Lactation induction in a transgender woman: case report and recommendations for clinical practice.

BACKGROUND: We present a case of non-puerperal induced lactation in transgender woman. Medical literature on lactation induction for transgender women is scarce, and the majority of literature and protocols on lactation induction is based on research in cisgender women. Healthcare professionals may lack the precise knowledge about lactation induction and may therefore feel insecure when advice is requested. Subsequently, there is a rising demand for guidelines and support. METHODS: Patient medical record was consulted and a semi-structured interview was conducted to explore the motive for lactation induction, the experience of lactation induction, and to gather additional information about the timeline and course of events. CASE PRESENTATION: In this case a 37-year-old transgender woman, who was under the care of the centre of expertise on gender dysphoria in Amsterdam, and in 2020 started lactation induction because she had the wish to breastfeed her future infant. She was in a relationship with a cisgender woman and had been using gender affirming hormone therapy for 13 years. Prior to initiating gender affirming hormone therapy she had cryopreserved her semen. Her partner conceived through Intracytoplasmic Sperm Injection, using our patient's cryopreserved sperm. To induce lactation, we implemented a hormone-regimen to mimic pregnancy, using estradiol and progesterone, and a galactogogue; domperidone. Our patient started pumping during treatment. Dosage of progesterone and estradiol were significantly decreased approximately one month before childbirth to mimic delivery and pumping was increased. Our patient started lactating and although the production of milk was low, it was sufficient for supplementary feeding and a positive experience for our patient. Two weeks after birth, lactation induction was discontinued due to suckling problems of the infant and low milk production. CONCLUSIONS: This case report underlined that lactation induction protocols commonly used for cisgender women are also effective in transgender women. However, the amount of milk produced may not be sufficient for exclusive nursing. Nevertheless, success of induced lactation may be attributed to its importance for parent-infant bonding, rather than the possibility of exclusive chestfeeding.

Successful restoration of spermatogenesis following gender-affirming hormone therapy in transgender women.

Increasing numbers of transgender individuals are presenting for gender-affirming medical care. For trans women, gender-affirming hormone therapy (GAHT) promotes feminization but also inhibits spermatogenesis. There is a common untested assumption that this inhibition is permanent, resulting in infertility. In this longitudinal study, we report the recovery of viable spermatozoa in nine trans women who stopped GAHT for reproductive purposes. Our preliminary findings suggest that the negative impact of GAHT on spermatogenesis can be reversed, casting doubt on previous claims that GAHT in trans women inevitably leads to permanent infertility. Larger studies are needed to confirm our findings, which have implications not only for fertility counseling and the reproductive options of transgender individuals but also efforts to restrict access to GAHT based on fertility grounds.

Effectiveness, complications, and reproductive outcomes after cesarean scar pregnancy management: a retrospective cohort study.

BACKGROUND: There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined. OBJECTIVE: This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management. STUDY DESIGN: We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth. RESULTS: Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P=.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P=.01) after a curettage, and 6 months (interquartile range, 4-15; P=.03) after a laparoscopic niche resection. CONCLUSION: Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies.

Endometrial thickness assessed by transvaginal ultrasound in transmasculine people taking testosterone compared with cisgender women.

RESEARCH QUESTION: What is the endometrial thickness of endometrium exposed to testosterone in transmasculine people compared with unexposed endometrium in cisgender women as determined by transvaginal ultrasound (TVU)? DESIGN: Single centre, cross-sectional cohort study conducted the Centre of Expertise on Gender Dysphoria in Amsterdam. Between 2013 and 2015, transmasculine people scheduled for gender affirming surgery (GAS) were included in this study after they provided informed consent. They were undergoing gender affirming hormone therapy (testosterone) for at least 1 year. Endometrial thickness (mm) was measured by TVU in transmasculine people, immediately before their GAS while under general anaesthesia. Cisgender control women from the general population underwent the exact same TVU measurements in an outpatient clinical setting on cycle days 2-5. RESULT: Fifty-one transmasculine people and 77 controls were included. The mean duration of testosterone use was 30.2 months (SD 8.8). Endometrial thickness was significantly lower in transmasculine people compared with cisgender women: median 3.9 mm (interquartile range [IQR] 2.8-5.1) and 4.9 mm (IQR 4.0-6.3), respectively (P < 0.001), after correcting for confounding factor (current gonadotrophin releasing hormone agonist use). CONCLUSIONS: Endometrial thickness in transmasculine people exposed to testosterone is significantly lower compared with cisgender women without testosterone exposure. These results suggest an absence of endometrial proliferation by exogenous testosterone.

