A European Network for the Investigation of Gender Incongruence in adolescents.

BACKGROUND: Knowledge regarding the effects and side effects of gender-affirming hormone therapy (GAHT) in adults is rapidly growing, partly through international research networks such as the European Network for the Investigation of Gender Incongruence (ENIGI). However, data on the effects of puberty suppression (PS) and GAHT in transgender and gender diverse (TGD) youth are limited, although these data are of crucial importance, given the controversies surrounding this treatment. AIM: We sought to present a detailed overview of the design of the ENIGI Adolescents study protocol, including the first baseline data. METHODS: The ENIGI Adolescents study is an ongoing multicenter prospective cohort study. This study protocol was developed by 3 European centers that provide endocrine care for TGD adolescents and were already part of the ENIGI collaboration: Amsterdam, Ghent, and Florence. OUTCOMES: Study outcomes include physical effects and side effects, laboratory parameters, bone mineral density, anthropometric characteristics, attitudes toward fertility and fertility preservation, and psychological well-being, which are measured in the study participants during PS and GAHT, up to 3 years after the start of GAHT. RESULTS: Between November 2021 and May 2023, 172 TGD adolescents were included in the ENIGI Adolescents protocol, of whom 51 were assigned male at birth (AMAB) and 121 were assigned female at birth (AFAB); 3 AFAB participants reported a nonbinary gender identification. A total of 76 participants were included at the start of PS, at a median (IQR) age of 13.7 (12.9-16.5) years in AMAB and 13.5 (12.4-16.1) years in AFAB individuals. The remaining 96 participants were included at start of GAHT, at a median (IQR) age of 15.9 (15.1-17.4) years in AFAB and 16.0 (15.1-16.8) years in AMAB individuals. At the time of this report the study was open for inclusion and follow-up measurements were ongoing. CLINICAL IMPLICATIONS: In response to the rising demand for gender-affirming treatment among TGD youth, this ongoing study is fulfilling the need for prospective data on the effects and safety of PS and GAHT, thus providing a foundation for evidence-based healthcare decisions. STRENGTHS AND LIMITATIONS: This study has a strong multicenter, prospective design that allows for systematic data collection. The use of clinical and self-reported data offers a broad range of outcomes to evaluate. Nevertheless, the burden of additional measurements and questionnaires may lead to withdrawal or lower response rates. Few participants with a non-binary gender identity have been included. CONCLUSION: With the ENIGI Adolescents study we aim to create a comprehensive dataset that we can use for a wide range of studies to address current controversies and uncertainties and to improve healthcare for TGD adolescents.

Guideline-based quality indicators for early pregnancy assessment units.

RESEARCH QUESTION: What valid guideline-based quality indicators can measure quality of care in early pregnancy assessment units (EPAU)? DESIGN: The systematic RAND-modified Delphi method was used to develop an indicator set from four evidence-based guidelines. An international expert panel was assembled to extract recommendations from these guidelines to establish quality indicators. RESULTS: A total of 119 recommendations were extracted. Eleven recommendations received a high median score and top five score above the 75th percentile and were selected as key recommendations. The expert panel reassessed 15 high score recommendations and top five score between the 50th and 75th percentile as well as one high score recommendation without consensus. Eight of these 16 recommendations were selected in the second round as key recommendations. The key recommendations were formulated into a set of 19 quality indicators, summarized as follows: women referred to an EPAU could be seen within 24 h and receive a clear explanation on treatment options; designated senior staff members could be responsible for the unit and staff could have had ultrasound training; protocols could be available for daily practice covering all treatment options for miscarriage and ectopic pregnancy; and an EPAU could have access to urine pregnancy testing and serum HCG assays. CONCLUSIONS: Nineteen quality indicators to measure early pregnancy care provided by EPAU were identified.

Anatomical Gynecological Anomalies in Girls Born with Anorectal Malformations: A Retrospective Cohort Study of 128 Patients.

