one third of the endometrial bacterial community. On the singular phylotype level, six women showed predominance of L. crispatus or L. iners in the presence of the Bacteroides core. Two endometrial communities were highly dissimilar, largely lacking the Bacteroides core, one dominated by L. crispatus and another consisting of a highly diverse community, including Prevotella spp., Atopobium vaginae, and Mobiluncus curtisii. Discussion. Our findings are, albeit not necessarily generalizable, consistent with the presence of a unique microbiota dominated by Bacteroides residing on the endometrium of the human non-pregnant uterus. The transcervical sampling approach may be influenced to an unknown extent by endocervical microbiota, which remain uncharacterised, and therefore warrants further validation. Nonetheless, consistent with our understanding of the human microbiome, the uterine microbiota are likely to have a previously unrecognized role in uterine physiology and human reproduction. Further study is therefore warranted to document community ecology and dynamics of the uterine microbiota, as well as the role of the uterine microbiome in health and disease.

Body composition, volumetric and areal bone parameters in male-to-female transsexual persons

CONTEXT Male-to-female (M-->F) transsexual persons undergo extreme changes in gonadal hormone concentrations, both by pharmacological and surgical interventions. Given the importance of sex steroids for developing and maintaining bone mass, bone health is a matter of concern in daily management of these patients. OBJECTIVE To provide data on bone metabolism, geometry and volumetric bone mineral density in M-->F transsexual persons. DESIGN/SETTING/PARTICIPANTS Twenty-three M-->F transsexual persons, recruited from our gender dysphoria clinic and at least 3 yrs after sex reassignment surgery, together with 46 healthy age- and height-matched control men were included in this cross-sectional study. MAIN OUTCOME MEASURES Body composition, areal and volumetric bone parameters determined using DXA and peripheral quantitative computed tomography. Hormone levels and markers of bone metabolism assessed using immunoassays. Peak torque of biceps and quadriceps muscles and grip strength assessed using an isokinetic and hand dynamometer, respectively. RESULTS M-->F transsexual persons presented lower total and regional muscle mass and lower muscle strength as compared to controls (all P<0.001). In addition, they had higher total and regional fat mass (P<0.010) and a lower level of sports-related activity index (P<0.010). Bone mineral content and areal density (aBMD) of the lumbar spine, total hip and distal radius, as well as trabecular vBMD of the distal radius was lower as compared to controls (P<0.010). At cortical sites, no differences in cortical vBMD were observed, whereas M-->F transsexual persons were characterized by smaller cortical bone size at both the radius and tibia (P<0.010). Lower levels of biochemical markers of bone formation and resorption (P<0.010) suggested decreased bone turnover. CONCLUSION M-->F transsexual persons have less lean mass and muscle strength, and higher fat mass. In addition, they present lower trabecular vBMD and aBMD at the lumbar spine, total hip and distal radius, and smaller cortical bone size as compared to matched controls. Both the lower level of sports-related physical activity as well testosterone deprivation could contribute to these findings. These results indicate that bone health should be a parameter of interest in the long-term follow-up care for M-->F transsexual persons.

Sexual Desire in Trans Persons: Associations with Sex Reassignment Treatment

INTRODUCTION Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons. AIM This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons. METHODS A cross-sectional single specialized center study including 214 trans women (male-to-female trans persons) and 138 trans men (female-to-male trans persons). MAIN OUTCOME MEASURES Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction. RESULTS In retrospect, 62.4% of trans women reported a decrease in sexual desire after SRT. Seventy-three percent of trans women never or rarely experienced spontaneous and responsive sexual desire. A third reported associated personal or relational distress resulting in a prevalence of HSDD of 22%. Respondents who had undergone vaginoplasty experienced more spontaneous sexual desire compared with those who planned this surgery but had not yet undergone it (P = 0.03). In retrospect, the majority of trans men (71.0%) reported an increase in sexual desire after SRT. Thirty percent of trans men never or rarely felt sexual desire; 39.7% from time to time, and 30.6% often or always. Five percent of trans men met the criteria for HSDD. Trans men who were less satisfied with the phalloplasty had a higher prevalence of HSDD (P = 0.02). Trans persons who were more satisfied with the hormonal therapy had a lower prevalence of HSDD (P = 0.02). CONCLUSION HSDD was more prevalent in trans women compared with trans men. The majority of trans women reported a decrease in sexual desire after SRT, whereas the opposite was observed in trans men. Our results show a significant sexual impact of surgical interventions and both hormonal and surgical treatment satisfaction on the sexual desire in trans persons.

Sperm freezing in transsexual women.

Gender Identity Disorder (GID) is a condition in which a person experiences discrepancy between the sex assigned atbirth and the gender they identify with. Transsexualism is considered the most extreme form of GID and is characterized by the desire to live and be treated as a member of the opposite gender. The prevalence of male-to-female transsexualism in Belgium is estimated at 1 per 12,900 males (De Cuypere et al., 2007). The treatment consists of cross-sex hormone therapy and sex reassignment surgery in accordance with the Standards of Care of the World Professional Association for Transgender Health (WPATH) (7th Version) (www.wpath.org). At the center in Ghent, male-to-female transsexual persons, denoted as transsexual women, are treated in a multidisciplinary approach, including cross-sex hormone therapy and sex reassignment surgery for most. Hormone therapy with anti-androgens and estrogens is used in the majority of transsexual women. After at least 1 year of hormonal therapy, sex reassignment surgery can be offered, which includes orchidectomy andpenectomy in combinationwith vaginoplasty (Selvaggiet al., 2005).Bothhormonalandsurgical interventionsnegativelyaffect the male reproductive system. Hormonal therapy itself leads to decreased spermatogenesis and eventually to azoospermia (Lubbert, Leo-Rossberg, & Hammerstein, 1992; Schulze, 1988). Currently, it is unknown whether spermatogenesis will restore after prolonged estrogen treatment or not (Hembree et al., 2009). Sex reassignment surgery, on the other hand, results in an irreversible loss of natural reproductive capacity in transsexual women. Current reproductive techniques can offer adult transsexual women the possibility of having genetically related children (De Sutter, 2001). They can store their sperm for long-term cryopreservation before undergoing hormonal therapy for future use in assisted reproductive techniques (ART). Sexual orientation of transsexual women may influence the future plans for using the frozen sperm. If transsexual women have a female partner, they can procure children through intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection, based upon the sperm quality after thawing. Reproductive options for transsexual women with a male partner are more difficult as they need oocyte donation as well as a surrogate mother. Reproductive needs and rights of transsexual persons have already been recognized for over 15 years (Lawrence, Shaffer, Snow, Chase, & Headlam, 1996) and since 2001 the WPATH Standards of Care contains a paragraph that addresses the need to discuss reproductive issues with transsexual persons, prior to starting hormonal treatment (Meyer et al., 2001). Also, the new WPATH Standards of Care (Seventh version) (2011) as well as the Clinical Practice Guidelines of the Endocrine Society (Hembree et al., 2009) clearly state that transsexual persons should be encouraged to consider fertility issues before starting cross-gender hormonal treatment. On the other hand, research on this topic is still scarce. In the past 10 years, only two studies have investigated the opinions of transsexual persons themselves concerning this topic (De Sutter, Kira, Verschoor, & Hotimsky, 2002; Wierckx et al., 2012) and few have addressed reproductive difficulties (e.g., access to ART in transsexual patients) (AlvarezK. Wierckx (&) G. T’Sjoen Department of Endocrinology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium e-mail: Katrien.Wierckx@ugent.be