Incidence of testicular cancer in trans women using gender-affirming hormonal treatment: a nationwide cohort study.

OBJECTIVE: To assess the incidence of testicular cancer in trans women (male sex assigned at birth, female gender identity) using gender-affirming hormonal treatment. PATIENTS AND METHODS: Data of trans women starting hormonal treatment at our gender identity clinic between 1972 and 2017 were linked to the national pathology database to obtain testicular cancer diagnoses. The standardised incidence ratio (SIR) was calculated using the number of observed testicular cancer cases in our cohort and the number of expected cases based on age-specific Dutch incidence rates. Subgroup analyses were performed in testicular tissues sent for histopathological analysis at the time of bilateral orchidectomy, and when follow-up exceeded 5 years. RESULTS: The cohort consisted of 3026 trans women with a median follow-up time of 2.3 interquartile range (IQR) (1.6-3.7) years. Two testicular cancer cases were identified whilst 2.4 cases were expected (SIR 0.8, 95% confidence interval 0.1-2.8). In addition, one testicular cancer case was encountered in an orchidectomy specimen (0.1%). In the 523 trans women with a follow-up time of >5 years (median [IQR] 8.9 [6.4-13.9] years), no testicular cancer was observed. CONCLUSION: Testicular cancer risk in trans women is similar to the risk in cis men. The testicular cancer cases occurred within the first 5 years after commencing hormonal treatment, and the percentage of cases encountered at the time of bilateral orchidectomy was low. As no testicular cancer was observed in trans women with a long follow-up period, long-term hormonal treatment does not seem to increase testicular cancer risk.

Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview.

INTRODUCTION: Genital gender affirming surgery (gGAS) is usually the final stage in the medical transition for transgender men and consists of creating a neophallus and neo-scrotum, with or without urethral lengthening(UL). To reduce the complication risks of UL, a mandatory colpectomy is performed prior to UL. Colpectomy is considered a complex surgery, which may lead to various perioperative complications. There are few long-term complications reported. AIM: To describe the clinical presentation and management of 3 consecutive transgender men presenting with a perineal cyst following gGAS. METHODS: After obtaining informed consent all clinical data was collected, including medical history, current symptoms, imaging, as well as surgery and histological outcomes. Furthermore, a literature search was performed. MAIN OUTCOME MEASURE: To hypothesize the aetiology of the perineal cyst based on current published literature. RESULTS: Three otherwise healthy transgender men, ages 26-46 with a similar medical history, presented with a perineal cyst several months or years following colpectomy and gGAS with UL. All patients underwent surgery to remove the cyst. Several theories regarding aetiology of this perineal cyst are discussed in this report. CONCLUSION: There remain several gaps in our knowledge regarding the aetiology and management of this perineal cyst. Therefore, further research is necessary. Asseler JD, Ronkes BL, Groenman FA, et al. Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview. J Sex Med 2021;9:100415.

Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway.

PURPOSE: Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? METHODS: Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 µM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. RESULTS: Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 µM GSK1070916 and the control. CONCLUSION: Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement.

Combining total laparoscopic hysterectomy and bilateral salpingo-oophorectomy with subcutaneous mastectomy in trans men: The effect on safety outcomes.