STUDY OBJECTIVE: In girls born with an anorectal malformation (ARM), anatomical gynecological anomalies (GA) may be present and might need treatment. Therefore, the aim of this study was to provide an overview of GA in girls born with ARM in our cohort. Additionally, diagnostic timing and methods for GA were assessed. METHODS: A retrospective mono-center study was performed from January 2000 to December 2022. All patients assigned female at birth were eligible for inclusion. GA were classified according to ESHRE/ESGE classification. Outcomes were the number of girls with GA with subsequent screening methods, factors associated with GA, and GA requiring treatment. Uni- and multivariable logistic regression analyses were performed to identify the association between baseline characteristics and the presence of GA. RESULTS: In total, 128 girls were included, of whom 30 (24.1%) had additional GA, with vaginal anomalies being present most often (n = 17). Fifty-six patients (43.8%) underwent full screening, and this number improved over time (37.7% before 2018 vs 72.7% after 2018; P = .003). Thirteen of 30 patients (43.3%) required surgical treatment for their GA, without the occurrence of postoperative complications. CONCLUSION: Additional GA were present in almost a quarter of the girls born with an ARM, with vaginal anomalies most often identified. Despite GA being most often found in patients with cloacal malformations, these anomalies were also identified in patients with other ARM types. Surgical treatment was required in almost half of the girls with GA. Therefore, this study emphasizes the importance of screening for GA in patients with an ARM, regardless of the ARM type.

Identification of barriers for good adherence to a guideline on recurrent miscarriage.

OBJECTIVE: Guidelines on recurrent miscarriage are poorly implemented in daily clinical practice. To ensure proper implementation, we identified existing barriers and facilitators for guideline adherence according to professionals and patients. DESIGN: Qualitative research. SETTING: Two different regions in the Netherlands. POPULATION: Forty-two professionals: gynecologists, residents in obstetrics and gynecology, fertility doctors and clinical geneticists. Ten patients with recurrent miscarriage. METHODS: Focus group interviews were performed with professionals and individual in-depth interviews with patients. Reports from the interviews were analyzed and barriers were identified. MAIN OUTCOME MEASURES: Identified barriers, categorized in four domains, including characteristics of: (I) the guideline, (II) professionals, (III) patients, (IV) organization. RESULTS: Ninety-six barriers, at all four domains, were identified among professionals. The most frequently mentioned barriers were: guideline being too complicated in the consultancy room and finding it difficult to refuse demands of insistent patients. Patients mentioned 40 barriers, of which lack of up-to-date patient information and lack of detailed knowledge about family history were most frequently mentioned. Potential facilitators, such as an electronic decision tool and patient questionnaires prior to their first visit, were mentioned by both professionals and patients. All participants agreed that complete adherence to the guideline was theoretically achievable. CONCLUSIONS: Both professionals and patients experienced barriers and facilitators for guideline adherence in recurrent miscarriage. Guideline implementation strategies should take these identified barriers into account.

Number and sequence of preceding miscarriages and maternal age for the prediction of antiphospholipid syndrome in women with recurrent miscarriage.

OBJECTIVE: To investigate the relationship between the number and sequence of preceding miscarriages and antiphospholipid syndrome (APS). DESIGN: Retrospective cohort study. SETTING: Recurrent miscarriage (RM) clinic. PATIENT(S): Women who attended the RM clinic from 1988 to 2006. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number, type, and sequence of previous pregnancies were compared between women with APS and women with unexplained RM. RESULT(S): A total of 1,719 patients were included; 312 (18%) had APS, and 1,407 (82%) had unexplained RM. The mean maternal age (32.6 years) did not differ between women with and without APS. The median number of miscarriages was three in both groups. A total of 865 women (50%) had a history of at least one live birth, with no difference between the two groups. In both groups, 97% of the women had a history of consecutive miscarriages. CONCLUSION(S): The number of preceding miscarriage, type and sequence of previous pregnancies, and maternal age were not associated with APS in women with RM. There is no increased diagnostic yield for APS after three miscarriages rather than after two miscarriages and no increased diagnostic yield for APS after consecutive miscarriages rather than after nonconsecutive miscarriages. Therefore, APS testing should be considered for all women with two or more miscarriages.

Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review.

BACKGROUND: Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy. METHODS: Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register. RESULTS: From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies. CONCLUSIONS: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.