Background: Masculinizing mastectomy is the most requested gender affirming surgery (GAS) in trans men, followed by genital GAS. Mastectomy and total laparoscopic hysterectomy, with or without bilateral salpingo-oophorectomy (TLH ± BSO), can both be performed in one single operation session. However, data on complication rates of the combined procedure is scarce and no consensus exists on the preferred order of procedures. Aims: To compare safety outcomes between mastectomy performed in a single procedure with those when performed in a combined procedure and assess whether the order of procedures matters when they are combined. Methods: A retrospective chart review was performed of trans men who underwent masculinizing mastectomy with or without TLH ± BSO in a combined session. The effects of the surgical procedure on complication and reoperation rate of the chest were assessed using logistic regression. Results: In total, 480 trans men were included in the study. Of these, 212 patients underwent the combined procedure. The gynecological procedure was performed first in 152 (71.7%) patients. In the total sample, postoperative hematoma of the chest occurred in 11.3%; 16% in the combined versus 7.5% in the single mastectomy group (p = 0.001). Reoperations due to hematoma of the chest were performed in 7.5% of all patients; 10.8% in the combined versus 4.9% in the single mastectomy group (p = 0.017). The order of procedures in the combined group had no significant effect on postoperative hematoma of the chest (p = 0.856), and reoperations (p = 0.689). Conclusion: Combining masculinizing mastectomy with TLH ± BSO in one session was associated with significantly more hematoma and reoperations compared with separately performing mastectomy. This increased risk of complications after a combined procedure should be considered when deciding on surgical options. The order of procedures in a combined procedure did not have an effect on safety outcomes.

Prostate Cancer Incidence under Androgen Deprivation: Nationwide Cohort Study in Trans Women Receiving Hormone Treatment.

CONTEXT: Trans women (male sex assigned at birth, female gender identity) mostly use antiandrogens combined with estrogens and can subsequently undergo vaginoplasty including orchiectomy. Because the prostate remains in situ after this procedure, trans women are still at risk for prostate cancer. OBJECTIVE: To assess the incidence of prostate cancer in trans women using hormone treatment. The incidence of prostate cancer in trans women using hormone treatment. DESIGN: In this nationwide retrospective cohort study, data of participants were linked to the Dutch national pathology database and to Statistics Netherlands to obtain data on prostate cancer diagnosis and mortality. SETTING: Gender identity clinic. PARTICIPANTS: Trans women who visited our clinic between 1972 and 2016 and received hormone treatment were included. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) were calculated using the number of observed prostate cancer cases in our cohort and the number of expected cases based on age-specific incidence numbers from the Netherlands Comprehensive Cancer Organization. RESULTS: The study population consisted of 2281 trans women with a median follow-up time of 14 years (interquartile range 7-24), and a total follow-up time of 37 117 years. Six prostate cancer cases were identified after a median 17 years of hormone treatment. This resulted in a lower prostate cancer risk in trans women than in Dutch reference males (SIR 0.20, 95% confidence interval 0.08-0.42). CONCLUSIONS: Trans women receiving androgen deprivation therapy and estrogens have a substantially lower risk for prostate cancer than the general male population. Our results support the hypothesis that androgen deprivation has a preventive effect on the initiation and development of prostate cancer.

Vaginal Colpectomy in Transgender Men: A Retrospective Cohort Study on Surgical Procedure and Outcomes.

BACKGROUND: Colpectomy, removal of the vaginal epithelium, may be performed in transgender men because of a disturbed male self-image, to reduce vaginal discharge, or to reduce the risk of fistula formation at the urethral-neourethral junction in future phalloplasty or metaidoioplasty. AIM: To demonstrate that vaginal colpectomy in transgender men, either alone or in combination with, for example, laparoscopic hysterectomy, metaidoioplasty, scrotoplasty, or urethroplasty, is a feasible procedure. METHODS: This single-center retrospective cohort study included 143 transgender men who underwent vaginal colpectomy between January 2006 and April 2018. Surgical details and clinical outcomes were collected from all patients. OUTCOMES: The primary outcome was the number of perioperative and postoperative complications, including intraoperative blood loss. Secondary outcomes were operating time, change in hemoglobin level, and duration of hospital stay. RESULTS: In 109 patients (76%), the procedure consisted of colpectomy only, whereas in 34 patients (23%), colpectomy was combined with other procedures. In the whole group (combined procedures included), the median blood loss was 300 mL (interquartile range [IQR] = 250 mL), the mean operating time was 132 ± 62 minutes, and the mean duration of hospital admission was 3.6 ± 1.9 days. In the colpectomy-only group, the median blood loss was 300 mL (IQR = 250 mL), mean operating time was 112 ± 40 minutes, and mean duration of hospital admission was 3.2 ± 1.5 days. For the total group, 15 patients (10%) experienced a major perioperative complication (ie, bowel injury, ureter injury, urethra injury, bladder injury, hemorrhage requiring transfusion and/or intervention and conversion to laparoscopy), and 1 patient (0.7%) had a minor perioperative complication (hemorrhage). Major postoperative complications (hemorrhage, hematoma, fistula, wound infection and prolonged pain complaints) were reported in 17 patients (12%), and minor postoperative complications (urinary tract infection, urinary retention, hemorrhage, and hematoma) occurred in 50 patients (35%). CLINICAL IMPLICATIONS: This study provides a detailed description of our technique and comprehensive reporting on perioperative and postoperative complications and reintervention rate. STRENGTHS & LIMITATIONS: Study strengths include the large number of patients included and the detailed reporting on the complications of vaginal colpectomy. The main limitation is the retrospective design, which can cause data to go missing during extraction and is prone to bias. CONCLUSION: Vaginal colpectomy is a procedure with a high complication rate, but its advantages seem to outweigh its disadvantages. In all but 1 case, no long-term sequelae were reported. However, the high complication rate and reintervention rate should be discussed with patients who are considering undergoing this procedure. Nikkels C, van Trotsenburg M, Huirne J, et al. Vaginal Colpectomy in Transgender Men: A Retrospective Cohort Study on Surgical Procedure and Outcomes. J Sex Med 2019;16:924-933.

Development of a Decision Aid for Genital Gender-Affirming Surgery in Transmen.

BACKGROUND: As genital gender-affirming surgery (GAS) is a demanding and life-changing intervention, transmen should be able to make choices about the surgical treatment based on outcomes that are most important to them, while taking into consideration the concomitant risks involved. AIM: Develop a decision aid (DA) for genital surgery in transmen (DA-GST) that can assist both transmen and health care professionals (HCPs) in making a well-informed decision about the surgical treatment. METHODS: A qualitative focus group study was performed. 5 Focus groups were organized with both HCPs and transmen. These were led by an independent professional moderator. Data collected during these focus groups were analyzed to provide content for the DA. OUTCOMES: To develop content for a DA-GST. RESULTS: Data collected during the focus groups related to the treatment options, information deemed relevant by transmen, and the arguments for or against each treatment option. Collected items were divided into the following themes: outcome, quality of life, environment, sexuality, and beliefs. CLINICAL IMPLICATIONS: The tool will be useful in assisting both transmen and HCPs in the shared decision-making process regarding genital GAS by exploring which domains are most relevant for each specific individual. STRENGTHS & LIMITATIONS: This DA was developed according to an iterative participatory design approach to fit the needs of both transmen and HCPs. Issues that transmen find important and relevant pertaining to genital GAS were translated into arguments that were incorporated in the DA-GST. The study is limited by the group that had participated. Not all arguments for or against specific surgical options may be covered by the DA-GST. CONCLUSION: An online DA was developed to support transmen with their decision-making process concerning all surgical options for removal of reproductive organs and genital GAS. Özer M, Pigot GL, Bouman M-B, et al. Development of a Decision Aid for Genital Gender-Affirming Surgery in Transmen. J Sex Med 2018;15:1041-1048.

Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy. METHODS: In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267. FINDINGS: 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [<1%]; RR 15·0, 2·0-113·4). Repeat ectopic pregnancy occurred in 18 women (8%) in the salpingotomy group and 12 (5%) women in the salpingectomy group (RR 1·6, 0·8-3·3). The number of ongoing pregnancies after ovulation induction, intrauterine insemination, or IVF did not differ significantly between the groups. 43 (20%) women in the salpingotomy group were converted to salpingectomy during the initial surgery because of persistent tubal bleeding. Our meta-analysis, which included our own results and those of one other study, substantiated the results of the trial. INTERPRETATION: In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy. FUNDING: Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee.

Ectopic pregnancy: how the diagnostic and therapeutic management has changed.

Nowadays ectopic pregnancy often can be diagnosed before the woman's condition has deteriorated, which has altered the former clinical picture of a life-threatening disease into a more benign condition. This review describes the historical developments in the diagnostic and therapeutic management of ectopic pregnancy leading up to current clinical practice. The first attempts to diagnose ectopic pregnancy originate from the beginning of the 20th century.

Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies.

OBJECTIVE: To determine the accuracy with which a single progesterone measurement in early pregnancy discriminates between viable and non-viable pregnancy. DESIGN: Systematic review and meta-analysis of diagnostic accuracy studies. DATA SOURCES: Medline, Embase, CINAHL, Web of Science, ProQuest, Conference Proceedings Citation Index, and the Cochrane Library from inception until April 2012, plus reference lists of relevant studies. STUDY SELECTION: Studies were selected on the basis of participants (women with spontaneous pregnancy of less than 14 weeks of gestation); test (single serum progesterone measurement); outcome (viable intrauterine pregnancy, miscarriage, or ectopic pregnancy) diagnosed on the basis of combinations of pregnancy test, ultrasound scan, laparoscopy, and histological examination; design (cohort studies of test accuracy); and sufficient data being reported. RESULTS: 26 cohort studies, including 9436 pregnant women, were included, consisting of 7 studies in women with symptoms and inconclusive ultrasound assessment and 19 studies in women with symptoms alone. Among women with symptoms and inconclusive ultrasound assessments, the progesterone test (5 studies with 1998 participants and cut-off values from 3.2 to 6 ng/mL) predicted a non-viable pregnancy with pooled sensitivity of 74.6% (95% confidence interval 50.6% to 89.4%), specificity of 98.4% (90.9% to 99.7%), positive likelihood ratio of 45 (7.1 to 289), and negative likelihood ratio of 0.26 (0.12 to 0.57). The median prevalence of a non-viable pregnancy was 73.2%, and the probability of a non-viable pregnancy was raised to 99.2% if the progesterone was low. For women with symptoms alone, the progesterone test had a higher specificity when a threshold of 10 ng/mL was used (9 studies with 4689 participants) and predicted a non-viable pregnancy with pooled sensitivity of 66.5% (53.6% to 77.4%), specificity of 96.3% (91.1% to 98.5%), positive likelihood ratio of 18 (7.2 to 45), and negative likelihood ratio of 0.35 (0.24 to 0.50). The probability of a non-viable pregnancy was raised from 62.9% to 96.8%. CONCLUSION: A single progesterone measurement for women in early pregnancy presenting with bleeding or pain and inconclusive ultrasound assessments can rule out a viable pregnancy.

The ESEP study: salpingostomy versus salpingectomy for tubal ectopic pregnancy; the impact on future fertility: a randomised controlled trial.

BACKGROUND: For most tubal ectopic pregnancies (EP) surgery is the treatment of first choice. Whether surgical treatment should be performed conservatively (salpingostomy) or radically (salpingectomy) in women wishing to preserve their reproductive capacity, is subject to debate. Salpingostomy preserves the tube, but bears the risks of both persistent trophoblast and repeat ipsilateral tubal EP. Salpingectomy, avoids these risks, but leaves only one tube for reproductive capacity. This study aims to reveal the trade-off between both surgical options: whether the potential advantage of salpingostomy, i.e. a better fertility prognosis as compared to salpingectomy, outweighs the potential disadvantages, i.e. persistent trophoblast and an increased risk for a repeat EP. METHODS/DESIGN: International multi centre randomised controlled trial comparing salpingostomy versus salpingectomy in women with a tubal EP without contra lateral tubal pathology. Hemodynamically stable women with a presumptive diagnosis of tubal EP, scheduled for surgery, are eligible for inclusion. Patients pregnant after in vitro fertilisation (IVF) and/or known documented tubal pathology are excluded. At surgery, a tubal EP must be confirmed. Only women with a tubal EP amenable to both interventions and a healthy contra lateral tube are included. Salpingostomy and salpingectomy are performed according to standard procedures of participating hospitals. Up to 36 months after surgery, women will be contacted to assess their fertility status at six months intervals starting form the day of the operation. The primary outcome measure is the occurrence of spontaneous viable intra uterine pregnancy. Secondary outcome measures are persistent trophoblast, repeat EP, all pregnancies including those resulting from IVF and financial costs. The analysis will be performed according to the intention to treat principle. A cost-effectiveness analysis will be performed within a decision analysis framework, based on costs per live birth, including IVF treatment whenever a spontaneous pregnancy does not occur. Patients' preferences will be assessed using a discrete choice experiment. DISCUSSION: This trial will provide evidence on the trade off between salpingostomy and salpingectomy for tubal EP in view of the pros and cons of both interventions and will offer guidance to clinicians in making the right treatment choice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37002267.

The METEX study: methotrexate versus expectant management in women with ectopic pregnancy: a randomised controlled trial.

BACKGROUND: Patients with ectopic pregnancy (EP) and low serum hCG concentrations and women with a pregnancy of unknown location (PUL) and plateauing serum hCG levels are commonly treated with systemic methotrexate (MTX). However, there is no evidence that treatment in these particular subgroups of women is necessary as many of these early EPs may resolve spontaneously. The aim of this study is whether expectant management in women with EP or PUL and with low but plateauing serum hCG concentrations is an alternative to MTX treatment in terms of treatment success, future pregnancy, health related quality of life and costs. METHODS/DESIGN: A multicentre randomised controlled trial in The Netherlands. Hemodynamically stable patients with an EP visible on transvaginal ultrasound and a plateauing serum hCG concentration < 1,500 IU/L or with a persisting PUL with plateauing serum hCG concentrations < 2,000 IU/L are eligible for the trial. Patients with a viable EP, signs of tubal rupture/abdominal bleeding, or a contra-indication for MTX will not be included. Expectant management is compared with systemic MTX in a single dose intramuscular regimen (1 mg/kg) in an outpatient setting. Serum hCG levels are monitored weekly; in case of inadequately declining, systemic MTX is installed or continued. In case of hemodynamic instability and/or signs of tubal rupture, surgery is performed. The primary outcome measure is an uneventful decline of serum hCG to an undetectable level by the initial intervention. Secondary outcomes are (re)interventions (additional systemic MTX injections and/or surgery), treatment complications, health related quality of life, financial costs, and future fertility. Analysis is performed according to the intention to treat principle. Quality of life is assessed by questionnaires before and at three time points after randomisation. Costs are expressed as direct costs with data on costs and used resources in the participating centres. Fertility is assessed by questionnaires after 6, 12, 18 and 24 months. Patients' preferences will be assessed using a discrete choice experiment. DISCUSSION: This trial will provide guidance on the present management dilemmas in women with EPs and PULs with low and plateauing serum hCG concentrations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 48210491.

Advances in vector-mediated gene transfer.

Clinical applications of gene transfer technology initially targeted the treatment of inherited monogenetic disorders and cancers refractory to conventional therapies. Today, gene transfer approaches are being developed for most tissues and for multiple disorders including those affecting quality of life. The focus herein is eventual application of gene transfer technology for the management of organ-directed autoimmunity. A specific example is presented: Sjögren's syndrome and localized salivary gland gene transfer. The status of relevant pre-clinical gene transfer studies is reviewed, with an emphasis on use of adenoviral and adeno-associated viral vectors. Current limitations of effective organ-directed gene transfer are also discussed.